MedWorm: Chronic Lymphocytic Leukemia

Translocation (6;13)(p21;q14.1) as a rare nonrandom cytogenetic abnormality in chronic lymphocytic leukemia

Cancer Genetics and Cytogenetics — Thu, 18 Mar 2010 16:03:07 +0100

We present here a novel conventional and molecular cytogenetic study of a CLL patient with t(6;13)(p21;q14.1), a rare chromosomal aberration. The findings contribute to the identification of rare recurrent aberrations and of any prognostic effect in CLL that could be used for prognostic and therapeutic purposes. The present study demonstrates that t(6;13)(p21;q14.1) as a secondary event to the interstitial deletion in 13q14 region, resulting in the loss of RB1, is a rare but nonrandom abnormality in CLL, resistant to the current treatment CLL protocols with a rather favorable or intermediate prognosis but definitely not an adverse prognosis. Further studies in more CLL patients are required to delineate the prognostic value of t(6;13)(p21;q14.1) and to identify any candidate genes with pot...

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Cladribine and Fludarabine Equally Helpful for Progressive CLL

Medscape Hematology-Oncology Headlines — Mon, 15 Mar 2010 18:56:36 +0100

As first-line treatment for progressive chronic lymphocytic leukemia (CLL), cladribine and fludarabine are equally effective and safe in combination with cyclophosphamide, according to phase III trial results. Reuters Health Information (Source: Medscape Hematology-Oncology Headlines)

A role for PKR in hematologic malignancies

Journal of Cellular Physiology — Mon, 15 Mar 2010 00:00:00 +0100

The double-stranded RNA-dependent kinase PKR has been described for many years as strictly a pro-apoptotic kinase. Recent data suggest that the main purpose of this kinase is damage control and repair following stress and, if all else fails, apoptosis. Aberrant activation of PKR has been reported in numerous neurodegenerative diseases and cancer. Although a subset of myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia contain low levels of PKR expression and activity, elevated PKR activity and/or expression have been detected in a wide range of hematologic malignancies, from bone marrow failure disorders to acute leukemia. With the recent findings that cancers containing elevated PKR activity are highly sensitive to PKR inhibition, we explore the role of PKR in hematologic mal...

Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia

Leukemia — Thu, 11 Mar 2010 00:00:00 +0100

Peptide vaccination elicits leukemia-associated antigen-specific cytotoxic CD8+ T-cell responses in patients with chronic lymphocytic leukemia Leukemia advance online publication, March 11, 2010. doi:10.1038/leu.2010.29 Authors: K Giannopoulos, A Dmoszynska, M Kowal, J Rolinski, E Gostick, D A Price, J Greiner, M Rojewski, S Stilgenbauer, H Döhner & M Schmitt (Source: Leukemia)

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells

Leukemia — Thu, 11 Mar 2010 00:00:00 +0100

Authors: T Vaisitti, S Aydin, D Rossi, F Cottino, L Bergui, G D'Arena, L Bonello, A L Horenstein, P Brennan, C Pepper, G Gaidano, F Malavasi & S Deaglio (Source: Leukemia)

Alemtuzumab by continuous intravenous infusion followed by subcutaneous injection plus rituximab in the treatment of patients with chronic lymphocytic leukemia recurrence

Cancer — Thu, 11 Mar 2010 00:00:00 +0100

Monoclonal antibodies may be used more effectively in combination. A previous study of intravenous (iv) bolus alemtuzumab plus rituximab in patients with chronic lymphocytic leukemia (CLL) recurrence produced a response rate of 54% after a 4-week treatment period.To optimize dose, schedule, and route of alemtuzumab, a study was designed exploring continuous intravenous infusion (civ) followed by subcutaneous (sc) alemtuzumab together with weekly iv rituximab in patients with previously treated CLL.Data from 40 patients with a median age of 59 years, and a median of 3 prior regimens (range, 1-8 regimens) were evaluable. Approximately 64% of patients were fludarabine-refractory. Seven patients (18%) achieved a complete response (CR), 4 (10%) a nodular partial response (nPR), and 10 (25%) a p...

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Isoform-selective phosphoinositide 3-kinase inhibitors induce apoptosis in chronic lymphocytic leukaemia cells

British Journal of Haematology — Thu, 11 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Assessment of Peripheral Blood and Bone Marrow Cells Apoptosis Caused by Purine Analogues in Patients with Chronic Lymphocytic Leukemia in Correlation with Parameters of Disease Progression.

Acta Haematologica — Thu, 11 Mar 2010 00:00:00 +0100

Authors: Podhorecka M, Klimek P, Kowal M, Chocholska S, Bojarska-Junak A, Dmoszynska A Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with variable clinical course and prognosis. Therefore, the role of prognostic factors is very important, especially for identifying the group of patients who require intensive treatment. The aim of this study was to assess whether the rate of apoptosis caused by purine analogues differs between patients with better or worse prognostic factors. The experiments were preformed in cultures of blood and bone marrow obtained from CLL patients. The cultures were supplemented with cladribine and fludarabine. We determined the percentage of caspase-3-positive cells and the BCL-2/BAX ratio, and subsequently these apoptosis markers were correlated w...

Phase III study shows cladribine and fludarabine equally effective for CLL when used in combination with cyclophosphamide

NeLM - News — Wed, 10 Mar 2010 00:00:00 +0100

Source: JCO Area: News According to research published early online in the Journal of Clinical Oncology, cladribine and fludarabine in combination with cyclophosphamide are equally effective and safe first-line regimens for progressive chronic lymphocytic leukaemia (CLL). The PALG-CLL3 study involved a total of 423 patients and was conducted to compare the efficacy and safety of cladribine and fludarabine, each combined with cyclophosphamide, in previously untreated progressive CLL. Patients were randomised to receive cladribine at 0.12 mg/kg combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (CC regimen, n=211) or fludarabine at 25 mg/m2 combined with cyclophosphamide at 250 mg/m2 for 3 days intravenously (FC regimen, n=212), every 28 days for up to six cycle...

Phase III study shows cladribine and fludarabine equally effective for CLL when used in combination with cyclophosphamide

NeLM - News — Wed, 10 Mar 2010 00:00:00 +0100

Source: JCO Area: News According to research published early online in the Journal of Clinical Oncology, no clinical benefit was observed from adding sorafenib to carboplatin and paclitaxel (CP) chemotherapy as first-line treatment for non-small-cell lung cancer (NSCLC). Researchers evaluated the efficacy and safety of sorafenib in combination with carboplatin and paclitaxel in 926 chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer (NSCLC). Patients were randomised to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m2 (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 4...

PRL-2 increases Epo and IL-3 responses in hematopoietic cells.

Blood Cells, Molecules & Diseases — Wed, 10 Mar 2010 00:00:00 +0100

Authors: Akiyama S, Dhavan D, Yi T Dual specificity protein tyrosine phosphatase PRL-2 is overexpressed in pediatric acute myeloid leukemia (AML) and is located at human chromosome 1p35, a region often rearranged or amplified in malignant lymphoma and B-cell chronic lymphocytic leukemia (B-CLL). Little is known of the significance of PRL-2 expression in hematopoietic malignancies. Herein we demonstrated that ectopic expression of PRL-2 in murine pre-B-cell line Baf3ER and mouse bone marrow cells induced key features associated with malignant progression and metastasis. PRL-2-transfected Baf3ER cells had augmented growth responses to hematopoietic growth factors Epo or IL-3 with shortened cell cycle, reduced requirement (5x) for Epo in cell survival, increased cell migration (3x), reduc...

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The Oncogene DEK Promotes Leukemic Cell Survival and Is Downregulated by both Nutlin-3 and Chlorambucil in B-Chronic Lymphocytic Leukemic Cells.

Clinical Cancer Research — Tue, 09 Mar 2010 00:00:00 +0100

CONCLUSIONS: These data show that the downregulation of DEK in response to either Nutlin-3 or chlorambucil represents an important molecular determinant in the cytotoxic response of leukemic cells, and suggest that strategies aimed to downregulate DEK might improve the therapeutic potential of these drugs. Clin Cancer Res; 16(6); 1824-33. PMID: 20215548 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

Second malignancies in B-cell chronic lymphocytic leukaemia: possible association with human papilloma virus

British Journal of Haematology — Mon, 08 Mar 2010 00:00:00 +0100

This report describes preliminary evidence for the presence of HPV in secondary malignancies, in patients with CLL. (Source: British Journal of Haematology)

Prognostic impact of ZAP-70 expression in chronic lymphocytic leukemia: mean fluorescence intensity T/B ratio versus percentage of positive cells

Journal of Translational Medicine — Mon, 08 Mar 2010 00:00:00 +0100

Conclusions: We suggest to evaluate ZAP-70 expression in routine settings using the T/B Ratio-method, given the operator and laboratory independent feature of this approach. We propose the 3.0 T/B Ratio value as optimal cut-off to discriminate ZAP-70+ (T/B Ratio less than 3.0) from ZAP-70- (T/B Ratio more/equal than 3.0) cases. (Source: Journal of Translational Medicine)

Intracellular Succinylation of 8-Chloroadenosine and Its Effect on Fumarate Levels [Bioenergetics]

Journal of Biological Chemistry — Fri, 05 Mar 2010 14:37:12 +0100

8-Chloroadenosine (8-Cl-Ado) is a ribosyl nucleoside analog currently in phase I testing for the treatment of chronic lymphocytic leukemia (CLL). 8-Cl-Ado activity is dependent on adenosine kinase and requires intracellular accumulation of 8-Cl-Ado as mono-, di-, and tri-phosphates. In the current study with four mantle cell lymphoma cell lines, we report a new major metabolic pathway for 8-Cl-Ado intracellular metabolism, the formation of succinyl-8-chloro-adenosine (S-8-Cl-Ado) and its monophosphate (S-8-Cl-AMP). 8-Cl-AMP levels were highly associated with S-8-Cl-AMP levels and reached a steady-state prior to the secondary metabolites, 8-Cl-ATP and S-8-Cl-Ado. Consistent with fumarate as a required substrate for formation of succinyl-8-Cl-adenylate metabolites, the S-8-Cl-adenylate conce...

NICE Set To Recommend Rituximab For Relapsed Or Refractory Chronic Lymphocytic Leukaemia

Health News from Medical News Today — Fri, 05 Mar 2010 04:00:00 +0100

The National Institute for Health and Clinical Excellence (NICE) has today (4 March) issued final draft guidance recommending the drug rituximab(MabThera) as a treatment for certain patients with relapsed or refractory chronic lymphocytic leukaemia. This draft is now with consultees who have the opportunity to appeal against the proposed recommendations before final guidance is published later this year. Chronic lymphocytic leukaemia is a cancer of the white blood cells and is the most common form of leukaemia in the UK... (Source: Health News from Medical News Today)

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NICE Set To Recommend Rituximab For Relapsed Or Refractory Chronic Lymphocytic Leukaemia

Cancer / Oncology News From Medical News Today — Fri, 05 Mar 2010 04:00:00 +0100

Pelvic radiotherapy and the risk of secondary leukemia and multiple myeloma

Cancer — Fri, 05 Mar 2010 00:00:00 +0100

Although several studies had examined secondary malignancies in patients with specific primary tumor types, to the authors' knowledge there are very few data examining the long-term sequelae of pelvic radiation as a whole. The goal of the current study was to examine the risk of treatment-associated leukemia and multiple myeloma in patients treated with pelvic radiotherapy.Patients with invasive tumors of the vulva, cervix, uterus, anus, and rectosigmoid treated from 1973 to 2005 and recorded in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Patients were stratified based on receipt of pelvic radiotherapy. The incidence of secondary leukemia (except chronic lymphocytic leukemia) and multiple myeloma were examined. Multivariate Cox proportional hazards models...

Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression

Blood — Thu, 04 Mar 2010 17:00:46 +0100

This study demonstrates the existence of separate MV phenotypes during leukemic disease progression and underscores the important role of MVs in activation of the tumor microenvironment. (Source: Blood)

Pharmacological activation of the p53 pathway in haematological malignancies

Journal of Clinical Pathology — Thu, 04 Mar 2010 15:42:49 +0100

p53 gene mutations are rarely detected at diagnosis in common haematological cancers such as multiple myeloma (MM), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL) and Hodgkin's disease (HD), although their prevalence may increase with progression to more aggressive or advanced stages. Therapeutic induction of p53 might therefore be particularly suitable for the treatment of haematological malignancies. Some of the anti-tumour activity of current chemotherapeutics has been derived from activation of p53. However, until recently it was unknown whether p53 signalling is functional in certain haematological cancers including MM and if p53 activity is sufficient to trigger an apoptotic response. With the recent discovery of nutlins, which represent the first highly selective...

NICE issues Final Appraisal Determination on rituximab for relapsed chronic lymphocytic leukaemia

NeLM - News — Thu, 04 Mar 2010 00:00:00 +0100

Source: NICE Area: News NICE has issued its Final Appraisal Determination on rituximab for relapsed chronic lymphocytic leukaemia, which contained the following preliminary recommendations: . Rituximab in combination with fludarabine and cyclophosphamide is recommended as a treatment option for people with relapsed or refractory chronic lymphocytic leukaemia except when the condition is refractory to fludarabine (i.e. not responded to fludarabine or has relapsed within 6 months of treatment) or has previously been treated with rituximab. . Rituximab in combination with fludarabine and cyclophosphamide is recommended only in the context of research for people with relapsed or refractory chronic lymphocytic leukaemia that has previously been treated with ritu...

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Fludarabine and cyclophosphamide with rituximab prolongs progression-free survival in previously treated CLL

NeLM - News — Tue, 02 Mar 2010 00:00:00 +0100

Source: JCO Area: News According to research published early online in the Journal of Clinical Oncology, rituximab in combination with fludarabine and cyclophosphamide (R-FC) significantly improved the outcome of patients with previously treated Chronic Lymphocytic Leukeamia (CLL). Researchers compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC; n=276) with six cycles of fludarabine and cyclophosphamide alone (FC; n=276) in patients with previously treated CLL. The trial involved a total of 552 patients with Binet stage A (10%), B (59%), or C (31%) disease. The following results were reported: . After a median follow-up time of 25 months, rituximab significantly improved progression-free survival (hazard ratio = 0.65; P < 0.001; media...

p53 flow cytometry evaluation in leukemias: Correlation to factors affecting clinical outcome

Cytometry Part B: Clinical Cytometry — Tue, 02 Mar 2010 00:00:00 +0100

p53 is a cell cycle checkpoint control protein that assesses DNA damage and acts as a transcription factor regulating genes, which control cell growth, DNA repair, and apoptosis. p53 mutations have been found in a wide variety of different cancers including flow cytometric assessment of p53 protein expression using anti-p53 monoclonal antibodies. We studied p53 protein expression by flow cytometry (FC) assay in 223 blood and/or bone marrow samples from 72 patients with chronic myeloid leukemia (CML): 54 in chronic phase (CML-CP), 7 in accelerated phase (CML-AP), and 11 in blastic phase (CML-BP); 64 patients with chronic lymphoid leukemia (CLL): (34 at diagnosis, 21 in previously treated, and 9 with Richter's syndrome); 44 patients with acute lymphoid leukemia (ALL): 36 at diagnosis and 8 i...

The Lysosomotropic Agent, Hydroxychloroquine, Delivered in a Biodegradable Nanoparticle System, Overcomes Drug Resistance of B-Chronic Lymphocytic Leukemia Cells In Vitro

Cancer Biotherapy and Radiopharmaceuticals — Mon, 01 Mar 2010 04:56:46 +0100

Cancer Biotherapy & Radiopharmaceuticals Feb 2010, Vol. 25, No. 1: 97-103. (Source: Cancer Biotherapy and Radiopharmaceuticals)

Unexpected detection of monoclonal B-cell lymphocytosis in a HLA-matched sibling donor on the day of allogeneic stem cell transplantation for a patient with chronic lymphocytic leukaemia: clinical outcome

British Journal of Haematology — Mon, 01 Mar 2010 00:00:00 +0100

(Source: British Journal of Haematology)

Urolithiasis in patients suffering from malignant hematologic diseases.

Yonsei Medical Journal — Mon, 01 Mar 2010 00:00:00 +0100

CONCLUSION: The incidence of urolithiasis for malignant hematologic patients was significantly higher than that for the control group. PMID: 20191017 [PubMed - in process] (Source: Yonsei Medical Journal)

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Genetic modification of primary chronic lymphocytic leukemia cells with a lentivirus expressing CD38.

Haematologica — Mon, 01 Mar 2010 00:00:00 +0100

Authors: Pearce L, Morgan L, Lin TT, Hewamana S, Matthews RJ, Deaglio S, Rowntree C, Fegan C, Pepper C, Brennan P Studies of the role of individual genes in chronic lymphocytic leukemia (CLL) have been hampered by the inability to consistently transfect primary tumor cells. Here, we describe a highly efficient method of genetically modifying primary CLL cells using a VSVG pseudotyped lentiviral vector. We transduced CD38 negative CLL cells with a lentiviral vector encoding CD38 which caused increased surface CD38 expression in all the samples tested (n=17) with no evidence of plasmacytoid differentiation. The mean percentage of positive cells expressing CD38 was 87%+/-8.5% and the mean cell viability 74%+/-17%. This high level of transduction of all the CLL cell samples tested demonstr...

[Eosinophilic dermatosis associated with haematological disorders: A clinical, histopathological and immunohistochemical study of six observations.]

Annales de Dermatologie et de Cenereologie — Mon, 01 Mar 2010 00:00:00 +0100

We describe six patients with the disorder in association with CLL and other blood dyscrasias. PATIENTS AND METHODS: We reviewed the medical records of patients with EDH seen between 2004 and 2009 in our department and re-examined histological slides. RESULTS: Mean age at dermatosis onset was 75.6 years and the sex ratio was 1. There were three CLL, two mantle-cell lymphomas and one MALT-type lymphoma. The dermatitis was quite polymorphic, with erythematous papules, wheals and plaques. The initial skin lesions appeared at the same time as or after the diagnosis of haematological neoplasm. Their reappearance heralded relapse of the blood disease in three cases. Histologically, all lesions had a dense dermal infiltrate of small, mostly CD4+ T-cells, with numerous eosinophils. In three patien...

A novel Rag2-/-{gamma}c-/--xenograft model of human CLL

Blood — Thu, 25 Feb 2010 17:22:40 +0100

Easily reproducible animal models that allow for study of the biology of chronic lymphocytic leukemia (CLL) and to test new therapeutic agents have been very difficult to establish. We have developed a novel transplantable xenograft murine model of CLL by engrafting the CLL cell line MEC1 into Rag2–/–c–/– mice. These mice lack B, T, and natural killer (NK) cells, and, in contrast to nude mice that retain NK cells, appear to be optimal recipient for MEC1 cells, which were successfully transplanted through either subcutaneous or intravenous routes. The result is a novel in vivo model that has systemic involvement, develops very rapidly, allows the measurement of tumor burden, and has 100% engraftment efficiency. This model closely resembles aggressive human CLL and co...

Membranoproliferative Glomerulonephritis Secondary to Monoclonal Gammopathy.

Clinical Journal of the American Society of Nephrology : CJASN — Thu, 25 Feb 2010 00:00:00 +0100

CONCLUSIONS: Monoclonal gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal gammopathy. PMID: 20185597 [PubMed - as supplied by publisher] (Source: Clinical Journal of the American Society of Nephrology : CJASN)

Merkel Cell Carcinoma in the Peripheral Blood of a Patient With Concomitant Chronic Lymphocytic Leukemia and Multiple Myeloma [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Wed, 24 Feb 2010 23:01:03 +0100

(Source: Journal of Clinical Oncology)

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Pentostatin and rituximab therapy for previously untreated patients with B-cell chronic lymphocytic leukemia

Cancer — Wed, 24 Feb 2010 00:00:00 +0100

The combination of pentostatin (P), cyclophosphamide (C), and rituximab (R) achieved an overall response (OR) rate >90%, with >40% complete responses (CRs) in patients with untreated chronic lymphocytic leukemia (CLL).To evaluate whether the tolerability of this regimen could be enhanced without sacrificing efficacy, a phase 2 trial was conducted of P and R without C, using a higher P dose (4 mg/m2). Among the 33 patients enrolled, 82% were male, the median age was 65 years (9 patients were aged [ge]70 years), and 64% were classified as having Rai stage III to IV disease.The OR rate was 76%, with 9 CRs (27%), 5 nodular partial responses, and 11 partial responses (PRs) reported. At the time of last follow-up, 29 of 33 patients were still alive at a median follow-up of 14 months (range, 1-34...

Chronic lymphocytic leukemia presenting with symptomatic peritoneal infiltration

Leukemia Research — Tue, 23 Feb 2010 14:33:41 +0100

We report the very rare case of CLL diagnosis in a patient suffering from epigastralgia due to peritoneal infiltration. (Source: Leukemia Research)

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

World Pharma News — Tue, 23 Feb 2010 00:00:00 +0100

Rituxan Approved for Chronic Lymphocytic Leukemia

MedicineNet Allergies General — Mon, 22 Feb 2010 07:00:00 +0100

Title: Rituxan Approved for Chronic Lymphocytic LeukemiaCategory: Health NewsCreated: 2/19/2010 12:10:00 PMLast Editorial Review: 2/22/2010 (Source: MedicineNet Allergies General)

Rituxan Approved for Chronic Lymphocytic Leukemia

MedicineNet Cancer General — Mon, 22 Feb 2010 07:00:00 +0100

Title: Rituxan Approved for Chronic Lymphocytic LeukemiaCategory: Health NewsCreated: 2/19/2010 12:10:00 PMLast Editorial Review: 2/22/2010 (Source: MedicineNet Cancer General)

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Rituxan Approved for Chronic Lymphocytic Leukemia

MedicineNet Skin General — Mon, 22 Feb 2010 07:00:00 +0100

Title: Rituxan Approved for Chronic Lymphocytic LeukemiaCategory: Health NewsCreated: 2/19/2010 12:10:00 PMLast Editorial Review: 2/22/2010 (Source: MedicineNet Skin General)

Rituximab for the Treatment of Non-Hodgkins Lymphoma and Chronic Lymphocytic Leukaemia

Drugs — Sat, 20 Feb 2010 14:12:41 +0100

(Source: Drugs)

US FDA Approves Rituxan/MabThera For The Most Common Type Of Adult Leukemia

Health News from Medical News Today — Sat, 20 Feb 2010 10:00:00 +0100

Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the US Food and Drug Administration (FDA) approved Rituxan/MabThera (rituximab) plus fludarabine and cyclophosphamide (FC) chemotherapy for people with either previously untreated (first-line) or previously treated (relapsed or refractory) CD20-positive chronic lymphocytic leukemia (CLL). CLL is the most common type of leukemia in adults, accounting for approximately 30-40% of all forms of leukemia in Western countries. Overall incidence of CLL is around four per 100,000 and is 50% more common in men than in women1... (Source: Health News from Medical News Today)

