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  • American Society of Hematology  (7)
  • 1
    Online Resource
    Online Resource
    Adult patients with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 9 ( 2012-08-30), p. 1868-1876
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 9 ( 2012-08-30), p. 1868-1876
    Abstract: Quantification of minimal residual disease (MRD) by real-time PCR directed to TCR and Ig gene rearrangements allows a refined evaluation of response in acute lymphoblastic leukemia (ALL). The German Multicenter Study Group for Adult ALL prospectively evaluated molecular response after induction/consolidation chemotherapy according to standardized methods and terminology in patients with Philadelphia chromosome-negative ALL. The cytologic complete response (CR) rate was 89% after induction phases 1 and 2. At this time point the molecular CR rate was 70% in 580 patients with cytologic CR and evaluable MRD. Patients with molecular CR after consolidation had a significantly higher probability of continuous complete remission (CCR; 74% vs 35%; P 〈 .0001) and of overall survival (80% vs 42%; P = .0001) compared with patients with molecular failure. Patients with molecular failure without stem cell transplantation (SCT) in first CR relapsed after a median time of 7.6 months; CCR and survival at 5 years only reached 12% and 33%, respectively. Quantitative MRD assessment identified patients with molecular failure as a new high-risk group. These patients display resistance to conventional drugs and are candidates for treatment with targeted, experimental drugs and allogeneic SCT. Molecular response was shown to be highly predictive for outcome and therefore constitutes a relevant study end point. The studies are registered at www.clinicaltrials.gov as NCT00199056 and NCT00198991.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2011-09-377713
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
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  • 2
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    New Definition of Treatment Response in Adult Acute Lymphoblastic Leukemia (ALL): Use of Molecular Markers for Minimal Residual Disease (MRD).
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 90-90
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 90-90
    Abstract: Abstract 90FN2 Response to treatment measured by cytologic bone marrow evaluation has been so far the most important prognostic factor in adult ALL, and cytological complete remission (cyCR) and relapse (cyREL) are accepted endpoints for clinical trials. However, measurement of MRD is a more sensitive approach for assessment of response. In the past decade it has been confirmed that MRD is an independent, strong prognostic factor in ALL. The most widely applied method is based on quantative PCR evaluation of individual rearrangements of TCR and Ig genes. Methodology, interpretation and definitions are highly standardised and confirmed in different labs (e.g. van der Velden et al, Leukemia, 2007). Therefore it is essential to define and validate MRD based response criteria – namely complete molecular/complete MRD response (molCR), molecular failure/MRD persistence (molFAIL) and molecular relapse/MRD relapse (molREL) - as endpoints for clinical trials. Since 1999 the German Multicenter Study Group for Adult ALL (GMALL) has conducted two consecutive studies (GMALL 06/99 and 07/2003) with a risk and MRD adapted treatment strategy and prospective MRD evaluation. 1489 evaluable pts (15–55 y) with Ph-negative standard (SR) and high risk (HR) ALL have been included so far. MRD evaluation as described above has taken place in central labs. For analysis of molCR MRD evaluation was restricted to pts with cyCR (prerequisite: at least one marker with sensitivity and quantitative range of minimum 10−4 for negative results). MolCR was defined as negative MRD status after induction therapy. MolREL was defined as reappearance of MRD above 10−4 after achievement of molCR. MolCR after induction: The overall cyCR rate was 89% with differences between SR and HR (92% vs 84%;p 〈 .0001) and age 〈 vs 〉 35 yrs (90% vs 86%;p=.01) but not B vs T-lineage (89% vs 88%). As expected the molCR was lower (69%) in 479 evaluable pts. Significant differences were seen between SR vs HR (77% vs 46%;p 〈 .0001) and B vs T-lineage (63% vs 79%;p=.0005). The most rapid decrease of MRD was observed after induction phase I (34% molCR) and phase II (69%), whereas the effect of first consolidation was limited (72%) indicating a progressive selection of chemotherapy resistant leukemic clones. MolCR evaluation was also used to assess treatment modifications such as