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. 2014 Dec 11;124(25):3817-27.
doi: 10.1182/blood-2014-07-587477. Epub 2014 Oct 14.

Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS

Christopher G Kanakry  1 , Hua-Ling Tsai  1 , Javier Bolaños-Meade  1 , B Douglas Smith  1 , Ivana Gojo  1 , Jennifer A Kanakry  1 , Yvette L Kasamon  1 , Douglas E Gladstone  1 , William Matsui  1 , Ivan Borrello  1 , Carol Ann Huff  1 , Lode J Swinnen  1 , Jonathan D Powell  1 , Keith W Pratz  1 , Amy E DeZern  1 , Margaret M Showel  1 , Michael A McDevitt  1 , Robert A Brodsky  1 , Mark J Levis  1 , Richard F Ambinder  1 , Ephraim J Fuchs  1 , Gary L Rosner  1 , Richard J Jones  1 , Leo Luznik  1
Affiliations

Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS

Christopher G Kanakry et al. Blood. .

Abstract

High-dose, posttransplantation cyclophosphamide (PTCy) reduces severe graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT), but the impact of PTCy on long-term, disease-specific outcomes is unclear. We conducted a retrospective study of 209 consecutive adult patients transplanted for acute myeloid leukemia (AML, n = 138), myelodysplastic syndrome (n = 28), or acute lymphoblastic leukemia (ALL, n = 43) using PTCy as sole GVHD prophylaxis after myeloablative conditioning and HLA-matched-related or -unrelated T-cell-replete allografting. At alloBMT, 30% of patients were not in morphologic complete remission. The cumulative incidences of grades II to IV and III to IV acute GVHD at 100 days and chronic GVHD at 2 years were 45%, 11%, and 13%, respectively. Forty-three percent of patients did not require immunosuppression for any reason beyond PTCy. At 3 years, relapse cumulative incidence was 36%, disease-free survival was 46%, survival free of disease and chronic GVHD was 39%, and overall survival was 58%. Lack of remission at alloBMT, adverse cytogenetics, and low allograft nucleated cell dose were associated with inferior survival for AML patients. Minimal residual disease but not t(9;22) was associated with inferior outcomes for ALL patients. The ability to limit posttransplantation immunosuppression makes PTCy a promising transplantation platform for the integration of postgrafting strategies to prevent relapse.

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Figures

Figure 1
Figure 1
GVHD, NRM, and relapse. Cumulative incidences are shown for (A) aGVHD, (B) cGVHD, (C) NRM, (D) relapse for the entire cohort by disease type, (E) relapse for the entire cohort by donor type, and (F) relapse for AML patients by their pretransplantation remission status.
Figure 2
Figure 2
Survival outcomes. Kaplan-Meier estimates of DFS and OS are shown for the entire cohort by (A-B) disease type and (C-D) donor type. Kaplan-Meier estimates of the composite outcome of cGVHD-DFS are shown for the entire cohort (E) by disease type and (F) for AML patients by remission status at the time of allogeneic transplantation. Pts, patients.
Figure 3
Figure 3
Survival outcomes for AML patients. Kaplan-Meier estimates of DFS and OS are shown for AML patients (n = 138) by (A-B) their pretransplantation remission status, (C-D) cytogenetics by the refined MRC criteria in those tested (n = 131), and (E-F) Flt3/ITD status in those tested (n = 92).
Figure 4
Figure 4
Survival outcomes for ALL patients. Kaplan-Meier estimates of DFS and OS for ALL patients by (A-B) the presence of the Philadelphia chromosome t(9;22) (Ph) and (C-D) the presence of MRD at their pretransplantation assessment.
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Comment in

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