US FDA Approves Rituxan/MabThera For The Most Common Type Of Adult Leukemia

Lymphoma / Leukemia News From Medical News Today — Sat, 20 Feb 2010 10:00:00 +0100

FDA Approves Rituxan Plus Chemotherapy For The Most Common Type Of Adult Leukemia

Health News from Medical News Today — Sat, 20 Feb 2010 01:00:00 +0100

Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), and Biogen Idec (Nasdaq: BIIB) announced today the U.S. Food and Drug Administration (FDA) approved Rituxan® (rituximab) in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL). CLL is the most common form of adult leukemia and is a slow growing cancer that occurs when abnormal or malignant white blood cells are found in the blood and bone marrow... (Source: Health News from Medical News Today)

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FDA Approves Rituxan Plus Chemotherapy For The Most Common Type Of Adult Leukemia

Cancer / Oncology News From Medical News Today — Sat, 20 Feb 2010 01:00:00 +0100

Genentech, Inc., a wholly owned member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), and Biogen Idec (Nasdaq: BIIB) announced today the U.S. Food and Drug Administration (FDA) approved Rituxan® (rituximab) in combination with fludarabine and cyclophosphamide (FC) for people with previously untreated and previously treated CD20-positive chronic lymphocytic leukemia (CLL)... (Source: Cancer / Oncology News From Medical News Today)

FDA Approves Rituxan to Treat Chronic Lymphocytic Leukemia

MedlinePlus Health News — Fri, 19 Feb 2010 22:55:32 +0100

Source: Food and Drug Administration Related MedlinePlus Topic: Leukemia, Adult Chronic (Source: MedlinePlus Health News)

FDA approves Rituxan for form of leukemia

bizjournals.com Health Care:Biotechnology headlines — Fri, 19 Feb 2010 19:37:15 +0100

Regulators approved the use of the Genentech Inc. and Biogen Idec treatment Rituxan as part of a combination therapy for chronic lymphocytic leukemia. (Source: bizjournals.com Health Care:Biotechnology headlines)

FDA Approves Rituximab for Chronic Lymphocytic Leukemia

Medscape Medical News Headlines — Fri, 19 Feb 2010 17:09:14 +0100

The FDA has approved a new indication for rituximab injection for the treatment of patients with newly diagnosed or relapsed CD20-positive chronic lymphocytic leukemia. Medscape Medical News (Source: Medscape Medical News Headlines)

Rituximab combination approved to treat adult CLL

HemOncToday.com — Fri, 19 Feb 2010 14:55:00 +0100

The drug is used in combination with fludarabine and cyclophosphamide. (Source: HemOncToday.com)

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FDA Adds to CLL Weapons

MedPage Today Hematology/Oncology — Fri, 19 Feb 2010 13:13:05 +0100

WASHINGTON (MedPage Today) -- The FDA has approved rituximab (Rituxan) for treatment of patients with previously untreated chronic lymphocytic leukemia (CLL) or with CLL that has failed prior therapy. (Source: MedPage Today Hematology/Oncology)

FDA Approves Rituxan to Treat Chronic Lymphocytic Leukemia

Drugs.com - New Drug Approvals — Fri, 19 Feb 2010 12:35:07 +0100

ROCKVILLE, Md., Feb. 18, 2010--The U.S. Food and Drug Administration today approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. Rituxan, an anti-cancer... (Source: Drugs.com - New Drug Approvals)

FDA Approves Rituxan To Treat Chronic Lymphocytic Leukemia

Lymphoma / Leukemia News From Medical News Today — Fri, 19 Feb 2010 11:00:00 +0100

The U.S. Food and Drug Administration approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. Rituxan, an anti-cancer drug, is intended for patients with CLL who are beginning chemotherapy for the first time and for those who have not responded to other cancer drugs for CLL... (Source: Lymphoma / Leukemia News From Medical News Today)

FDA Approves Rituxan To Treat Chronic Lymphocytic Leukemia

Health News from Medical News Today — Fri, 19 Feb 2010 11:00:00 +0100

The U.S. Food and Drug Administration approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. Rituxan, an anti-cancer drug, is intended for patients with CLL who are beginning chemotherapy for the first time and for those who have not responded to other cancer drugs for CLL. Rituxan is administered with two other chemotherapy drugs, fludarabine and cyclophosphamide... (Source: Health News from Medical News Today)

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Media News — Fri, 19 Feb 2010 06:00:00 +0100

Roche announced today that the US Food and Drug Administration (FDA) approved Rituxan/MabThera (rituximab) plus fludarabine and cyclophosphamide (FC) chemotherapy for people with either previously untreated (first-line) or previously treated (relapsed or refractory) CD20-positive chronic lymphocytic leukemia (CLL). (Source: Roche Media News)

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US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Investor Update — Fri, 19 Feb 2010 06:00:00 +0100

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Media News — Fri, 19 Feb 2010 06:00:00 +0100

US FDA approves Rituxan/MabThera for the most common type of adult leukemia

Roche Investor Update — Fri, 19 Feb 2010 06:00:00 +0100

Rituxan Approved for Chronic Lymphocytic Leukemia

Modern Medicine — Fri, 19 Feb 2010 00:00:00 +0100

(Source: Modern Medicine)

FDA Approves Rituxan to Treat Chronic Lymphocytic Leukemia

Food and Drug Administration — Thu, 18 Feb 2010 22:06:00 +0100

The U.S. Food and Drug Administration today approved Rituxan (rituximab) to treat certain patients with chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow cancer. (Source: Food and Drug Administration)

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The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation

Cancer — Wed, 17 Feb 2010 00:00:00 +0100

Patients with recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) often have chemotherapy-resistant disease, resulting in poor prognosis. The aim of this study was to learn if inhibition of the mammalian target of rapamycin (mTOR) would produce tumor responses.This was a phase 2 study of oral single-agent everolimus (10 mg/day) for recurrent/refractory indolent lymphoid malignancies including CLL.Four of 22 patients with CLL (18%; 95% confidence interval, 5%-40%) achieved a partial remission to therapy. An unanticipated finding in this study was an increase in absolute lymphocyte count (ALC) associated with a decrease in lymphadenopathy in 8 (36%) patients. ALC increased a median of 4.8-fold (range, 1.9- to 25.1-fold), and the clinically measurable lymphadeno...

Circulating endothelial cells in patients with chronic lymphocytic leukemia

Cancer — Wed, 17 Feb 2010 00:00:00 +0100

In patients with cancer, circulating endothelial cells (CECs) are increased and are correlated with an aggressive disease course. However, the clinical and biologic significance of CECs in chronic lymphocytic leukemia (CLL) remains uncertain.In 170 patients with CLL, CEC levels were quantified by flow cytometry and were correlated with clinical and biologic data. In addition, CECs were characterized by immunophenotypic, fluorescence in situ hybridization (FISH), and gene expression profile analyses.In patients with CLL, CECs were increased compared with controls. A higher level of CECs (>20/[mu]L) identified a subset of patients with a more aggressive disease course characterized by a shorter time to first treatment both in univariate and multivariate analyses. In FISH analysis, 7 patients...

Matrix Metalloproteinase-9 Promotes Chronic Lymphocytic Leukemia B Cell Survival through Its Hemopexin Domain

Cancer Cell — Tue, 16 Feb 2010 04:00:09 +0100

Javier Redondo-Muñoz, Estefanía Ugarte-Berzal, María José Terol, Philippe E. Van den Steen, Mercedes Hernández del Cerro, Martin Roderfeld, Elke Roeb, Ghislain Opdenakker, José A. García-Marco, Angeles García-Pardo. Matrix metalloproteinase-9 (MMP-9) is the major MMP produced by B-CLL cells and contributes to their tissue infiltration by degrading extracellular and membrane-anchored substrates. Here we descri.... (Source: Cancer Cell)

The Bcl-2 Family as a Rational Target for the Treatment of B-Cell Chronic Lymphocytic Leukaemia.

Current Medicinal Chemistry — Tue, 16 Feb 2010 00:00:00 +0100

Authors: Capitani N, Baldari CT B-cell chronic lymphocytic leukaemia (B-CLL) is the most common lymphoid malignancy in the Western world, characterized by clonal growth and accumulation of monoclonal CD5+ B-cells in peripheral blood, bone marrow and peripheral lymphoid organs. Although the clinical course in B-CLL patients is highly variable, the most conserved feature is the prolonged survival of malignant B-cells, which has been associated to defects in the apoptotic machinery. The apoptosis defects are mainly determined by a defective balance among pro- and anti-apoptotic members of the Bcl-2 family, often related to resistance of CLL B-cells to chemotherapy. Purine nucleoside analogs or alkylating agents, alone or in combination, are the first-line treatment for B-CLL patients. Alt...

Serologic Markers of Effective Tumor Immunity against Chronic Lymphocytic Leukemia Include Nonmutated B-Cell Antigens

Cancer Research — Mon, 15 Feb 2010 05:08:31 +0100

Cellular immunotherapy can achieve durable responses, but stable blood borne biomarkers associated with positive outcomes have yet to be determined. (Source: Cancer Research)

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Lipoprotein lipase is differentially expressed in prognostic subsets of chronic lymphocytic leukemia but displays invariably low catalytical activity

Leukemia Research — Fri, 12 Feb 2010 14:22:42 +0100

Abstract: Lipoprotein lipase (LPL) expression has been shown to correlate with IGHV mutational status and to predict outcome in chronic lymphocytic leukemia (CLL). We here investigated the prognostic impact of LPL expression in relation to other prognostic markers including IGHV3-21 usage in 140 CLL patients. Additionally, we studied the catalytic activity of LPL in CLL cells. A significant difference in LPL mRNA expression was detected in IGHV unmutated compared to mutated CLL patients (p (Source: Leukemia Research)

Increased angiogenesis induced by chronic lymphocytic leukemia B cells is mediated by leukemia-derived Ang2 and VEGF

Leukemia Research — Fri, 12 Feb 2010 14:22:42 +0100

Abstract: Emerging evidence suggests that angiogenic signalling pathways play important role in the patho-biology of chronic lymphocytic leukemia (CLL). Our goal was to investigate: (i) the spontaneous and hypoxia-induced production of pro-angiogenic factors, VEGF and Ang2, by Real-time PCR and ELISA, (ii) the degree of vascularization in CLL-infiltrated bone marrow (BM) compartment by CD34 immunohistochemical staining of microvessels and (iii) the direct angiogenic effect of CLL-derived VEGF and Ang2 by function-blocking experiments in Matrigel assays. The results demonstrated that CLL cells spontaneously express both VEGF and Ang2 and are able to secrete these factors in surrounding microenvironment. Full-length Ang2 mRNA and truncated form Ang2443 were detectable. Moreover, CLL cells we...

Lack of association between the MDM2 promoter polymorphism SNP309 and clinical outcome in chronic lymphocytic leukemia

Leukemia Research — Fri, 12 Feb 2010 14:22:42 +0100

Abstract: The 309T>G polymorphism in the promoter region of the MDM2 gene, known as SNP309, has recently been suggested as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL) although this has been questioned. To investigate this further, we analyzed the MDM2 SNP309 genotypes in 418 CLL patients and correlated the results with established CLL prognostic factors, time to treatment and overall survival. In this Swedish cohort, no association existed between any particular MDM2 SNP309 genotype, overall survival and time to treatment. Furthermore, no correlation was shown between the MDM2 SNP309 genotypes and Binet stage, IGHV mutational status and recurrent genomic aberrations. In summary, this study argues against the use of the MDM2 SNP309 as a prognostic marker in CLL. (...

