Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Hematopoietic Stem Cell Transplantation , Recovery of Function/immunology , Adolescent , Adult , Aged , Allografts , Biomarkers/blood , Cytomegalovirus/immunology , Cytomegalovirus/metabolism , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/immunology , Female , HLA Antigens , Hematologic Neoplasms/blood , Hematologic Neoplasms/immunology , Hematologic Neoplasms/therapy , Humans , Male , Middle AgedABSTRACT
Hematopoietic stem cell transplantation (HSCT) from human leukocyte antigen (HLA) haploidentical family donors is a promising therapeutic option for high-risk hematologic malignancies. Here we explored in 121 patients, mostly with advanced stage diseases, a sirolimus-based, calcineurin-inhibitor-free prophylaxis of graft-versus-host disease (GvHD) to allow the infusion of unmanipulated peripheral blood stem cell (PBSC) grafts from partially HLA-matched family donors (TrRaMM study, Eudract 2007-5477-54). Conditioning regimen was based on treosulfan and fludarabine, and GvHD prophylaxis on antithymocyte globulin Fresenius (ATG-F), rituximab and oral administration of sirolimus and mycophenolate. Neutrophil and platelet engraftment occurred in median at 17 and 19 days after HSCT, respectively, and full donor chimerism was documented in patients' bone marrow since the first post-transplant evaluation. T-cell immune reconstitution was rapid, and high frequencies of circulating functional T-regulatory cells (Treg) were documented during sirolimus prophylaxis. Incidence of acute GvHD grade II-IV was 35%, and occurrence and severity correlated negatively with Treg frequency. Chronic GvHD incidence was 47%. At 3 years after HSCT, transpant-related mortality was 31%, relapse incidence 48% and overall survival 25%. In conclusion, GvHD prophylaxis with sirolimus-mycophenolate-ATG-F-rituximab promotes a rapid immune reconstitution skewed toward Tregs, allowing the infusion of unmanipulated haploidentical PBSC grafts.
Subject(s)
Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , HLA Antigens/immunology , Peripheral Blood Stem Cell Transplantation , Sirolimus/therapeutic use , T-Lymphocytes, Regulatory/immunology , Administration, Oral , Adolescent , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Antilymphocyte Serum/therapeutic use , Blood Platelets/cytology , Busulfan/analogs & derivatives , Busulfan/therapeutic use , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/therapeutic use , Neutrophils/cytology , Prospective Studies , Rituximab , T-Lymphocytes/immunology , Tissue Donors , Transplantation Conditioning , Treatment Outcome , Vidarabine/analogs & derivatives , Vidarabine/therapeutic use , Young AdultABSTRACT
The clinical outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is strongly influenced from the potential complications arising during the delicate phase of post-transplant immune restoration. The quantitative aspects of immune-cell repopulation after HSCT and the qualitative features their functional restitution have been extensively reported. Nevertheless, measurable immune biomarkers predicting the clinical outcome of HSCT await formal validation. The aim of this review is an appraisal of most studies published so far on the predictive value of different T and NK-cell biomarkers after HSCT with emphasis on defined thresholds endorsed by multivariate analysis.
