Immune reconstitution in patients with Fanconi anemia after allogeneic bone marrow transplantation.
OBJECTIVE
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.
Flow Cytometry Service Core, Clinics Hospital, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: mbeltrame@ufpr.br.
Miriam
M
Perlingeiro Beltrame
Flow Cytometry Service Core, Clinics Hospital, Federal University of Paraná, Curitiba, PR, Brazil.
Mariester
M
Malvezzi
Pediatric Bone Marrow Transplantation Division, Federal University of Paraná, Curitiba, Brazil.
Carmem
C
Bonfim
Regional Blood Center of Ribeirão Preto, Ribeirão Preto, Brazil.
Dimas Tadeu
DT
Covas
Cancer Research Center (IBMCC-CSIC/USAL), Department of Medicine, Cytometry Service and IBSAL, University of Salamanca, Salamanca, Spain.
Alberto
A
Orfao
Hematology Division, Federal University of Paraná, Curitiba, Brazil.
Ricardo
R
Pasquini
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000637:transplantation; D008297:Male; D014184:Transplantation, Homologous / Q000379:methods*
Fanconi anemia; bone marrow; immune system; transplantation