Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma

A. P. Nair, P. Walker, A. Kalff, K. Bergin, J. Hocking, S. Avery, D. J. Curtis, S. Patil, T. Das, D. Klarica, S. Morgan, J. Muirhead, Malgorzata B Gorniak, J. Reynolds, A. Spencer

Research output: Contribution to journalArticleResearchpeer-review

Abstract

High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30% and 48% respectively. High CD3+ cell dose (>3 × 10 8 /kg) infusion was associated with more acute GvHD (grade 2-4) (47% vs 17.5%; P=0.03), extensive chronic GvHD (80% vs 50%; P=0.04), increased transplant-related mortality (26.3% vs 5%; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (<CR vs CR vs stringent CR; hazard ratio=5.54, confidence interval=2.67-11.5; P<0.0001) and CD3+ cell dose infused (hazard ratio=1.42; confidence interval=1.21-1.67; P<0.0001) emerged as factors influencing OS. We conclude that tandem ASCT-NMA allogeneic SCT is an effective therapy for HR or relapsed MM and that higher CD3+ doses have an adverse impact on transplant outcome.

Original languageEnglish
Pages (from-to)839-845
Number of pages7
JournalBone Marrow Transplantation
Volume52
Issue number6
DOIs
Publication statusPublished - 1 Jun 2017

Cite this

Nair, A. P. ; Walker, P. ; Kalff, A. ; Bergin, K. ; Hocking, J. ; Avery, S. ; Curtis, D. J. ; Patil, S. ; Das, T. ; Klarica, D. ; Morgan, S. ; Muirhead, J. ; Gorniak, Malgorzata B ; Reynolds, J. ; Spencer, A. / Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma. In: Bone Marrow Transplantation. 2017 ; Vol. 52, No. 6. pp. 839-845.
@article{f1a0217674e546949a20f5cc63851da6,
title = "Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma",
abstract = "High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30{\%} and 48{\%} respectively. High CD3+ cell dose (>3 × 10 8 /kg) infusion was associated with more acute GvHD (grade 2-4) (47{\%} vs 17.5{\%}; P=0.03), extensive chronic GvHD (80{\%} vs 50{\%}; P=0.04), increased transplant-related mortality (26.3{\%} vs 5{\%}; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (<CR vs CR vs stringent CR; hazard ratio=5.54, confidence interval=2.67-11.5; P<0.0001) and CD3+ cell dose infused (hazard ratio=1.42; confidence interval=1.21-1.67; P<0.0001) emerged as factors influencing OS. We conclude that tandem ASCT-NMA allogeneic SCT is an effective therapy for HR or relapsed MM and that higher CD3+ doses have an adverse impact on transplant outcome.",
author = "Nair, {A. P.} and P. Walker and A. Kalff and K. Bergin and J. Hocking and S. Avery and Curtis, {D. J.} and S. Patil and T. Das and D. Klarica and S. Morgan and J. Muirhead and Gorniak, {Malgorzata B} and J. Reynolds and A. Spencer",
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Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma. / Nair, A. P.; Walker, P.; Kalff, A.; Bergin, K.; Hocking, J.; Avery, S.; Curtis, D. J.; Patil, S.; Das, T.; Klarica, D.; Morgan, S.; Muirhead, J. ; Gorniak, Malgorzata B; Reynolds, J.; Spencer, A.

In: Bone Marrow Transplantation, Vol. 52, No. 6, 01.06.2017, p. 839-845.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma

AU - Nair, A. P.

AU - Walker, P.

AU - Kalff, A.

AU - Bergin, K.

AU - Hocking, J.

AU - Avery, S.

AU - Curtis, D. J.

AU - Patil, S.

AU - Das, T.

AU - Klarica, D.

AU - Morgan, S.

AU - Muirhead, J.

AU - Gorniak, Malgorzata B

AU - Reynolds, J.

AU - Spencer, A.

N1 - Supplementary information available for this article at http://www.nature.com/bmt/journal/v52/n6/suppinfo/bmt201737s1.html

PY - 2017/6/1

Y1 - 2017/6/1

N2 - High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30% and 48% respectively. High CD3+ cell dose (>3 × 10 8 /kg) infusion was associated with more acute GvHD (grade 2-4) (47% vs 17.5%; P=0.03), extensive chronic GvHD (80% vs 50%; P=0.04), increased transplant-related mortality (26.3% vs 5%; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (<CR vs CR vs stringent CR; hazard ratio=5.54, confidence interval=2.67-11.5; P<0.0001) and CD3+ cell dose infused (hazard ratio=1.42; confidence interval=1.21-1.67; P<0.0001) emerged as factors influencing OS. We conclude that tandem ASCT-NMA allogeneic SCT is an effective therapy for HR or relapsed MM and that higher CD3+ doses have an adverse impact on transplant outcome.

AB - High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0.36; median overall survival (OS) not reached in both cohorts, P=0.31). The 5-year PFS and OS of patients who had ASCT-NMA allogeneic SCT after relapsing from previous ASCT were 30% and 48% respectively. High CD3+ cell dose (>3 × 10 8 /kg) infusion was associated with more acute GvHD (grade 2-4) (47% vs 17.5%; P=0.03), extensive chronic GvHD (80% vs 50%; P=0.04), increased transplant-related mortality (26.3% vs 5%; P=0.009) and inferior OS (median OS 752 days vs not reached; P=0.002). On multivariate analysis, response achieved with tandem transplant (<CR vs CR vs stringent CR; hazard ratio=5.54, confidence interval=2.67-11.5; P<0.0001) and CD3+ cell dose infused (hazard ratio=1.42; confidence interval=1.21-1.67; P<0.0001) emerged as factors influencing OS. We conclude that tandem ASCT-NMA allogeneic SCT is an effective therapy for HR or relapsed MM and that higher CD3+ doses have an adverse impact on transplant outcome.

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U2 - 10.1038/bmt.2017.37

DO - 10.1038/bmt.2017.37

M3 - Article

VL - 52

SP - 839

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JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

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ER -