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In: Blood, American Society of Hematology, Vol. 121, No. 5 ( 2013-01-31), p. 812-821

Abstract: Targeted deletion of the gene for macrophage migration inhibitory factor (MIF) delays development of chronic lymphocytic leukemia and prolongs survival in mice. MIF recruits leukemia-associated macrophages to spleen or liver.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2012-05-431452

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 27-27

Abstract: Introduction: Tumor formation results from a complex interplay between genetic/epigenetic alterations, cell cycle dysregulation and promotion by the tumor environment. Stimulation by extracellular survival factors is important for chronic lymphocytic leukemia (CLL), since the leukemic cells undergo spontaneous apoptosis when removed from their normal milieu. Since preliminary experiments demonstrated that macrophage migration inhibitory factor (MIF), a chemokine-like proinflammatory mediator and an intracellular regulator of growth and apoptosis, is overexpressed in human CLL, we investigated whether MIF participates in the pathogenesis of murine CLL. Methods: We studied the role of MIF in CLL by crossing the Eμ-TCL1-transgenic mouse model with MIF knockout (MIF−/−) mice. B-cell-specific overexpression of T cell leukemia-1 (TCL1) leads to accumulation and proliferation of IgM+/CD5+ mature B-cells via activation of AKT. This results in a CLL-like disease with peripheral lymphocytic leukemia, lymphadenopathy, splenomegaly, BM infiltration and premature death after 8–15 months. TCL1+/wtMIF−/− and TCL1+/wtMIF+/+ mice were compared with respect to leukemia development, tumor burden, cytogenetics and survival. Results: The MIF receptors CD74/CD44 and CXCR2 are expressed on murine B-cells. TCL1+/wtMIF+/+ mice exhibited increased numbers of IgM+/CD5+ B-cells already in the preleukemic phase at month 3 and developed overt leukemia (WBC & gt; 20G/l) 3 months earlier than their MIF−/− counterparts (p = 0.02). Leukemia load at 12 months of age as measured by hepatosplenomegaly was increased in TCL1+/wtMIF+/+ animals and lymphatic organs were densely infiltrated by small, mature lymphocytes. The accelerated disease progression in the presence of MIF translated into a median survival which was 60 days shorter than in the absence of MIF (TCL1+/wtMIF+/+ 400 days, TCL1+/wtMIF−/− 460 days, p = 0.04). SKY analysis in leukemic splenocytes yielded various complex genetic aberrations with trisomies (e.g. +15), tetraploidy, translocations and deletions. Overexpression of tp53 due to the presence of an inactivating mutation in the p53 gene was found more frequently in TCL1+/wtMIF+/+ than in TCL1+/wtMIF−/− animals. Although the rates of DNA-damage-induced apoptosis in pre-leukemic and leukemic mice ex vivo were not significantly different between the genotypes, this defect in the p53-dependent apoptosis pathway corresponded with a reduced rate of spontaneous apoptosis in spleens of leukemic TCL1+/wtMIF+/+ animals. Conclusions: Our experience with the Eμ-TCL-1-transgenic mice shows that this model is suitable for the identification of novel regulators of CLL-like disease. We provide genetic proof that MIF acts to promote the early preleukemic and the leukemic phase of TCL1-induced CLL and thereby identify MIF as a novel regulator of CLL pathogenesis. Ongoing efforts are focussing on further characterizing the differences in pathology, the activation of the AKT pathway and cell cycle control between TCL1+/wtMIF−/− and TCL1+/wtMIF+/+ mice.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V112.11.27.27

Language: English

Publisher: American Society of Hematology

Publication Date: 2008

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 24 ( 2015-12-10), p. 2646-2649

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2015-09-670802

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 131, No. 9 ( 2018-03-01), p. 955-962

Abstract: Meta-analysis of 3 randomized clinical trials shows a statistically significant relationship between treatment effects on PFS and MRD. Meta-regression model supports use of MRD as a primary end point in clinical trials of chemoimmunotherapy in CLL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2017-06-792333

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Cancer, Wiley, Vol. 119, No. 12 ( 2013-06-15), p. 2258-2267

