The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen

Alvaro Urbano-Ispizua; Steven Z. Pavletic; Mary E. Flowers; John P. Klein; Mei Jie Zhang; Jeanette Carreras; Silvia Montoto; Miguel Angel Perales; Mahmoud D. Aljurf; Görgün Akpek; Christopher N. Bredeson; Luciano J. Costa; Christopher Dandoy; César O. Freytes; Henry C. Fung; Robert Peter Gale; John Gibson; Mehdi Hamadani; Robert J. Hayashi; Yoshihiro Inamoto; David J. Inwards; Hillard M. Lazarus; David G. Maloney; Rodrigo Martino; Reinhold Munker; Taiga Nishihori; Richard F. Olsson; David A. Rizzieri; Ran Reshef; Ayman Saad; Bipin N. Savani; Harry C. Schouten; Sonali M. Smith; Gérard Socié; Baldeep Wirk; Lolie C. Yu; Wael Saber

doi:10.1016/j.bbmt.2015.05.010

The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen

Alvaro Urbano-Ispizua, Steven Z. Pavletic, Mary E. Flowers, John P. Klein, Mei Jie Zhang, Jeanette Carreras, Silvia Montoto, Miguel Angel Perales, Mahmoud D. Aljurf, Görgün Akpek, Christopher N. Bredeson, Luciano J. Costa, Christopher Dandoy, César O. Freytes, Henry C. Fung, Robert Peter Gale, John Gibson, Mehdi Hamadani, Robert J. Hayashi, Yoshihiro InamotoDavid J. Inwards, Hillard M. Lazarus, David G. Maloney, Rodrigo Martino, Reinhold Munker, Taiga Nishihori, Richard F. Olsson, David A. Rizzieri, Ran Reshef, Ayman Saad, Bipin N. Savani, Harry C. Schouten, Sonali M. Smith, Gérard Socié, Baldeep Wirk, Lolie C. Yu, Wael Saber

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

45 Scopus citations

Abstract

The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.

Original language	English
Pages (from-to)	1746-1753
Number of pages	8
Journal	Biology of Blood and Marrow Transplantation
Volume	21
Issue number	10
DOIs	https://doi.org/10.1016/j.bbmt.2015.05.010
State	Published - Oct 1 2015

Keywords

Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Combined Modality Therapy
Disease-Free Survival
Female
Follow-Up Studies
Graft vs Host Disease/complications
Hematopoietic Stem Cell Transplantation
Histocompatibility
Humans
Immunosuppressive Agents/therapeutic use
Kaplan-Meier Estimate
Lymphoma/drug therapy
Male
Middle Aged
Proportional Hazards Models
Recurrence
Rituximab/administration & dosage
Transplantation Conditioning/methods
Treatment Outcome
Young Adult

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10.1016/j.bbmt.2015.05.010

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Urbano-Ispizua, A., Pavletic, S. Z., Flowers, M. E., Klein, J. P., Zhang, M. J., Carreras, J., Montoto, S., Perales, M. A., Aljurf, M. D., Akpek, G., Bredeson, C. N., Costa, L. J., Dandoy, C., Freytes, C. O., Fung, H. C., Gale, R. P., Gibson, J., Hamadani, M., Hayashi, R. J., ... Saber, W. (2015). The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen. Biology of Blood and Marrow Transplantation, 21(10), 1746-1753. https://doi.org/10.1016/j.bbmt.2015.05.010

@article{18d3994a7527446eb4aa0ea341ed3706,

title = "The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen",

abstract = "The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.",

keywords = "Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Combined Modality Therapy, Disease-Free Survival, Female, Follow-Up Studies, Graft vs Host Disease/complications, Hematopoietic Stem Cell Transplantation, Histocompatibility, Humans, Immunosuppressive Agents/therapeutic use, Kaplan-Meier Estimate, Lymphoma/drug therapy, Male, Middle Aged, Proportional Hazards Models, Recurrence, Rituximab/administration & dosage, Transplantation Conditioning/methods, Treatment Outcome, Young Adult",

