Hematopoietic stem cell transplantation in Iran: 1991 to 2008

Since 1991, 2042 first hematopoietic stem cell transplants (HSCT) have been performed at the Hematology-Oncology and Stem Cell Transplantation Research Center at Tehran University of Medical Sciences. Acute myelogenous leukemia (548 patients), thalassemia major (335 patients) and acute lymphoblastic leukemia (275 patients) have been the most common transplanted disorders. There were 1418 cases that received allogeneic HSCT and 624 cases that have received autologous HSCT. The numbers of allogeneic and autologous HSCT have increased, but the allogeneic to autologous ratio has remained constant. The first peripheral blood hematopoietic stem cell transplantation was performed in 1996; since then, 1671 have been done. The donor types for 1418 allogeneic first HSCT were 1367 (96.4%) human leukocyte antigen (HLA) matched-identical siblings, 29 (2%) HLA-mismatched sibling/other relative, 13 (0.9%) syngeneic twins, 5 (0.4%) HLA-matched other relatives and 4 (0.3%) unrelated. The first cord blood hematopoietic stem cell transplantation was performed in 1998 and since then there have been 14 patients that have obtained cord blood transplantations. Recently, new methods have been used like donor lymphocyte infusion (DLI) and cellular therapy. There were 111 patients with cellular therapy for post-myocardial infarction, cirrhosis, thalassemia major, multiple sclerosis, head of femur necrosis and renal cell carcinoma

The outcome of Autologous Stem Cell Transplantation in First Complete Remission Acute Myeloid Leukemia Patients- Single Center Study

Post-remission treatment in patients with acute myeloid leukemia is still controversial. One potent choice for patients with no donor available is autologous stem cell transplantation. The median follow-up period was 18 months and the median age was 26 years old. In the review of 116 recently diagnosed AML patients (except AML- M3) who underwent autologous stem cell transplantation, 72.4% of patients remained alive and 27.6% relapsed. Relapse was the most common causes of death in patients. The one- year OS and DFS of patients was 73.8% and 59.8%, respectively. There was no statistically significant difference between age, sexuality and waiting time from diagnosis to transplantation. For more comprehensive results, longer follow- up is required

Hematopoietic Stem Cell Transplantation in Patients with Severe Acquired Aplastic Anemia: Iranian Experience

Introduction: Severe acquired aplastic anemia (SAA) is a rare disease and matched related hematopoietic stem cell transplantation (HSCT) is the treatment of choice especially in pediatric patients. Immunosuppressive therapy is the alternative treatment in patients who do not have a donor. We retrospectively analyzed patients who received allogeneic HSCT at our institution. Methods: Between 1991 and 2011, 190 patients received allogeneic HSCT from HLA-matched donors (182 siblings and 8 other relatives). Median age was 20.5 years (range 1 to 50 years). The graft source was peripheral blood stem cells in majority of patients. Conditioning regimen consist with a myeloablative regimen containing cyclophosphamide with or without antithymocyte globulin. For graft-versus-host disease (GvHD) prophylaxis, we used cyclosporine with or without methotrexate at the standard doses. Results: The median follow-up time was 30 months and 3 year overall survival and disease free survival was 82% and 75% respectively. The median time to neutrophil engraftment and median time to platelet engraftment was 12 day and 15 day respectively. Grade 3 and 4 of aGvHD occurred in 26 (23.7%) patients and chronic GvHD occurred in 46 (29.1%) of survived patients 100 days after HSCT. At time of report 82.1% of patients were alive with normal hematologic parameters. The engraftment failure rate was about 8%. The most common cause of death was GvHD. Conclusions: However an available treatment in SAA is immunosuppressive therapy, HSCT should be seriously considered as a therapeutic option particularly if a matched sibling donor is available. The outcome of allogeneic HSCT in patients with SAA at our center was consistent with the result of other previous studies

Study of relationship between IL-1Ra gene polymorphism and GVHD in HLA – identical sibling allogenic transplants

Introduction: The interleukin-1 (IL-1) gene family includes three members (IL-1a, IL-1b and IL-1Ra) that mediate immune and inflammatory responses. Interleukin-1 (IL-1) is an inflammatory cytokine involved in various autoimmune and inflammatory diseases. IL-1 receptor antagonist (IL-1Ra) is the naturally occurring antagonist to IL-1a and IL-1b. A variable number tandem repeat (VNTR) polymorphism in the IL-1Ra gene has been associated with increased IL-1Ra production and affects the severity of aGVHD. Material and methods: Three hundred and fifty pairs (175 HSCT recipients and their donors) were analyzed by VNTR/PCR. Because of haematological disorders all patients were transplanted. All genotypes were screened blind to the clinical outcome of the transplants. GVHD was graded using Glucksberg criteria. Results: The influence of different alleles on incidence of aGVHD was investigated with univariate analysis. None of them showed an association with aGVHD, but possession of allele 2 in donors was associated with less severe aGVHD, although the frequency of allele 2 in our study population was low. However, aGVHD correlated with recipient age, donor age and recipient disease, particularly thalassaemia. Conclusions: No significant correlation was observed between the IL-1Ra polymorphism and incidence of aGVHD. In addition there was a powerful association between diagnosis, particularly thalassaemia, and GVHD (26 out of 30 thalassaemia patients). These findings may help to predict the risk/severity of GVHD, which may contribute to selecting strategies for treatment/prevention in thalassaemia patients

Autologous Hematopoietic Stem Cell Transplantation in Acute Lymphoblastic Lymphoma

Introduction: Despite high remission rates in acute lymphoblastic leukemia (ALL) patients after induction chemotherapies, post- remission therapies needed to avoiding relapse. Autologous hematopoietic stem cell transplantation (HSCT) role in the treatment of ALL is still controversial. In this retrospective study, we assessed the outcome of auto- HSCT in the treatment of ALL patients treated in this center.Patients and methods: From March 1991 to December 2005, 25 ALL patients with no suitable donors underwent auto-HSCT. All patients received Endoxan, Cytarabin and Etoposide according to the center- approved protocol for conditioning regimen. The sources of graft were peripheral blood and bone marrow. The patients hospitalized in same special rooms and circumstances. The Kaplan-Meier method was used for the data analysis.Results: The median age of patients was 18 years old (range: 8-54). The majority of patients were male. The mean number of WBC count at diagnosis was 48.5×103/µl. Seventy- two percent of patients received autologous HSCT in CR1. Eighty percent of ALL subtypes were B- lineage. Primary central nervous system involvement at diagnosis time was observed in 16%. The median number of harvested nucleated cells: 4.16×108/kg, MNC: 3.69×108/kg, CD3: 1.52×108/kg and CD34+ cells were 0.07×108/kg of recipient weight. The median time of neutrophil and platelet recovery was 12 (range: 9-37) and 17 (range: 10-74) days, respectively. The median follow-up period for survivors was 12 months (range: 4-110 months). Relapse occurred in 17(68%) of patients. Relapse was the only cause of death in patients. The one-year overall survival (OS) and disease-free survival (DFS) were 46% (SE: 10.2%) and 38% (SE: 9.9%), respectively. Age at transplantation and WBC count at diagnosis time had no significant effect on DFS and OS. Source of stem cells had no significant effect on survival outcome too. Transplantation in first complete remission had the best survival outcome (p =0.01).Conclusion: The role of autologous HSCT in ALL patients who do not have suitable donors is still inferior to chemotherapy alone. Regarding poor results of the current study, further studies on the role of auto- HSCT in specific subtypes of ALL patients is suggested