Type of Medium: Online Resource

ISSN: 0008-543X

URL: Article

DOI: 10.1002/cncr.27972

Language: English

Publisher: Wiley

Publication Date: 2013

detail.hit.zdb_id: 1479932-7

detail.hit.zdb_id: 1429-1

In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 671-671

Abstract: Telomeres are sequences at the ends of each chromosome that confer genomic stability. The presence of dysfunctional telomeres is associated with increased genomic abnormalities and tumorigenesis. In CLL, telomere length has been described as an independent prognostic factor (e.g. Roos et al., Blood 2008) but these analyses have been performed on heterogeneous patient cohorts and have not yet been confirmed within clinical trials. Here, we studied the impact of telomere length on outcome in the international CLL8 trial of the GCLLSG evaluating first-line treatment with fludarabine and cyclophosphamide (FC) versus FC with rituximab (Anti-CD20). Telomere length was analyzed using quantitative PCR of DNA (in triplicates) from baseline samples of 620 patients enrolled on CLL8, and this cohort was representative of the full trial population. The technique was validated using terminal restriction fragment length analysis (TRF) (R2=0.859, P 〈 0.001) in an independent control sample set (n=18) and 6 of these samples were included in every batch as controls. Telomere length was found to be highly variable in CLL (1.94 kb – 33.56 kb), whereas normal B-cells from age matched healthy probands (n=20) showed limited variability (5.39 – 9.60 kb; median 7.54 kb). Analysis of paired CD19+ (malignant) and CD19- (non-malignant) fractions (n=48) showed that telomere shortening in CLL was restricted to the malignant cell population (median: CD19+ 3.37 kb vs. CD19- 5.42 kb; P 〈 0.001). Comparison of clinical characteristics between the groups defined by short and long telomeres (cut-off at the median of 4.54 kb) showed no significant associations with age (P=0.931), sex (P=0.116), presence of B-symptoms (P=0.297), ECOG status (P=0.288), CIRS score (P=0.438) and ß2-MG (P=0.586). Short telomeres were significantly associated with high WBC (≥50 Giga/L; P=0.004), high thymidine kinase levels (≥10.0 U/L; P 〈 0.001) and presence of larger lymph nodes ( 〉 5cm; P=0.048). Also, unmutated IGHV (P 〈 0.001), ZAP70+ (≥20%; P=0.005), del(17p) (P 〈 0.001) and del(11q) (P 〈 0.001) were significantly more frequent in the group with short telomeres. Interestingly, cases with Binet C stage were significantly associated with long telomeres (P=0.007). After a median follow up time of 69.97 months, there were 423 events for progression free survival (PFS) and 209 for overall survival (OS). Short telomeres were significantly associated in both treatment arms with poor PFS (FC: median 27.4 vs. 44.0 months, P 〈 0.001; FCR: median 44.3 vs. 70.0 months, P 〈 0.001) (Figure) and OS (FC: median 35.1 vs. 62.5 months, P 〈 0.001; FCR: median 79.5 vs. 86.2 months, P=0.010). Multivariable analysis by Cox regression with backward selection was performed for the identification of independent prognostic factors, including as variables the treatment arms, age, sex, stage, ECOG status, B-symptoms, WBC, thymidine kinase, ß2-MG, CIRS, del(11q), +(12q), del(13q), del(17p), mutation status of IGHV, TP53, NOTCH1, SF3B1 and telomere length. Regarding PFS, we identified the following independent prognostic markers: FCR (HR 0.493; P 〈 0.001), male sex (HR 1.330; P=0.035), ECOG status 〉 0 (HR 1.256; P=0.037), thymidine kinase 〉 10 (HR 1.312; P=0.042), del(11q) (HR 1.378; P=0.012), del(17p) (HR 3.225; P 〈 0.001), unmutated IGVH (HR 1.478; P=0.007), TP53 mutation (HR 2.031; P=0.001) and short telomere length (HR 1.425; 95% CI 1.109-1.832; P=0.006). Regarding OS, the following independent prognostic markers were identified: FCR (HR 0.657; P=0.007), age ≥65 years (HR 1.453; P=0.021), ECOG status 〉 0 (HR 1.617; P=0.003), thymidine kinase 〉 10 (HR 1.850; P=0.007), beta2 microglobulin (HR 1.486; P=0.016), del(17p) (HR 2.716; P 〈 0.001), unmutated IGHV (HR 2.001; P=0.001) and TP53 mutation (HR 3.034; P=0.001). When not including NOTCH1, SF3B1 and TP53 in the multivariable models, short telomeres where identified as independent prognostic markers for PFS (HR 1.543; P 〈 0.001) and OS (HR 1.473; P=0.029). In conclusion, the characterization of telomere length in the CLL8 trial revealed significant associations with other biological high-risk features and an independent prognostic impact on outcome after FC or FCR treatment. This points to a role of telomere dysfunction in CLL pathogenesis, progression and response to therapy. Further study of telomere dysfunction in the evolution of CLL and in the context of novel non-genotoxic treatments is warranted. Disclosures: Wenger: F. Hoffmann-La Roche: Employment, Ownership interests (including stock options) in a start-up company, the stock of which is not publicly traded Other. Fingerle-Rowson:F. Hoffmann-La Roche : Employment. Wendtner:Hoffmann-La Roche: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Fischer:Roche: Travel grants Other; Mundipharma: Travel grants, Travel grants Other. Hallek:Roche: Consultancy, Honoraria, Research Funding. Stilgenbauer:Roche: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V122.21.671.671

