George B. McDonald, MD; Brenda M. Sandmaier, MD; Marco Mielcarek, MD; Mohamed Sorror, MD, MSc; Steven A. Pergam, MD; Guang-Shing Cheng, MD; Sangeeta Hingorani, MD, MPH; Michael Boeckh, MD; Mary D. Flowers, MD; Stephanie J. Lee, MD, MPH; Frederick R. Appelbaum, MD; Rainer Storb, MD; Paul J. Martin, MD; H. Joachim Deeg, MD; Gary Schoch, BS; Ted A. Gooley, PhD
Disclaimer: Drs. McDonald and Gooley had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs. Sandmaier and Storb were responsible for data related to patients who received reduced-intensity conditioning therapy. Dr. Mielcarek was responsible for data analysis related to prednisone exposure. Dr. Sorror was responsible for data related to the Hematopoietic Cell Transplantation Comorbidity Index. Drs. Pergam and Boeckh were responsible for the integrity of data related to infectious disease end points. Dr. Cheng was responsible for data related to mechanical ventilation after transplant. Dr. Hingorani was responsible for data related to renal insufficiency and dialysis/hemofiltration after transplant. Drs. Flowers and Lee were responsible for data related to chronic GVHD. Drs. Appelbaum and Deeg were responsible for classification of underlying hematologic disorders with regard to risk assessment. Dr. Martin determined acute GVHD stages and grades for all patients in the 2 cohorts and was responsible for the integrity of those data. Mr. Schoch was responsible for extracting data from our longitudinal database that contains demographic information, laboratory results, and clinical end points. All coauthors reviewed the manuscript for accuracy and concur with its submission.
Acknowledgment: The authors thank the many physicians, nurses, physician assistants, pharmacists, social workers, and support staff who cared for our patients during this decade and the patients who participated in our ongoing clinical research.
Financial Support: By grants CA18029, CA15704, CA78902, HL36444, HL088201, HL088021, HL096831, DK063038, HL122173, and HL108307 from the National Institutes of Health. Dr. Sorror was also supported by Research Scholar Grant RSG-13-084-01-CPHPS from the American Cancer Society and by contract CE-1304-7451 from the Patient-Centered Outcomes Research Institute.
Disclosures: Dr. McDonald reports data and safety monitoring for Sangamo Therapeutics and consultancy for Soligenix Therapeutics and Lucent Medical Systems. Dr. Sandmaier reports consultancy for Actinium Pharmaceuticals, Bristol-Myers Squibb, and Kiadis Pharma and her spouse/partner's employment with Mavupharma; consultancy for AbbVie, AnaptysBio, Frazier Healthcare Ventures, Inipharm, and OncoResponse; and stock options/holdings with AnaptysBio, Blaze, Inipharm, Mavupharma, and OncoResponse. Dr. Sorror reports grants/contracts from Celgene and the National Cancer Institute and consultancy for Jazz Pharmaceuticals. Dr. Pergam reports grants/contracts from Chimerix, Global Life Technologies, and Merck through his institution. Dr. Boeckh reports grants/contracts from Astellas Pharma, Chimerix, Gilead Sciences, Merck, Takeda Pharmaceutical, and Vir Biotechnology through Fred Hutchinson Cancer Research Center; consultancy for AlloVir, Artemis Therapeutics, Astellas Pharma, Chimerix, Gilead Sciences, GlaxoSmithKline, Merck, Takeda Pharmaceutical, and Vir Biotechnology; and other from Helocyte. Dr. Martin reports grants/contracts from AbGenomics and Xenikos through his institution; consultancy for Enlivex Therapeutics, Genentech, Neovii, and Pharmacyclics (an AbbVie company); data and safety monitoring for Pfizer; and stock options/holdings with Procter & Gamble. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-2936.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol: This study was conducted under the aegis of Fred Hutchinson Cancer Research Center IR#3759 / Protocol 881.01 – Chart Reviews for Medical and Surgical Complications Associated with Hematopoietic Cell Transplantation. Statistical code: Available from Dr. Gooley (address, Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024). Data set: Not available because sharing of patient-level data is beyond the scope of the institutional review board waivers that were obtained for the study.
Corresponding Author: George B. McDonald, MD, Clinical Research Division (D5-114), Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. McDonald, Sandmaier, Mielcarek, Sorror, Pergam, Cheng, Hingorani, Boeckh, Flowers, Lee, Appelbaum, Storb, Martin, Deeg, and Gooley and Mr. Schoch: Clinical Research Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024.
Author Contributions: Conception and design: G.B. McDonald, B.M. Sandmaier, M. Sorror, G.S. Cheng, F.R. Appelbaum, R. Storb.
