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Uniform graft-versus-host disease prophylaxis with posttransplant cyclophosphamide, sirolimus, and mycophenolate mofetil following hematopoietic stem cell transplantation from haploidentical, matched sibling and unrelated donors

Bone Marrow Transplantation volume 55, pages 2147–2159 (2020)Cite this article

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Abstract

Following the success of posttransplant cyclophosphamide (PT-CY) as graft-versus-host disease (GVHD) prophylaxis in haploidentical transplantation, this prevention strategy has progressively been used for allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched sibling (MSD) and unrelated donor (MUD). We have introduced PT-CY plus sirolimus and micophenolate mofetil (PT-CY-Sir-MMF) as GVHD prophylaxis in allo-HSCT, irrespective of donor type. This study reports on the safety and efficacy of PT-CY-Sir-MMF in 158 consecutive allo-HSCT from MSD (n = 52), MUD (n = 64), and haploidentical (n = 42) donor. Median age was 53 years and 66% had acute leukemia or myelodysplastic syndrome. Cumulative incidences of acute GHVD grade II–IV, III–IV and moderate to severe cGVHD were 27%, 9% and 27%, respectively. The incidence of hepatic sinusoidal obstruction syndrome was 9.5%. The 1-year cumulative incidence of non-relapse mortality, relapse and event-free survival were 14%, 12% and 75%, respectively. Compared with MSD and MUD, haploidentical transplantation had a higher incidence of CMV DNAemia requiring therapy (34% vs 35% and 52%, respectively, p = 0.04) and was a risk factor for grade III–IV acute GVHD (RR 2.8, p = 0.05). Our study shows that PT-CY-Sir-MMF is not only feasible and effective in preventing GVHD after haploidentical HSCT, but also in allo-HSCT from MSD and MUD.

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Fig. 1: Two myeloablative conditioning (MAC) and two reduced-intensity conditioning (RIC) regimens were used according to age, comorbidity index, and type of malignancy: (i) TBF-MAC, consisted i.v. of thiotepa 5 mg/kg/day on days −7 and −6, i.v. busulfan 3.2 mg/kg/day as a single daily dose on days −5 to −3, and fludarabine 50 mg/m2/day on days −5 to −3 or (ii) Bu-Flu-MAC containing i.v. busulfan 3.2 mg/kg/day as a single daily dose on days −6 to −3, and fludarabine 40 mg/m2/day on days −6 to −3 or (iii) TBC-RIC consisting of thiotepa 5 mg/kg/day on days −7 and −6, i.v. busulfan 3.2 mg/kg/day as a single daily dose on days −5 to −4, and fludarabine 50 mg/m2/day on days −5 to −3 or (iv) Bu-Flu-Cy RIC containing i.v. busulfan 3.2 mg/kg/day as a single daily dose on days −4 to −3, fludarabine 30 mg/m2/day on days −6 to −2 and cyclophosphamide at 14.5 mg/kg/d intravenously on days −6 and −5.
Fig. 2: Cumulative incidence of acute GVHD.
Fig. 3: Cumulative incidence of chronic GVHD.
Fig. 4: Cumulative incidence of NRM.
Fig. 5: Survival outcomes.

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Author notes

  1. These authors contributed equally: Juan Montoro, José Luis Piñana, Carlos Solano, Jaime Sanz

Authors and Affiliations

  1. Department of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain

    Juan Montoro, José Luis Piñana, Ignacio Lorenzo, Manuel Guerreiro, Aitana Balaguer-Rosello, Guillermo F. Sanz, Carlos Carretero, Miguel A. Sanz & Jaime Sanz

  2. CIBERONC, Instituto Carlos III, Madrid, Spain

    José Luis Piñana, Guillermo F. Sanz, Miguel A. Sanz & Jaime Sanz

  3. Department of Hematology, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain

    Juan C. Hernández-Boluda, Rafael Hernani, Ariadna Pérez & Carlos Solano

  4. Department of Medicine, University of Valencia, Valencia, Spain

    Juan C. Hernández-Boluda, Guillermo F. Sanz, David Navarro, Miguel A. Sanz, Carlos Solano & Jaime Sanz

  5. Microbiology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain

    Eliseo Albert & David Navarro

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Contributions

JM, JS, and JLP conceived the study and interpreted the data; JM, JS, and JLP wrote the paper; JM, JS, and JLP performed the statistical analyses; JCHB, RH, IL, AP, ABR, MG, CC, EA, DN, GFS, and MAS reviewed the paper and contributed to the final draft.

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Correspondence to José Luis Piñana.

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Montoro, J., Piñana, J.L., Hernández-Boluda, J.C. et al. Uniform graft-versus-host disease prophylaxis with posttransplant cyclophosphamide, sirolimus, and mycophenolate mofetil following hematopoietic stem cell transplantation from haploidentical, matched sibling and unrelated donors. Bone Marrow Transplant 55, 2147–2159 (2020). https://doi.org/10.1038/s41409-020-0921-6

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