Language: English

Publisher: American Society of Hematology

Publication Date: 2013

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 4401-4401

Abstract: Introduction: There are a growing number of therapeutic options for elderly patients with previously untreated chronic lymphocytic leukemia (CLL) and comorbidities, thus making clinical aids necessary to choose between available treatments. CLL-IPI is a validated tool for prognostication of overall survival in CLL (with age, stage, beta2-microglobulin, 17p deletion / TP53 mutation, and IGHV mutational status used as weighted factors to stratify patients for low, intermediate, high, or very high risk of death). We here evaluated CLL-IPI in a large sample of elderly patients with comorbidities. Methods: CLL-IPI was analyzed in the population of the CLL11 study, a randomized trial having enrolled 781 patients with previously untreated CLL and increased comorbidity burden for treatment with obinutuzumab (formerly GA101) plus chlorambucil (G-Clb, n=333), rituximab plus chlorambucil (R-Clb, n=330), or chlorambucil alone (Clb, n=118). Patients with all five CLL-IPI factors available were stratified into CLL-IPI risk groups. Overall survival (OS) was estimated for low, intermediate, high, and very high risk. Additionally, risk-specific time to next treatment (TTNT) and progression-free survival (PFS) were assessed. Methods included Kaplan-Meier curve, log-rank test, and Cox regression analyses. Results: Among 781 patients enrolled in the CLL11 study, 691 were evaluable in this analysis while 90 had to be excluded due to missing information for beta2-microglobulin, 17p deletion / TP53 mutation, or IGHV mutational status. Of the 691 patients, 299 were treated with G-Clb, 294 with R-Clb, and 98 with Clb. Median age, cumulative illness rating scale (CIRS), and ECOG performance status were 74 years, 8 and 1, respectively. Median observation time was 41.8 months. Stratification according to CLL-IPI was as follows: 62 (9%) low risk, 206 (30%) intermediate risk, 361 (52%) high risk, 62 (9%) very high risk. In a pooled analysis of all 691 evaluable patients, OS was significantly different between CLL-IPI risk groups (p 〈 0.001, Figure), with statistically satisfying values regarding both discrimination and calibration (C-statistics: C=0.633, 95%-CI 0.596-0.676; Hosmer-Lemeshow-Test: p=0.716). Similarly, graduating differences in OS between CLL-IPI risk groups were found in the subset of patients treated with chemoimmunotherapy and subsets of patients of each antibody arm, respectively. TTNT and PFS also differed between CLL-IPI risk groups. Favorable risk as assessed by CLL-IPI was associated with greater likelihood of OS benefit from treatment with G-Clb versus R-Clb (HR 0.232, 95%-CI, 0.027-1.983 for low risk; HR 0.540, 95%-CI 0.249-1.170 for intermediate risk; HR 0.884, 95%-CI 0.595-1.315 for high risk; HR 0.830, 95%-CI 0.372-1.852 for very high risk). Previously observed TTNT and PFS benefits from G-Clb versus R-Clb were maintained across CLL-IPI risk groups. Conclusions: This is the first validation study of CLL-IPI in elderly patients with previously untreated CLL in need of therapy and comorbidities. Results suggest good performance of the CLL-IPI in this patient population. CLL-IPI may provide help to physicians to choose between available treatment options in these patients. Figure OS by CLL-IPI risk groups in the analyzed CLL11 study sample (n=691) Figure. OS by CLL-IPI risk groups in the analyzed CLL11 study sample (n=691) Disclosures Goede: F- Hoffmann-LaRoche: Consultancy, Honoraria, Other: Travel grants; Gilead: Consultancy; Janssen: Consultancy, Other: Travel grants; Glaxo Smith Kline: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria; Bristol Myer Squibb: Honoraria. Bahlo:F. Hoffman-La Roche: Honoraria, Other: Travel grant. Fischer:Roche: Other: travel grants. Fink:Mundipharma: Other: Travel grants; AbbVie: Other: Travel grants; Roche: Honoraria, Other: Travel grants; Celgene: Research Funding. Fingerle-Rowson:Roche: Employment. Stilgenbauer:Mundipharma: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Genzyme: Consultancy, Honoraria, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Hoffman La-Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding. Bergmann:Janssen: Honoraria; Gilead: Consultancy, Honoraria; Glaxo-SmithKline: Honoraria; Celgene: Honoraria; Roche: Consultancy, Honoraria; Mundipharma: Honoraria. Eichhorst:Mundipharma: Consultancy, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau. Hallek:F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.4401.4401

