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Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies.
Biol Blood Marrow Transplant. 2018 11; 24(11):2259-2264.BB

Abstract

Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m2/day on days -5 to -2), busulfan (3.2 mg/m2/day on days -3 and -2), and total body irradiation (200 cGy) on day -1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days -3 to -1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.

Authors+Show Affiliations

Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada.Allogeneic Blood and Marrow Transplantation Program, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada. Electronic address: auro.viswabandya@uhn.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30009980

Citation

Law, Arjun Datt, et al. "Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression With Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies." Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, vol. 24, no. 11, 2018, pp. 2259-2264.
Law AD, Salas MQ, Lam W, et al. Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies. Biol Blood Marrow Transplant. 2018;24(11):2259-2264.
Law, A. D., Salas, M. Q., Lam, W., Michelis, F. V., Thyagu, S., Kim, D. D. H., Lipton, J. H., Kumar, R., Messner, H., & Viswabandya, A. (2018). Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies. Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation, 24(11), 2259-2264. https://doi.org/10.1016/j.bbmt.2018.07.008
Law AD, et al. Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression With Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies. Biol Blood Marrow Transplant. 2018;24(11):2259-2264. PubMed PMID: 30009980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced-Intensity Conditioning and Dual T Lymphocyte Suppression with Antithymocyte Globulin and Post-Transplant Cyclophosphamide as Graft-versus-Host Disease Prophylaxis in Haploidentical Hematopoietic Stem Cell Transplants for Hematological Malignancies. AU - Law,Arjun Datt, AU - Salas,Maria Queralt, AU - Lam,Wilson, AU - Michelis,Fotios V, AU - Thyagu,Santhosh, AU - Kim,Dennis Dong Hwan, AU - Lipton,Jeffrey Howard, AU - Kumar,Rajat, AU - Messner,Hans, AU - Viswabandya,Auro, Y1 - 2018/08/07/ PY - 2018/05/02/received PY - 2018/07/04/accepted PY - 2018/7/17/pubmed PY - 2019/9/17/medline PY - 2018/7/17/entrez KW - Antithymocyte globulin KW - Dual T cell suppression KW - Haploidentical hematopoietic stem cell transplantation KW - Post-transplant cyclophosphamide SP - 2259 EP - 2264 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 - 11 N2 - Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m2/day on days -5 to -2), busulfan (3.2 mg/m2/day on days -3 and -2), and total body irradiation (200 cGy) on day -1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days -3 to -1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD. SN - 1523-6536 UR - https://www.unboundmedicine.com/medline/citation/30009980/Reduced_Intensity_Conditioning_and_Dual_T_Lymphocyte_Suppression_with_Antithymocyte_Globulin_and_Post_Transplant_Cyclophosphamide_as_Graft_versus_Host_Disease_Prophylaxis_in_Haploidentical_Hematopoietic_Stem_Cell_Transplants_for_Hematological_Malignancies_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1083-8791(18)30395-1 DB - PRIME DP - Unbound Medicine ER -