ABSTRACT
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for some hematological diseases; however, graft-versus-host disease (GVHD) is still one of the most important and deleterious complications. Regulatory T cells and iNKT cells can decrease the incidence and severity of GVHD, while preserving the graft-versus-tumor response. In order to analyze the relationship between the transfused dose of these cells, the presence of GVHD and survival, 15 normal donors and 15 patients with hematological diseases who underwent allogeneic HSCT from HLA-identical siblings were studied. The mobilization and infused doses of valpha24-vbeta11(iNKT cells) lymphocytes and CD4+CD25+FoxP3+, CD4+CD25+FoxP3+CD62L+, regulatory T cells were analyzed. All patients were conditioned with busulfan and cyclophosphamide and received cyclosporine and methotrexate as GVHD prophylaxis. iNKT and FoxP3 cells were mobilized after G-CSF administration. Acute GVHD was present in 9 of 15 (60%) and cGVHD in 7 of 13 (54%) patients. Patients who received a dose <0.6 x 10(6)/kg of iNKT cells and >4 x 10(6)/kg of FoxP3 had better disease-free survival and overall survival. Individuals transfused with >1.1 x 10(6)/kg of FoxP3+ CD62L+ Treg cells had better overall survival. In conclusion, iNKT and Treg cells are mobilized with G-CSF in healthy donors and the dose of iNKT cells and FoxP3 and CD62L+ regulatory T cells is of clinical importance in human HSCT.
Subject(s)
Graft vs Host Disease/immunology , Hematopoietic Stem Cell Transplantation/methods , Killer Cells, Natural/immunology , T-Lymphocytes, Regulatory/immunology , Female , Flow Cytometry , Forkhead Transcription Factors/immunology , Graft Survival/immunology , Graft vs Host Disease/etiology , Granulocyte Colony-Stimulating Factor/pharmacology , Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Interleukin-2 Receptor alpha Subunit/immunology , Killer Cells, Natural/cytology , Killer Cells, Natural/drug effects , L-Selectin/immunology , Male , Survival Analysis , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/drug effects , Time Factors , Transplantation Conditioning/methods , Transplantation, HomologousABSTRACT
The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 x 10(9)/l, partial remission (PR) if platelets were >50 x 10(9)/l, minimal response (MR) if the platelet count was >30 x 10(9)/l and <50 x 10(9)/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 x 10(9)/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events.