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 3327-3327

Abstract: Introduction: Chemoimmunotherapy with the glycoengineered type II anti-CD20 antibody obinutuzumab plus the alkylating drug chlorambucil (G-Clb regimen) has been investigated in the CLL11 study and demonstrated clinical benefit in patients with previously untreated CLL and comorbidities. Whether G-Clb is also an active treatment in patients with refractory CLL after frontline therapy with Clb alone has been explored in the subpopulation of CLL11 subjects treated with such salvage therapy. Methods: Thirty patients who received Clb alone as initial study treatment, but developed progressive CLL within up to 6 months after end of Clb treatment were offered G-Clb as optional salvage therapy. The dosing schedule for obinutuzumab was 100 mg intravenously on day 1, 900 mg on day 2, and 1000 mg on day 8 and 15 of cycle 1, and 1000 mg on day 1 of cycles 2-6. Clb was administered orally with 0.5 mg/kg body weight on day 1 and 15 of each 28-day cycle. Results: The median age in the crossover patient population (n=30) was 72 years. The comorbidity burden was high as assessed at study entry (median cumulative illness rating scale total score 8), and renal function was reduced (median calculated creatinine clearance 67 mL/min). Deletions of 11q and 17p were present in 12% and 20% of the patients, respectively; and 64% had unmutated IGHV genes. When crossing over to G-Clb, the majority (93%) had not responded to the initial study treatment with Clb while two patients had responded transiently to Clb with a partial remission, but had relapsed early (median time from start of Clb to crossover: 9.7 months). After crossover, all but one patient completed the 6 cycles of salvage therapy with G-Clb; one subject discontinued after the first infusion of obinutuzumab due to an infusion-related reaction (IRR). Grade 3 or 4 IRRs occurred in 17% of the patients. Grade 3 or 4 neutropenia, anemia, thrombocytopenia, and infection were reported in 33%, 7%, 10%, and 13% of the patients, respectively. Response rates at the end of crossover treatment with G-Clb are given in the table. Negativity for minimal residual disease in bone marrow and/or peripheral blood after crossover treatment was achieved in 23% of the patients. The median progression-free survival from start of crossover treatment was 17.2 months (95% CI 14.2; 22.4 months) (median observation time: 23 months). Conclusions: These results suggest that, besides its established role as frontline treatment of CLL, chemoimmunotherapy with G-Clb could be a safe and active treatment for patients with CLL refractory to prior chlorambucil chemotherapy. Table: Clinical response to G-Clb after failure of Clb alone n (%) Responders 26 (87) Complete response 2 (7) Complete response incomplete 1 (3) Partial response 23 (77) Non-Responders 4 (13) Stable disease 2 (7) Progressive disease 1 (3) Not evaluable* 1 (3) * Due to early treatment discontinuation after IRR Disclosures Goede: Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel grants Other. Off Label Use: Obinutuzumab (GA101, Gazyva); approved for 1st line treatment of CLL; paper includes results / discussion of drug use in 2nd line treatment of CLL. Engelke:Roche: Travel grants Other. Langerak:Roche: Research Funding. Ritgen:Roche: Research Funding. Stilgenbauer:Roche: Consultancy, Honoraria, Research Funding. Asikanius:Roche: Employment. Humphrey:Roche: Employment. Wenger:Genentech: Employment. Fingerle-Rowson:Roche: Employment. Hallek:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V124.21.3327.3327

Language: English

Publisher: American Society of Hematology

Publication Date: 2014

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detail.hit.zdb_id: 80069-7

In: Leukemia, Springer Science and Business Media LLC, Vol. 33, No. 9 ( 2019-9), p. 2183-2194

