4.19 Prediction of Poor Outcome in Chronic Lymphocytic Leukemia Patients treated with FCR (Fludarabine, Cyclophosphamide, Rituximab) in the CLL8 Trial of the German CLL Study Group

2011 ◽  
Vol 11 ◽  
pp. S230
Author(s):  
Anna Fink ◽  
Raymonde Busch ◽  
Natali Pflug ◽  
Sebastian Boettcher ◽  
Dirk Winkler ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Poor Outcome

High CD49d protein and mRNA expression predicts poor outcome in chronic lymphocytic leukemia

2009 ◽  
Vol 131 (3) ◽  
pp. 472-480 ◽  
Author(s):  
Holger Nückel ◽  
Magdalena Switala ◽  
Crista H. Collins ◽  
Ludger Sellmann ◽  
Hans Grosse-Wilde ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Mrna Expression ◽  
Lymphocytic Leukemia ◽  
Poor Outcome

CD79b Expression in Chronic Lymphocytic Leukemia

2003 ◽  
Vol 127 (5) ◽  
pp. 561-566 ◽  
Author(s):  
Ellen Schlette ◽  
L. Jeffrey Medeiros ◽  
Michael Keating ◽  
Raymond Lai
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Initial Study ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Cell Marker ◽  
Trisomy 12 ◽  
Conventional Cytogenetics

Abstract Context.—CD79b is a relatively newly characterized B-cell marker that is expressed in a minority of chronic lymphocytic leukemia (CLL) cases. Objective.—To systematically correlate CD79b expression with specific morphologic and immunophenotypic findings and trisomy 12. Design.—We assessed CD79b expression in 100 consecutively accrued CLL cases that were also analyzed by conventional cytogenetics. Based on the association between trisomy 12 and CD79b expression, we then assessed 43 additional CLL cases with trisomy 12. CD79b expression was correlated with morphology and expression of other immunophenotypic markers. Results.—Eighteen (18%) of 100 consecutively accrued cases were CD79b positive. No significant association was found between CD79b expression and atypical morphology. CD79b expression correlated with CD22 and FMC7 positivity. Eight (8%) cases had trisomy 12; 4 (50%) of these were CD79b positive, suggesting an association with trisomy 12. Examination of a second group of 51 CLL cases with trisomy 12 (including 8 cases from the initial study group) showed that CD79b was positive in 26 cases (49%), a frequency significantly higher than that of the consecutively accrued CLL cases without trisomy 12 (P < .05). Conclusions.—We conclude that CD79b immunoreactivity is positive in approximately 20% of CLL cases and that expression correlates with trisomy 12 and atypical immunophenotypic findings.

Long-term Efficacy of Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia: Results of the Polish Adult Leukemia Study Group Observational Study

2020 ◽  
Vol 40 (7) ◽  
pp. 4059-4066 ◽  
Author(s):  
BARTOSZ PULA ◽  
ELZBIETA ISKIERKA-JAZDZEWSKA ◽  
MONIKA DLUGOSZ-DANECKA ◽  
AGNIESZKA SZYMCZYK ◽  
MAREK HUS ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Observational Study ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Term Efficacy ◽  
Adult Leukemia

Low-Dose Fludarabine and Cyclophosphamide Combined with Rituximab In the Treatment of Elderly/Comorbid Patients with chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Preliminary Results of Project Q-Lite by Czech CLL Study Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2466-2466 ◽  
Author(s):  
Lukas Smolej ◽  
Martin Spacek ◽  
Yvona Brychtova ◽  
David Belada ◽  
Jiri Schwarz ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Low Dose ◽  
Antimicrobial Prophylaxis ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Bulky Disease ◽  
Intention To Treat ◽  
Serious Infections ◽  
Attending Physician

