Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma

Timothy S. Fenske; Parameswaran N. Hari; Jeanette Carreras; Mei Jie Zhang; Rammurti T. Kamble; Brian J. Bolwell; Mitchell S. Cairo; Richard E. Champlin; Yi Bin Chen; César O. Freytes; Robert Peter Gale; Gregory A. Hale; Osman Ilhan; H. Jean Khoury; John Lister; Dipnarine Maharaj; David I. Marks; Reinhold Munker; Andrew L. Pecora; Philip A. Rowlings; Thomas C. Shea; Patrick Stiff; Peter H. Wiernik; Jane N. Winter; J. Douglas Rizzo; Koen van Besien; Hillard M. Lazarus; Julie M. Vose

doi:10.1016/j.bbmt.2009.07.017

Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma

Timothy S. Fenske, Parameswaran N. Hari, Jeanette Carreras, Mei Jie Zhang, Rammurti T. Kamble, Brian J. Bolwell, Mitchell S. Cairo, Richard E. Champlin, Yi Bin Chen, César O. Freytes, Robert Peter Gale, Gregory A. Hale, Osman Ilhan, H. Jean Khoury, John Lister, Dipnarine Maharaj, David I. Marks, Reinhold Munker, Andrew L. Pecora, Philip A. RowlingsThomas C. Shea, Patrick Stiff, Peter H. Wiernik, Jane N. Winter, J. Douglas Rizzo, Koen van Besien, Hillard M. Lazarus, Julie M. Vose

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

52 Scopus citations

Abstract

Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy beforeAuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P <.001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM.

Original language	English
Pages (from-to)	1455-1464
Number of pages	10
Journal	Biology of Blood and Marrow Transplantation
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.bbmt.2009.07.017
State	Published - Nov 2009

Funding

Financial disclosure: The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; Contract HHSH234200637015C from the Health Resources and Services Administration; Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc; anonymous donation to the Medical College of Wisconsin; Association of Medical Microbiology and Infectious Disease Canada; Astellas Pharma US, Inc; Baxter International, Inc; Bayer HealthCare Pharmaceuticals; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; Celgene Corp; CellGenix GmbH; Centers for Disease Control and Prevention; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex, Inc; CytoTherm; DOR BioPharma, Inc; Dynal Biotech, an Invitrogen Company; Enzon Pharmaceuticals, Inc; European Group for Blood and Marrow Transplantation; Gambro BCT, Inc; Gamida Cell, Ltd; Genzyme Corp; Histogenetics, Inc; HKS Medical Information Systems; Hospira, Inc; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co, Ltd; Merck & Company; Medical College of Wisconsin; MGI Pharma, Inc; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc; Miller Pharmacal Group; Milliman USA, Inc; Miltenyi Biotec, Inc; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc; Otsuka Pharmaceutical Development & Commercialization, Inc; Pall Life Sciences; PDL BioPharma, Inc; Pfizer Inc; Pharmion Corp; Saladax Biomedical, Inc; Schering Plough Corp; Society for Healthcare Epidemiology of America; StemCyte, Inc; StemSoft Software, Inc; Sysmex; Teva Pharmaceutical Industries; The Marrow Foundation; THERAKOS, Inc; Vidacare Corp; Vion Pharmaceuticals, Inc; ViraCor Laboratories; ViroPharma, Inc; and Wellpoint, Inc.

Funders	Funder number
Bone Marrow Foundation
Cubist Pharmaceuticals, Inc.
Invitrogen Company
Nature Publishing Group
Society for Healthcare Epidemiology of America
Office of Naval Research Naval Academy
National Heart, Lung, and Blood Institute (NHLBI)
National Childhood Cancer Registry – National Cancer Institute	U24CA076518
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...	5U01HL069294, HHSH234200637015C
Health Resources and Services Administration	N00014-06-1-0704, N00014-08-1-0058
Teva Pharmaceutical Industries Ltd.
AABB
Enzon Pharmaceuticals
American Society for Blood and Marrow Transplantation
Association of Medical Microbiology and Infectious Disease Canada
Astellas Pharma Inc.

Keywords

Autologous hematopoietic stem cell transplantation
Lymphoma
Rituximab

ASJC Scopus subject areas

Hematology
Transplantation

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10.1016/j.bbmt.2009.07.017

Cite this

Fenske, T. S., Hari, P. N., Carreras, J., Zhang, M. J., Kamble, R. T., Bolwell, B. J., Cairo, M. S., Champlin, R. E., Chen, Y. B., Freytes, C. O., Gale, R. P., Hale, G. A., Ilhan, O., Khoury, H. J., Lister, J., Maharaj, D., Marks, D. I., Munker, R., Pecora, A. L., ... Vose, J. M. (2009). Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma. Biology of Blood and Marrow Transplantation, 15(11), 1455-1464. https://doi.org/10.1016/j.bbmt.2009.07.017

