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. Hashmi; Peiman 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

doi:10.1016/j.bbmt.2018.11.005

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. Hashmi

Peiman 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

Internal Medicine

Research output: Contribution to journal › Article › peer-review

13 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 language	English
Pages (from-to)	480-487
Number of pages	8
Journal	Biology of Blood and Marrow Transplantation
Volume	25
Issue number	3
DOIs	https://doi.org/10.1016/j.bbmt.2018.11.005
State	Published - Mar 2019

Bibliographical note

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

Funding

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. 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.

Funders	Funder number
Actinium Pharmaceuticals, Inc.
AMGEN, Inc.
Amneal Biosciences, *Angiocrine Bioscience
Angiocrine Bioscience, Inc.
Department of the Navy
US Government or NYU
National Institutes of Health (NIH)
U.S. Department of Defense
Office of Naval Research Naval Academy
National Heart, Lung, and Blood Institute (NHLBI)	UG1HL069290
National Childhood Cancer Registry – National Cancer Institute
National Institute of Allergy and Infectious F32-AI286447 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI168214 Jason W. Rosch Diseases National Institute of Allergy and Infectious P30 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R00-AI166116 Christopher D. Radka Diseases National Institute of Allergy and Infectious T32-AI106700 Cydney N. Johnson Diseases National Institute of Allergy and Infectious R01AI192221 Jason W. Rosch Diseases National Inst...	HHSH250201200016C, 4U10HL069294
Health Resources and Services Administration	N00014-17-1-2388, N0014-17-1-2850
AMGen
Minnesota State University-Mankato
Actinium Pharmaceuticals Incorporated
Angiocrine Bioscience

Keywords

Autologous hematopoietic cell transplantation
Conditioning regimen
Obesity

ASJC Scopus subject areas

Hematology
Transplantation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbmt.2018.11.005

Cite this

Brunstein, C. G., Pasquini, M. C., Kim, S., Fei, M., Adekola, K., Ahmed, I., Aljurf, M., Agrawal, V., Auletta, J. J., Battiwalla, M., Bejanyan, N., Bubalo, J., Cerny, J., Chee, L., Ciurea, S. O., Freytes, C., Gadalla, S. M., Gale, R. P., Ganguly, S., ... Perales, M. A. (2019). Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation. Biology of Blood and Marrow Transplantation, 25(3), 480-487. https://doi.org/10.1016/j.bbmt.2018.11.005

@article{f0cbbf35d87f44508e1faf20d6c89e15,

title = "Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation",

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.",

keywords = "Autologous hematopoietic cell transplantation, Conditioning regimen, Obesity",

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

note = "Publisher Copyright: {\textcopyright} 2018 American Society for Blood and Marrow Transplantation",

year = "2019",

month = mar,

doi = "10.1016/j.bbmt.2018.11.005",

language = "English",

volume = "25",

pages = "480--487",

number = "3",

}

Brunstein, CG, Pasquini, MC, Kim, S, Fei, M, Adekola, K, Ahmed, I, Aljurf, M, Agrawal, V, Auletta, JJ, Battiwalla, M, Bejanyan, N, Bubalo, J, Cerny, J, Chee, L, Ciurea, SO, Freytes, C, Gadalla, SM, Gale, RP, Ganguly, S, Hashmi, SK, Hematti, P, Hildebrandt, G, Holmberg, LA, Lahoud, OB, Landau, H, Lazarus, HM, de Lima, M, Mathews, V, Maziarz, R, Nishihori, T, Norkin, M, Olsson, R, Reshef, R, Rotz, S, Savani, B, Schouten, HC, Seo, S, Wirk, BM, Yared, J, Mineishi, S, Rogosheske, J & Perales, MA 2019, 'Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 25, no. 3, pp. 480-487. https://doi.org/10.1016/j.bbmt.2018.11.005

TY - JOUR

T1 - Effect of Conditioning Regimen Dose Reduction in Obese Patients Undergoing Autologous Hematopoietic Cell Transplantation

AU - Brunstein, Claudio G.

AU - Pasquini, Marcelo C.

AU - Kim, Soyoung

AU - Fei, Mingwei

AU - Adekola, Kehinde

AU - Ahmed, Ibrahim

AU - Aljurf, Mahmoud

AU - Agrawal, Vaibhav

AU - Auletta, Jeffrey J.

AU - Battiwalla, Minoo

AU - Bejanyan, Nelli

AU - Bubalo, Joseph

AU - Cerny, Jan

AU - Chee, Lynette

AU - Ciurea, Stefan O.

AU - Freytes, Cesar

AU - Gadalla, Shahinaz M.

AU - Gale, Robert Peter

AU - Ganguly, Siddhartha

AU - Hashmi, Shahrukh K.

AU - Hematti, Peiman

AU - Hildebrandt, Gerhard

AU - Holmberg, Leona A.

AU - Lahoud, Oscar B.

AU - Landau, Heather

AU - Lazarus, Hillard M.

AU - de Lima, Marcos

AU - Mathews, Vikram

AU - Maziarz, Richard

AU - Nishihori, Taiga

AU - Norkin, Maxim

AU - Olsson, Richard

AU - Reshef, Ran

AU - Rotz, Seth

AU - Savani, Bipin

AU - Schouten, Harry C.

AU - Seo, Sachiko

AU - Wirk, Baldeep M.

AU - Yared, Jean

AU - Mineishi, Shin

AU - Rogosheske, John

AU - Perales, Miguel Angel

PY - 2019/3

Y1 - 2019/3

N2 - 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.

AB - 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.

KW - Autologous hematopoietic cell transplantation

KW - Conditioning regimen

KW - Obesity

UR - https://www.scopus.com/pages/publications/85058228349

UR - https://www.scopus.com/pages/publications/85058228349#tab=citedBy

U2 - 10.1016/j.bbmt.2018.11.005

DO - 10.1016/j.bbmt.2018.11.005

M3 - Article

C2 - 30423481

AN - SCOPUS:85058228349

SN - 1083-8791

VL - 25

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JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 3

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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