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

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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 × 108/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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