Miriam Perlingeiro Beltrame1, Mariester Malvezzi2, Carmem Bonfim3, Dimas Tadeu Covas4, Alberto Orfao5, Ricardo Pasquini6. 1. Flow Cytometry Service Core, Clinics Hospital, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: mbeltrame@ufpr.br. 2. Flow Cytometry Service Core, Clinics Hospital, Federal University of Paraná, Curitiba, PR, Brazil. 3. Pediatric Bone Marrow Transplantation Division, Federal University of Paraná, Curitiba, Brazil. 4. Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil. 5. Cancer Research Center (IBMCC-CSIC/USAL), Department of Medicine, Cytometry Service and IBSAL, University of Salamanca, Salamanca, Spain. 6. Hematology Division, Federal University of Paraná, Curitiba, Brazil.
Abstract
BACKGROUND AIMS: Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by bone marrow (BM) failure/aplasia. Failure of hematopoiesis results in depletion of the BM stem cell reservoir, which leads to severe anemia, neutropenia and thrombocytopenia, frequently requiring therapeutic interventions, including hematopoietic stem cell transplantation (HSCT). Successful BM transplantation (BMT) requires reconstitution of normal immunity. METHODS: In the present study, we performed a detailed analysis of the distribution of peripheral blood subsets of T, B and natural killer (NK) lymphocytes in 23 patients with Fanconi anemia before and after BMT on days +30, +60, +100, +180, +270 and +360. In parallel, we evaluated the effect of related versus unrelated donor marrow as well as the presence of graft-versus-host disease (GVHD). RESULTS: After transplantation, we found different kinetics of recovery for the distinct major subsets of lymphocytes. NK cells were the first to recover, followed by cytotoxic CD8(+) T cells and B cells, and finally CD4(+) helper T cells. Early lymphocyte recovery was at the expense of memory cells, potentially derived from the graft, whereas recent thymic emigrant (CD31(+) CD45RA(+)) and naive CD4(+) or CD8(+) T cells rose only at 6 months after HSCT, in the presence of immunosuppressive GVHD prophylactic agents. Only slight differences were observed in the early recovery of cytotoxic CD8(+) T cells among those cases receiving a graft from a related donor versus an unrelated donor. Patients with GVHD displayed a markedly delayed recovery of NK cells and B cells as well as of regulatory T cells and both early thymic emigrant and total CD4(+) T cells. CONCLUSIONS: Our results support the utility of post-transplant monitoring of a peripheral blood lymphocyte subset for improved follow-up of patients with Fanconi anemia undergoing BMT.
BACKGROUND AIMS: Fanconi anemia is an autosomal recessive or X-linked genetic disorder characterized by bone marrow (BM) failure/aplasia. Failure of hematopoiesis results in depletion of the BM stem cell reservoir, which leads to severe anemia, neutropenia and thrombocytopenia, frequently requiring therapeutic interventions, including hematopoietic stem cell transplantation (HSCT). Successful BM transplantation (BMT) requires reconstitution of normal immunity. METHODS: In the present study, we performed a detailed analysis of the distribution of peripheral blood subsets of T, B and natural killer (NK) lymphocytes in 23 patients with Fanconi anemia before and after BMT on days +30, +60, +100, +180, +270 and +360. In parallel, we evaluated the effect of related versus unrelated donor marrow as well as the presence of graft-versus-host disease (GVHD). RESULTS: After transplantation, we found different kinetics of recovery for the distinct major subsets of lymphocytes. NK cells were the first to recover, followed by cytotoxic CD8(+) T cells and B cells, and finally CD4(+) helper T cells. Early lymphocyte recovery was at the expense of memory cells, potentially derived from the graft, whereas recent thymic emigrant (CD31(+) CD45RA(+)) and naive CD4(+) or CD8(+) T cells rose only at 6 months after HSCT, in the presence of immunosuppressive GVHD prophylactic agents. Only slight differences were observed in the early recovery of cytotoxic CD8(+) T cells among those cases receiving a graft from a related donor versus an unrelated donor. Patients with GVHD displayed a markedly delayed recovery of NK cells and B cells as well as of regulatory T cells and both early thymic emigrant and total CD4(+) T cells. CONCLUSIONS: Our results support the utility of post-transplant monitoring of a peripheral blood lymphocyte subset for improved follow-up of patients with Fanconi anemia undergoing BMT.
Authors: Juan Gea-Banacloche; Krishna V Komanduri; Paul Carpenter; Sophie Paczesny; Stefanie Sarantopoulos; Jo-Anne Young; Nahed El Kassar; Robert Q Le; Kirk R Schultz; Linda M Griffith; Bipin N Savani; John R Wingard Journal: Biol Blood Marrow Transplant Date: 2016-10-14 Impact factor: 5.742