Type of Medium: Online Resource

ISSN: 0887-6924 , 1476-5551

URL: Article

DOI: 10.1038/s41375-019-0446-4

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2008023-2

In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 3438-3438

Abstract: Abstract 3438 Poster Board III-326 INTRODUCTION Chemoimmunotherapies like the FCR combination have been shown to increase complete remission rates and progression-free survival in patients with CLL in comparison to chemotherapies without biologicals (Hallek et al., ASH 2008). Until now little is known on HRQOL outcome of CLL patients receiving chemoimmunotherapy. Therefore we assessed the HRQOL in patients with advanced CLL, who were randomized between FC and FCR treatment within an international randomized trial of the German CLL Study Group (GCLLSG). METHODS 817 pts with good physical fitness as defined by a cumulative illness rating scale (CIRS) score of up to 6 and a creatinine clearance (cr cl) ≥ 70 ml/min were enrolled between July 2003 and March 2006. Pts were randomly assigned to receive 6 courses of either FC (N=409; F 25mg/m2 i.v. d1–3 and C 250 mg/m2 i.v. d1–3; q 28 days) or FC plus R (N=408; 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent cycles; q 28 days). The EORTC C30 questionnaires were sent to all patients included in Germany or Austria at baseline, after 3, 6, 12 months (mo) and then in yearly follow-up (FU). In all other countries questionnaires were handed out to the patients personally on the same time points during their visits in the study center. The analysis of the questionnaires was performed according to the EORTC recommendations (Aaronson et al., 1993). The questionnaire contained a global health scale, five functional scales (physical, role, cognitive, emotional and social), three symptom scales (fatigue, pain, nausea and vomiting) as well as six single items (dyspnea, appetite loss, sleep disturbances, financial impact, constipation and diarrhea). Mean score values of the EORTC scales ranged between 0 and 100. High scores in the functional scales represent good HRQOL, low scores in the symptom scales a low symptom burden. RESULTS HRQOL was evaluated in 763 (93%) of the included patients who completed at least one questionnaire (376 (49%) FC and 387 (51%) FCR treated patients). The compliance rate was significantly higher in those countries, where the questionnaire was handed out personally (96% in other countries versus 92% in Germany and Austria; P=0.013). Pts answering the baseline questionnaire and at least one further questionnaire (444; 58%) were compared to those how did not (319, 42%): pts with only one or a missing baseline questionnaire had a significantly higher CIRS score (1,7 vs 1,4; P=0.007) and more frequently leukocytopenias (24% CTC grade 3 and 4 leukocytopenias vs 13%; P 〈 0.001). Age, distribution of Binet stages, gender, poor prognostic factors (del(11q) or del(17p), unmutated IgVH) and treatment arms were similar distributed between both groups. There were also no differences in the rate of other toxicities or response rates. A total of 482 questionnaires were available initially, 406 at interim staging, 454 at final staging, 496 after 12 mo FU, 414 after 24 mo FU and 198 after 36 mo FU. A comparison of the two treatment arms at interim or final staging after 3 and 6 months respectively showed no significant difference between both arms with regards to the global health status, functional scales and symptom scales. Dyspnoe was scored significantly higher during FC treatment in comparison to FCR (23 versus 18; P = 0.023). At 12, 24 and 36 months of FU no significant difference between FC and FCR in all functional scales, symptom scales, single item and global health status was found. Both treatment arms showed slight improvement (defined as difference of 5-10 points) of global health status at 12 months FU in comparison to baseline (FC: 62 at baseline vs 68 at FU 12; FCR: 62 vs 70). CONCLUSIONS Although the FCR regimen is associated with a higher rate of cytopenias in patients' perception this increased hematological toxicity does not result in a difference in HRQOL between both treatment arms. After a median observation time of 38 mo the better efficacy of the FCR regimen with regards on response rates and progression-free survival does not yet result in an improved HRQOL. For the final evaluation of HRQOL outcome after chemoimmunotherapy a longer is FU is needed. Disclosures Eichhorst: Roche: Honoraria, Research Funding; Mundipharma: Research Funding; Hospira: Honoraria. Fischer:Roche: Travel Grand; Munipharma: Travel Grand. Fink:Roche: Travel Grand. Fingerle-Rowson:OrthoBiotech: Employment; Roche: Honoraria. Westermann:Roche: Travel Grand. Wendtner:Roche: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; BayerSchering: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Hallek:Roche: Research Funding, Speakers Bureau; Mundipharma: Research Funding, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V114.22.3438.3438

Language: English

Publisher: American Society of Hematology

Publication Date: 2009

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detail.hit.zdb_id: 80069-7