How to improve the treatment outcome in chronic lymphocytic leukemia?

Leukemia Research — Fri, 12 Feb 2010 14:22:41 +0100

Despite improvements in the therapy of patients with chronic lymphocytic leukemia (CLL), the vast majority of patients cannot be cured with current treatment strategies. Purine nucleoside analog (PNA) therapy has had an important impact on the treatment of CLL in the last 20 years. The most widely used agent from this group of antileukemic drugs, fludarabine (FA), induces response in approximately 70% of previously untreated patients, with a minority achieving a complete response (CR). The advantage of PNA over alkylating agent, chlorambucil as the first-line therapy was confirmed in randomized clinical trials . PNA combined with cyclophosphamide (CY) represents a significant advantage over a single agent in terms of an overall response (OR), CR and progression free survival (PFS) . Howeve...

Fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL

Leukemia Research — Fri, 12 Feb 2010 14:22:41 +0100

Abstract: Randomized trials demonstrated the superiority of chemoimmunotherapy over chemotherapy in the frontline treatment of CLL. Based on favorable experience with the addition of mitoxantrone (M) to fludarabine (F) plus cyclophosphamide (C), we designed a pilot study testing the combination of FCM plus rituximab (R). Thirty patients with previously untreated, symptomatic CLL, (Source: Leukemia Research)

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The BCL-2 Family Reunion

Molecular Cell — Fri, 12 Feb 2010 04:00:16 +0100

Jerry E. Chipuk, Tudor Moldoveanu, Fabien Llambi, Melissa J. Parsons, Douglas R. Green. B cell CLL/lymphoma-2 (BCL-2) and its relatives comprise the BCL-2 family of proteins, which were originally characterized with respect to their roles in controlling outer mitochondrial membrane i.... (Source: Molecular Cell)

CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain-engineered monoclonal antibody

Blood — Thu, 11 Feb 2010 17:01:45 +0100

CD19 is a B cell–specific antigen expressed on chronic lymphocytic leukemia (CLL) cells but to date has not been effectively targeted with therapeutic monoclonal antibodies. XmAb5574 is a novel engineered anti-CD19 monoclonal antibody with a modified constant fragment (Fc)–domain designed to enhance binding of FcRIIIa. Herein, we demonstrate that XmAb5574 mediates potent antibody-dependent cellular cytotoxicity (ADCC), modest direct cytotoxicity, and antibody-dependent cellular phagocytosis but not complement-mediated cytotoxicity against CLL cells. Interestingly, XmAb5574 mediates significantly higher ADCC compared with both the humanized anti-CD19 nonengineered antibody it is derived from and also rituximab, a therapeutic antibody widely used in the treatment of CLL. The XmAb...

The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) induces apoptosis, downregulates the CXCR4 chemokine receptor and impairs migration of chronic lymphocytic leukemia cells.

Haematologica — Tue, 09 Feb 2010 00:00:00 +0100

Conclusions In conclusion, SAHA induces apoptosis in CLL cells via the extrinsic pathway and downregulates CXCR4 expression leading to decreased cell migration. SAHA in combination with other drugs represents a promising therapeutic approach to inhibiting migration, CLL cell survival and potentially overcoming drug resistance. PMID: 20145270 [PubMed - as supplied by publisher] (Source: Haematologica)

CXCL12-induced chemotaxis is impaired in T cells from ZAP-70- chronic lymphocytic leukemia patients.

Haematologica — Tue, 09 Feb 2010 00:00:00 +0100

Conclusions The impaired migration towards CXCL12 may reduce the access of T cells from ZAP-70(-) patients to lymphoid organs, creating a less favorable microenvironment for leukemic cell survival and proliferation. PMID: 20145264 [PubMed - as supplied by publisher] (Source: Haematologica)

Impact of the host genetic background on prognosis of chronic lymphocytic leukemia

Blood — Thu, 04 Feb 2010 17:01:42 +0100

(Source: Blood)

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Significant change in ZAP-70 expression during the course of chronic lymphocytic leukemia

European Journal of Haematology — Tue, 02 Feb 2010 00:00:00 +0100

Conclusions: In contrast to commonly accepted opinion, significant change in ZAP-70 expression in time was detected in a substantial proportion of our patients with CLL. While the conversion to ZAP-70 negativity was found predominantly in patients with stable disease, change to positivity was typical in patients with unmutated IgVH genes at the time of progression or relapse. Based on our pilot results, repeated assessment of ZAP-70 expression might be especially useful at the time of progression or relapse in patients who were initially ZAP-70-negative. (Source: European Journal of Haematology)

Ofatumumab

Nature Reviews Drug Discovery — Mon, 01 Feb 2010 14:19:42 +0100

Authors: Michael J. Keating, Argyris Dritselis, Uma Yasothan & Peter Kirkpatrick Ofatumumab (Arzerra; Genmab/GlaxoSmithKline) — a fully human cytolytic monoclonal antibody that is specific for CD20 — was approved by the US FDA for the treatment of chronic lymphocytic leukaemia in October 2009. (Source: Nature Reviews Drug Discovery)

Complications of chronic lymphocytic leukemia: Analysis of 203 cases in China

Leukemia Research — Sat, 30 Jan 2010 14:33:22 +0100

Chronic lymphocytic leukemia (CLL) patients are prone to various complications, such as infections, autoimmune diseases (AID), second tumors or transformations. CLL is the most frequent type of leukemia in the western world, but it is rarely seen in Asian countries . Very limited data published in Chinese patients with respect to the incidence rate, category and prognosis of CLL complications. To explore the characteristics of complications in Chinese CLL patients, 203 cases of CLL patients from the Institute of Hematology and Blood Diseases Hospital, Tianjin, China, from the year 2000 to 2007 were reviewed and followed-up retrospectively. (Source: Leukemia Research)

The TCL1 mouse as a model for chronic lymphocytic leukemia

Leukemia Research — Sat, 30 Jan 2010 14:33:13 +0100

Abstract: The TCL1 mouse has been proposed as a mouse model for chronic lymphocytic leukemia. This review details how it resembles the aggressive form of the disease rather than the more common indolent form. Although fulfilled predictions in the human disease based on investigations in the mouse model are at present lacking, there are remarkable similarities between human and mouse leukemias that have led to interesting observations on the pathophysiology of chronic lymphocytic leukemia and have identified putative therapeutic targets. (Source: Leukemia Research)

Citrobacter koseri Cellulitis During Anti-CD20 Monoclonal Antibody (Ofatumumab) Treatment for B-cell Chronic Lymphocytic Leukaemia.

Acta Derm Venereol A... — Sat, 30 Jan 2010 10:22:03 +0100

Authors: Kluger N, Cartron G, Bessis D, Guillot B, Girard C PMID: 20107742 [PubMed - in process] (Source: Acta Derm Venereol A...)

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The frequency, manifestations, and duration of prolonged cytopenias after first-line fludarabine combination chemotherapy

Annals of Oncology — Fri, 29 Jan 2010 00:07:10 +0100

Conclusions: Cytopenias often persist >3 months after first-line fludarabine combination therapy and can lead to important clinical sequelae. Although cytopenias generally resolve over time, treating physicians should be aware of these factors when considering fludarabine combination chemotherapy and when documenting treatment response status in chronic lymphocytic leukaemia. (Source: Annals of Oncology)

VEGF/VEGFR2 interaction down-regulates matrix metalloproteinase-9 via STAT1 activation and inhibits B chronic lymphocytic leukemia cell migration

Blood — Thu, 28 Jan 2010 17:01:59 +0100

B-cell chronic lymphocytic leukemia (B-CLL) migration involves several molecules, including matrix metalloproteinase–9 (MMP-9) and vascular endothelial growth factor (VEGF). We have studied whether VEGF regulates MMP-9. VEGF significantly reduced MMP-9 protein expression in a dose-dependent manner, measured by gelatin zymography. Blocking the VEGFR2 receptor restored MMP-9 levels, implicating this receptor in the observed effect. Down-regulation of MMP-9 by VEGF resulted in significant inhibition of B-CLL cell migration through Matrigel or human umbilical vein endothelial cells, confirming the crucial role of MMP-9 in these processes. Reverse-transcription polymerase chain reaction analyses revealed that VEGF regulated MMP-9 at the transcriptional level. Indeed, VEGF induced STAT1 ty...

Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer

Carcinogenesis — Thu, 28 Jan 2010 00:05:51 +0100

Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations...

Activation-induced cytidine deaminase splicing patterns in chronic lymphocytic leukemia.

Blood Cells, Molecules & Diseases — Thu, 28 Jan 2010 00:00:00 +0100

Authors: Marantidou F, Dagklis A, Stalika E, Korkolopoulou P, Saetta A, Anagnostopoulos A, Laoutaris N, Stamatopoulos K, Belessi C, Scouras Z, Patsouris E Activation-induced cytidine deaminase (AID) is critically implicated in somatic hypermutation (SHM) and class switch recombination (CSR). AID is expressed as a native transcript and as several splice variants, with as yet undefined roles. Chronic lymphocytic leukemia (CLL) leukemic B cells have also been shown to express AID transcripts, especially in cases with unmutated immunoglobulin (IG) genes. Therefore, AID expression in CLL might potentially be relevant to the disease. The available data on AID-mRNA splicing patterns in CLL are limited and conflicting. Here, we investigated AID-mRNA isoform expression in a series of 195 CLL pa...

Ocular and cerebral aspergillosis in a non-neutropenic patient following alemtuzumab and methyl prednisolone treatment for chronic lymphocytic leukaemia

Journal of Infection and Chemotherapy — Wed, 27 Jan 2010 20:29:24 +0100

Content Type Journal ArticleCategory Letter to the EditorDOI 10.1007/s10156-010-0028-xAuthors Parameswaran Anoop, Royal Marsden Hospital Department of Haematology Fulham Road London SW3 6JJ UKMiles Stanford, St Thomas’ Hospital Department of Ophthalmology Westminster Bridge Road London UKRadovan Saso, Royal Marsden Hospital Department of Haematology Fulham Road London SW3 6JJ UKClaire E. Dearden, Royal Marsden Hospital Department of Haematology Fulham Road London SW3 6JJ UK Journal Journal of Infection and ChemotherapyOnline ISSN 1437-7780Print ISSN 1341-321X (Source: Journal of Infection and Chemotherapy)

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Preventing infectious complications in patients with chronic lymphocytic leukemia

HemOncToday.com — Mon, 25 Jan 2010 09:50:00 +0100

(Source: HemOncToday.com)

Arzerra(TM) (Ofatumumab) Receives Positive Opinion for Conditional Approval in Europe for Refractory Chronic Lymphocytic Leukaemia

HSMN NewsFeed — Fri, 22 Jan 2010 13:20:08 +0100

GSK and Genmab have received a positive opinion for conditional approval of Arzerra (ofatumumab) in Europe for CLL that is refractory to fludarabine and alemtuzumab. COPENHAGEN, Denmark, Jan. 22 --(HSMN NewsFeed)-- GlaxoSmithKline (GSK) and Genmab A/S (... Biopharmaceuticals, Oncology, RegulatoryGenmab, Arzerra, ofatumumab, GlaxoSmithKline, chronic lymphocytic leukaemia (Source: HSMN NewsFeed)

