Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients With Myelofibrosis—A Systematic Review and Meta-Analysis

Jan Philipp Bewersdorf, Amar H. Sheth, Shaurey Vetsa, Alyssa Grimshaw, Smith Giri, Nikolai A. Podoltsev, Lohith Gowda, Roni Tamari, Martin S. Tallman, Raajit K. Rampal, Amer M. Zeidan, Maximilian Stahl*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Allogeneic hematopoietic cell transplant (allo-HCT) remains the only potentially curative therapeutic modality for patients with primary or secondary myelofibrosis (MF). However, many patients are considered ineligible for allo-HCT, and transplant-related mortality can be substantial. Data on the efficacy and safety of allo-HCT are mixed and largely derived from retrospective studies. We aimed to synthesize the available evidence on the safety and efficacy of allo-HCT in MF and to identify patient, disease, and transplant characteristics with prognostic impact on outcomes of patients with MF undergoing allo-HCT. For this systematic review and meta-analysis, Cochrane Library, Google Scholar, Ovid Medline, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection were searched from inception to October 11, 2020, for studies on allo-HCT in MF. Random-effects models were used to pool response rates for the co-primary outcomes of 1-year, 2-year, and 5-year overall survival (OS). Rates of non-relapse mortality and acute and chronic graft-versus-host-disease (GVHD) were studied as secondary endpoints. Subgroup analyses on the effect of conditioning regimen intensity, baseline dynamic international prognostic scoring system (DIPSS) score, and patient age were performed. The study protocol has been registered on PROSPERO (CRD42020188706). Forty-three studies with 8739 patients were identified and included in this meta-analysis. Rates of 1-year, 2-year, and 5-year OS were 66.7% (95% confidence interval [CI], 63.5%-69.8%), 64.4% (95% CI, 57.6%-70.6%), and 55.0% (95% CI, 51.8%-58.3%), respectively. Rates of 1-year, 2-year, and 5-year nonrelapse mortality were 25.9% (95% CI, 23.3%-28.7%), 29.7% (95% CI, 24.5%-35.4%), and 30.5% (95% CI, 25.9%-35.5%), respectively. The combined rate of graft failure was 10.6% (95% CI, 8.9%-12.5%) with primary and secondary graft failure occurring in 7.3% (95% CI, 5.7%-9.4%) and 5.9% (95% CI, 4.3%-8.0%) of patients, respectively. Rates of acute and chronic graft-versus-host disease were 44.0% (95% CI, 39.6%-48.4%; grade III/IV: 15.2%) and 46.5% (95% CI, 42.2%-50.8%; extensive or moderate/severe: 26.1%), respectively. Subgroup analyses did not show any significant difference between conditioning regimen intensity (myeloablative versus reduced-intensity), median patient age, and proportion of DIPSS-intermediate-2/high patients. The quality of the evidence is limited by the absence of randomized clinical trials in the field and the heterogeneity of patient and transplant characteristics across included studies. Given the poor prognosis of patients not receiving transplants and in the absence of curative nontransplantation therapies, our results support consideration of allo-HCT for eligible patients with MF.

Original languageEnglish (US)
Pages (from-to)873.e1-873.e13
JournalTransplantation and Cellular Therapy
Volume27
Issue number10
DOIs
StatePublished - Oct 2021