asparaginase intensification or addition of rituximab to induction therapy. Prognostic impact of molCR: SR pts were scheduled for chemotherapy. Those with molCR had a superior overall survival (OS) when compared to molFAIL (67% vs 38%;p 〈 .0001) which was mainly due to a lower relapse rate (RR) (26% vs 59%;p 〈 .0001) leading to better remission duration (RD) (57% vs 29%;p 〈 .0001). MolFAIL pts had a better OS with SCT in CR1 than without (60% vs 27%;p=.09). All HR pts were scheduled for SCT in CR1. OS was superior for MolCR vs MolFAIL (66% vs 42%; p=.003). The RR was higher for molFAIL vs molCR on chemotherapy (66% vs 18%;p=.04) and after SCT (34% vs 11%;p=.04). Even after SCT pts with molCR had a better OS (75% vs 58%; p=.03). MolREL: The incidence and outcome of molREL was evaluated in 432 pts with MRD tests during and after treatment. 36 molREL without additional extramedullary relapse were observed. The OS was 36% and the probability of cyREL was 82% with median of 75 d from molREL to cyREL. All pts not treated at molREL relapsed (N=12). Only 1/11 (9%) pts who were transferred to SCT in cyCR1 after additional treatment, including experimental drugs, relapsed compared to 21/25 (84%) pts without SCT in cyCR1 (p 〈 .0001). Overall these data show in the largest cohort of adult ALL pts with MRD analysis reported so far, the proof of principle for molecular response evaluation. In a study with high cyCR rate it allows to detect differences between subgroups and treatment approaches and thereby refines the evaluation of treatment efficacy. It is a clinically relevant endpoint since molFAIL is associated with significantly poorer RD and OS even after subsequent SCT. Detection of molFAIL and molREL identifies pts with resistance to conventional drugs and the need for targeted, experimental drugs and SCT in cyCR1 before occurrence of cyREL. Molecular response evaluation with standardised methods provides new refined endpoints for future trials, including pivotal trials with new drugs with the major advantage of early decision points and strong correlation to clinical outcome. Supported by Deutsche Krebshilfe 702657Ho2 and BMBF 01GI9971/8 Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.90.90
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 3
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    Improved Outcome in High Risk and Very High Risk ALL by Risk Adapted SCT and in Standard Risk ALL by Intensive Chemotherapy in 713 Adult ALL Patients Treated According to the Prospective GMALL Study 07/2003.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 12-12
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 12-12
    Abstract: In 2003 the German Multicenter ALL Study Group (GMALL) initiated the trial GMALL 07/2003. Major aims were improvement of outcome by shortened, intensified induction, intensified consolidation, risk adapted and extended SCT indication and minimal residual disease (MRD) based treatment stratification. 8drug-induction was followed by uniform 1st consolidation based on HDARAC and HDMTX. Further treatment was stratified according to the following risk factors (RF): WBC 〉 30.000 in B-prec. ALL, late CR ( 〉 3wks), proB-, earlyT and mature T-ALL, Ph/BCR-ABL and t(4;11)/ALL1-AF4. The risk groups were defined as follows: standard risk (SR, no RF), high risk (HR, 〉 = 1RF) and very high risk (VHR,Ph/BCR-ABL). HR and VHR pts were scheduled for SCT in CR1 with the following priorities: allo sibling, allo matched unrelated and autologous. VHR pts mostly received Imatinib according to different schedules. SR pts received 5 consolidation cycles (HDMTX/ASPx3, VP16/ARAC, CYCLO/ARAC) and reinduction. SR pts with high MRD after consolidation I were allocated to SCT. In the remaining SR pts decision on maintenance therapy was based on MRD. Between 04/03-12/06 713 evaluable (15–55 yrs) pts were included. The median age was 34 yrs. The CR rate after induction was 89% with 5% early death and 6% failure. 50%, 33% and 17% were allocated to SR (N=353), HR (N=235) and VHR (N=117) with similar CR rates of 92%, 88% and 85%. CR rate was not different in pts 〈 vs 〉 35 yrs (90% vs 89%). 5 year overall survival (OS) was 54% and survival of CR (S-CR) pts was 59%. HR and VHR pts obtained 55% and 49% S-CR at 3 yrs resp. HR subgroups showed different S-CR for early T (58%), mature T (70%), pro B (66%) and other B-lineage ALL (37%). 