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Introduction: Hematopoietic stem cell transplantation (HSCT) is being increasingly used as curative therapy for severe disorders of the hematopoietic system and transfusional iron overload (TIO) contributes considerably to treatment-related morbidity and mortality after HSCT. Management of iron overload in the post-HSCT setting may be complicated since the use of therapeutic phlebotomies is often not feasible due to ongoing anemia and compliance to deferoxamine is low. Studies that evaluate the safety dose of deferasirox (DFX), which is the most commonly used chelation therapy, in this setting are limited. Purpose & Methods: This is a prospective, phase 2, multicenter, single-arm study to evaluate the efficacy and safety of iron chelation with oral DFX in beta-thalassemia major (TM) patients who have undergone HSCT. The study was conducted in 7 centers from Turkey. The primary objective was to evaluate if DFX could provide clinically safe chelation in a target pool of 26 pediatric patients with TIO within a minimum of 6 months and maximum of 2 years after related/unrelated HSCT. Patients had to be transfusion-independent and have iron overload at screening defined by serum ferritin (SF) of >1000 μg/L or cardiac MRI T2* Results: Interim data from the first 18 of 26 patients (mean age 8.3 years, 66.7% males) who completed 12 months follow up are presented in this analysis. A total of 97 AEs were recorded in the 18 patients. The majority of AEs were of Grade I (n=57) or II (n=34) severity. Five (5.2%) were suspected to be related to study drug and 6 AEs (6.2%) were considered serious. Five (5.2%) AEs resulted in study drug temporary interruption or dose adjustment, 2 (2.1%) required hospitalization, 54 (55.7%) required concomitant medication, while 36 (37.1%) had no action taken. Three patients had dose decrease due to AEs. The dose was re-escalated up to 20 mg/kg/day after the AEs resolved. In total, 11 (61.1%) patients achieved 20 mg/kg/day. Only one patient dropped out due to progressive ALT increase. Median ALT level decreased from 26 IU/L (range: 10-117) at baseline to 18 IU/L (range: 9-101) at week 52. The median SCr was similar at baseline 0.4 mg/dL (range: 0.2-0.6) and week 52 0.4 mg/dL (range: 0.2-0.8). Median cystatin C was similar at baseline 0.7 mg/mL (range: 0.6-0.9) and week 52 0.7 mg/mL (range: 0.5-1.1) (Figure 1A-B). Five patients had proteinuria at baseline and increased proteinuria compared to previous visit by dipstick analysis was described in 7 (38.9%) patients, irrespective of DFX dose by 52 weeks. No patient with proteinuria required any dose adjustments by 52 weeks. SF significantly and consistently decreased throughout the 52 weeks from a median of 1752.3 μg/L (range: 873.7-2716) to 915.2 μg/L (range: 250.1-2740), p Conclusions: Our preliminary results showed that DFX up to 20 mg/kg/day is safe and effective in reducing iron burden for TM patients following HSCT. This was evident through significant reductions of systemic, hepatic and cardiac iron overload. Final data from the completed study should confirm these findings and establish the role for DFX in this patient population. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Dag: Novartis: Employment. Birkent:Novartis: Employment.

Background: Graft-versus-host disease (GVHD) is a serious complication with a significant negative impact on survival following allogeneic hematopoietic stem cell transplantation (HSCT) in both adults and children. Immunosuppressants like steroids remain the mainstay of treatment which carries risks of increased infection frequency, a negative impact on the graft-versus-leukemia effect, and an increased probability of secondary malignancies. Extracorporeal photopheresis (ECP) treatment, seems to ameliorate GVHD by immunomodulation, rather than immunosuppression. However it is difficult to perform in pediatric population. This is a retrospective review of 17 pediatric patients who underwent photopheresis with the Therakos Cellex system for graft-versus-host disease (GVHD). Procedure: Extracorporeal photopheresis regimen was same for all acute and chronic GVHD patients: initially every week (2 sessions/week) for two months, then every two weeks for two months; and finally, every month for at least one year. Demographic data, degree of GVHD before photopheresis, adverse reactions during photopheresis procedure, modification in immunosuppressive treatment, and response to photopheresis were recorded. Results: Acute GVHD occurred in seven patients, overlap and chronic GVHD occurred in five patients in each group. The improvement observed in eleven of twelve patients who have acute GVHD (90%) and in seven of ten chronic GVHD patients (70%). Thirteen patients had skin involvement before ECP and eleven of them responded to treatment (84%). Gastrointestinal involvement occurred in ten patients and seven of them improved during ECP treatment (70%). All of the four patient´s liver involvements failed to respond. No serious adverse reactions occurred. Conclusions: In conclusion, our study demonstrates that ECP with the Therakos Cellex system is a safe treatment option for GVHD in children. Disclosures No relevant conflicts of interest to declare.

