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

Autor: Fotios V. Michelis, Rajat Kumar, Hans A. Messner, Arjun Datt Law, Maria Queralt Salas, Santhosh Thyagu, Jeffrey H. Lipton, Dennis Dong Hwan Kim, Auro Viswabandya, Wilson Lam
Rok vydání: 2018
Předmět:
Adult
Male
medicine.medical_specialty
Transplantation Conditioning
Haploidentical hematopoietic stem cell transplantation
medicine.medical_treatment
Graft vs Host Disease
Hematopoietic stem cell transplantation
Gastroenterology
Article
Young Adult
03 medical and health sciences
0302 clinical medicine
hemic and lymphatic diseases
Internal medicine
medicine
Humans
Cumulative incidence
Cyclophosphamide
Aged
Antilymphocyte Serum
Dual T cell suppression
Transplantation
Neutrophil Engraftment
business.industry
Hematopoietic Stem Cell Transplantation
Hematology
Middle Aged
Total body irradiation
medicine.disease
Anti-thymocyte globulin
Fludarabine
surgical procedures
operative
Graft-versus-host disease
Hematologic Neoplasms
030220 oncology & carcinogenesis
Female
Antithymocyte globulin
Post-transplant cyclophosphamide
business
Immunosuppressive Agents
Busulfan
030215 immunology
medicine.drug
Zdroj: Biology of Blood and Marrow Transplantation
ISSN: 1083-8791
Popis: Highlights • HaploHSCT after RIC with ATG, PTCy, and cyclosporine is a feasible transplant regimen. • Low rates of grade II to IV acute GVHD were observed. • ATG use leads to higher rates of viral reactivation, particularly CMV and EBV.
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.
Databáze: OpenAIRE
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