Use of Granulocyte Colony-Stimulating Factor after Allogeneic Peripheral Blood Stem Cell Transplantation in Children with Thalassemia Major: Single Center Experience.

Abstract

High dose chemo-radiotherapy followed by either allogeneic or autologous hematopoietic stem cell transplantation (HSCT) is the treatment of choice for an increasing number of congenital or acquired diseases of childhood. One of the major drawbacks of this procedure is the prolonged period of profound neutropenia and complications associated with neutropenia. Although administration of granulocyte colony-stimulating factor (G-CSF) to adult patients undergoing high-dose chemotherapy and HSCT is believed to accelerate neutrophil recovery, the actual clinical benefits of G-CSF in children remain a controversial point requiring controlled studies and also the optimal timing for G-CSF infusion has not been established yet. It is well-known that children frequently recover faster than adults after HSCT and suffer less from life-threatening infections. In addition, studies demonstrating that these cytokines may also modify T-cell and dendritic cell function brought about a question whether the effect is strong enough to alter the risk of graft-versus-host disease (GVHD).In this retrospective three armed study we reviewed our experience at Akdeniz University School of Medicine Pediatric Hematology/Oncology Department to determine whether G-CSF administration on posttransplant period affects neutrophil and platelet engrafment time and alters the risk of acute or chronic GVHD in a relatively homogeneous nonmalignant group, thalassemia major patients. Fortyseven patients transplanted with peripheral blood stem cells were studied. G-CSF, if administered, were started on posttransplant day 1 or day 5. 25 patients in day 1 and 11 patients in day 5 group with other 11 non-administered patients were revealed retrospectively in respect to main outcomes that were hematopoietic recovery (neutrophil and platelet recovery defined by a neutrophil count of ≥0.5x109/L for 3 consecutive days and nontransfused platelet count of ≥20x109/L for 7 consecutive days) and GVHD. They were all given methotrexate combined with cyclosporine as GVHD prophylaxis with ATG in 35 patients. In G-CSF non-administered group neutrophil recovery was delayed compared with G-CSF administered group (16.5±2.8 vs 13.8±3.6 p=0.009) although transplanted MNC count was higher (16.8±3.5 vs 9.4±4.1 p<0.001). Although there was no any significant difference, platelet recovery seems to delay in G-CSF group (15.9±7.1 vs 21.8±14.5 p>0.05). The mean days to neutrophil recovery (14.0 ±3.7 vs 3.7±3.5 p>0.05) and the mean days to platelet recovery (22.7±15.5 vs 19.8±12.6 p>0.05) were not significantly different between day 1 and day 5 group. There were 5 grade II-IV acute and 5 chronic GVHD, both in G-CSF administered group but there were not any statistical differences in respect to GVHD between G-CSF or non-administered group and also within the G-CSF administered group according to administration time. In conclusion, administration of G-CSF after allogeneic PBSCT in children with thalassemia cause faster neutrophil recovery but administration on day 1 seems as if there is no additive effect compared to day 5 and do not alter the risk of acute or chronic GVHD. More studies in larger scales are needed to determine whether greater delay or non-use is feasible or not.