Umbilical cord blood (CB) are increasingly used for allogeneic transplantation as an alternative source to bone marrow or peripheral stem cell for patients who lack a human leucocyte antigen (HLA)-matched donor. Cell dose is one of the main determinant factor for selection of the unit and it has been shown to correlate with time and probability of engraftment. Cell doses available for selection of the unit are the ones evaluated before cryopreservation. Processing of the graft either with cryopreservation and/or thawing inevitably lead to cell loss but the data showing to what extent is very limited although this has great importance especially for the units with critical cell counts. To evaluate the extent of the cell loss after thawing and the effect of preservation duration on cell loss and the viability, we retrospectively analyzed our single center experience in a cohort of patients receivingunrelated CBT. Sixty cord blood units used for unrelated CBT in fifty-eight patients in our Pediatric Stem Cell Transplantation Unit were included in the study. One of the patient was transplanted with double cord blood unit and one had recurrent CBT because of previous graft failure. Median number of declared TNC per kilogram of recipient body weight was 16x107/kg (range: 3,16-59,1). After thawing the median TNC dose decreased to 11,1x107/kg (range:1,5-34), with median cell viability at 80%. The median TNC recovery was found as 70%. Median CD 34+ cell count declared by the banks per kilogram body weight of recipient was 6,0x105/kg (range: 0,5-37). The CD 34 cell count of one of the units used in a patient having double cord blood infusion was not available. The CD34 cell count of the other complementary unit was 0,48x105/kg. Since the total cell counts received bu the recipient was given, the CD34 cell count of the patient having double CB infusion was not included in statistical analysis. The median postthawed CD 34 cell count was 3,4 x105/kg (range: 0-21)and median CD34 cell recovery was %58. The storage duration of the CB units in liquid nitrogen was available for 59 units and that was 52±30 months (range:3-130 months). Correlation analysis did not show any significant correlation between CB unit storage duration and viability (r=-0,2 p=0.07). Also any correlation between storage time and also TNC and CD34 cell recovery were not identified. Our study indicated that approximately 30% of cell loss is expectable in cord blood transplantation because of either cryopreservation or thawing. It should be kept in mind while assessing acceptibility of cord blood units with limited cell counts Disclosures No relevant conflicts of interest to declare.

Abstract 4521 The only curative option for ß talasemia remains allogeneic hematopoietic stem cell transplantation (HSCT) to correct the genetic defect and provide a normal hemoglobin level in the recipient. Engraftment of donor derived cells is necessary for a success of transplantation. However, it has been shown that complete donor hematopoesis is not essential for sustained engraftment in thalassemia. Donor and recipient cells may coexist and produce a functional graft commonly referred to as donor/recipient mixed chimerism (MC) even with a low amount of engrafted donor cells. We documented our experience in a cohort of 19 beta thalassemia patients receiving DLI (donor lymphocyte infusions) following 21 transplantations with unstable mixed chimerism (MC). Seven patients received DLI with the indication of having more than 25% residual host cells (RHC) (MClevel3(residual host cells>25%)) early after transplantation and assigned as early-DLI group. Four patients although had MClevel3 in the early period, received deferred DLI and assigned as late-DLI group. The difference between these two groups, in respect to preserving functional graft, was not found statistically significant. However the chimerism kinetics of these early and late-DLI groups were also different and a slower decline in percentage of donor cells were observed in patients preserving grafts. Ten patients received DLI in the later period and although a significant increase in percentage of donor cells was not detected, increase in hemoglobin levels was provided. The infusions were safe with acceptable risk for GVHD. We believe that patients with more than 25% of RHC within two months early intervention with DLI seems feasible. Deferring DLI to a later period especially if the decrease in percentage of donor cells is so prompt, seems less effective. In the later period, we propose to consider the hemoglobin level as the main determinative factor for DLI application rather than the percentage of donor cells in line with expectance of better long-term tolerance. A better understanding of the mechanisms underlying the occurrence of persistent MC and strategies for induction and maintenance of tolerance will provide better interventions and outcomes for these patients. Disclosures: No relevant conflicts of interest to declare.

