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

Jessica Wu, Yanjun Chen, Lindsey Hageman, Liton Francisco, Emily C. Ness, Mariel Parman, Michelle Kung, James A. Watson, Daniel J. Weisdorf, David S. Snyder, Philip B. McGlave, Stephen J. Forman, Mukta Arora, Saro H. Armenian, Ravi Bhatia, Smita Bhatia

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)4033-4042
Number of pages10
JournalCancer
Volume125
Issue number22
DOIs
StatePublished - Nov 15 2019

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Protein-Tyrosine Kinases
Survivors
Bone Marrow
Transplants
Mortality
Cyclophosphamide
Busulfan
Whole-Body Irradiation
Incidence
Graft vs Host Disease
Proportional Hazards Models
Medical Records
Therapeutics
Survival Rate
Transplantation

Keywords

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

Cite this

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. / Wu, Jessica; Chen, Yanjun; Hageman, Lindsey; Francisco, Liton; Ness, Emily C.; Parman, Mariel; Kung, Michelle; Watson, James A.; Weisdorf, Daniel J.; Snyder, David S.; McGlave, Philip B.; Forman, Stephen J.; Arora, Mukta; Armenian, Saro H.; Bhatia, Ravi; Bhatia, Smita.

In: Cancer, Vol. 125, No. 22, 15.11.2019, p. 4033-4042.

Research output: Contribution to journalArticle

Wu, J, Chen, Y, Hageman, L, Francisco, L, Ness, EC, Parman, M, Kung, M, Watson, JA, Weisdorf, DJ, Snyder, DS, McGlave, PB, Forman, SJ, Arora, M, Armenian, SH, Bhatia, R & Bhatia, S 2019, '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', Cancer, vol. 125, no. 22, pp. 4033-4042. https://doi.org/10.1002/cncr.32443
Wu, Jessica ; Chen, Yanjun ; Hageman, Lindsey ; Francisco, Liton ; Ness, Emily C. ; Parman, Mariel ; Kung, Michelle ; Watson, James A. ; Weisdorf, Daniel J. ; Snyder, David S. ; McGlave, Philip B. ; Forman, Stephen J. ; Arora, Mukta ; Armenian, Saro H. ; Bhatia, Ravi ; Bhatia, Smita. / 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. In: Cancer. 2019 ; Vol. 125, No. 22. pp. 4033-4042.
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title = "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",
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",
author = "Jessica Wu and Yanjun Chen and Lindsey Hageman and Liton Francisco and Ness, {Emily C.} and Mariel Parman and Michelle Kung and Watson, {James A.} and Weisdorf, {Daniel J.} and Snyder, {David S.} and McGlave, {Philip B.} and Forman, {Stephen J.} and Mukta Arora and Armenian, {Saro H.} and Ravi Bhatia and Smita Bhatia",
year = "2019",
month = "11",
day = "15",
doi = "10.1002/cncr.32443",
language = "English (US)",
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TY - JOUR

T1 - Late mortality after bone marrow transplant for chronic myelogenous leukemia in the context of prior tyrosine kinase inhibitor exposure

T2 - A Blood or Marrow Transplant Survivor Study (BMTSS) report

AU - Wu, Jessica

AU - Chen, Yanjun

AU - Hageman, Lindsey

AU - Francisco, Liton

AU - Ness, Emily C.

AU - Parman, Mariel

AU - Kung, Michelle

AU - Watson, James A.

AU - Weisdorf, Daniel J.

AU - Snyder, David S.

AU - McGlave, Philip B.

AU - Forman, Stephen J.

AU - Arora, Mukta

AU - Armenian, Saro H.

AU - Bhatia, Ravi

AU - Bhatia, Smita

PY - 2019/11/15

Y1 - 2019/11/15

N2 - 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.

AB - 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.

KW - blood or bone marrow transplant

KW - bone marrow transplant

KW - chronic myelogenous leukemia

KW - late mortality after bone marrow transplant

KW - tyrosine kinase inhibitor

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U2 - 10.1002/cncr.32443

DO - 10.1002/cncr.32443

M3 - Article

C2 - 31412155

AN - SCOPUS:85070747925

VL - 125

SP - 4033

EP - 4042

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 22

ER -