Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients

Abstract

While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2–4.9; p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5–1.1; p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8–4.9), p = .13] and AP [HR = 1.1 (0.6–2.1); p = .80] is less clear and should be determined on a case-by-case basis.

Keywords:

• Chronic myeloid leukemia
• allogeneic stem cell transplant
• tyrosine kinase inhibitors

Acknowledgements

We appreciate the suggestions and comments by the CIBMTR committee in the writing of the protocol and the manuscript.

Disclosure statement

B.H., X.L., X.H. R.S.T., Z.H., K.W.A., Y.L., U.P., W.S. have no relevant conflicts of interest to report. H.C.L. has received consulting fees and research funding from Takeda pharmaceuticals. Dr. Ayman Saad’s institution receives research funding from Amgen, Kadmon, OrcaBio. Jan Cerny has received research funds from Pfizer pharmaceuticals, Incyte, Jazz Pharmaceuticals, Daiichi Sankyo. Dr. Aaron Gers has received research funding from Celgene, Pfizer, CTI biopharma, Dr. Michael Grunwald’s institution has received research funding from Forma Therapeautics, Amgen, Genentech, Incyte, Janssen, Novartis, and has stock ownership in Medtronic, and has provided consulting for Agios, Abbvie, Amgen, Cardinal Health, Celgene, Incyte, Merck, Pfizer, Trovagene, Daiichi Sankyo. Dr. Richard Olsson has received research funding from AstraZeneca. Dr. Farhad Ravandi has received research funding from Bristol Myers Squibb, Novartis, Pfizer. Dr. Jorge Cortes has received research funding to his institution from Bristol Myers Squibb, Novartis, Pfizer, Takeda, Sun Pharma and has acted as a consultant for Bristol Myers Squibb, Novartis, Pfizer, and Takeda.

Author contributions

B.H. designed the study, wrote the protocol, analyzed the results, performed chart extractions to collect patient data, and wrote the manuscript. X.L. contributed to the design of study, performed statistical analysis, discovered that the Markov analysis underestimated life expectancy in the alloHCT cohort, and contributed to the writing of the manuscript. H.C.L. conceived the original idea, designed the study, wrote the protocol, performed chart extractions to collect patient data. X.H. performed the statistical analysis, discovered that the Markov analysis underestimated life expectancy in the alloHCT cohort. R.S. performed the statistical analysis and contributed to the design of study. E.J., S.V., F.R, G.G.M., J.C., R.C., U.P., H.K. contributed patients in the study. M. DL. conceived the original idea for the study. Z.H. contributed to the statistical analysis and data collection. J.C. co-designed the study, reviewed and edited the protocol, analyzed the data and results, reviewed and edited the manuscript. H.K., J.C. and W.S. contributed to the writing, editing, provided important suggestions and contributions for the protocol and manuscript. All authors provided critical feedback and helped shape the research, analysis and manuscript, and approved the final version of the manuscript.

Additional information

Funding

The CIBMTR is supported primarily by Public Health Service Grant/Cooperative Agreement 5U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-17-1-2388 and N0014-17-1-2850 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals, Inc.; *Amgen, Inc.; *Amneal Biosciences; *Angiocrine Bioscience, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US; Atara Biotherapeutics, Inc.; Be the Match Foundation; *bluebird bio, Inc.; *Bristol Myers Squibb Oncology; *Celgene Corporation; Cerus Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Juno Therapeutics; Karyopharm Therapeutics, Inc.; Kite Pharma, Inc.; Medac, GmbH; MedImmune; The Medical College of Wisconsin; *Mediware; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; *Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Otsuka Pharmaceutical Co, Ltd. – Japan; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick’s Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Takeda Oncology; Telomere Diagnostics, Inc.; and University of Minnesota. This study was also supported by Center for Strategic Scientific Initiatives. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government (*signifies corporate members).