Arzerra(TM) (Ofatumumab) Receives Positive Opinion for Conditional Approval in Europe for Refractory Chronic Lymphocytic Leukaemia

Medical News (via PRIMEZONE) — Fri, 22 Jan 2010 10:45:00 +0100

COPENHAGEN, Denmark, Jan. 22, 2010 (GLOBE NEWSWIRE) -- Summary: GSK and Genmab have received a positive opinion for conditional approval of Arzerra (ofatumumab) in Europe for CLL that is refractory to fludarabine and alemtuzumab. (Source: Medical News (via PRIMEZONE))

Arzerra (ofatumumab) receives positive opinion for conditional approval in Europe for refractory chronic lymphocytic leukaemia

GSK news — Fri, 22 Jan 2010 10:30:00 +0100

GlaxoSmithKline (GSK) and Genmab A/S announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for Arzerraä (ofatumumab) for the treatment of refractory chronic lymphocytic leukaemia (CLL) (Source: GSK news)

Horizon Scanning: European CHMP issues positive opinion on Arzerra® (ofatumumab) for use in chronic lymphocytic leukaemia (CLL)

NeLM - Oncology — Fri, 22 Jan 2010 00:00:00 +0100

Source: EMEA Area: News The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has adopted a positive opinion, recommending the granting of a conditional marketing authorisation for Arzerra® (ofatumumab, Glaxo Group Ltd) 20mg/ml, concentrate for solution for infusion intended for the treatment of chronic lymphocytic leukaemia (CLL). Arzerra was designated as an orphan medicinal product on 7 November 2008. The approved indication is given in the link below as: "Treatment of CLL in patients refractory to fludarabine and alemtuzumab". (Source: NeLM - Oncology)

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Improving FCR immunochemotherapy in CLL

Blood — Thu, 21 Jan 2010 17:02:34 +0100

(Source: Blood)

Phase 1/2 study of lumiliximab combined with fludarabine, cyclophosphamide, and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia

Blood — Thu, 21 Jan 2010 17:02:34 +0100

Preclinical data demonstrate enhanced antitumor effect when lumiliximab, an anti-CD23 monoclonal antibody, is combined with fludarabine or rituximab. Clinical data from a phase 1 trial with lumiliximab demonstrated an acceptable toxicity profile in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). We therefore pursued a phase 1/2 dose-escalation study of lumiliximab added to fludarabine, cyclophosphamide, and rituximab (FCR) in previously treated CLL patients. Thirty-one patients received either 375 mg/m2 (n = 3) or 500 mg/m2 (n = 28) of lumiliximab in combination with FCR for 6 cycles. The toxicity profile was similar to that previously reported for FCR in treatment of relapsed CLL. The overall response rate was 65%, with 52% of patients achieving a complete respons...

The use of low-dose alemtuzumab in pretreated B-cell chronic lymphocytic leukemia

Leukemia — Thu, 21 Jan 2010 00:00:00 +0100

Authors: M Tarnani, G D'Arena, D G Efremov, S Marietti, Sica S, G Leone & L Laurenti (Source: Leukemia)

Variant IRF4/MUM1 associates with CD38 status and treatment-free survival in chronic lymphocytic leukaemia

Leukemia — Thu, 21 Jan 2010 00:00:00 +0100

Variant IRF4/MUM1 associates with CD38 status and treatment-free survival in chronic lymphocytic leukaemia Leukemia advance online publication, January 21, 2010. doi:10.1038/leu.2009.298 Authors: J M Allan, N J Sunter, J R Bailey, A R Pettitt, R J Harris, C Pepper, C Fegan, A G Hall, L Deignan, C M Bacon, J C Pointon, R S Houlston, P Broderick, T Mainou-Fowler, G H Jackson, G Summerfield, P A Evans, J C Strefford, A Parker, D Oscier, G Pratt & D J Allsup (Source: Leukemia)

Serum metabolome analysis by 1H-NMR reveals differences between chronic lymphocytic leukaemia molecular subgroups

Leukemia — Thu, 21 Jan 2010 00:00:00 +0100

Authors: D A MacIntyre, B Jiménez, E Jantus Lewintre, C Reinoso Martín, H Schäfer, C García Ballesteros, J Ramón Mayans, M Spraul, J García-Conde & A Pineda-Lucena (Source: Leukemia)

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Biclonal origin prevails in concomitant chronic lymphocytic leukemia and multiple myeloma

Leukemia — Thu, 21 Jan 2010 00:00:00 +0100

Authors: M Pantic, P Schroettner, D Pfeifer, J Rawluk, U Denz, A Schmitt-Gräff, H Veelken, R Wäsch & M Engelhardt (Source: Leukemia)

All You Need Is a Mir-acle: The Role of Nontranslated RNAs in the Suppression of B Cell Chronic Lymphocytic Leukemia

Cancer Cell — Wed, 20 Jan 2010 04:00:10 +0100

Peter Lichter. miR-15a and miR-16-1 were the first microRNAs linked to cancer because their genes are commonly deleted in human chronic lymphocytic leukemia (CLL). In this issue of Cancer Cell, Klein and .... (Source: Cancer Cell)

Effects of Chronic Lymphocytic Leukemia on the Development and Progression of Malignant Melanoma

Dermatologic Surgery — Tue, 19 Jan 2010 00:00:00 +0100

An association exists between chronic lymphocytic leukemia and malignant melanoma. To study the clinical behavior of malignant melanoma in patients with chronic lymphocytic leukemia. A retrospective chart review was conducted of patients with chronic lymphocytic leukemia and malignant melanoma. Sixty-nine patients had malignant melanoma and chronic lymphocytic leukemia. The recurrence-free and metastasis-free survival rates at 2, 5, and 10 years were 93.4% and 89.1%, 83.8% and 93.4%, and 87.4% and 82.1%, respectively. No significant difference was observed in age- and sex-adjusted mortality rates between patients with chronic lymphocytic leukemia diagnosed before malignant melanoma and those with chronic lymphocytic leukemia diagnosed after malignant melanoma. Retrospective study and small...

Aggressive Chronic Lymphocytic Leukemia with Elevated Genomic Complexity Is Associated with Multiple Gene Defects in the Response to DNA Double-Strand Breaks.

Clinical Cancer Research — Tue, 19 Jan 2010 00:00:00 +0100

CONCLUSIONS: Our quantitative analysis links multiple molecular defects, including for the first time del11q and large 13q14 deletions (type II), to elevated genomic complexity in CLL, thereby suggesting mechanisms for the observed clinical aggressiveness of CLL in patients with unstable genomes. Clin Cancer Res; 16(3); OF1-13. PMID: 20086003 [PubMed - as supplied by publisher] (Source: Clinical Cancer Research)

SMC accepts rituximab (MabThera®) for restricted use in the treatment of CLL

NeLM - Oncology — Mon, 18 Jan 2010 00:00:00 +0100

Source: Scottish Medicines Consortium (SMC) Area: Evidence > Drug Specific Reviews The Scottish Medicines Consortium (SMC) has accepted rituximab (MabThera®) for use within NHS Scotland for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukaemia (CLL) in combination with chemotherapy. It is restricted to use by specialists in haematology and haemato-oncology. According to the drug advice (see link below), rituximab in combination with fludarabine and cyclophosphamide resulted in significantly longer progression-free survival than fludarabine and cyclophosphamide alone. The patient population in the pivotal clinical study had an Eastern Cooperative Oncology Group Performance Status of 0 or 1 and was a younger population th...

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BioCryst's CTCL Pivotal Study Achieves Enrollment Target

Health News from Medical News Today — Sat, 16 Jan 2010 09:00:00 +0100

BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) announced that it has achieved its protocol specified objective of enrolling 100 late-stage patients (Stage IIB to IVA) in its pivotal study for forodesine in the treatment of cutaneous T-cell lymphoma (CTCL). Top-line data is expected in the second half of 2010. Additionally, BioCryst's exploratory Phase 2 study for forodesine in subjects with chronic lymphocytic leukemia (CLL) is continuing to progress and has enrolled over half of its targeted number of patients... (Source: Health News from Medical News Today)

Ribosome-lamella complexes in the peripheral blood of patients with chronic lymphocytic leukemia are associated with serological immune deficiency.

Ultrastructural Pathology — Sat, 16 Jan 2010 00:56:11 +0100

Authors: Kravic-Stevovic T, Bogdanovic A, Boskovic D, Bumbasirevic V The ribosome-lamella complex (RLC) is a cylindrical structure composed of different numbers of circular lamellae with associated particles, regarded as ribosomes, around a central core. Structures resembling RLC, but lacking the typical mature appearance of RLC, have been called pre-RLC. The authors have found RLCs and pre-RLCs in peripheral lymphocytes of 3 patients with chronic lymphocytic leukemia (CLL). The fact that CLL patients with RLCs were in early Rai clinical stages, had good clinical prognostic factors, and did not require immediate therapy indicates that RLCs occurred in the early course of some cases of CLL. Moreover, the presence of RLC was associated with hypogammaglobulinemia M. PMID: 20070151 [Pu...

Bilateral Occipital Lobe Invasion in Chronic Lymphocytic Leukemia [DIAGNOSIS IN ONCOLOGY]

Journal of Clinical Oncology — Fri, 15 Jan 2010 23:02:20 +0100

(Source: Journal of Clinical Oncology)

Flavopiridol, Fludarabine, and Rituximab in Mantle Cell Lymphoma and Indolent B-Cell Lymphoproliferative Disorders [Hematologic Malignancies]

Journal of Clinical Oncology — Fri, 15 Jan 2010 23:02:20 +0100

Conclusion FFR was active in MCL, indolent B-NHL, and CLL and should be studied for older patients with MCL who are not candidates for aggressive chemotherapy. (Source: Journal of Clinical Oncology)

Challenges in the Frontline Treatment of Patients With Chronic Lymphocytic Leukemia

Current Hematologic Malignancy Reports — Fri, 15 Jan 2010 18:05:22 +0100

Abstract Therapy for chronic lymphocytic leukemia has improved dramatically over the past 20 years. Traditional therapy with oral chlorambucil led to complete responses in less than 5% of treated patients, in marked contrast to modern regimens, which can reliably produce complete responses in over 50% of patients. This remarkable improvement is attributable to the use of purine analogue-based treatment as well as monoclonal antibodies. Novel combinations of these agents have emerged as effective new therapies for previously untreated patients. Clinical studies indicate that such combinations can induce higher response rates (including complete responses) than single-agent therapy. Those patients who achieve a complete response have superior progression-free survival c...

