Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Ayman Saad; Lawrence Lamb; Tao Wang; Michael T. Hemmer; Stephen Spellman; Daniel Couriel; Amin Alousi; Joseph Pidala; Hisham Abdel-Azim; Vaibhav Agrawal; Mahmoud Aljurf; Amer M. Beitinjaneh; Vijaya Raj Bhatt; David Buchbinder; Michael Byrne; Jean Yves Cahn; Mitchell Cairo; Paul Castillo; Saurabh Chhabra; Miguel Angel Diaz; Shatha Farhan; Yngvar Floisand; Hadar A. Frangoul; Shahinaz M. Gadalla; James Gajewski; Robert Peter Gale; Manish Gandhi; Usama Gergis; Betty Ky Hamilton; Peiman Hematti; Gerhard C. Hildebrandt; Rammurti T. Kamble; Abraham S. Kanate; Pooja Khandelwal; Aleksandr Lazaryn; Margaret MacMillan; David I. Marks; Rodrigo Martino; Parinda A. Mehta; Taiga Nishihori; Richard F. Olsson; Sagar S. Patel; Muna Qayed; Hemalatha G. Rangarajan; Ran Reshef; Olle Ringden; Bipin N. Savani; Harry C. Schouten; Kirk R. Schultz; Sachiko Seo; Brian C. Shaffer; Melhem Solh; Takanori Teshima; Alvaro Urbano-Ispizua; Leo F. Verdonck; Ravi Vij; Edmund K. Waller; Basem William; Baldeep Wirk; Jean A. Yared; Lolie C. Yu; Mukta Arora; Shahrukh Hashmi

doi:10.1016/j.bbmt.2019.05.007

Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Ayman Saad, Lawrence Lamb, Tao Wang, Michael T. Hemmer, Stephen Spellman, Daniel Couriel, Amin Alousi, Joseph Pidala, Hisham Abdel-Azim, Vaibhav Agrawal, Mahmoud Aljurf, Amer M. Beitinjaneh, Vijaya Raj Bhatt, David Buchbinder, Michael Byrne, Jean Yves Cahn, Mitchell Cairo, Paul Castillo, Saurabh Chhabra, Miguel Angel DiazShatha Farhan, Yngvar Floisand, Hadar A. Frangoul, Shahinaz M. Gadalla, James Gajewski, Robert Peter Gale, Manish Gandhi, Usama Gergis, Betty Ky Hamilton, Peiman Hematti, Gerhard C. Hildebrandt, Rammurti T. Kamble, Abraham S. Kanate, Pooja Khandelwal, Aleksandr Lazaryn, Margaret MacMillan, David I. Marks, Rodrigo Martino, Parinda A. Mehta, Taiga Nishihori, Richard F. Olsson, Sagar S. Patel, Muna Qayed, Hemalatha G. Rangarajan, Ran Reshef, Olle Ringden, Bipin N. Savani, Harry C. Schouten, Kirk R. Schultz, Sachiko Seo, Brian C. Shaffer, Melhem Solh, Takanori Teshima, Alvaro Urbano-Ispizua, Leo F. Verdonck, Ravi Vij, Edmund K. Waller, Basem William, Baldeep Wirk, Jean A. Yared, Lolie C. Yu, Mukta Arora, Shahrukh Hashmi

Internal Medicine

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

12 Scopus citations

Abstract

Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3⁺ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3⁺ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3⁺ T cell dose cutoff of 14 × 10⁷ cells/kg identified MSD/low CD3⁺ (n = 223) and MSD/high CD3⁺ (n = 1214), and a dose of 15 × 10⁷ cells/kg identified MUD/low CD3⁺ (n = 197) and MUD/high CD3⁺ (n = 1102). On univariate analysis, the MSD/high CD3⁺ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3⁺ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3⁺ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3⁺ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3⁺ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4⁺ T cells, CD8⁺ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3⁺ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4⁺ and CD8⁺ T cell doses were not possible given our small sample size.

Original language	English
Pages (from-to)	1875-1883
Number of pages	9
Journal	Biology of Blood and Marrow Transplantation
Volume	25
Issue number	9
DOIs	https://doi.org/10.1016/j.bbmt.2019.05.007
State	Published - Sep 2019

Bibliographical note

Publisher Copyright:
© 2019 American Society for Transplantation and Cellular Therapy

