Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation

Claudio G Brunstein, Marcelo C. Pasquini, Soyoung Kim, Mingwei Fei, Kehinde Adekola, Ibrahim Ahmed, Mahmoud Aljurf, Vaibhav Agrawal, Jeffrey J. Auletta, Minoo Battiwalla, Nelli Bejanyan, Joseph Bubalo, Jan Cerny, Lynette Chee, Stefan O. Ciurea, Cesar Freytes, Shahinaz M. Gadalla, Robert Peter Gale, Siddhartha Ganguly, Shahrukh K. HashmiPeiman Hematti, Gerhard Hildebrandt, Leona A. Holmberg, Oscar B. Lahoud, Heather Landau, Hillard M. Lazarus, Marcos de Lima, Vikram Mathews, Richard Maziarz, Taiga Nishihori, Maxim Norkin, Richard Olsson, Ran Reshef, Seth Rotz, Bipin Savani, Harry C. Schouten, Sachiko Seo, Baldeep M. Wirk, Jean Yared, Shin Mineishi, John Rogosheske, Miguel Angel Perales

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Data are limited on whether to adjust high-dose chemotherapy before autologous hematopoietic cell transplant (autoHCT) in obese patients. This study explores the effects of dose adjustment on the outcomes of obese patients, defined as body mass index (BMI) ≥ 30 kg/m 2 . Dose adjustment was defined as a reduction in standard dosing ≥20%, based on ideal, reported dosing and actual weights. We included 2 groups of US patients who had received autoHCT between 2008 and 2014. Specifically, we included patients with multiple myeloma (MM, n = 1696) treated with high-dose melphalan and patients with Hodgkin or non-Hodgkin lymphomas (n = 781) who received carmustine, etoposide, cytarabine, and melphalan conditioning. Chemotherapy dose was adjusted in 1324 patients (78%) with MM and 608 patients (78%) with lymphoma. Age, sex, BMI, race, performance score, comorbidity index, and disease features (stage at diagnosis, disease status, and time to transplant) were similar between dose groups. In multivariate analyses for MM, adjusting for melphalan dose and for center effect had no impact on overall survival (P =.894) and treatment-related mortality (TRM) (P =.62), progression (P =.12), and progression-free survival (PFS; P =.178). In multivariate analyses for lymphoma, adjusting chemotherapy doses did not affect survival (P =.176), TRM (P =.802), relapse (P =.633), or PFS (P =.812). No center effect was observed in lymphoma. This study demonstrates that adjusting chemotherapy dose before autoHCT in obese patients with MM and lymphoma does not influence mortality. These results do not support adjusting chemotherapy dose in this population.

Original languageEnglish (US)
Pages (from-to)480-487
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number3
DOIs
StatePublished - Mar 2019

Bibliographical note

Funding Information:
Financial disclosure: 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 ; Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; contract HHSH250201200016C with Health Resources and Services Administration ; 2 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. The asterisk indicates Corporate Members. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government.

Funding Information:
The authors thank Jennifer Motl for assistance with the editorial review of the manuscript. Financial disclosure: 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; Grant/Cooperative Agreement 4U10HL069294 from NHLBI and NCI; contract HHSH250201200016C with Health Resources and Services Administration; 2 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. The asterisk indicates Corporate Members. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the US Government. Conflict of interest statement: There are no conflicts of interest to report. Financial disclosure: See Acknowledgments on page 486.

Publisher Copyright:
© 2018 American Society for Blood and Marrow Transplantation

Keywords

  • Autologous hematopoietic cell transplantation
  • Conditioning regimen
  • Obesity

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