The effect of imatinib therapy on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia

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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“…2,3 These secondary benefits may have contributed to the lower NRM in patients who received pre-transplant imatinib administration.…”

Section: Discussionmentioning

confidence: 99%

“…[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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“…may deepen remissions through effects on cancer cells or the tumor microenvironment and thus improve outcomes. A role for novel agents in the pre-transplant setting is suggested by observations of improved AlloSCT outcomes following their use in “bridge” therapy, such as with tyrosine kinase inhibitors in Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) (9) and brentuximab vedotin in Hodgkin’s lymphoma (10); distinct toxicity profiles and unique mechanisms of action have led to investigation of incorporating monoclonal antibodies into reduced-intensity conditioning (RIC) regimens, resulting in immunomodulatory as well as direct antitumor effects (11). New cancer drugs with novel targets and innovative methods of drug delivery are entering the clinic at a phenomenal rate; their potential to permit or augment GVT is an important research opportunity.…”

Section: Preventionmentioning

confidence: 99%

Proceedings from the National Cancer Institute’s Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part III. Prevention and Treatment of Relapse after Allogeneic Transplantation

Lima

Porter

Battiwalla

et al. 2014

Biology of Blood and Marrow Transplantation

128

102

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In the 2nd NCI Workshop on the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Prevention and Treatment of Relapse after Allogeneic Transplantation highlighted progress in developing new therapeutic approaches since the 1st Relapse Workshop. Recent insights that might provide a basis for the development of novel, practical clinical trials were emphasized, including utilization of newer agents, optimization of donor lymphocyte infusion (DLI), and investigation of novel cellular therapies. Dr. de Lima discussed preemptive and maintenance strategies to prevent relapse after transplantation, e.g., recent promising results suggestive of enhanced graft-versus-tumor activity with hypomethylating agents. Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy for relapse, including cytoreduction prior to DLI, combination of targeted agents with DLI, and considerations in use of second transplants. Dr. Porter addressed strategies to enhance T-cell function, including ex-vivo activated T cells and T-cell engineering, and immunomodulatory approaches to enhance T-cell function in vivo, including exogenous cytokines and modulation of costimulatory pathways.

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Section: Introductionmentioning

confidence: 99%

“…Therefore, application of imatinib pretransplant might have benefits for patients with Ph + ALL 54. In a retrospective analysis of 69 patients with Ph + ALL,54 44 patients received imatinib therapy, including 24 pretransplant, 9 post-transplant, and 11 both pre- and post-transplant. The 3-year estimated OS and DFS were 62.3% and 53.6%, respectively, in patients who received imatinib therapy pretransplant, and 25.9% and 23.6%, respectively, in patients who did not receive imatinib therapy pretransplant.…”

Section: Introductionmentioning

confidence: 99%

Clinical efficacy and safety of imatinib in the management of Ph+ chronic myeloid or acute lymphoblastic leukemia in Chinese patients

Zhu

Shen

2014

OTT

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Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukemia (CML) and functions by targeting BCR-ABL tyrosine kinases. Imatinib has substantially changed the clinical management and improved the prognosis of CML and Philadelphia chromosome-positive acute lymphocytic leukemia (Ph+ ALL). Here, we review the pharmacology, mode of action, and pharmacokinetics of imatinib; Chinese efficacy studies in CML and Ph+ ALL; safety and tolerability; patient-focused perspectives, such as quality of life, patient satisfaction, acceptability, and adherence; and uptake of imatinib.

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The effect of imatinib therapy on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia

Abstract: Application of imatinib pre-transplant might have benefited for patients with Ph+ ALL. Whether administration of imatinib, regardless of the molecular status of the disease post-transplant increases relapse, is a worthy goal for further study.

Cited by 18 publications

References 24 publications

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

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

Proceedings from the National Cancer Institute’s Second International Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation: Part III. Prevention and Treatment of Relapse after Allogeneic Transplantation

Clinical efficacy and safety of imatinib in the management of Ph+ chronic myeloid or acute lymphoblastic leukemia in Chinese patients

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