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 (NIAID); a Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; a contract HHSH250201700006C with Health Resources and Services Administration (HRSA/DHHS); Grants N00014-17-1-2388 , N00014-17-1-2850 and N00014-18-1-2045 from the Office of Naval Research ; and grants from Adaptive Biotechnologies; *Amgen, 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; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. 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 (NIAID); a Grant/Cooperative Agreement 1U24HL138660 from NHLBI and NCI; a contract HHSH250201700006C with Health Resources and Services Administration (HRSA/DHHS); Grants N00014-17-1-2388, N00014-17-1-2850 and N00014-18-1-2045 from the Office of Naval Research; and grants from Adaptive Biotechnologies; *Amgen, 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; *Chimerix, Inc.; *CytoSen Therapeutics, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Gilead Sciences, Inc.; HistoGenetics, Inc.; Immucor; *Incyte Corporation; Janssen Scientific Affairs, LLC; *Jazz Pharmaceuticals, Inc.; Karius, Inc.; Karyopharm Therapeutics, Inc.; *Kite Pharma, Inc.; Medac, GmbH; *Mediware; The Medical College of Wisconsin; *Merck & Co, Inc.; *Mesoblast; MesoScale Diagnostics, Inc.; Millennium, the Takeda Oncology Co.; *Miltenyi Biotec, Inc.; Mundipharma EDO; National Marrow Donor Program; Novartis Pharmaceuticals Corporation; PCORI; *Pfizer, Inc; *Pharmacyclics, LLC; PIRCHE AG; *Sanofi Genzyme; *Seattle Genetics; Shire; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Swedish Orphan Biovitrum, Inc.; *Takeda Oncology; and University of Minnesota. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the U.S. Government. *Corporate Members. Conflict of interest statement: There are no conflicts of interest to report. Financial disclosure: See Acknowledgments on page 1882.

Funders	Funder number
CytoSen Therapeutics, Inc.
Department of the Navy
HRSA/DHHS
National Institutes of Health/National Institute of Environmental Health Sciences
U.S. Government
U.S. Department of Defense
Office of Naval Research Naval Academy	N00014-18-1-2045, N00014-17-1-2388, N00014-17-1-2850
Office of Naval Research Naval Academy
National Heart, Lung, and Blood Institute (NHLBI)	U24HL138660
National Heart, Lung, and Blood Institute (NHLBI)
National Childhood Cancer Registry – National Cancer Institute	5U24CA076518
National Childhood Cancer Registry – National Cancer Institute
National Institute of Allergy and Infectious Diseases
Health Resources and Services Administration	HHSH250201700006C
Health Resources and Services Administration
Minnesota State University-Mankato
Novartis Pharmaceuticals Corporation

Keywords

Allogeneic
GVHD dose
T cell
Transplantation

ASJC Scopus subject areas

Hematology
Transplantation

Access to Document

10.1016/j.bbmt.2019.05.007

Cite this

Saad, A., Lamb, L., Wang, T., Hemmer, M. T., Spellman, S., Couriel, D., Alousi, A., Pidala, J., Abdel-Azim, H., Agrawal, V., Aljurf, M., Beitinjaneh, A. M., Bhatt, V. R., Buchbinder, D., Byrne, M., Cahn, J. Y., Cairo, M., Castillo, P., Chhabra, S., ... Hashmi, S. (2019). Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation. Biology of Blood and Marrow Transplantation, 25(9), 1875-1883. https://doi.org/10.1016/j.bbmt.2019.05.007

@article{d5873dcfbb584e2db937e41d7eb440c1,

title = "Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation",

abstract = "Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.",

keywords = "Allogeneic, GVHD dose, T cell, Transplantation",

author = "Ayman Saad and Lawrence Lamb and Tao Wang and Hemmer, {Michael T.} and Stephen Spellman and Daniel Couriel and Amin Alousi and Joseph Pidala and Hisham Abdel-Azim and Vaibhav Agrawal and Mahmoud Aljurf and Beitinjaneh, {Amer M.} and Bhatt, {Vijaya Raj} and David Buchbinder and Michael Byrne and Cahn, {Jean Yves} and Mitchell Cairo and Paul Castillo and Saurabh Chhabra and Diaz, {Miguel Angel} and Shatha Farhan and Yngvar Floisand and Frangoul, {Hadar A.} and Gadalla, {Shahinaz M.} and James Gajewski and Gale, {Robert Peter} and Manish Gandhi and Usama Gergis and Hamilton, {Betty Ky} and Peiman Hematti and Hildebrandt, {Gerhard C.} and Kamble, {Rammurti T.} and Kanate, {Abraham S.} and Pooja Khandelwal and Aleksandr Lazaryn and Margaret MacMillan and Marks, {David I.} and Rodrigo Martino and Mehta, {Parinda A.} and Taiga Nishihori and Olsson, {Richard F.} and Patel, {Sagar S.} and Muna Qayed and Rangarajan, {Hemalatha G.} and Ran Reshef and Olle Ringden and Savani, {Bipin N.} and Schouten, {Harry C.} and Schultz, {Kirk R.} and Sachiko Seo and Shaffer, {Brian C.} and Melhem Solh and Takanori Teshima and Alvaro Urbano-Ispizua and Verdonck, {Leo F.} and Ravi Vij and Waller, {Edmund K.} and Basem William and Baldeep Wirk and Yared, {Jean A.} and Yu, {Lolie C.} and Mukta Arora and Shahrukh Hashmi",