Funding

Conflict of interest statement: N.A.P. consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squib, CTI biopharma and PharmaEssentia. N.A.P. received research funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI biopharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals and Kartos Therapeutics . L.G. has received research support from Bristol-Myers Squib. M.S.T. has received research funding from Abbvie, Cellerant, Orsenix, ADC Therapeutics, and Biosight. M.S.T. has received honoraria for M.S.T. has received research funding from AbbVie, Cellerant, Orsenix, ADC Therapeutics, Biosight, Glycomimetics, Rafael Pharmaceuticals, and Amgen. M.S.T. has received honoraria for advisory board membership from AbbVie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, Jazz Pharmaceuticals, Roche, Biosight, Novartis, Innate Pharmaceuticals, Kura, and Syros Pharmaceuticals. M.S.T. received royalties from UpToDate. R.K.R has received consulting fees from Bristol-Myers Squibb, Constellation, Incyte, Celgene, Promedior, CTI, Jazz Pharmaceuticals, Blueprint, Stemline, and research funding from Incyte, Constellation, Stemline. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics. A.M.Z participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Trovagene/Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Aprea, Janssen, and Tyme. A.M.Z served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, and Celgene/BMS. A.M.Z received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology None of these relationships were related to the development of this manuscript. All other authors report no relevant disclosures/competing interests. Part of this work has been presented at the 2021 annual meeting of the American Society of Clinical Oncology (J Clin Oncol 39, 2021 (suppl 15; abstr 7045)). Financial disclosure: Amer Zeidan is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a National Cancer Institute (NCI) Cancer Clinical Investigator Team Leadership Award (CCITLA). Maximilian Stahl received funding from the MSKCC Clinical Scholars T32 Program under award number 2T32 CA009512-31 and support from an ASCO/Conquer Cancer Foundation Young Investigator Award. Research reported in this publication was supported by the NCI of the National Institutes of Health under Award Number P30 CA016359 and Cancer Center Support Grant/Core Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748) The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Conflict of interest statement: N.A.P. consulted for and received honoraria from Alexion, Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squib, CTI biopharma and PharmaEssentia. N.A.P. received research funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI biopharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals and Kartos Therapeutics. L.G. has received research support from Bristol-Myers Squib. M.S.T. has received research funding from Abbvie, Cellerant, Orsenix, ADC Therapeutics, and Biosight. M.S.T. has received honoraria for M.S.T. has received research funding from AbbVie, Cellerant, Orsenix, ADC Therapeutics, Biosight, Glycomimetics, Rafael Pharmaceuticals, and Amgen. M.S.T. has received honoraria for advisory board membership from AbbVie, BioLineRx, Daiichi-Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta Fly Pharma, Tetraphase, Oncolyze, Jazz Pharmaceuticals, Roche, Biosight, Novartis, Innate Pharmaceuticals, Kura, and Syros Pharmaceuticals. M.S.T. received royalties from UpToDate. R.K.R has received consulting fees from Bristol-Myers Squibb, Constellation, Incyte, Celgene, Promedior, CTI, Jazz Pharmaceuticals, Blueprint, Stemline, and research funding from Incyte, Constellation, Stemline. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics. A.M.Z participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Trovagene/Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Aprea, Janssen, and Tyme. A.M.Z served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, and Celgene/BMS. A.M.Z received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology None of these relationships were related to the development of this manuscript. All other authors report no relevant disclosures/competing interests. Authorship statement: JPB, AS, SV, AG, and MS performed the research. JPB, AMZ, and MS designed the research study. JPB and MS analysed the data. JPB wrote the initial draft of the paper. All authors reviewed and contributed to subsequent manuscript drafts. Financial disclosure: Amer Zeidan is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a National Cancer Institute (NCI) Cancer Clinical Investigator Team Leadership Award (CCITLA). Maximilian Stahl received funding from the MSKCC Clinical Scholars T32 Program under award number 2T32 CA009512-31 and support from an ASCO/Conquer Cancer Foundation Young Investigator Award. Research reported in this publication was supported by the NCI of the National Institutes of Health under Award Number P30 CA016359 and Cancer Center Support Grant/Core Grant to Memorial Sloan Kettering Cancer Center (P30 CA008748) The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Keywords

  • Allogeneic Hematopoietic Cell Transplant
  • Graft-versus-host disease
  • Meta-analysis
  • Myelofibrosis
  • Survival

ASJC Scopus subject areas

  • Transplantation
  • Molecular Medicine
  • Hematology
  • Immunology and Allergy
  • Cell Biology

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