Does Post-Transplant Maintenance Therapy With Tyrosine Kinase Inhibitors Improve Outcomes of Patients With High-Risk Philadelphia Chromosome-Positive Leukemia?

Zachariah DeFilipp, Amelia A. Langston, Zhengjia Chen, Chao Zhang, Martha L. Arellano, Fuad El Rassi, Christopher R. Flowers, Vamsi K. Kota, Zaid Al-Kadhimi, Rachel Veldman, Anand P. Jillella, Sagar Lonial, Edmund K. Waller, Hanna J. Khoury

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Relapse is the major cause of allogeneic hematopoietic stem cell transplantation failure in high-risk Philadelphia chromosome-positive (Ph+) leukemia. Post-transplant maintenance therapy is a promising strategy. We found maintenance imatinib and dose-reduced newer generation tyrosine kinase inhibitors to be feasible and generally well tolerated. This approach might reduce the incidence of relapse and improve the outcomes after allogeneic hematopoietic stem cell transplantation for high-risk Ph+ leukemia. Introduction The effect of post-transplant maintenance tyrosine kinase inhibitors (TKIs) on the outcomes of allogeneic hematopoietic stem cell transplantation in high-risk Philadelphia chromosome-positive (Ph+) leukemia remains unknown. Patients and Methods A retrospective analysis that included allograft recipients with accelerated phase and blast phase chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia who had received post-transplant maintenance TKI therapy from 2004 to 2014. Results A total of 26 patients, 9 with accelerated phase/blast phase CML and 17 with Ph+ acute lymphoblastic leukemia, received maintenance post-transplant therapy with imatinib, dasatinib, nilotinib, or ponatinib. The TKI was selected according to the pretransplantation TKI response, anticipated toxicities, and ABL1 domain mutations, when present. Newer generation TKIs were initiated at a ≥ 50% dose reduction from the standard pretransplantation dosing to limit the toxicities and avoid therapy interruptions. TKIs were started a median of 100 days (range, 28-238 days) after transplantation and were administered for a median of 16 months (range, 8 days to 105 months). Eight patients discontinued therapy because of adverse events. With a median follow-up of 3.6 years (range, 4 months to 8.7 years), the 5-year relapse-free survival rate was 61%. All 3 patients who developed a relapse underwent successful salvage treatment and remained disease-free. The 5-year overall survival rate was 78%. Conclusion Maintenance TKI therapy after transplantation is feasible and might reduce the incidence of relapses and improve outcomes after allogeneic hematopoietic stem cell transplantation for patients with high-risk Ph+ leukemia.

Original languageEnglish (US)
Pages (from-to)466-471.e1
JournalClinical Lymphoma, Myeloma and Leukemia
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Fingerprint

Philadelphia Chromosome
Protein-Tyrosine Kinases
Leukemia
Transplants
Hematopoietic Stem Cell Transplantation
Maintenance
Recurrence
Blast Crisis
Therapeutics
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Survival Rate
Transplantation
Salvage Therapy
Incidence
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Allografts
Mutation

Keywords

  • Acute lymphoblastic leukemia
  • Chronic myeloid leukemia
  • Ph
  • Relapse
  • TKIs

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Does Post-Transplant Maintenance Therapy With Tyrosine Kinase Inhibitors Improve Outcomes of Patients With High-Risk Philadelphia Chromosome-Positive Leukemia? / DeFilipp, Zachariah; Langston, Amelia A.; Chen, Zhengjia; Zhang, Chao; Arellano, Martha L.; El Rassi, Fuad; Flowers, Christopher R.; Kota, Vamsi K.; Al-Kadhimi, Zaid; Veldman, Rachel; Jillella, Anand P.; Lonial, Sagar; Waller, Edmund K.; Khoury, Hanna J.

In: Clinical Lymphoma, Myeloma and Leukemia, Vol. 16, No. 8, 01.08.2016, p. 466-471.e1.

Research output: Contribution to journalArticle

DeFilipp, Z, Langston, AA, Chen, Z, Zhang, C, Arellano, ML, El Rassi, F, Flowers, CR, Kota, VK, Al-Kadhimi, Z, Veldman, R, Jillella, AP, Lonial, S, Waller, EK & Khoury, HJ 2016, 'Does Post-Transplant Maintenance Therapy With Tyrosine Kinase Inhibitors Improve Outcomes of Patients With High-Risk Philadelphia Chromosome-Positive Leukemia?', Clinical Lymphoma, Myeloma and Leukemia, vol. 16, no. 8, pp. 466-471.e1. https://doi.org/10.1016/j.clml.2016.04.017
DeFilipp, Zachariah ; Langston, Amelia A. ; Chen, Zhengjia ; Zhang, Chao ; Arellano, Martha L. ; El Rassi, Fuad ; Flowers, Christopher R. ; Kota, Vamsi K. ; Al-Kadhimi, Zaid ; Veldman, Rachel ; Jillella, Anand P. ; Lonial, Sagar ; Waller, Edmund K. ; Khoury, Hanna J. / Does Post-Transplant Maintenance Therapy With Tyrosine Kinase Inhibitors Improve Outcomes of Patients With High-Risk Philadelphia Chromosome-Positive Leukemia?. In: Clinical Lymphoma, Myeloma and Leukemia. 2016 ; Vol. 16, No. 8. pp. 466-471.e1.
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abstract = "Relapse is the major cause of allogeneic hematopoietic stem cell transplantation failure in high-risk Philadelphia chromosome-positive (Ph+) leukemia. Post-transplant maintenance therapy is a promising strategy. We found maintenance imatinib and dose-reduced newer generation tyrosine kinase inhibitors to be feasible and generally well tolerated. This approach might reduce the incidence of relapse and improve the outcomes after allogeneic hematopoietic stem cell transplantation for high-risk Ph+ leukemia. Introduction The effect of post-transplant maintenance tyrosine kinase inhibitors (TKIs) on the outcomes of allogeneic hematopoietic stem cell transplantation in high-risk Philadelphia chromosome-positive (Ph+) leukemia remains unknown. Patients and Methods A retrospective analysis that included allograft recipients with accelerated phase and blast phase chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia who had received post-transplant maintenance TKI therapy from 2004 to 2014. Results A total of 26 patients, 9 with accelerated phase/blast phase CML and 17 with Ph+ acute lymphoblastic leukemia, received maintenance post-transplant therapy with imatinib, dasatinib, nilotinib, or ponatinib. The TKI was selected according to the pretransplantation TKI response, anticipated toxicities, and ABL1 domain mutations, when present. Newer generation TKIs were initiated at a ≥ 50{\%} dose reduction from the standard pretransplantation dosing to limit the toxicities and avoid therapy interruptions. TKIs were started a median of 100 days (range, 28-238 days) after transplantation and were administered for a median of 16 months (range, 8 days to 105 months). Eight patients discontinued therapy because of adverse events. With a median follow-up of 3.6 years (range, 4 months to 8.7 years), the 5-year relapse-free survival rate was 61{\%}. All 3 patients who developed a relapse underwent successful salvage treatment and remained disease-free. The 5-year overall survival rate was 78{\%}. Conclusion Maintenance TKI therapy after transplantation is feasible and might reduce the incidence of relapses and improve outcomes after allogeneic hematopoietic stem cell transplantation for patients with high-risk Ph+ leukemia.",
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AU - El Rassi, Fuad

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