The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia

Blood ◽  
2005 ◽  
Vol 105 (9) ◽  
pp. 3449-3457 ◽  
Author(s):  
Seok Lee ◽  
Yoo-Jin Kim ◽  
Chang-Ki Min ◽  
Hee-Je Kim ◽  
Ki-Sung Eom ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Newly Diagnosed ◽  
First Line

AbstractPreviously, we suggested that imatinib incorporation into conventional chemotherapy as an alternative (imatinib interim therapy) might be a useful strategy for bridging the time to allogeneic stem cell transplantation (SCT) for newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL). Here, we provide an updated report on this strategy in 29 patients. At the time of enrollment, 23 patients (79.3%) achieved complete remission (CR). After the first imatinib cycle, the median breakpoint cluster region–Abelson oncogene locus (BCR-ABL)/ABL ratios decreased by 0.77 log in 25 (86.2%) responders, and their BCR-ABL/ABL ratios decreased further by 0.34 log after the second imatinib cycle, which included 7 molecular CR. One patient (4.3%) relapsed during the imatinib therapy. The remaining 3 patients were primarily refractory to both imatinib and chemotherapy. Twenty-five (86.2%) of the 29 patients received transplants in first CR. With a median follow-up duration of 25 months after SCT, the 3-year estimated probabilities of relapse, nonrelapse mortality, disease-free survival, and overall survival were 3.8%, 18.7%, 78.1%, and 78.1%, respectively. In comparison to our historical control data, first-line imatinib interim therapy appears to provide a good quality of CR and a survival advantage for patients with Ph+ ALL. Further long-term follow-up is needed to validate the results of this study.

Minimal residual disease–based role of imatinib as a first-line interim therapy prior to allogeneic stem cell transplantation in Philadelphia chromosome–positive acute lymphoblastic leukemia

Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 3068-3070 ◽  
Author(s):  
Seok Lee ◽  
Dong-Wook Kim ◽  
Yoo-Jin Kim ◽  
Nak-Gyun Chung ◽  
Yoo-Li Kim ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
First Line ◽  
Philadelphia Chromosome Positive

Abstract Fourteen adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) were studied to evaluate the role of imatinib prior to allogeneic stem cell transplantation (SCT). Of these, 12 patients were in complete hematologic response (CHR), and 2 were refractory. Imatinib was administered as an interim schedule after each chemotherapy course. After the first imatinib cycle, 11 patients remained in sustained CHR with a decrease in the BCR-ABL/ABL ratios (0.89 logs), and one refractory patient achieved CHR. Meanwhile, 2 patients were resistant to imatinib. Ten patients receiving a second imatinib cycle following consolidation showed sustained CHR, including 2 molecular CR, with a further decrease in the BCR-ABL/ABL ratios (0.19 logs). Twelve patients underwent SCT in a favorable status, and of these, 11 are still alive in a leukemia-free status at 9 to 28+ months after SCT. First-line imatinib interim therapy appears to be a useful strategy to bridge the time to SCT for patients with Ph+ ALL.

Impact of donor source on allogeneic stem cell transplantation for Philadelphia chromosome-negative acute lymphoblastic leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6533-6533
Author(s):  
Satoshi Nishiwaki ◽  
Koichi Miyamura ◽  
Kazuteru Ohashi ◽  
Mineo Kurokawa ◽  
Shuichi Taniguchi ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
The Impact ◽  
Donor Source