Veno-occlusive disease (VOD) of the liver is a major complication of allogeneic or autologous stem cell transplantation (HSCT), particularly after busulfan-based conditioning regimens. Clinically, VOD is characterized by fluid retention, weight gain, hyperbilirubinemia and painful hepatomegaly. Efficacy and safety of defibrotide for the treatment of VOD, especially in pediatric patients, has not been adequately confirmed or the results are still preliminary. This retrospective report describes experience with defibrotide in children with hepatic veno-occlusive disease (HVOD) following HSCT in a single institution. Materials and Method: Children who had undergone HSCT between April 2005–June 2006 and who received defibrotide for the treatment of HVOD during their admission were identified. Demographic data and clinical information of these patients were abstracted from their health records. Results: Eight children (median age: 4.5 years; range: 1–14 years) who underwent HSCT during the study period received defibrotide for the treatment of HVOD; 5 were boys and 3 were girls. Three patients underwent HSCT for hematologic malignancies, 2 for neuroblastoma, 1 for hemoglobinopathy, 1 for severe combined immunodeficiency (SCID) and 1 for fanconi aplastic anemia. Conditioning regimens included busulfan (16 mg/kg) in four, melphelan (140 mg/m2) in two and total body irradiation in 1 patient as being risk factors for HVOD. Two patients with neuroblastoma had undergone autologous HSCT, three patients had been transplanted from matched sibling donor and the other three were either unrelated donor or unrelated cord blood transplantation. HVOD was diagnosed on transplant day +4 to +19 (median: +12 ). The median initial defibrotide dose was 31.5 mg/kg/day (25–46 mg/kg/day). The median duration of defibrotide therapy was 27 days (1–46 days). Defibrotide was discontinued due to clinical improvement (5), gastrointestinal hemorrhage (2), death (1). Two patients in whom defibrotide was discontinued because of gastrointestinal hemorrhage died. The primary cause of death in these two children was: progressive HVOD and multiorgan failue following sepsis. As a result of this experience and under the light of literature, we believed that defibrotide is an effective treatment for children with HVOD and should be instituted in each children without delay in the event of at least one of the criteria for HVOD is established. But it is necessary to carry out further studies in larger group of patients with longer follow-up to validate the efficacy and safety of defibrotide.

Although improvements in conventional treatment have enhanced the prognosis of thalassaemia, stem cell transplantation remains the only cure. Studies have shown that peripheral blood stem cell transplantation (PBSCT) results in rapid hematological and immunological recovery but increased risk for graft versus host disease (GVHD). We report the PBSCT experience of Akdeniz University School of Medicine Pediatric Hematology&Oncology department concerning 54 patients with beta-thalessemia. Median age was 6 years (1–18 years), 26 were girls, 28 were boys. Thirteen were Class I, twenty-two were Class II, nineteen were Class III according to Pesaro criteria. 12 patients were given BU+CY and 39 BU+CY plus ATG as conditioning regimen. Three Class III patients were conditioned with Pesaro protocol 26. BU dosage was 16 mg/kg for Class I and Class II patients followed by CY 200 mg/kg totally. Class III patients received 14 mg/kg BU and 160 mg/kg CY. All patients received MTX (+1, +3, +6) and CsA for GVHD prophylaxis. All of the donors were HLA identical (51 sibling, 3 parents). Median age of the donors was 7 years (range: 2–40 years). G-CSF was given for 5 days with the dosage of 5 μgr/kg/day to child and 10 μgr/kg/day to adult donors for peripheral blood stem cell mobilization. Stem cell apheresis was performed on fifth day, but continued to day 7 if adequate cell count was not achieved. In older children and parents if appropriate, antecubital veins were used for harvesting but for younger donors, femoral dual lumen catheters were emplaced. Fresenius AS. TEC204 or Haemonetics MCS+ cell separators were used for apheresis. The median apheresis count was 1 (range 1–3). Median transfused MNC and CD34 cell counts were 10.1×108/kg (range:5.3–27.7×108/kg) and 4,65×106/kg (range:1.1–29.4×106 /kg) respectively. Median neutrophil and platelet engraftment times were day 14 and day 15, respectively. Grade II–IV acute GVHD were observed in five patients, chronic GVHD were in four of two were extensive. One patient died on posttransplant day 32 because of acute GVHD. Death because of chronic GVHD was not observed. At a median follow-up of 26 months (1–92 months), overall survival for the whole group is 92.6 % and evet-free survival is %80.4. Autologous reconstitution developed in six patients and graft failure in two.

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 p0.05). 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.