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Cancer. 2019 Nov 15;125(22):4033-4042. doi: 10.1002/cncr.32443. Epub 2019 Aug 14.

Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure: A Blood or Marrow Transplant Survivor Study (BMTSS) report.

Author information

1
Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, Alabama.
2
Department of Medicine, University of Minnesota, Minneapolis, Minnesota.
3
Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California.
4
Department of Medicine, City of Hope National Medical Center, Duarte, California.
5
Hematology-Oncology and Blood and Marrow Transplantation, University of Minnesota, Minneapolis, Minnesota.
6
Department of Social Sciences and Pediatrics, City of Hope National Medical Center, Duarte, California.
7
Division of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, Alabama.
8
Department of Pediatrics, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

BACKGROUND:

Late mortality was investigated in patients with chronic myelogenous leukemia (CML) who underwent blood or bone marrow transplant (BMT) with or without prior tyrosine kinase inhibitor (TKI) therapy.

METHODS:

By using data from the Blood or Marrow Transplant Survivor Study, the authors examined late mortality in 447 patients with CML who underwent BMT between 1974 and 2010, conditional on surviving ≥2 years post-BMT. For vital status information, the medical records, the National Death Index, and the Accurint database were used. Standardized mortality ratios (SMRs) were calculated using general population age-specific, sex-specific, and calendar-specific mortality rates. Kaplan-Meier techniques and Cox regression were used for all-cause mortality analyses. Cumulative incidence and proportional subdistribution hazards models for competing risks were used for cause-specific mortality analyses.

RESULTS:

The 10-year overall survival rate was 65.7% and 73% for those who underwent transplant with and without pre-BMT exposure to TKI therapy, respectively. Patients who underwent transplant with and without pre-BMT TKI experienced SMRs of 6.4 and 6.4, respectively (P = .8); and the SMRs were 11.6 and 8.1, respectively, for those with high-risk disease (P = .2). Independent predictors of non-CML-related mortality included chronic graft-versus-host disease (hazard ratio [HR], 2.8; 95% CI, 1.8-4.4) and busulfan/cyclophosphamide conditioning (HR, 0.5; 95% CI, 0.3-0.9; reference, total body irradiation/cyclophosphamide conditioning). The 20-year cumulative incidence of CML-related and non-CML-related mortality was 6% and 36%, respectively, for the entire cohort. Both CML-related mortality (HR, 1.0; 95% CI, 0.1-12.6) and non-CML-related mortality (HR, 1.3; 95% CI, 0.6-3.1) were comparable for those with and without pre-BMT TKI therapy.

CONCLUSIONS:

The similar late mortality experienced by patients with CML who undergo transplantation with or without pre-BMT TKIs suggests that allogeneic BMT can be considered in the context of TKI intolerance or nonadherence. The prevention of post-BMT non-CML-related mortality could favorably affect long-term survival.

KEYWORDS:

blood or bone marrow transplant; bone marrow transplant; chronic myelogenous leukemia; late mortality after bone marrow transplant; tyrosine kinase inhibitor

PMID:
31412155
DOI:
10.1002/cncr.32443

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