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      Early lymphocyte recovery as a predictor of outcome, including relapse, after hematopoietic stem cell transplantation

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          Abstract

          Background

          Despite advances in the treatment of acute leukemia, many patients need to undergo hematopoietic stem cell transplantation. Recent studies show that early lymphocyte recovery may be a predictor of relapse and survival in these patients.

          Objective

          To analyze the influence of lymphocyte recovery on Days +30 and +100 post-transplant on the occurrence of relapse and survival.

          Methods

          A descriptive, retrospective study was performed of 137 under 21-year-old patients who we resubmitted to hematopoietic stem cell transplantation for acute leukemia between 1995 and 2008. A lymphocyte count < 0.3 x 10 9/L on Day +30 post-transplant was considered to be inadequate lymphocyte recovery and counts ≥ 0.3 x 10 9/L were considered adequate. Lymphocyte recovery was also analyzed on Day +100 with < 0.75 x 10 9/Land ≤ 0.75 x 10 9/L being considered inadequate and adequate lymphocyte recovery, respectively.

          Results

          There was no significant difference in the occurrence of relapse between patients with inadequate and adequate lymphocyte recovery on Day +30 post-transplant. However, the transplant-related mortality was significantly higher in patients with inadequate recovery on Day +30. Patients with inadequate lymphocyte recovery on Day +30 had worse overall survival and relapse-free survival than patients with adequate recovery. There was no significant difference in the occurrence of infections and acute or chronic graft-versus-host disease. Patients with inadequate lymphocyte recovery on Day +100 had worse overall survival and relapse-free survival and a higher cumulative incidence of relapse.

          Conclusion

          The evaluation of lymphocyte recovery on Day +30 is not a good predictor of relapse after transplant however patients with inadequate lymphocyte recovery had worse overall survival and relapse-free survival. Inadequate lymphocyte recovery on Day +100 is correlated with higher cumulative relapse as well as lower overall survival and relapse-free survival.

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          Most cited references49

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          Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients.

          (1980)
          This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotrophic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.
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            Acute lymphoblastic leukemia.

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              Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation.

              Interactions between killer immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) class I ligands influence development of natural killer (NK) cell repertoire and response to infection, cancer, and allogeneic tissue. As KIRs and HLA class I molecules are highly polymorphic, clinical allogeneic hematopoietic cell transplantation is predicted to frequently involve KIR mismatch, and thus to provide a unique system for study of human NK cell receptor repertoire development. Eighteen leukemia patients undergoing HLA-matched transplantation and their donors were analyzed for KIR genotype. Ten of 13 HLA-identical donor-patient pairs were KIR mismatched and 3 were matched; all HLA-matched unrelated pairs were KIR mismatched. Reconstitution of recipient NK cell repertoire following transplantation was examined using flow cytometry and monoclonal antibodies specific for KIR and CD94:NKG2A. These data form 3 groups. Six to 9 months after transplantation, 8 patients (group 1) reconstituted an NK cell repertoire resembling that of their donor, and for KIR-mismatched transplants, distinct from the recipient before transplantation. In the first year after transplantation, 5 patients (group 2) exhibited a generally depressed frequency of KIR-expressing NK cells and concomitant high frequency of CD94:NKG2A expression. By 3 years after transplantation, the frequency of KIR-expressing NK cells had increased to donor values, in the 3 patients from group 2 analyzed for this period. The remaining 5 patients experienced severe clinical complications following transplantation and displayed unique features in their NK cell receptor reconstitution. These results demonstrate that a majority of HLA-matched hematopoietic cell transplantations involve KIR mismatch and reveal differences in NK cell repertoire having potential impact for immune responsiveness and transplantation outcome.
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                Author and article information

                Journal
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Rev Bras Hematol Hemoter
                Revista Brasileira de Hematologia e Hemoterapia
                Associação Brasileira de Hematologia e Hemoterapia
                1516-8484
                1806-0870
                2012
                : 34
                : 6
                : 430-435
                Affiliations
                Universidade Federal do Paraná - UFPR, Curitiba, PR, Brazil
                Author notes
                Corresponding author: Juliane Morando, Serviço de Transplante de Medula Óssea da Universidade Federal do Paraná - UFPR, Rua Amintas de Barros, 871/204, 80045-155 Curitiba, PR, Brazil, julimorando@ 123456terra.com.br
                Article
                10.5581/1516-8484.20120108
                3545430
                23323067
                d858d031-038c-4708-91e6-ec53bf2518ec

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 11 April 2012
                : 29 June 2012
                Categories
                Original Article

                Hematology
                leukemia,lymphocyte count,hematopoietic stem cell transplantation
                Hematology
                leukemia, lymphocyte count, hematopoietic stem cell transplantation

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