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CytRx To Conduct Phase 2 Clinical Trial With Bafetinib In B-cell Chronic Lymphocytic Leukemia

Health News from Medical News Today — Fri, 15 Jan 2010 05:00:00 +0100

CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical company specializing in oncology, today announced plans to initiate a Phase 2 proof-of-concept clinical trial to evaluate the efficacy and safety of bafetinib (formerly known as INNO-406) in patients with high-risk B-cell chronic lymphocytic leukemia (B-CLL). CytRx President and CEO Steven A. Kriegsman, stated, "We believe bafetinib is a cutting-edge treatment that could be efficacious in a wide range of hematological cancers... (Source: Health News from Medical News Today)

CytRx To Conduct Phase 2 Clinical Trial With Bafetinib In B-cell Chronic Lymphocytic Leukemia

Cancer / Oncology News From Medical News Today — Fri, 15 Jan 2010 05:00:00 +0100

CytRx Corporation (NASDAQ:CYTR), a biopharmaceutical company specializing in oncology, today announced plans to initiate a Phase 2 proof-of-concept clinical trial to evaluate the efficacy and safety of bafetinib (formerly known as INNO-406) in patients with high-risk B-cell chronic lymphocytic leukemia (B-CLL). CytRx President and CEO Steven A... (Source: Cancer / Oncology News From Medical News Today)

Differential genome-wide array-based methylation profiles in prognostic subsets of chronic lymphocytic leukemia

Blood — Thu, 14 Jan 2010 17:03:28 +0100

Global hypomethylation and regional hypermethylation are well-known epigenetic features of cancer; however, in chronic lymphocytic leukemia (CLL), studies on genome-wide epigenetic modifications are limited. Here, we analyzed the global methylation profiles in CLL, by applying high-resolution methylation microarrays (27 578 CpG sites) to 23 CLL samples, belonging to the immunoglobulin heavy-chain variable (IGHV) mutated (favorable) and IGHV unmutated/IGHV3-21 (poor-prognostic) subsets. Overall, results demonstrated significant differences in methylation patterns between these subgroups. Specifically, in IGHV unmutated CLL, we identified methylation of 7 known or candidate tumor suppressor genes (eg, VHL, ABI3, and IGSF4) as well as 8 unmethylated genes involved in cell proliferation and tu...

How I treat CLL up front

Blood — Thu, 14 Jan 2010 17:03:27 +0100

Although chronic lymphocytic leukemia (CLL) remains incurable, over the past decade there have been major advances in understanding the pathophysiology of CLL and in the treatment of this disease. This has led to greatly increased response rates and durations of response but not yet improved survival. Advances in the use of prognostic factors that identify patients at high risk for progression have led us to the question whether there is still a role for a "watch and wait" approach in asymptomatic high-risk patients or whether they should be treated earlier in their disease course. Questions remain, including, what is the optimal first-line treatment and its timing and is there any role of maintenance therapy or stem cell transplantation in this disease? CLL is a disease of the elderly and...

Selective elimination of a chemoresistant side population of B-CLL cells by cytotoxic T lymphocytes in subjects receiving an autologous hCD40L/IL-2 tumor vaccine

Leukemia — Thu, 14 Jan 2010 00:00:00 +0100

Selective elimination of a chemoresistant side population of B-CLL cells by cytotoxic T lymphocytes in subjects receiving an autologous hCD40L/IL-2 tumor vaccine Leukemia advance online publication, January 14, 2010. doi:10.1038/leu.2009.281 Authors: A E Foster, F V Okur, E Biagi, A Lu, G Dotti, E Yvon, B Savoldo, G Carrum, M A Goodell, H E Heslop & M K Brenner (Source: Leukemia)

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Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place

Leukemia — Thu, 14 Jan 2010 00:00:00 +0100

Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place Leukemia advance online publication, January 14, 2010. doi:10.1038/leu.2009.285 Authors: B Herreros, S M Rodríguez-Pinilla, R Pajares, M Á Martínez-Gónzalez, R Ramos, I Munoz, S Montes-Moreno, M Lozano, L Sánchez-Verde, G Roncador, M Sánchez-Beato, R D de Otazu, M Pérez-Guillermo, M J Mestre, C Bellas & M Á Piris (Source: Leukemia)

Insertional Mutagenesis in Mice Deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 Reveals Cancer Gene Interactions and Correlations with Tumor Phenotypes.

Cell Research — Tue, 12 Jan 2010 00:00:00 +0100

Authors: Kool J, Uren AG, Martins CP, Sie D, de Ridder J, Turner G, van Uitert M, Matentzoglu K, Lagcher W, Krimpenfort P, Gadiot J, Pritchard C, Lenz J, Lund AH, Jonkers J, Rogers J, Adams DJ, Wessels L, Berns A, van Lohuizen M The cyclin dependent kinase (CDK) inhibitors p15, p16, p21, and p27 are frequently deleted, silenced, or downregulated in many malignancies. Inactivation of CDK inhibitors predisposes mice to tumor development, showing that these genes function as tumor suppressors. Here, we describe high-throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors. We retrieved 9,117 retroviral insertions from 476 lymphomas to define hundreds of loci that are mutated more frequently than expected by chance. Many of t...

Immunoglobulin Heavy Chain Variable Gene Usage and (Super)-antigen Drive in Chronic Lymphocytic Leukemia.

Cell Research — Tue, 12 Jan 2010 00:00:00 +0100

Authors: Bühler A, Zenz T, Stilgenbauer S Increasing evidence supports the prognostic relevance of specific immunoglobulin heavy chain variable (IGHV) genes or stereotyped B-cell receptors (BCR) in chronic lymphocytic leukemia (CLL). The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups. Clin Cancer Res; 16(2); 373-5. PMID: 20068107 [PubMed - as supplied by publisher] (Source: Cell Research)

Activities of SYK and PLC{gamma}2 Predict Apoptotic Response of CLL Cells to SRC Tyrosine Kinase Inhibitor Dasatinib.

Cell Research — Tue, 12 Jan 2010 00:00:00 +0100

CONCLUSIONS: Thus, SYK inhibition predicts cellular response to dasatinib. SYK, together with phospholipase Cgamma2, may serve as potential biomarkers to predict dasatinib therapeutic response in patients. From the pathogenic perspective, our study suggests the existence of alternative mechanisms or pathways that activate SYK, independent of SRC kinase activities. The study further implicates that SYK might serve as a more effective therapeutic target in CLL treatment. Clin Cancer Res; 16(2); 587-99. PMID: 20068106 [PubMed - as supplied by publisher] (Source: Cell Research)

Time to Treatment Response in Patients with Follicular Lymphoma Treated with Bortezomib Is Longer Compared with Other Histologic Subtypes.

Cell Research — Tue, 12 Jan 2010 00:00:00 +0100

CONCLUSIONS: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response. Clin Cancer Res; 16(2); 719-26. PMID: 20068103 [PubMed - as supplied by publisher] (Source: Cell Research)

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Expression of Mutated IGHV3-23 Genes in Chronic Lymphocytic Leukemia Identifies a Disease Subset with Peculiar Clinical and Biological Features.

Cell Research — Tue, 12 Jan 2010 00:00:00 +0100

CONCLUSIONS: Altogether, expression of the IGHV3-23 gene characterizes a CLL subset with distinct clinical and biological features. Clin Cancer Res; 16(2); 620-8. PMID: 20068100 [PubMed - as supplied by publisher] (Source: Cell Research)

Eradicating Minimal Residual Disease in Chronic Lymphocytic Leukemia: Should This Be the Goal of Treatment?

Current Hematologic Malignancy Reports — Mon, 11 Jan 2010 18:25:12 +0100

This article reviews our current understanding of MRD eradication and analyzes whether it is a desirable goal in the routine clinical treatment of CLL, which will optimize the management of individual patients. Content Type Journal ArticleDOI 10.1007/s11899-009-0041-2Authors Abraham M. Varghese, Bexley Wing, St James’s Institute of Oncology Department of Haematology Beckett Street Leeds LS9 7TF UKAndy C. Rawstron, Bexley Wing, St James’s Institute of Oncology Department of Haematology Beckett Street Leeds LS9 7TF UKPeter Hillmen, Bexley Wing, St James’s Institute of Oncology Department of Haematology Beckett Street Leeds LS9 7TF UK Journal Current Hematologic Malignancy ReportsOnline ISSN 1558-822XPrint ISSN 1558-8211 (Source: Current Hematologic Malignancy Reports)

Genetic Factors Can Increase Leukaemia Risk Seven-Fold

Health News from Medical News Today — Mon, 11 Jan 2010 10:00:00 +0100

Scientists have found four new regions of the genome that increase the risk of a common blood cancer, according to results published in the journal Nature Genetics. Professor Richard Houlston and his team at The Institute of Cancer Research (ICR) have now found the location of 10 genetic variants, common in the European population, that are associated with an increased risk of chronic lymphocytic leukaemia (CLL). Professor Houlston's team last year proved that people's genes could make them more susceptible to CLL, identifying six regions of the genome more common among sufferers... (Source: Health News from Medical News Today)

Common variants at 2q37.3, 8q24.21, 15q21.3 and 16q24.1 influence chronic lymphocytic leukemia risk

Nature Genetics — Sun, 10 Jan 2010 00:00:00 +0100

Authors: Dalemari Crowther-Swanepoel, Peter Broderick, Maria Chiara Di Bernardo, Sara E Dobbins, María Torres, Mahmoud Mansouri, Clara Ruiz-Ponte, Anna Enjuanes, Richard Rosenquist, Angel Carracedo, Jesper Jurlander, Elias Campo, Gunnar Juliusson, Emilio Montserrat, Karin E Smedby, Martin J S Dyer, Estella Matutes, Claire Dearden, Nicola J Sunter, Andrew G Hall, Tryfonia Mainou-Fowler, Graham H Jackson, Geoffrey Summerfield, Robert J Harris, Andrew R Pettitt, David J Allsup, James R Bailey, Guy Pratt, Chris Pepper, Chris Fegan, Anton Parker, David Oscier, James M Allan, Daniel Catovsky & Richard S Houlston To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional se...

The DLEU2/miR-15a/16-1 Cluster Controls B Cell Proliferation and Its Deletion Leads to Chronic Lymphocytic Leukemia

Cancer Cell — Fri, 08 Jan 2010 04:00:11 +0100

Ulf Klein, Marie Lia, Marta Crespo, Rachael Siegel, Qiong Shen, Tongwei Mo, Alberto Ambesi-Impiombato, Andrea Califano, Anna Migliazza, Govind Bhagat, Riccardo Dalla-Favera. Chronic lymphocytic leukemia (CLL) is a malignancy of B cells of unknown etiology. Deletions of the chromosomal region 13q14 are commonly associated with CLL, with monoclonal B cell lymphocytosis .... (Source: Cancer Cell)

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The normal IGHV1-69-derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL

Blood — Thu, 07 Jan 2010 17:02:11 +0100

The cell of origin of chronic lymphocytic leukemia (CLL) has long been sought, and immunoglobulin gene analysis provides new clues. In the unmutated subset (U-CLL), there is increased usage of the 51p1-related alleles of the immunoglobulin heavy chain variable 1-69 gene, often combined with selected genes and with immunoglobulin heavy chain diversity IGHJ6. Stereotypic characteristics of the HCDR3 result and suggest antigen selection of the leukemic clones. We have now analyzed 51p1/IGHJ6 combinations in normal blood B cells from 3 healthy persons for parallel sequence patterns. A high proportion (33.3% of sequences) revealed stereotypic patterns, with several (15.0%) being similar to those described in U-CLL. Previously unreported CLL-associated stereotypes were detected in 4.8%. Stereoty...

Review: Investigational immunotherapies for B-Cell malignancies

NeLM - Oncology — Thu, 07 Jan 2010 00:00:00 +0100

Source: J Clin Oncol Area: News Some promising investigational immunotherapies for the treatment of B-cell malignancies are discussed in this review in the Journal of Clinical Oncology. Topics covered include: . Are novel agents really needed in B-cell NHL and CLL? . Investigational monoclonal antibodies (mAbs) in clinical development: ofatumumab, lumiliximab . Investigational mAbs in early phases of development: anti-CD20 mAbs and those with other specificities . Novel classes of targeted immunotherapeutics: bispecific mAbs, small-modular immunopharmaceuticals, T-cell engaging antibodies (Source: NeLM - Oncology)

IGHD3-3 fails to behave as unfavourable prognostic marker in chronic lymphocytic leukaemia

British Journal of Haematology — Thu, 07 Jan 2010 00:00:00 +0100

(Source: British Journal of Haematology)

IL-7 receptor is expressed on adult pre-B-cell acute lymphoblastic leukemia and other B-cell derived neoplasms and correlates with expression of proliferation and survival markers.

