High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed <i>BCR</i>-<i>ABL</i>–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group

Yanada, Masamitsu; Jin, Tao; Sugiura, Isamu; Akiyama, Hideki; Usui, Noriko; Yagasaki, Fumiharu; Kobayashi, Toshimitsu; Ueda, Yasunori; Takeuchi, Makoto; Miyawaki, Shuichi; Maruta, Atsuo; Emi, Nobuhiko; Miyazaki, Yasushi; Ohtake, Shigeki; Jinnai, Itsuro; Matsuo, Keitaro; Naoe, Tomoki; Ohno, Ryuzo

doi:10.1200/jco.2005.03.2177

Cited by 415 publications

(321 citation statements)

References 24 publications

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“…The combination of imatinib with conventional chemotherapy as the first-line treatment has demonstrated an improved CR rate and an increased applicability in allogeneic SCT, thus allowing better outcomes in adults with Ph-positive ALL [33][34][35][36][37]. Previously, we also conducted a prospective, phase II trial of allogeneic SCT following firstline imatinib-based chemotherapy, and our recently updated results continue to show the positive impact of imatinib on long-term outcomes of allogeneic SCT [21][22][23].…”

Section: Discussionmentioning

confidence: 89%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

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The role of reduced-intensity conditioning (RIC) in adult acute lymphoblastic leukemia (ALL) remains unclear because of the small sample size, short follow-up duration, various regimens for conditioning and graft-versus-host disease (GVHD) prophylaxis, and the heterogeneity of selection criteria for transplantation. We compared long-term outcomes of 60 consecutive RIC transplants (fludarabine plus melphalan) with 120 myeloablative conditioning (MAC) transplants (total body irradiation plus cyclophosphamide) for adult high-risk ALL in first or second complete remission. All transplants received a uniform strategy of pretransplant chemotherapy and GVHD prophylaxis. Compared to MAC transplants, RIC transplants had older age (46 years vs. 33 years, P < 0.001) and higher proportions of transplantation using peripheral blood (93.3% vs. 13.3%; P < 0.001) but otherwise showed similar characteristics. After a median follow-up of 67 months, RIC transplants showed comparable nonrelapse mortality (21.2% vs. 24.3%) and disease-free survival (50.8% vs. 54.9%) to MAC transplants, although relapse risk was higher (34.2% vs. 26.4%; HR, 2.07; P 5 0.019) in multivariate analysis. Other independent factors associated with better outcomes were the presence of chronic GVHD and transplantation in first complete remission. Interestingly, the negative impact of RIC on relapse risk was seen only for Philadelphia-positive ALL transplants (32.7% vs. 19.6%; HR, 3.46; P 5 0.020), while no difference was found between RIC and MAC for Philadelphia-negative ALL transplants (35.0% vs. 32.1%; HR, 1.39; P 5 0.429). RIC can be considered as a reasonable choice for providing a sufficient long-term graft-versus-leukemia effect for adult high-risk ALL patients ineligible for MAC. Am. J. Hematol. 88:634-641,

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Section: Discussionmentioning

confidence: 89%

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

et al. 2013

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“…[1][2][3][4][5][6] However, with an extended follow-up, a substantial proportion of transplant patients and practically almost all non-transplant patients continue to die as a result of relapse. Consequently, patients at the highest risk of relapse are likely to benefit from the identification of new criteria that enable predictable patient outcome.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11] Most published studies in the imatinib era include quantitative MRD findings, [1][2][3][4][5][6] but the longterm outcome in relation to molecular response to any given therapeutic approach remains to be determined. Previously, we conducted a prospective, phase 2 trial of allogeneic SCT following first-line imatinib-based chemotherapy in adults with Ph-positive ALL, and in the trial, BCR-ABL1 transcript levels in the bone marrow (BM) were routinely monitored using real-time quantitative PCR (RQ-PCR).…”

Section: Introductionmentioning

confidence: 99%

Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

et al. 2012

Leukemia

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We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinibbased chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n ¼ 33), late molecular responders (LMRs, n ¼ 35), intermediate molecular responders (IMRs, n ¼ 9) and poor molecular responders (PMRs, n ¼ 18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.

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“…[1][2][3][4][5] Since hematological CR can be achieved in many patients in the era of tyrosine kinase inhibitors (TKIs), 6,7 monitoring minimal residual disease (MRD) is important for long-term disease control. [8][9][10][11][12] Therefore, increasing attention has been paid to MRD status at allo-HCT.…”

Section: Introductionmentioning

confidence: 99%

Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT

Nishiwaki

Imai

Mizuta

et al. 2015

Bone Marrow Transplant

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To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(− )) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD( − ) was significantly better than that in patients transplanted in MRD(+) (MRD( − ): 67% vs MRD(+): 55% at 4 years; P = 0.001). MRD( − ) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD( − ) was significantly lower than that in patients transplanted in MRD(+) (MRD( − ): 19% vs MRD(+): 29% at 4 years; P = 0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P o0.0001). MRD status at allo-HCT is one of the most important predictive factors for Ph +ALL patients transplanted in CR1.

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High Complete Remission Rate and Promising Outcome by Combination of Imatinib and Chemotherapy for Newly Diagnosed BCR-ABL–Positive Acute Lymphoblastic Leukemia: A Phase II Study by the Japan Adult Leukemia Study Group

Cited by 415 publications

References 24 publications

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

Comparable long‐term outcomes after reduced‐intensity conditioning versus myeloablative conditioning allogeneic stem cell transplantation for adult high‐risk acute lymphoblastic leukemia in complete remission

Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT

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