68% and 71% of HR and VHR pts received SCT in CR1 as scheduled which thus contributed substantially to improved outcome. In SR- ALL S-CR was 69% (68% c/preB, 66% thymicT). The CCR probability was 52% at 3 yrs. CNS prophylaxis was very effective since only 2% of the CR pts had CNS involvement at relapse. Univariate analysis confirmed a significant prognostic impact of immunphenotype, WBC in B-lin ALL, time to CR and Ph/BCR-ABL. WBC was no prognostic factor in T-lin-ALL. Age was highly significant for survival with 64% survival 〈 35 yrs vs 48% above 35 yrs. In adolescents below 25 years the most favourable survival of 67% was achieved. In standard risk pts below 35 yrs the survival was 73% without SCT in CR1. Overall the study yielded improved CR rates (89%) and survival (54%). Risk adapted SCT indication was feasible (realised in 70% of HR/VHR pts) and lead to improved survival particularly in early/mature T-ALL and pro B-ALL. In standard risk (SR) the survival is favourable, even above 70% in young pts; however, the relapse rate is still high. Further intensification of therapy during the first year seems required. By definition of new risk factors additional SR patients could be allocated to SCT in CR1. There is however no intention to transfer all SR patients to SCT. Future improvement will be attempted by further inclusion of subtype specific and targeted therapies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.12.12
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
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    Substantially Improved Outcome of Adult Burkitt Non-Hodgkin Lymphoma and Leukemia Patients with Rituximab and a Short-Intensive Chemotherapy; Report of a Large Prospective Multicenter Trial
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 667-667
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 667-667
    Abstract: Abstract 667 Aim. The aim of this study was to prove in a large prospective multicenter trial the tolerance and efficacy of short-intensive chemotherapy combined with the antibody Rituximab directed against CD20 for patients with Burkitt Non-Hodgkin lymphoma (B-NHL) and Burkitt leukemia (B-L). Background. In adult Burkitt lymphoma/leukemia with short-intensive chemotherapy regimen - mostly derived from pediatric protocols - a complete remission (CR) rate of 83% and an overall survival (OS) of 62% (both weighted mean) could be achieved. Further intensification of chemotherapy apparently did not improve the overall outcome. This was the rationale to integrate the monoclonal anti-CD20 antibody Rituximab in B-NHL / leukemia patients with a CD20 expression of 〉 90%. Patients and Methods. 363 adult patients (229 B-NHL and 134 B-L), 15 years or older (without age limit) were recruited from 98 centers in the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) B-ALL/NHL 2002 protocol, initiated in 8/2002 until 06/2011. Median age of the Burkitt lymphoma cohort was 40 years (16–79) and for the Burkitt leukemia cohort 47 years (16–85). CNS involvement was observed in 6% / 18%. In the Burkitt lymphoma cohort, 6% had mediastinal tumor, 53% had stage III/IV and IPI 〉 2 of 35%. Treatment. The treatment consisted of 6 five-day chemotherapy cycles with high-dose methotrexate (HD-MTX) 1500 mg/m2 (total 6 doses), high-dose cytosine arabinoside (HD-AraC) 2000 mg/m2 (total 4 doses), cyclophosphamide, etoposide, ifosphamide and corticosteroids, and a triple intrathecal therapy (MTX, AraC, Dexa). Elderly patients 〉 55 years received reduced drug doses (500 mg/m2), particularly no C-cycles with HD-AraC among other drugs. Rituximab was given d ⦵1 before each cycle and twice at 4 week intervals thereafter, for overall 8 doses. Total treatment duration was 28 weeks (figure 1). Results. CR rate in B-NHL patients was 91% (182/229) and 86% (162/182) in B-L patients. For the B-NHL cohort the results were excellent with an OS of 88%, and a progression-free survival (PFS) of 83% at 〉 7 yrs, with no significant difference in OS for adolescents 15-≤25 yrs with 91%, adults 26-'55 yrs with 91% or elderly 〉 55 yrs with 80%. In Burkitt leukemia the OS for adolescents was also very promising with 90%, for adults OS was 71%, but inferior for elderly patients with 46%. Therefore two cycles C, including high dose AraC, were added for older patients in an amendment. Prognostic factors. In B-NHL patients the age adapted International Prognostic Index (aIPI) was the only significant prognostic factor for OS (p = 0.02) whereas in B-L patients the factors age 15-≤25, 26-≤55 and 〉 55 yrs (p = 0.0007) and a lower platelet count 〈 25000/μl (p = 0.01) had an adverse influence on OS. Major toxicity grade III/IV was less pronounced in B-NHL than in B-L, neutropenia 64% vs. 68%, mucositis 31% vs. 54% and infections 23% vs. 49%. Neurotoxicity was low in both cohorts. Conclusion. In the largest prospective trial for adult Burkitt NHL/leukemia, overall survival and progression-free survival could be substantially improved by a combination of short-intensive chemotherapy with Rituximab with manageable toxicity. Even with lower doses of HD-MTX outcome of B-NHL was excellent in all age groups, including elderly. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.667.667