Analysis and interpretation of the data: G.B. McDonald, B.M. Sandmaier, M. Mielcarek, M. Sorror, S.A. Pergam, G.S. Cheng, S. Hingorani, M. Boeckh, S.J. Lee, F.R. Appelbaum, R. Storb, P.J. Martin, G. Schoch, T.A. Gooley.
Drafting of the article: G.B. McDonald, M. Sorror, S. Hingorani, F.R. Appelbaum, T.A. Gooley.
Critical revision of the article for important intellectual content: G.B. McDonald, B.M. Sandmaier, M. Mielcarek, M. Sorror, S.A. Pergam, G.S. Cheng, M. Boeckh, M.D. Flowers, S.J. Lee, F.R. Appelbaum, R. Storb, P.J. Martin, H.J. Deeg.
Final approval of the article: G.B. McDonald, B.M. Sandmaier, M. Mielcarek, M. Sorror, S.A. Pergam, G.S. Cheng, S. Hingorani, M. Boeckh, M.D. Flowers, S.J. Lee, F.R. Appelbaum, R. Storb, P.J. Martin, H.J. Deeg, G. Schoch, T.A. Gooley.
Provision of study materials or patients: B.M. Sandmaier, M. Sorror, M.D. Flowers, P.J. Martin, H.J. Deeg.
Statistical expertise: T.A. Gooley.
Obtaining of funding: B.M. Sandmaier, M. Sorror, R. Storb.
Administrative, technical, or logistic support: F.R. Appelbaum, R. Storb.
Collection and assembly of data: G.B. McDonald, B.M. Sandmaier, M. Mielcarek, M. Sorror, S.A. Pergam, G.S. Cheng, S. Hingorani, M. Boeckh, M.D. Flowers, S.J. Lee, F.R. Appelbaum, P.J. Martin, H.J. Deeg, G. Schoch.
Allogeneic hematopoietic cell transplantation is indicated for refractory hematologic cancer and some nonmalignant disorders. Survival is limited by recurrent cancer and organ toxicity.
To determine whether survival has improved over the past decade and note impediments to better outcomes.
The authors compared cohorts that had transplants during 2003 to 2007 versus 2013 to 2017. Survival outcome measures were analyzed, along with transplant-related complications.
A center performing allogeneic transplant procedures.
All recipients of a first allogeneic transplant during 2003 to 2007 and 2013 to 2017.
Patients received a conditioning regimen, infusion of donor hematopoietic cells, then immunosuppressive drugs and antimicrobial approaches to infection control.
Day-200 nonrelapse mortality (NRM), recurrence or progression of cancer, relapse-related mortality, and overall mortality, adjusted for comorbidity scores, source of donor cells, donor type, patient age, disease severity, conditioning regimen, patient and donor sex, and cytomegalovirus serostatus.
During the 2003-to-2007 and 2013-to-2017 periods, 1148 and 1131 patients, respectively, received their first transplant. Over the decade, decreases were seen in the adjusted hazards of day-200 NRM (hazard ratio [HR], 0.66 [95% CI, 0.48 to 0.89]), relapse of cancer (HR, 0.76 [CI, 0.61 to 0.94]), relapse-related mortality (HR, 0.69 [CI, 0.54 to 0.87]), and overall mortality (HR, 0.66 [CI, 0.56 to 0.78]). The degree of reduction in overall mortality was similar for patients who received myeloablative versus reduced-intensity conditioning, as well as for patients whose allograft came from a matched sibling versus an unrelated donor. Reductions were also seen in the frequency of jaundice, renal insufficiency, mechanical ventilation, high-level cytomegalovirus viremia, gram-negative bacteremia, invasive mold infection, acute and chronic graft-versus-host disease, and prednisone exposure.
Cohort studies cannot determine causality, and current disease severity criteria were not available for patients in the 2003-to-2007 cohort.
Improvement in survival and reduction in complications were substantial after allogeneic transplant. Relapse of cancer remains the largest obstacle to better survival outcomes.
National Institutes of Health.
McDonald GB, Sandmaier BM, Mielcarek M, et al. Survival, Nonrelapse Mortality, and Relapse-Related Mortality After Allogeneic Hematopoietic Cell Transplantation: Comparing 2003–2007 Versus 2013–2017 Cohorts. Ann Intern Med. 2020;172:229–239. [Epub ahead of print 21 January 2020]. doi: https://doi.org/10.7326/M19-2936
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Published: Ann Intern Med. 2020;172(4):229-239.
Published at www.annals.org on 21 January 2020
Emergency Medicine, Endocrine and Metabolism, Gastroenterology/Hepatology, Hematology/Oncology, Liver Disease.
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