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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1875-1883
Number of pages9
JournalBiology of Blood and Marrow Transplantation
Volume25
Issue number9
DOIs
StatePublished - Sep 2019

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Peripheral Blood Stem Cell Transplantation
Unrelated Donors
Siblings
T-Lymphocytes
Tissue Donors
Graft vs Host Disease
Disease-Free Survival
Transplantation
Recurrence
Sample Size
Survival
Mortality
CD4-CD8 Ratio
Myelodysplastic Syndromes
Incidence
Cell Transplantation
Registries
Leukemia
Multivariate Analysis
Bone Marrow

Keywords

  • Allogeneic
  • GVHD dose
  • T cell
  • Transplantation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

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

In: Biology of Blood and Marrow Transplantation, Vol. 25, No. 9, 09.2019, p. 1875-1883.

Research output: Contribution to journalArticle

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
Saad, Ayman ; Lamb, Lawrence ; Wang, Tao ; Hemmer, Michael T. ; Spellman, Stephen ; Couriel, Daniel ; Alousi, Amin ; Pidala, Joseph ; Abdel-Azim, Hisham ; Agrawal, Vaibhav ; Aljurf, Mahmoud ; Beitinjaneh, Amer M. ; Bhatt, Vijaya Raj ; Buchbinder, David ; Byrne, Michael ; Cahn, Jean Yves ; Cairo, Mitchell ; Castillo, Paul ; Chhabra, Saurabh ; Diaz, Miguel Angel ; Farhan, Shatha ; Floisand, Yngvar ; Frangoul, Hadar A. ; Gadalla, Shahinaz M. ; Gajewski, James ; Gale, Robert Peter ; Gandhi, Manish ; Gergis, Usama ; Hamilton, Betty Ky ; Hematti, Peiman ; Hildebrandt, Gerhard C. ; Kamble, Rammurti T. ; Kanate, Abraham S. ; Khandelwal, Pooja ; Lazaryn, Aleksandr ; MacMillan, Margaret ; Marks, David I. ; Martino, Rodrigo ; Mehta, Parinda A. ; Nishihori, Taiga ; Olsson, Richard F. ; Patel, Sagar S. ; Qayed, Muna ; Rangarajan, Hemalatha G. ; Reshef, Ran ; Ringden, Olle ; Savani, Bipin N. ; Schouten, Harry C. ; Schultz, Kirk R. ; Seo, Sachiko ; Shaffer, Brian C. ; Solh, Melhem ; Teshima, Takanori ; Urbano-Ispizua, Alvaro ; Verdonck, Leo F. ; Vij, Ravi ; Waller, Edmund K. ; William, Basem ; Wirk, Baldeep ; Yared, Jean A. ; Yu, Lolie C. ; Arora, Mukta ; Hashmi, Shahrukh. / Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation. In: Biology of Blood and Marrow Transplantation. 2019 ; Vol. 25, No. 9. pp. 1875-1883.
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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.",
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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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