note = "Publisher Copyright: {\textcopyright} 2019 American Society for Transplantation and Cellular Therapy",

year = "2019",

month = sep,

doi = "10.1016/j.bbmt.2019.05.007",

language = "English",

volume = "25",

pages = "1875--1883",

number = "9",

}

Saad, A, Lamb, L, Wang, T, Hemmer, MT, Spellman, S, Couriel, D, Alousi, A, Pidala, J, Abdel-Azim, H, Agrawal, V, Aljurf, M, Beitinjaneh, AM, Bhatt, VR, Buchbinder, D, Byrne, M, Cahn, JY, Cairo, M, Castillo, P, Chhabra, S, Diaz, MA, Farhan, S, Floisand, Y, Frangoul, HA, Gadalla, SM, Gajewski, J, Gale, RP, Gandhi, M, Gergis, U, Hamilton, BK, Hematti, P, Hildebrandt, GC, Kamble, RT, Kanate, AS, Khandelwal, P, Lazaryn, A, MacMillan, M, Marks, DI, Martino, R, Mehta, PA, Nishihori, T, Olsson, RF, Patel, SS, Qayed, M, Rangarajan, HG, Reshef, R, Ringden, O, Savani, BN, Schouten, HC, Schultz, KR, Seo, S, Shaffer, BC, Solh, M, Teshima, T, Urbano-Ispizua, A, Verdonck, LF, Vij, R, Waller, EK, William, B, Wirk, B, Yared, JA, Yu, LC, Arora, M & Hashmi, S 2019, 'Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation', Biology of Blood and Marrow Transplantation, vol. 25, no. 9, pp. 1875-1883. https://doi.org/10.1016/j.bbmt.2019.05.007

TY - JOUR

T1 - Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

AU - Saad, Ayman

AU - Lamb, Lawrence

AU - Wang, Tao

AU - Hemmer, Michael T.

AU - Spellman, Stephen

AU - Couriel, Daniel

AU - Alousi, Amin

AU - Pidala, Joseph

AU - Abdel-Azim, Hisham

AU - Agrawal, Vaibhav

AU - Aljurf, Mahmoud

AU - Beitinjaneh, Amer M.

AU - Bhatt, Vijaya Raj

AU - Buchbinder, David

AU - Byrne, Michael

AU - Cahn, Jean Yves

AU - Cairo, Mitchell

AU - Castillo, Paul

AU - Chhabra, Saurabh

AU - Diaz, Miguel Angel

AU - Farhan, Shatha

AU - Floisand, Yngvar

AU - Frangoul, Hadar A.

AU - Gadalla, Shahinaz M.

AU - Gajewski, James

AU - Gale, Robert Peter

AU - Gandhi, Manish

AU - Gergis, Usama

AU - Hamilton, Betty Ky

AU - Hematti, Peiman

AU - Hildebrandt, Gerhard C.

AU - Kamble, Rammurti T.

AU - Kanate, Abraham S.

AU - Khandelwal, Pooja

AU - Lazaryn, Aleksandr

AU - MacMillan, Margaret

AU - Marks, David I.

AU - Martino, Rodrigo

AU - Mehta, Parinda A.

AU - Nishihori, Taiga

AU - Olsson, Richard F.

AU - Patel, Sagar S.

AU - Qayed, Muna

AU - Rangarajan, Hemalatha G.

AU - Reshef, Ran

AU - Ringden, Olle

AU - Savani, Bipin N.

AU - Schouten, Harry C.

AU - Schultz, Kirk R.

AU - Seo, Sachiko

AU - Shaffer, Brian C.

AU - Solh, Melhem

AU - Teshima, Takanori

AU - Urbano-Ispizua, Alvaro

AU - Verdonck, Leo F.

AU - Vij, Ravi

AU - Waller, Edmund K.

AU - William, Basem

AU - Wirk, Baldeep

AU - Yared, Jean A.

AU - Yu, Lolie C.

AU - Arora, Mukta

AU - Hashmi, Shahrukh

PY - 2019/9

Y1 - 2019/9

N2 - Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.

AB - Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3+ T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3+ T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3+ T cell dose cutoff of 14 × 107 cells/kg identified MSD/low CD3+ (n = 223) and MSD/high CD3+ (n = 1214), and a dose of 15 × 107 cells/kg identified MUD/low CD3+ (n = 197) and MUD/high CD3+ (n = 1102). On univariate analysis, the MSD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3+ group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3+ group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3+ group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3+ T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4+ T cells, CD8+ T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3+ T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4+ and CD8+ T cell doses were not possible given our small sample size.

KW - Allogeneic

KW - GVHD dose

KW - T cell

KW - Transplantation

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JF - Biology of Blood and Marrow Transplantation

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ER -

Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

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