Abstract Abstract 2466 Background: Combination of fludarabine, cyclophosphamide and rituximab (FCR) is currently considered the treatment of choice in physically fit patients (pts) with chronic lymphocytic leukemia (CLL). However, many patients cannot tolerate this aggresive treatment because of advanced age and/or serious comorbid conditions. For these patients, chlorambucil has remained so far the standard of treatment. Low-dose fludarabine-based regimens have recently demonstrated promising results in small studies. Aims: to assess efficacy and safety of low-dose FC or FCR regimen used in elderly/comorbid patients with CLL. Patients and Methods: Between March 2009 and June 2010, we treated 74 pts with active disease (CLL, n=70, SLL, n=4, 57% males, median age, 70 years [range, 58–83], median Cumulative Illness Rating Score 4 [range, 0–10]) by low-dose FC/FCR at fourteen centers cooperating within Czech CLL Study Group. Dose reduction of chemotherapy was as follows: fludarabine to 50% (12 mg/m2 i.v. or 20 mg/m2 orally on Days 1–3), cyclophosphamide to 60% (150mg/m2 i.v./p.o. D1-3). The dose of rituximab was standard (375mg/m2 in 1st cycle, 500mg/m2 from 2nd cycle). The choice of regimen (FC vs FCR) was at the discretion of the attending physician. Treatment was repeated every 4 weeks. Antimicrobial prophylaxis with cotrimoxazole and aciclovir or equivalents was recommended. Fifty per cent of pts were treated in first line, the remaining half had relapsed/refractory CLL. Rai stage III/IV was present in 57% pts; 39% had bulky disease. IgVH genes were unmutated in 74%; according to hierarchical model, del 11q was present in 32% and del 17p in 8%. Results: FCR was used in 72 pts, FC in 2. Based on intention-to-treat principle, the overall response/complete response rate (including clinical CR and CR with incomplete blood count recovery) was 70/35%; 34 pts are still on treatment. No data on PFS/OS are available yet. Serious (CTC grade III/IV) neutropenia occurred in 51%, thrombocytopenia in 13% and anemia in 10% of pts. Serious infections were diagnosed in 13% of pts. Three pts (4%) died, all of them after failure of treatment (pneumonia, n=2, pulmonary embolism, n=1). Conclusions: Treatment of elderly/comorbid CLL patients with low-dose FC/FCR demonstrated very promising results. Toxicity was acceptable and manageable. Longer follow-up is needed for the assessment of PFS and OS. Supported by research project MZO 00179906 from Ministry of Health, Czech Republic. Disclosures: Smolej: Roche: Honoraria; Bayer-Schering: Honoraria; Genzyme: Honoraria. Off Label Use: Low-dose FCR in elderly/comorbid patients with CLL. Belada: Roche: Consultancy, Honoraria. Motyckova: Roche: Honoraria.

Analysis of Stereotyped IGHV Distribution In a Series of 1133 Chronic Lymphocytic Leukemia Patients: The Experience of a Multicenter Italian Study Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2423-2423
Author(s):  
Francesco Maura ◽  
Giovanna Cutrona ◽  
Massimo Gentile ◽  
Serena Matis ◽  
Monica Colombo ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Conflicts Of Interest ◽  
Pairwise Alignment ◽  
Immunoglobulin Heavy Chain ◽  
Lymphocytic Leukemia ◽  
Study Group ◽  
Data Set ◽  
Italian Study ◽  
Mutational Status

Abstract Abstract 2423 Chronic lymphocytic leukemia (CLL) is characterized by an extremely variable clinical course. Mutational status of the immunoglobulin heavy-chain variable (IGHV) region defines two disease subsets with different prognosis. A fraction of CLL cases carries highly homologous B-cell receptors (BCR), i.e. characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3). We performed sequence analysis to characterize IGHV regions in a panel of 1133 CLL patients investigated by a multicenter Italian study group. A total of 1148 rearrangements were identified; the analysis of stereotyped subsets was performed based on previously reported criteria (Messmer et al, J Exp Med 2004; Stamatopuolos et al, Blood 2007). Specifically, we compared all our sequences with those found in three different publicly available data sets (Stamatopoulos et al, Blood 2007; Murray et al, Blood 2008 and Rossi et al, 2009 Clin Cancer Res). In addition, a pairwise alignment within all sequences was performed in order to discover novel potential subsets (HCDR3 identity > 60%). Based on the 2% cut-off used to discriminate between Mutated (M) and Unmutated (UM) cases, 777 sequences (67.59%) were classified as M, while 371 sequences (32.3%) as UM. The most represented IGHV genes within mutated cases were IGHV4-34 (104/118) and IGHV3-23 (85/96), whereas IGHV1-69 (97/112) was the most frequently used in the UM group. Interestingly, the IGHV3-21 gene, reported to be frequently expressed in CLL patients from Northern Europe, was present in only a small fraction of cases (24; 2.07%), confirming a previous finding reported by Ghia et al (Blood 2005) in a smaller panel. In our series, stereotyped HCDR3 sequences were found in 407/1148 (35.45%) patients, 177 of whom were M and 230 were UM cases. Overall, we observed that stereotyped sequences were significantly associated with UM IGHV status (Fisher's exact test, P<0.0001). Among the 407 stereotyped HCDR3 sequences, 345 belong to the clusters reported by Murray et al and 14 to those described by Rossi et al., 2009 Clin Cancer Res. The most frequent stereotyped subsets identified in our panel were #1 (35 cases), #7 (28 cases), #4 (24 cases), #3 and #9 (16 cases), #28 (13 cases), and #2 (12 cases), together with subsets #5, #8, #10, #12, #13, #16 and #22 (all ranging from 6 to 9 cases). Finally, we were able to identify by auto-matching analysis 48 sequences potentially specific for 23 novel putative stereotype subsets. In our series we identified 407/1148 (35.45%) stereotyped HCDR3 sequences. The percentage was higher than that reported by Stamatopoulos et al and Murray et al. This discrepancy may partially be due to the different approach used in our analysis, namely the matching to a general data set including all published stereotyped subsets instead of the auto-matching performed by those Authors. We demonstrated a significant association between IGHV status and stereotyped sequences and confirmed the finding that #1 is the most frequent subset identified so far. Finally, we were able to identify a series of 23 novel putative subsets that will require further confirmation. Disclosures: No relevant conflicts of interest to declare.

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