6533 Background: Although allogeneic stem cell transplantation (allo-SCT) could improve the outcome of adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source, particularly the position of cord blood (CB) transplantation, is still uncertain. Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients transplanted at the first time between 1998 and 2009 with myeloablative preparative regimens who were registered in the Japan Society for Hematopoietic Cell Transplantation database. Two hundred and thirty-three received CB transplantation [first complete remission (CR1): 95, subsequent CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor (URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR: 207). Results: Overall survival (OS) in patients after CB transplantation in CR1 was comparable with that after allo-SCT from URD or RD [57% in CB, 64% in URD, and 65% in RD at 4 years, respectively, P=0.11]. Donor source was not a significant risk factor for OS in multivariate analysis. Although URD was a favorable factor for relapse and an unfavorable factor for non-relapse mortality (NRM), CB was not a significant factor for them [Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively (P=0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years, respectively (P=0.0001)]. Among CB recipients in CR1, age at allo-SCT (45 years or older) was solely a significant adverse prognostic factor in multivariate analysis. Among patients younger than 45 years who received allo-SCT in CR1, OS after CB transplantation was significantly better than that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%, P=0.04). Similarly, OS was not different by donor source in subsequent CR or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD, P=0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P=0.20 at 4 years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes as either RD or URD in any disease status. CB transplantation is a good alternative for adult Ph(-) ALL patients without a suitable RD or URD.

No Impact of Adverse Karyotype on Outcome after Allogeneic Stem Cell Transplantation in Patients with High-Risk Acute Lymphoblastic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3152-3152
Author(s):  
Ingo Tamm ◽  
Gero Massenkeil ◽  
Mandy Wagner ◽  
Theis Terwey ◽  
Christoph Lutz ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Normal Karyotype ◽  
Chromosomal Anomalies

Abstract Karyotypes like Philadelphia-chromosome (Ph+) and t(4;11) adversely influence clinical outcome in adult patients with acute lymphoblastic leukemia (ALL) after chemotherapy. Here, we analyze the potential impact of karyotype on outcome after allogeneic hematopoietic stem cell therapy (HSCT) in ALL. We present a retrospective analysis of 135 adult ALL patients treated unicentrically within the German ALL (GMALL) protocol using allogeneic HSCT. All patients were high-risk patients in CR1 according to GMALL definitions (i.e., WBC > 30.000/μl, pro-B-ALL, t(4;11), t(9;22), early T- or mature T-ALL, no CR after first induction) or were beyond CR1. Median age of all patients was 29 years (range 16 – 55), 99 B-lineage and 36 T-lineage ALLs were transplanted. Normal karyotype was present in 57 patients, Ph+ in 36 patients, complex chromosomal anomalies in six patients, t(4;11) in five patients, other aberrations in 22 patients and no growth/no cytogenetic data were available for 9 patients. Patients were transplanted in complete remission (CR) CR1 (60), CR2 (23), CR3 (7), first relapse (30), second relapse (6), third relapse (1) and eight patients had primary induction failure. 41 patients received bone marrow and 94 patients received peripheral blood stem cell transplants. Patients received standard high-dose (n=125) or reduced intensity conditioning (RIC) (n=10) HSCT from related (n=58) or unrelated (n=77) donors. Overall, after a median follow-up of 11 months (range 1–120), 74 (55%) patients died and 61 (45%) are alive. Median follow-up of the living is 29 months (range 1–120). Deaths were due to treatment-related mortality (TRM; n=33; 24%) or relapse (n=41; 31%). Leukemia-free survival (LFS), overall survival, and TRM were not significantly different between the karyotype subgroups studied. LFS at 6 months, 1 year, 3 years, and five years was 62%, 60%, 50%, and 41% for patients with a normal karyotype; 63%, 47%, 40%, and 28% for patients with Ph+; and 61%, 40%, 27%, and 27% for patients with other aberrations. 4/5 patients with t(4;11) and 4/6 patients with complex chromosomal abnormalities are alive in CR. In conclusion, there is no adverse impact of classical poor risk karyotypes on outcome within this high-risk group of ALL patients after allogeneic stem cell transplantation. In contrast, there was a trend that patients with t(4;11) and complex chromosomal anomalies did better (4/5 alive, 1/5 TRM and 4/6 alive, 1/6 TRM, 1/6 relapse, respectively) than patients with other aberrations (8/22 alive, 8/22 death due to relapse, 6/22 TRM). High-risk ALL patients with poor risk cytogenetics are candidates for allogeneic stem cell transplantation which can be curative. Whether other conditioning regimens or adoptive immunotherapy can reduce relapse rate in this patient group is a matter of ongoing clinical research.

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