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Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors.
Biol Blood Marrow Transplant. 2018 06; 24(6):1196-1202.BB

Abstract

The optimal prophylaxis regimen for graft-versus-host disease (GVHD) in the setting of mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation (alloHSCT) is not defined. The use of high-dose post-transplant cyclophosphamide (PTCy) in haploidentical transplantation has proven feasible and effective in overcoming the negative impact of HLA disparity on survival. We hypothesized that PTCy could also be effective in the setting of MMUD transplantation. We retrospectively analyzed 86 consecutive adult recipients of alloHSCT in our institution, comparing 2 contemporaneous groups: PTCy MMUD (n = 26) versus matched unrelated donor (MUD) (n = 60). Graft source was primarily peripheral blood (92%). All PTCy MMUD were HLA 7/8 (differences in HLA class I loci in 92% of patients) and received PTCy plus tacrolimus ± mofetil mycophenolate as GVHD prophylaxis. No differences were observed between PTCy MMUD and MUD in the 100-day cumulative incidence of acute GVHD grades II to IV (31% versus 22%, respectively; P = .59) and III to IV (8% versus 10%, P = .67). There was a trend for a lower incidence of moderate to severe chronic GVHD at 1 year after PTCy MMUD in comparison with MUD (22% versus 41%, P = .098). No differences between PTCy MMUD and MUD were found regarding nonrelapse mortality (25% versus 18%, P = .52) or relapse rate (11% versus 19%, P = .18). Progression-free survival and overall survival at 2 years were similar in both cohorts (67% versus 54% [HR, .84; 95% CI, .38 to 1.88; P = .68] and 72% versus 57% [HR, .71; 95% CI, .31 to 1.67; P = .44], respectively). The 2-year cumulative incidence of survival free of moderate to severe chronic GVHD and relapse tended to be higher in the PTCy MMUD group (47% versus 24%; HR, .60; 95% CI, .31 to 1.14; P = .12). We conclude that HLA 7/8 MMUD transplantation using PTCy plus tacrolimus is a suitable alternative for those patients who lack a MUD.

Authors+Show Affiliations

Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain.Hemotherapy and Hemostasis Department, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Foundation, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Foundation, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Foundation, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Foundation, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Foundation, Hospital Clínic, Barcelona, Spain.Hematopoietic Stem Cell Transplantation Unit, Hematology Department, Institute of Hematology and Oncology, Hospital Clínic, Barcelona, Spain; August Pi i Sunyer Biomedical Research Institute-IDIBAPS, Barcelona, Spain; Josep Carreras Leukaemia Research Foundation, Hospital Clínic, Barcelona, Spain. Electronic address: cmarti@clinic.ub.es.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29410343

Citation

Jorge, Ana Sofia, et al. "Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 24, no. 6, 2018, pp. 1196-1202.
Jorge AS, Suárez-Lledó M, Pereira A, et al. Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors. Biol Blood Marrow Transplant. 2018;24(6):1196-1202.
Jorge, A. S., Suárez-Lledó, M., Pereira, A., Gutierrez, G., Fernández-Avilés, F., Rosiñol, L., Llobet, N., Solano, T., Urbano-Ispízua, Á., Rovira, M., & Martínez, C. (2018). Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 24(6), 1196-1202. https://doi.org/10.1016/j.bbmt.2018.01.021
Jorge AS, et al. Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors. Biol Blood Marrow Transplant. 2018;24(6):1196-1202. PubMed PMID: 29410343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Single Antigen-Mismatched Unrelated Hematopoietic Stem Cell Transplantation Using High-Dose Post-Transplantation Cyclophosphamide Is a Suitable Alternative for Patients Lacking HLA-Matched Donors. AU - Jorge,Ana Sofia, AU - Suárez-Lledó,María, AU - Pereira,Arturo, AU - Gutierrez,Gonzalo, AU - Fernández-Avilés,Francesc, AU - Rosiñol,Laura, AU - Llobet,Noemí, AU - Solano,Teresa, AU - Urbano-Ispízua,Álvaro, AU - Rovira,Montserrat, AU - Martínez,Carmen, Y1 - 2018/02/02/ PY - 2017/12/12/received PY - 2018/01/17/accepted PY - 2018/2/8/pubmed PY - 2019/4/2/medline PY - 2018/2/8/entrez KW - Graft-versus-host disease KW - HLA-mismatched transplantation KW - Post-transplantation cyclophosphamide KW - Unrelated donor SP - 1196 EP - 1202 JF - Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation JO - Biol Blood Marrow Transplant VL - 24 IS - 6 N2 - The optimal prophylaxis regimen for graft-versus-host disease (GVHD) in the setting of mismatched unrelated donor (MMUD) allogeneic hematopoietic stem cell transplantation (alloHSCT) is not defined. The use of high-dose post-transplant cyclophosphamide (PTCy) in haploidentical transplantation has proven feasible and effective in overcoming the negative impact of HLA disparity on survival. We hypothesized that PTCy could also be effective in the setting of MMUD transplantation. We retrospectively analyzed 86 consecutive adult recipients of alloHSCT in our institution, comparing 2 contemporaneous groups: PTCy MMUD (n = 26) versus matched unrelated donor (MUD) (n = 60). Graft source was primarily peripheral blood (92%). All PTCy MMUD were HLA 7/8 (differences in HLA class I loci in 92% of patients) and received PTCy plus tacrolimus ± mofetil mycophenolate as GVHD prophylaxis. No differences were observed between PTCy MMUD and MUD in the 100-day cumulative incidence of acute GVHD grades II to IV (31% versus 22%, respectively; P = .59) and III to IV (8% versus 10%, P = .67). There was a trend for a lower incidence of moderate to severe chronic GVHD at 1 year after PTCy MMUD in comparison with MUD (22% versus 41%, P = .098). No differences between PTCy MMUD and MUD were found regarding nonrelapse mortality (25% versus 18%, P = .52) or relapse rate (11% versus 19%, P = .18). Progression-free survival and overall survival at 2 years were similar in both cohorts (67% versus 54% [HR, .84; 95% CI, .38 to 1.88; P = .68] and 72% versus 57% [HR, .71; 95% CI, .31 to 1.67; P = .44], respectively). The 2-year cumulative incidence of survival free of moderate to severe chronic GVHD and relapse tended to be higher in the PTCy MMUD group (47% versus 24%; HR, .60; 95% CI, .31 to 1.14; P = .12). We conclude that HLA 7/8 MMUD transplantation using PTCy plus tacrolimus is a suitable alternative for those patients who lack a MUD. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/29410343/Single_Antigen_Mismatched_Unrelated_Hematopoietic_Stem_Cell_Transplantation_Using_High_Dose_Post_Transplantation_Cyclophosphamide_Is_a_Suitable_Alternative_for_Patients_Lacking_HLA_Matched_Donors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(18)30037-5 DB - PRIME DP - Unbound Medicine ER -