Cytokine — Thu, 07 Jan 2010 00:00:00 +0100

Authors: Sasson SC, Smith S, Seddiki N, Zaunders JJ, Bryant A, Koelsch KK, Weatherall C, Munier ML, McGinley C, Yeung J, Mulligan SP, Moore J, Cooper DA, Milliken S, Kelleher AD The interleukin (IL)-7 receptor (IL-7R) is expressed on human pre-B but not mature B-cells. We hypothesised that aberrant expression of IL-7R contributes to B-cell oncogenesis. Surface expression of IL-7R components CD127 and CD132, and intracellular Ki-67 and Bcl-2 were examined by flow cytometry on peripheral blood or bone marrow mononuclear cells (PBMC; BMMC) from patients with B-cell derived neoplasms, chronic human immunodeficiency virus type-1 (HIV-1) infection alone, or healthy volunteers. Plasma IL-7, IL-2, IL-4, IL-6, IL-10, IL-21, TNF-alpha, IFN-gamma and BAFF were measured by enzyme-linked immuno-sor...

Epstein-barr virus latent membrane protein 1 mRNA is expressed in a significant proportion of patients with chronic lymphocytic leukemia

Cancer — Tue, 05 Jan 2010 00:00:00 +0100

Epstein-Barr virus (EBV) infection has been associated with Richter transformation in patients with chronic lymphocytic leukemia (CLL).A direct isothermal mRNA amplification method was developed for detection of EBV latent membrane protein 1 (LMP1) mRNA transcriptional activity in the peripheral blood of 135 chronic lymphocytic leukemia patients and 98 hematologically healthy control subjects.EBV LMP1 mRNA transcripts were found in 19 of 135 (14%) of the CLL cases, but only 1% of the healthy controls (P < .0001). In contrast, 23 solid tumor patients tested negative for EBV LMP1 transcripts. In a later cohort of patients after hematopoietic stem cell transplantation, 4 of 7 patients with Hodgkin lymphoma or Burkitt lymphoma had EBV LMP1 detected. In a preliminary analysis, outcome data were...

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Free light chain: a novel predictor of adverse outcome in chronic lymphocytic leukemia

European Journal of Haematology — Tue, 05 Jan 2010 00:00:00 +0100

Conclusions: This study highlighted the adverse prognostic impact of high sFLC levels and abnormal FLCR with regard to survival in CLL, even in early stage patients. Prospective studies are warranted to validate the adverse impact of sFLC and FLCR on clinical outcome. (Source: European Journal of Haematology)

New Agents in Chronic Lymphocytic Leukemia

Current Hematologic Malignancy Reports — Mon, 04 Jan 2010 18:02:16 +0100

Abstract Despite advances in treatment, chronic lymphocytic leukemia (CLL) remains incurable with standard therapies. Novel therapeutic agents are needed, particularly for patients with high-risk cytogenetic abnormalities such as del(17p13). The past year has seen several advances in this field. The immunomodulatory drug lenalidomide and the cyclin-dependent kinase inhibitor flavopiridol demonstrated clinical activity in fludarabine-refractory CLL patients with high-risk cytogenetic features and bulky lymphadenopathy, but they were associated with toxicities such as tumor flare and tumor lysis. Second-generation monoclonal anti-CD20 antibodies in clinical trials include ofatumumab, which demonstrated activity in fludarabine-refractory patients with bulky lymphadenopathy. O...

VentX, a Novel Lymphoid-Enhancing Factor/T-Cell Factor-Associated Transcription Repressor, Is a Putative Tumor Suppressor

Cancer Research — Mon, 04 Jan 2010 17:20:00 +0100

Attenuations in the expression of a novel LEF/TCF pathway effector in hemtopoeitic cells might contribute to the development of chronic lymphocytic leukemia (CLL). (Source: Cancer Research)

Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia

European Journal of Cancer — Mon, 04 Jan 2010 00:00:00 +0100

In conclusion, CLL cells show the apoptosis-resistant profile of IAPs/IAP-antagonist expression. Upregulation of IAPs is associated with a progressive course of the disease. Co-expression of cIAP1 and survivin seems to be an unfavourable prognostic factor in CLL patients. Further studies with longer follow up are warranted to confirm and expand these findings. (Source: European Journal of Cancer)

Gain of the short arm of chromosome 2 (2p) is a frequent recurring chromosome aberration in untreated chronic lymphocytic leukemia (CLL) at advanced stages

Leukemia Research — Fri, 01 Jan 2010 00:00:00 +0100

Abstract: Using array-based CGH, we identified 2p gain in 22/78 (28%) untreated Binet stages B/C CLL, which was the second most frequent copy number change after 13q deletion. It never occurred as a sole abnormality and was associated with other changes (6q deletion; 1p gain). The region of 2p gain frequently included two oncogenes, REL and MYCN. All patients with gain of REL were unmutated for IGHV (p=0.03). Gain of MYCN was associated with increased mRNA expression (p=0.005), suggesting a pathogenic role for MYCN. Gain of 2p appears to be a marker of progression and may contribute to the poor prognosis. (Source: Leukemia Research)

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ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia.

Cancer Biomarkers : Section A of Disease Markers — Fri, 01 Jan 2010 00:00:00 +0100

Conclusions: We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL. PMID: 20164537 [PubMed - in process] (Source: Cancer Biomarkers : Section A of Disease Markers)

Targeted therapy in haematological malignancies

The Journal of Pathology — Wed, 30 Dec 2009 00:00:00 +0100

The recent and rapid development of molecularly targeted therapy is best illustrated by advances in the management of haematological malignancy. In myeloid diseases we have seen dramatic improvements in the overall survival and quality of life for patients with chronic myeloid leukaemia treated with ABL and Src/ABL kinase inhibitors and we are poised to discover whether JAK2 inhibitors may offer similar benefit in myeloproliferative diseases. For acute myeloid leukaemia, the introduction of ATRA and myelotarg have had major impacts on the design of therapy regimens and many novel targeted agents, including farnesyl transferase, FLT3 and histone deacetylase inhibitors, are now in clinical trial. In lymphoid malignancies the highlight has been the introduction of rituximab, with significant ...

In defence of the use of modern chemotherapy regimens for the treatment of patients with chronic lymphocytic leukaemia

Internal Medicine Journal — Wed, 30 Dec 2009 00:00:00 +0100

(Source: Internal Medicine Journal)

Addition of rituximab improves OS in chronic lymphocytic leukemia

Cancer Network — Mon, 28 Dec 2009 12:00:00 +0100

NEW ORLEANS—Genentech and Biogen announced at ASH 2009 that the three-year follow-up of the CLL8 trial demonstrated that rituximab (Rituxan) plus fludarabine and cyclophosphamide (FC) chemotherapy improved overall survival in patients with previously untreated chronic lymphocytic leukemia (CLL) vs FC therapy alone. (Source: Cancer Network)

B-cell CLL/Lymphoma 10 (BCL10) Is Required for NF-{kappa}B Production by Both Canonical and Noncanonical Pathways and for NF-{kappa}B-inducing Kinase (NIK) Phosphorylation [Mechanisms Of Signal Transduction]

Journal of Biological Chemistry — Fri, 25 Dec 2009 17:35:57 +0100

B-cell CLL/lymphoma 10 (BCL10), the caspase recruitment domain (CARD)-containing protein involved in the etiology of the mucosa-associated lymphoid tissue (MALT) lymphomas, has been implicated in inflammatory processes in epithelial cells, as well as in immune cells. Experiments in this report indicate that BCL10 is required for activation of nuclear factor (NF)-B by both canonical and noncanonical pathways, following stimulation by the sulfated polysaccharide carrageenan (CGN). In wild type and IB-kinase (IKK)–/– mouse embryonic fibroblasts, increases in phospho-IB, nuclear NF-B p65 (RelA) and p50, and KC, the mouse analog of human interleukin-8, were markedly reduced by silencing BCL10 or by exposure to the free radical scavenger Tempol. In IKKβ–/– cells, BCL...

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The use of tetradecanoylphorbol acetate-stimulated peripheral blood cells enhances the prognostic value of interphase fluorescence in situ hybridization in patients with chronic lymphocytic leukemia

Genes, Chromosomes and Cancer — Thu, 24 Dec 2009 00:00:00 +0100

Pasteurella multocida tracheobronchitis in a patient with CLL on rituximab

American Journal of Hematology — Thu, 24 Dec 2009 00:00:00 +0100

No abstract. (Source: American Journal of Hematology)

Concurrent and Apposed Hepatocellular Carcinoma and Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia in a Patient with Hepatitis C Virus.

Acta Haematologica — Wed, 23 Dec 2009 00:00:00 +0100

Authors: Becker DJ, Sevilla DW, O'Connor O A patient with chronic hepatitis C virus (HCV) presented to our clinic with a hepatic mass as well as lymphocytosis. Biopsy of the hepatic mass revealed apposed hepatocellular carcinoma (HCC) and small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL). Dramatic examples of lymphoma regression during treatment with antiviral medication in chronic HCV patients have suggested an etiologic role for HCV in lymphomagenesis. A growing body of research seeks to clarify the details of the interaction between HCV and B-cell lymphomas. This case of adjacent SLL/CLL and HCC is the first published diagnosis of these two diseases in the liver at one time, and the only published example of the physical apposition of any lymphoma and HCC. The case...

Aberrant Nuclear p53 Expression Predicts Hemizygous 17p (TP53) Deletion in Chronic Lymphocytic Leukemia.

American Journal of Clinical Pathology — Tue, 22 Dec 2009 20:08:38 +0100

Authors: Chang H, Jiang AM, Qi CX Hemizygous TP53 gene deletion is the most important adverse risk factor in chronic lymphocytic leukemia (CLL), but its relationship with p53 protein expression is unclear. We investigated 110 CLL cases and correlated nuclear p53 protein immunoreactivity with TP53 gene deletion status and other CLL-associated genetic risk factors. Fluorescence in situ hybridization detected hemizygous TP53 deletions in 15 cases (13.6%), whereas immunohistochemical analysis detected nuclear p53 protein expression in 14 (12.7%). All cases expressing nuclear p53 protein had hemizygous TP53 deletions. Hemizygous TP53 gene deletion and p53 protein expression were strongly correlated (P < .001). There was no association between p53 expression and del(13q), del(11q) or tris...

Benzene as a Cause of Lymphoproliferative Disorders.

Chemico-Biological Interactions — Tue, 22 Dec 2009 00:00:00 +0100

Authors: Goldstein BD There is a long standing issue concerning the strength of evidence relating benzene to lymphocytic neoplasms. Because benzene is a known cause of human acute myelogenous leukemia there has been little reason for organizations such as the International Agency for Research on Cancer (IARC) or the US National Toxicology Program (NTP) to perform standard hazard identification reviews of benzene as a possible cause of other cancers such as lymphomas. Increased understanding of underlying mechanisms of carcinogenesis, as is reflected in the greater scope given to mechanistic evidence in assigning overall sufficiency of evidence for carcinogenicity by both IARC and NTP, suggests that the evidence supporting benzene as a cause of lymphoma likely has passed the threshold r...