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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  • 5
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    Overall Outcome of Relapsed Acute Lymphoblastic Leukemia Can Be Improved by Stem Cell Transplantation and Early Treatment in Stage of Molecular Relapse
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. 250-250
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 250-250
    Abstract: Abstract 250 Survival of adult ALL has improved over the past decade to 〉 50% with contemporary, risk adapted, targeted treatment strategies. However, published results of relapsed ALL are poor. In 4 retrospective studies with 1494 patients (pts) the CR rate after first salvage therapy was 40% and the long-term survival was only 6% including stem cell transplantation (SCT) (Thomas et al 1999, Tavernier et al 2007, Fielding et al 2007, Oriol et al, 2010). 1638 patients with newly diagnosed ALL were included in studies 06/99 and 07/03 of the German Multicenter Study Group for Adult ALL (GMALL). 547 patients with first hematologic relapse (HemRel) were evaluable for a retrospective analysis (378 chemotherapy, 169 post SCT). Median age was 33 (15–55) yrs. 432 pts had early ( 〈 18 mo of 1st remission duration) and 115 late relapse. Salvage therapy was given according to physicians' choice and results are available in part of the pts. The aim was to achieve a CR and to perform SCT. Molecular relapse (MolRel) defined by standard criteria (Brüggemann et al, Leukemia, 2010) as reappearance of minimal residual disease (MRD) above 10-4 after prior molecular CR and measured by quantitative PCR of individual IgH/TCR rearrangements was detected in 43 pts. Response to salvage was evaluable in 224 pts with Ph-neg ALL with bone marrow (BM) relapse (no CNS involvement) during/after chemotherapy. The CR rate after first salvage was 42% and significantly inferior in early vs late relapse (36% vs 58%; p=.003). In early relapse the most frequently used regimens were FLAG-IDA (N=38; 42% CR) or a combination of HDAC/HDMTX/VP16/VCR/DEXA (N=38; 29% CR) in B-lineage and CLAEG (N=16; 19% CR) in T-lineage. In late relapses most frequently induction was repeated (N=30; 90% CR). In pts with failure after 1st salvage (N=82) the CR-rate after 2nd salvage was 33%. In relapse after SCT (N=48) the CR rate after 1st salvage was 23%. Median overall survival after relapse was 8.4 months and survival at 5 yrs 24%. Survival was significantly inferior in relapse post-SCT versus relapse on chemotherapy (15% vs 28%; p 〈 .0001) and in BM±other vs CNS±other vs isolated extramedullary relapse (23% vs 27% vs 47%; p=.02). Prognostic factors for survival were analysed in 291 pts with Ph-neg ALL and BM relapse (no CNS involvement) on chemotherapy. Survival was superior in late vs early relapse (43% vs 22%; p 〈 .0001), in pts aged 15–25 yrs vs 26–45 yrs vs 46–55 yrs (38% vs 28% vs 12%; p 〈 .0001) and in pts with CR compared to failure/PR after 1st salvage (47% vs 13%; p 〈 .0001). 75% of evaluable pts received SCT in any stage after relapse. Their survival at 5 yrs was 38% vs 0% without SCT (p 〈 .0001). Survival was significantly better if SCT was performed in CR after 1st salvage vs later CR vs no CR (56% vs 39% vs 20%;p 〈 .0001). Of pts with MolRel (N=43) 26% remained untreated, 19% received specific salvage therapy and in 55% first-line treatment was continued without modification. 11% (N=5) remained in CCR, 30% (N=13) underwent SCT in 1st CR and 58% (N=25) developed HemRel. Median remission duration without SCT in CR1 was 92 d until HemRel and no pt was in continuous CR after 3.5 yrs. Survival after 5 yrs was significantly superior in pts with SCT in CR1 (N=13; 100%) compared to those without (N=30; 24%) (p=.0006). Overall survival after 5 yrs was significantly superior after MolRel (45%) compared to HemRel (22%) (p=.003). Survival of pts with relapse during/after chemotherapy was 28% in the GMALL trials and superior compared to published data. Outcome after relapse was not uniformly poor but depended on prognostic factors such as age and time to relapse. The most important prognostic factor, however, was response to first salvage therapy, being very poor in early relapse. These pts suffer from chemorefractory disease and are candidates for experimental, targeted approaches. Improved overall outcome was mainly an effect of a high rate of SCT (75%) which was possible due to stringent donor search (related/unrelated) at diagnosis of relapse. Survival was significantly better if SCT was performed in CR. For the first time it could be demonstrated that outcome after molecular relapse is superior to outcome after hematologic relapse and this result underlines the relevance of MRD follow-up testing. Further improvement should therefore be achievable by early detection of molecular relapse, stratified relapse treatment, experimental approaches in early relapse and rapid transplant realisation with optimised procedures. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.250.250