@article{45e96d7b61a54434b899c28e5fe69c6d,

title = "Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma",

abstract = "Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy beforeAuHCT. The +R cohort had superior progression-free survival (PFS; 50\% vs 38\%; P = .008) and overall survival (OS; 57\% vs 45\%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P <.001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM.",

keywords = "Autologous hematopoietic stem cell transplantation, Lymphoma, Rituximab",

author = "Fenske, \{Timothy S.\} and Hari, \{Parameswaran N.\} and Jeanette Carreras and Zhang, \{Mei Jie\} and Kamble, \{Rammurti T.\} and Bolwell, \{Brian J.\} and Cairo, \{Mitchell S.\} and Champlin, \{Richard E.\} and Chen, \{Yi Bin\} and Freytes, \{C{\'e}sar O.\} and Gale, \{Robert Peter\} and Hale, \{Gregory A.\} and Osman Ilhan and Khoury, \{H. Jean\} and John Lister and Dipnarine Maharaj and Marks, \{David I.\} and Reinhold Munker and Pecora, \{Andrew L.\} and Rowlings, \{Philip A.\} and Shea, \{Thomas C.\} and Patrick Stiff and Wiernik, \{Peter H.\} and Winter, \{Jane N.\} and Rizzo, \{J. Douglas\} and \{van Besien\}, Koen and Lazarus, \{Hillard M.\} and Vose, \{Julie M.\}",

year = "2009",

month = nov,

doi = "10.1016/j.bbmt.2009.07.017",

language = "English",

volume = "15",

pages = "1455--1464",

number = "11",

}

Fenske, TS, Hari, PN, Carreras, J, Zhang, MJ, Kamble, RT, Bolwell, BJ, Cairo, MS, Champlin, RE, Chen, YB, Freytes, CO, Gale, RP, Hale, GA, Ilhan, O, Khoury, HJ, Lister, J, Maharaj, D, Marks, DI, Munker, R, Pecora, AL, Rowlings, PA, Shea, TC, Stiff, P, Wiernik, PH, Winter, JN, Rizzo, JD, van Besien, K, Lazarus, HM & Vose, JM 2009, 'Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma', Biology of Blood and Marrow Transplantation, vol. 15, no. 11, pp. 1455-1464. https://doi.org/10.1016/j.bbmt.2009.07.017

TY - JOUR

T1 - Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma

AU - Fenske, Timothy S.

AU - Hari, Parameswaran N.

AU - Carreras, Jeanette

AU - Zhang, Mei Jie

AU - Kamble, Rammurti T.

AU - Bolwell, Brian J.

AU - Cairo, Mitchell S.

AU - Champlin, Richard E.

AU - Chen, Yi Bin

AU - Freytes, César O.

AU - Gale, Robert Peter

AU - Hale, Gregory A.

AU - Ilhan, Osman

AU - Khoury, H. Jean

AU - Lister, John

AU - Maharaj, Dipnarine

AU - Marks, David I.

AU - Munker, Reinhold

AU - Pecora, Andrew L.

AU - Rowlings, Philip A.

AU - Shea, Thomas C.

AU - Stiff, Patrick

AU - Wiernik, Peter H.

AU - Winter, Jane N.

AU - Rizzo, J. Douglas

AU - van Besien, Koen

AU - Lazarus, Hillard M.

AU - Vose, Julie M.

PY - 2009/11

Y1 - 2009/11

N2 - Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy beforeAuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P <.001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM.

AB - Incorporation of the anti-CD20 monoclonal antibody rituximab into front-line regimens to treat diffuse large B cell lymphoma (DLBCL) has resulted in improved survival. Despite this progress, however, many patients develop refractory or recurrent DLBCL and then undergo autologous hematopoietic stem cell transplantation (AuHCT). It is unclear to what extent pre-transplant exposure to rituximab affects outcomes after AuHCT. Outcomes of 994 patients receiving AuHCT for DLBCL between 1996 and 2003 were analyzed according to whether rituximab was (n = 176; +R cohort) or was not (n = 818; -R cohort) administered with front-line or salvage therapy beforeAuHCT. The +R cohort had superior progression-free survival (PFS; 50% vs 38%; P = .008) and overall survival (OS; 57% vs 45%; P = .006) at 3 years. Platelet and neutrophil engraftment were not affected by exposure to rituximab. Nonrelapse mortality (NRM) did not differ significantly between the 2 cohorts. In multivariate analysis, the +R cohort had improved PFS (relative risk of relapse/progression or death, 0.64; P <.001) and improved OS (relative risk of death, 0.74; P = .039). We conclude that pre-transplant rituximab is associated with a lower rate of progression and improved survival after AuHCT for DLBCL, with no evidence of impaired engraftment or increased NRM.

KW - Autologous hematopoietic stem cell transplantation

KW - Lymphoma

KW - Rituximab

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U2 - 10.1016/j.bbmt.2009.07.017

DO - 10.1016/j.bbmt.2009.07.017

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AN - SCOPUS:70350587347

SN - 1083-8791

VL - 15

SP - 1455

EP - 1464

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 11

ER -

Impact of pre-transplant rituximab on survival after autologous hematopoietic stem cell transplantation for diffuse large B cell lymphoma

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