RESUMO
An increase in large granular lymphocytes (LGL) is frequently seen in patients following allogeneic hematopoietic cell transplantation (allo-HCT) and it has been associated with better outcomes in some reports. We assessed 826 consecutive patients at our institution with over 12 years of follow-up for the occurrence of LGL lymphocytosis after allo-HCT. The 3-year cumulative incidence of LGL lymphocytosis was 14.5% with a median duration of over 3.5 years. The development of LGL lymphocytosis was strongly correlated with CMV viremia and GVHD. The clinical course of patients with LGL lymphocytosis after allo-HCT was indolent, with the majority of these patients not displaying any clinical signs or symptoms related to the LGL proliferation. LGL lymphocytosis was associated with better outcomes, including higher overall survival (OS 86.6% vs 44.7% at 3 years), lower non-relapse mortality (NRM 5.5% vs 30.4% at 3 years), and lower risk of relapse (8.9% vs 22.9% at 3 years). A time-dependent multivariable analysis confirmed the favorable impact of LGL lymphocytosis on OS and NRM, but not on the risk of relapse. In multivariable analysis, a longer duration of LGL lymphocytosis was associated with better OS and NRM. Improved immunomodulatory properties of these cells, regulating GVHD and infections, may explain the observed favorable outcomes of patients who developed LGL lymphocytosis following allo-HCT.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/mortalidade , Segunda Neoplasia Primária/diagnóstico , Segunda Neoplasia Primária/mortalidade , Adolescente , Adulto , Idoso , Infecções por Citomegalovirus/etiologia , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunofenotipagem , Incidência , Leucemia Linfocítica Granular Grande/epidemiologia , Leucemia Linfocítica Granular Grande/etiologia , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Prognóstico , Fatores de Risco , Análise de Sobrevida , Avaliação de Sintomas , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Adulto JovemRESUMO
INTRODUCTION: Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder that has become the neoplastic poster child for understanding the disease biology of a malignant disease and targeting effective therapy. The targeted therapy of BCR-ABL inhibition by tyrosine kinase inhibitors (TKI) has provided the epitome for "Ehlrich's magic bullet" postulated decades ago. AREAS COVERED: Due to the therapy with these drugs, the survival of newly diagnosed patients with this disease now approaches that of age matched controls. Progression to advanced phases of CML had decreased over the years, though resistance has now been increasingly identified. Expert commentary: Ponatinib is a third generation TKI, which has shown to be effective in both early and advanced phases of CML and those bearing resistant mutations, specifically T315I. However, new side effect considerations need to be balanced with the efficacy, to establish the role of ponatinib in the therapy of CML.