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
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  • 6
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    Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 26 ( 2014-12-18), p. 3870-3879
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 26 ( 2014-12-18), p. 3870-3879
    Abstract: Largest prospective trial for adult Burkitt lymphoma/leukemia patients. Substantial cure rates and high treatment-realization rates in all age groups.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2014-03-563627
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
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  • 7
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    High Survival Rate in Adult Burkitt’s Lymphoma/Leukemia and Diffuse Large B-Cell Lymphoma with Mediastinal Involvement.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 518-518
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 518-518
    Abstract: With short intensive chemotherapy mainly based on HDMTX, fractionated alkylators and HDAC outcome of Burkitt’s NHL and mature B-ALL (B-ALL) in adults could be improved substantially to CR rates of 80% and overall survival (OS) of 50–70% (Hoelzer et al, Blood, 1996). Further intensification - namely increase of MTX dose - failed to improve these results. Therefore the German Multicenter Study Group for Adult ALL (GMALL) invented in 2002 a new protocol for mature B-ALL/Burkitt and other high-grade NHL, namely primary mediastinal (med) DLBCL, including 6x Rituximab® 375 mg/m2 before each chemo cycle and two R maintenance cycles. In addition 2 cycles based on HDAC 2 g /m2 were included. HDMTX was 1,5 g/m2 in the protocol for younger pts ( 〈 55 yrs). Older pts ( 〉 55 yrs) received a dose reduced regimen without HDAC and with MTX at 500 mg/m2. 227 pts with Burkitt (27=Burkitt-like), B-ALL or med DLBCL aged between 16 and 78 enrolled between 09/02 and 12/06 were evaluable for response after the first two cycles. The median age was 36 yrs for Burkitt, 46 for B-ALL and 35 for med DLBCL; 18%, 41% and 12% were older than 55 yrs respectively. The subgroups were characterised as follows: 115 Burkitt (stage III–IV 52%, extranodal inv. 78%, aaIPI 〉 1 47%), 70 B-ALL, 42 med DLBCL (stage III–IV 55%, extranodal inv. 71%, aaIPI 〉 1 61%). The CR rate was 90% in Burkitt, 83% in B-ALL and 69% in med DLBCL; death under therapy occurred in 3%, 11% and 0% respectively. The overall survival at 3 yrs was 91% for Burkitt, 79% for B-ALL and 90% for med DLBCL in pts at the age of 15–55 yrs and 84%, 39% and 67% (N=5) respectively in pts 〉 55 yrs. CNS relapses were observed in 3 out of 22 older CR patients with B-ALL whereas in younger pts the CNS relapse rate was 0. CNS relapses are among the reasons for inferior outcome in elderly B-ALL in contrast to elderly pts with Burkitt or med DLBCL. CNS relapse rate may hopefully be reduced by inclusion of an intermediate dose ARAC cycle in the elderly B-ALL. There was no difference in OS between pts with Burkitt (92%) vs Burkitt-like NHL (86%). Since no prognostic factors could be identified in younger pts, there was no need for SCT in CR1. Major grade III/IV toxicity was hematological (28–37%) and mucositis (36%, 37%, 28% in cycles A1, B1, C1 respectively). Compared to the previous GMLL trial B-NHL90 (without Rituximab) with 270 pts the OS of 272 patients (including LBL, LCAL, DLBCL) at 3 yrs improved significantly from 54% to 80% (p 〈 .0001) overall, 56% to 85% (p 〈 .0001) in younger and 39% to 65% (p=.01) in older pts. In this largest prospective study of adult Burkitt’s lymphoma/leukemia and med DLBCL the combination of Rituximab and 6 short intensive chemo cycles was feasible and lead to an OS of 90% in NHL and 79% in mature B-ALL in the younger patient cohort. Even in older pts with Burkitt’s NHL survival was 84%. The further aim is now to reduce toxicity, namely mucositis.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.518.518
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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