Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma.
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.
Malignant Haematology, Alfred Hospital, Melbourne, Australia.|Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
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Nair
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Walker
Malignant Haematology, Alfred Hospital, Melbourne, Australia.|Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
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Kalff
Malignant Haematology, Alfred Hospital, Melbourne, Australia.|Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
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Bergin
Malignant Haematology, Alfred Hospital, Melbourne, Australia.|Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
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Hocking
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Avery
Malignant Haematology, Alfred Hospital, Melbourne, Australia.|Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
D J
DJ
Curtis
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Patil
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Das
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Klarica
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Morgan
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Muirhead
Malignant Haematology, Alfred Hospital, Melbourne, Australia.
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Gorniak
Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
J
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Reynolds
Malignant Haematology, Alfred Hospital, Melbourne, Australia.|Australian Centre for Blood Diseases, Monash University, Melbourne, Australia.
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Spencer
D000208:Acute Disease; D000328:Adult; D000368:Aged; D064591:Allografts; D064592:Autografts; D017252:CD3 Complex; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000401:mortality* / Q000628:therapy*; D033581:Stem Cell Transplantation; D015996:Survival Rate
D017252:CD3 Complex