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Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis in Multiple Myeloma.

Allogeneic Blood or Marrow Transplantation with Post-Transplantation Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis in Multiple Myeloma.
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Ghosh N, Ye X, Tsai HL, Bolaños-Meade J, Fuchs EJ, Luznik L, Swinnen LJ, Gladstone DE, Ambinder RF, Varadhan R, Shanbhag S, Brodsky RA, Borrello IM, Jones RJ, Matsui W, Huff CA,


Ghosh N, Ye X, Tsai HL, Bolaños-Meade J, Fuchs EJ, Luznik L, Swinnen LJ, Gladstone DE, Ambinder RF, Varadhan R, Shanbhag S, Brodsky RA, Borrello IM, Jones RJ, Matsui W, Huff CA, (click to view)

Ghosh N, Ye X, Tsai HL, Bolaños-Meade J, Fuchs EJ, Luznik L, Swinnen LJ, Gladstone DE, Ambinder RF, Varadhan R, Shanbhag S, Brodsky RA, Borrello IM, Jones RJ, Matsui W, Huff CA,

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Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 2017 07 12() pii S1083-8791(17)30572-4
Abstract

Allogeneic blood or marrow transplantation (alloBMT) may lead to long-term disease control in patients with multiple myeloma (MM). However, historically, the use of alloBMT in MM has been limited by its high non-relapse mortality (NRM) rates primarily from graft versus host disease (GVHD). We previously demonstrated that post-transplantation cyclophosphamide (PTCy) decreases the toxicities of both acute and chronic GVHD rates following alloBMT. Here we examine the impact of PTCy in MM patients undergoing alloBMT at Johns Hopkins Hospital. From 2003 to 2011, 39 patients with MM underwent bone marrow or peripheral blood alloBMT from HLA-matched related/unrelated or haploidentical related donors following either myeloablative or non-myeloablative conditioning. Post-transplant GVHD prophylaxis consisted of cyclophosphamide (50mg/kg) on days +3 and +4 with or without mycophenolate mofetil and tacrolimus. Engraftment was detected in 95% of patients with median neutrophil and platelet recovery at 15 and 16 days, respectively. The cumulative incidence of acute grade 2-4 and grade 3-4 GVHD was 0.41 and 0.08, respectively, and no cases of grade 4 acute GVHD were observed. The cumulative incidence of chronic GVHD was 0.13. Only one patient succumbed to NRM. All cases of chronic GVHD involved extensive disease, and 60% of these patients received systemic therapy with complete resolution. Following alloBMT, the overall response rate was 62% with complete, very good partial, and partial response rates of 26%, 21%, and 15%, respectively. The median progression free survival was 12 months and was associated with the depth of response but not cytogenetic risk. The estimated cumulative incidence of relapse was 0.46 (95% CI: 0.3-0.62) at one year and 0.56 (95% CI: 0.41-0.72) at two years. At last follow up, 23% of patients remain without evidence of disease at a median follow up of 10.3 years after alloBMT. The median overall survival was 4.4 years and the 5 and 10-year overall survival probabilities were 49% (95%CI:35-67%) and 43% (95%CI:29-62%), respectively. The use of PTCy following alloBMT for MM is feasible and results in low NRM and GVHD rates. The safety of this approach may allow the development of novel post-transplant maintenance strategies to improve long-term disease control.

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