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CD154 expression triggered by purine analogues in vitro: Correlation with treatment response and autoimmune events in chronic lymphocytic leukemia

Experimental Hematology — Mon, 21 Dec 2009 00:00:00 +0100

Objective: Despite a fludarabine-based treatment is the first choice of therapy in chronic lymphocytic leukemia (CLL), not all patients achieve a partial or complete response and some of them develop autoimmune manifestations. The aim of this study was to evaluate the influence of CD154 on these adverse effects because CD154 is involved in both B-cell survival and autoimmunity.Materials and Methods: Peripheral blood mononuclear cells (PBMC) from 36 patients with CLL were cultured in vitro with fludarabine or 2-chlorodeoxyadenosine for 24, 48, and 72hours.Results: Seven patients (19.4%) presented CD154 expression in PBMC cultured with purine analogues in vitro for 24 and/or 48hours, while no expression was found when cultured in media alone. These seven patients showed a decreased apoptotic...

Targeted elimination of leukemia stem cells; a new therapeutic approach in hemato-oncology.

Current Drug Targets — Sun, 20 Dec 2009 13:42:16 +0100

Authors: Ten Cate B, de Bruyn M, Wei Y, Bremer E, Helfrich W Despite recent advances, treatment of leukemia is often not curative. New insights indicate that this may be attributable to a small population of therapy-resistant malignant cells with self-renewal capacity and the ability to generate large numbers of more differentiated leukemia cells. These leukemia-initiating cells are commonly referred to as Leukemia Stem Cells (LSCs). LSCs are regarded as the root of leukemia origin and leukemia recurrence after seemingly successful therapy. Not surprisingly therefore, contemporary leukemia research has focused on ways to specifically eliminate LSCs, leading to the identification of several promising anti-LSC strategies. Firstly, LSCs may be eliminated by antibody- or ligand-based cell ...

The role of chemokines in B cell chronic lymphocytic leukaemia: pathophysiological aspects and clinical impact

Annals of Hematology — Fri, 18 Dec 2009 07:05:44 +0100

Abstract Chemokines are centrally involved in leukocyte migration, homing and haematopoiesis. Besides these physiological aspects, their role in pathological processes especially with respect to solid tumour and haematological neoplasias is well established. In this context, the focus was set here on disclosing their contribution in B cell chronic lymphocytic leukaemia (B-CLL), which is regarded as the most characteristic low-grade lymphoma. Up to now, it has been demonstrated that several chemokines are involved in migration of B-CLL cells to lymph nodes, secondary lymphoid organs and bone marrow. Moreover, some chemokines are known to have an anti-apoptotic effect and thus contribute to the survival of B-CLL cells. By interfering with both of these aspects, new therapeut...

Monoallelic and biallelic inactivation of TP53 gene in chronic lymphocytic leukemia: selection, impact on survival, and response to DNA damage

Blood — Thu, 17 Dec 2009 17:02:21 +0100

Deletion of TP53 gene, under routine assessment by fluorescence in situ hybridization analysis, connects with the worst prognosis in chronic lymphocytic leukemia (CLL). The presence of isolated TP53 mutation (without deletion) is associated with reduced survival in CLL patients. It is unclear how these abnormalities are selected and what their mutual proportion is. We used methodologies with similar sensitivity for the detection of deletions (interphase fluorescence in situ hybridization) and mutations (yeast functional analysis) and analyzed a large consecutive series of 400 CLL patients; a subset of p53–wild-type cases (n = 132) was screened repeatedly during disease course. The most common type of TP53 inactivation, ie, mutation accompanied by deletion of the remaining allele, occ...

IL-21 and T follicular helper cells

International Immunology — Thu, 17 Dec 2009 14:34:25 +0100

Upon encounter with antigen, CD4+ T cells differentiate into effector Th subsets with distinctive functions that are related to their unique cytokine profiles and anatomical locations. One of the most important Th functions is to provide signals to developing B cells that induce specific and appropriate antibody responses. The major CD4+ T cell subset that helps B cells is the T follicular helper (TFH) cell, whose expression of the chemokine receptor CXCR5 [chemokine (C–X–C motif) receptor 5] serves to localize this cell to developing germinal centers (GCs) where it provides instructive signals leading to Ig class switching and somatic mutation. TFH cells produce high levels of IL-21, a cytokine that is critical for GC formation and also for the generation of TFH cells. Althoug...

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Steroid responsive metastatic epidural nerve root infiltration with chronic lymphocytic leukaemia

QJM — Thu, 17 Dec 2009 10:51:55 +0100

(Source: QJM)

Soluble CD138 serum levels are not associated with other poor prognostic markers in patients with B-chronic lymphocytic leukaemia

Medical Oncology — Wed, 16 Dec 2009 07:04:58 +0100

Abstract The clinical course of CLL is highly variable, and survival from the time of diagnosis of CLL can range from months to decades. Novel biological markers such as IgVH mutation, CD38, and ZAP-70 expression have shown to offer important prognostic informations. Few reports deal with the sCD138 levels and bad prognostic factors in patients with CLL, and contrasting data are reported in literature. In our study, we evaluated the serum level of sCD138 in patients with B-CLL and its relationship with other prognostic markers. There was a significant association between advanced Rai stage and serum sCD138 levels in CLL subjects. Patients with Rai stage III-IV had significantly higher levels of sCD138 with respect to controls (48.85 ± 34 ng/ml vs. 31.1 ...

Dic(17;18)(p11.2;p11.2) is a recurring abnormality in chronic lymphocytic leukaemia associated with aggressive disease

British Journal of Haematology — Wed, 16 Dec 2009 00:00:00 +0100

Interphase cytogenetics are commonly used to identify clonal abnormalities in chronic lymphocytic leukemia (CLL) patients but fail to identify recurrent translocations that ultimately can direct more focused molecular characterization. Given the importance of del(17p13.1) in CLL outcome, we performed an extensive review of 1213 patients undergoing metaphase cytogenetics at our institution and identified 16 (1·3%) with a recurrent unbalanced translocation between the p arms of chromosomes 17 and 18 that results in a dicentric chromosome with loss of much of 17p and 18p. The dic(17;18)(p11.2;p11.2) was associated with a complex (three or more unrelated cytogenetic abnormalities) karyotype in 12 patients (75%) at the time that the abnormality was first identified, and eventually associated w...

Comparative Analysis of Normal versus CLL B-Lymphocytes Reveals Patient-Specific Variability in Signaling Mechanisms Controlling LFA-1 Activation by Chemokines

Cancer Research — Tue, 15 Dec 2009 05:07:48 +0100

Activation of lymphocyte function–associated antigen-1 (LFA-1) by chemokines is fine-tuned by inside-out signaling mechanisms responsible for integrin-mediated adhesion modulation. In the present study, we investigated the possibility of qualitative variability of signaling mechanisms controlling LFA-1 activation in chronic lymphocytic leukemia (CLL) cells. We pursued a multiplexed comparative analysis of the role of the recently described chemokine-triggered rho-signaling module in human normal versus CLL B-lymphocytes. We found that the rho-module of LFA-1 affinity triggering is functionally conserved in normal B-lymphocytes. In contrast, in malignant B-lymphocytes isolated from patients with B-CLL, the role of the rho-module was not maintained, showing remarkable differences and v...

Correlation between ZAP-70, phospho-ZAP-70, and phospho-Syk expression in leukemic cells from patients with CLL

Cytometry Part B: Clinical Cytometry — Tue, 15 Dec 2009 00:00:00 +0100

For patients with chronic lymphocytic leukemia (CLL), expression of ZAP-70 in the leukemic cells is an indicator of poor prognosis. However, the mechanism that accounts for this effect is not known. ZAP-70 expression has previously been associated with increased B cell antigen receptor signaling upon surface immunoglobulin ligation in vitro as shown by ZAP-70 and Syk phosphorylation. This finding has led to the suggestion that a more aggressive clinical course is correlated with B cell antigen receptor signaling. Using high resolution immunophenotyping to analyze CLL cells ex vivo (without stimulation in vitro), we have demonstrated CLL cells from all patients express some ZAP-70 and that increased expression of ZAP-70 is correlated with decreased levels of phosphorylated ZAP-70 and phosph...

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Genomic profiling of Richter's syndrome: recurrent lesions and differences with de novo diffuse large B-cell lymphomas

Hematological Oncology — Mon, 14 Dec 2009 00:00:00 +0100

In conclusion, the genomic profile of RS seems to differ from what observed in de novo DLBCL and in other transformed DLBCL. Genomic lesions occurring in RS are heterogeneous suggesting the existence of different RS subsets, possibly due to different transforming mechanisms. A deregulation of MYC pathway might represent one of the main transformation events in the pathogenesis of a subset of RS clonally related to the previous CLL. Copyright © 2009 John Wiley & Sons, Ltd. (Source: Hematological Oncology)

ASH: Flu-Cam Combo Tops Fludarabine Alone for CLL (CME/CE)

MedPage Today Hematology/Oncology — Fri, 11 Dec 2009 14:30:39 +0100

NEW ORLEANS (MedPage Today) -- Progression-free survival in relapsed and refractory chronic lymphocytic leukemia (CLL) improved significantly with the addition of alemtuzumab (Campath) to fludarabine, long-term data from a multicenter clinical trial showed. (Source: MedPage Today Hematology/Oncology)

Focal 9p instability in hematologic neoplasias revealed by comparative genomic hybridization and single-nucleotide polymorphism microarray analyses

Genes, Chromosomes and Cancer — Fri, 11 Dec 2009 00:00:00 +0100

In this study overviewing 9p losses in hematologic neoplasias, we introduce the term focal 9p instability to indicate multiple areas of copy number loss or homozygous loss within a larger heterozygous one in 9p. We have used microarray comparative genomic hybridization to study patients with acute lymphoblastic leukemia (ALL, n = 140), acute myeloid leukemia (n = 50), chronic lymphocytic leukemia (n = 20), and myelodysplastic syndromes (n = 37). Our results show that 9p instability is restricted to ALL. In total, 58/140 (41%) patients with ALL had a loss in 9p. The 9p instability was detected in 19% of the patients with ALL and always included homozygous loss of CDKN2A along with loss of CDKN2B. Other possibly important genes included MTAP, IFN, MLLT3, JAK2, PTPLAD2, and PAX5. 13/27 (48%) ...

Data from CAM314 phase III trial of alemtuzumab/fludarabine as second line treatment of chronic lymphocytic leukaemia presented at ASH

NeLM - Oncology — Fri, 11 Dec 2009 00:00:00 +0100

Source: PharmaLive Area: News Interim data from CAM314, a phase III open-label, randomised study in patients with progressive chronic lymphocytic leukaemia (CLL) have been presented at the American Society of Hematology (ASH) Annual Meeting. The study involving 335 patients with relapsed or refractory (one prior therapy) Rai stage I-IV CLL investigated whether treatment with alemtuzumab/fludarabine (FluCAM) was more beneficial than treatment with fludarabine alone. FluCAM patients received alemtuzumab in escalating doses of 3, 10, 30 mg IV (days 1-3 up to 14 days) followed by fludarabine 30mg/m2 IV (days 1-3) followed by alemtuzumab 30 mg IV (days 1-3) every 28 days for up to 6 cycles. Patients in the fludarabine arm received 25 mg/m2 IV daily for 5 consecutive days (days 1-5) ...