author = "Alvaro Urbano-Ispizua and Pavletic, {Steven Z.} and Flowers, {Mary E.} and Klein, {John P.} and Zhang, {Mei Jie} and Jeanette Carreras and Silvia Montoto and Perales, {Miguel Angel} and Aljurf, {Mahmoud D.} and G{\"o}rg{\"u}n Akpek and Bredeson, {Christopher N.} and Costa, {Luciano J.} and Christopher Dandoy and Freytes, {C{\'e}sar O.} and Fung, {Henry C.} and Gale, {Robert Peter} and John Gibson and Mehdi Hamadani and Hayashi, {Robert J.} and Yoshihiro Inamoto and Inwards, {David J.} and Lazarus, {Hillard M.} and Maloney, {David G.} and Rodrigo Martino and Reinhold Munker and Taiga Nishihori and Olsson, {Richard F.} and Rizzieri, {David A.} and Ran Reshef and Ayman Saad and Savani, {Bipin N.} and Schouten, {Harry C.} and Smith, {Sonali M.} and G{\'e}rard Soci{\'e} and Baldeep Wirk and Yu, {Lolie C.} and Wael Saber",

note = "Publisher Copyright: {\textcopyright} 2015 American Society for Blood and Marrow Transplantation.",

year = "2015",

month = oct,

day = "1",

doi = "10.1016/j.bbmt.2015.05.010",

language = "English",

volume = "21",

pages = "1746--1753",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier BV",

number = "10",

}

Urbano-Ispizua, A, Pavletic, SZ, Flowers, ME, Klein, JP, Zhang, MJ, Carreras, J, Montoto, S, Perales, MA, Aljurf, MD, Akpek, G, Bredeson, CN, Costa, LJ, Dandoy, C, Freytes, CO, Fung, HC, Gale, RP, Gibson, J, Hamadani, M, Hayashi, RJ, Inamoto, Y, Inwards, DJ, Lazarus, HM, Maloney, DG, Martino, R, Munker, R, Nishihori, T, Olsson, RF, Rizzieri, DA, Reshef, R, Saad, A, Savani, BN, Schouten, HC, Smith, SM, Socié, G, Wirk, B, Yu, LC & Saber, W 2015, 'The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen', Biology of Blood and Marrow Transplantation, vol. 21, no. 10, pp. 1746-1753. https://doi.org/10.1016/j.bbmt.2015.05.010

The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen. / Urbano-Ispizua, Alvaro; Pavletic, Steven Z.; Flowers, Mary E. et al.
In: Biology of Blood and Marrow Transplantation, Vol. 21, No. 10, 01.10.2015, p. 1746-1753.

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

TY - JOUR

T1 - The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen

AU - Urbano-Ispizua, Alvaro

AU - Pavletic, Steven Z.

AU - Flowers, Mary E.

AU - Klein, John P.

AU - Zhang, Mei Jie

AU - Carreras, Jeanette

AU - Montoto, Silvia

AU - Perales, Miguel Angel

AU - Aljurf, Mahmoud D.

AU - Akpek, Görgün

AU - Bredeson, Christopher N.

AU - Costa, Luciano J.

AU - Dandoy, Christopher

AU - Freytes, César O.

AU - Fung, Henry C.

AU - Gale, Robert Peter

AU - Gibson, John

AU - Hamadani, Mehdi

AU - Hayashi, Robert J.

AU - Inamoto, Yoshihiro

AU - Inwards, David J.

AU - Lazarus, Hillard M.

AU - Maloney, David G.

AU - Martino, Rodrigo

AU - Munker, Reinhold

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Rizzieri, David A.

AU - Reshef, Ran

AU - Saad, Ayman

AU - Savani, Bipin N.

AU - Schouten, Harry C.

AU - Smith, Sonali M.

AU - Socié, Gérard

AU - Wirk, Baldeep

AU - Yu, Lolie C.

AU - Saber, Wael

PY - 2015/10/1

Y1 - 2015/10/1

N2 - The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.

AB - The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.

KW - Adolescent

KW - Adult

KW - Aged

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Combined Modality Therapy

KW - Disease-Free Survival

KW - Female

KW - Follow-Up Studies

KW - Graft vs Host Disease/complications

KW - Hematopoietic Stem Cell Transplantation

KW - Histocompatibility

KW - Humans

KW - Immunosuppressive Agents/therapeutic use

KW - Kaplan-Meier Estimate

KW - Lymphoma/drug therapy

KW - Male

KW - Middle Aged

KW - Proportional Hazards Models

KW - Recurrence

KW - Rituximab/administration & dosage

KW - Transplantation Conditioning/methods

KW - Treatment Outcome

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=84941315276&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2015.05.010

DO - 10.1016/j.bbmt.2015.05.010

M3 - Article

C2 - 25981509

AN - SCOPUS:84941315276

SN - 1083-8791

VL - 21

SP - 1746

EP - 1753

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 10

ER -

The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen

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Keywords

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