3521 From 02/2006 to 02/2010, we performed 28 RIC G-CSF-primed allo-BMT for patients with AML in our center. Median age 29yr (range, 7 to 52 yrs); 15 male; 15 pts were in 1st CR and 13 pts in ≥ 2nd CR. FAB classification: AML M1 (3 cases); AML M2 (18); AML-M4 (5); AML M5 (1) and AML M7 (1). Among the pts in 1st CR, 2 had AML refractory to induction chemotherapy; one had secondary AML after chemotherapy for penile carcinoma; and one had secondary AML after treatment for T-cell ALL. The protocol was approved by our institutional review board and informed consent was obtained from each pt and donor and or their guardians. Conditioning consisted of busulfan 4mg/kg/day (d -5 and d -4) and fludarabine 30 mg/m2/day (day-7 to day -2). Four pts also received ATG 10mg/kg/day (D-4 to D-1), including the unrelated BMT, as our institution was participating in a multicentric clinical trail. GVHD prophylaxis consisted of CSA 5mg/kg/day orally from d -1 to d+90 and methotrexate 10mg/m2 on d +1, +3 and +6. Donors received G-CSF 5 μg/kg/d subcutaneously for 5 days before BM harvest (d –4 to d 0). Median age of the related donors was 28 years (range, 8 to 66 yrs). The unrelated donor did not received GCSF prior to BM harvest. Median CD34+, CD3+ and CD8+ cell count were respectively 3.8×106 cells/kg (2.4 to 6.8), 43 ×106 (22 to 60) and 13×106 cells/kg (7 to 26). All pts received G-CSF 10 micrograms/kg/d SQ from day zero until neutrophil engraftment. Four of the 28 pts never become neutropenic (neutrophil < 500/ mm3). The median time for neutrophil recovery was 4 days (2 to 18 days). All pts had low transfusion requirements. One pt developed BK-associated hemorrhagic cystitis which rapidly resolved after treatment with leflunomide. One pt rejected the graft; 04 pts had mixed chimerism on D+30 and relapsed few weeks later; 23 pts achieved complete and stable chimerism. Eighteen per cent of the pts (5 out of 28) developed grade ≥ II acute GVHD. The unrelated-BMT pt developed steroid-resistant aGVHD which was successfully treated with alemtuzumab. The incidence of extensive chronic GVHD was 21% and all pts, except for one, had complete response to immunosuppressive therapy. Causes of deaths included 2 cases of aGVHD, one cGVHD involving the lung, one provoked pulmonary embolism (after 12 hours bus-ride) in a pt that was in complete remission on D+413, and 7 relapses (25%). One pt had a late relapse and underwent a second conventional BMT from the same donor. He is currently alive and in CR 8 months after his second transplant. 16 out of 28 pts (57%) are alive and in CR after median follow up of 36 months (12 to 48 mo), including the pt that was re-transplanted. Among the pts who were transplanted in 1st CR, 11 out of15 pts (73%) are alive and in CR after median follow up of 24 months (range, 12 to 48 mo). Among the pts who were in 2nd CR, 5 out of 12 pts (42%) are alive and in CR after median follow up of 36 months (12 to 48 mo). G-CSF primed BMT with RIC regimen for pts with AML in 1st CR who are not eligible for myeloablative conditioning regimens can be successful, offering low incidence of cGVHD and rapid neutrophil engraftment. Disclosures: No relevant conflicts of interest to declare.
4566 There are few data on reduced intensity conditioning regimen in children with AML and no data for GCSF-primed BMT in this patient population. The related donors for these patients are commonly children as well and the peripheral blood stem cells collection is not often indicated. Primed-GCSF bone marrow harvest yields a higher number of CD34+ cells and a lower number of lymphocytes when compared to PBSCT resulting in faster neutrophil recovery and lower rate of chronic GVHD. From 2003 to 2009, we performed 12 GCSF-primed BMT in children with AML in our center median age 8 y (2-12); 10‰, 2 S; 8 pts in first CR (1 pt with AML 2ary to ALL-T treatment; 1 AML M7; 1 induction failure) and 04 pts with ≥ 2nd CR. FAB classification: 7 patients had AML M2; 2, AML M4; 1, AML-M5; 2, AML M7). These patients were not eligible for myeloablative SCT due to aspergilosis (4 patients), hepato-splenic abscess due to candidia (1 patient), recent sepsis due to Candida 2 pts, giant hamartoma causing restrictive pulmonary disease, severe asthma (1 patient), elevated transaminitis (greater than 5 times of the upper normal limit) due to recent multiple chemotherapies (2 patients), recent treatments with myeolosuppresive chemotherapies greater than 4 cycles complicated by recent infection (2 patients). The protocol was approved by our institutional review board and informed consent was obtained from each patient and donor and or their guardians. Conditioning consisted of fludarabine and TBI in 2 patients; busulfan 4mg/kg/day (day -5 and day -4) and fludarabine 30 mg/m2/day (from day-7 to day -2) in 9 patients. Three of these patients also received Ara-C 1g/m2 (day-5 to day -2). One patient undergoing unrelated donor BMT was conditioned with busulfan 4mg/kg/day (day -5 and day -4) and fludarabine 30 mg/m2/day (from day-7 to day -2) and ATG 10mg/kg/day (day -4 to day -1). GVHD prophylaxis consisted of CSA 5mg/kg/day orally from day -1 to day +90 and MMF 45mg/kg/day orally until day +30. The donors received G-CSF 5 μ g/kg/d subcutaneously for five days (day –4 to day 0) prior to harvest the bone marrow. The median age of the related donors was 9 years (range, 4 to 18 years). The stem cells harvest from the unrelated donor was not primed with GCSF. The median CD34+, CD3+ and CD8+ cell counts collected were respectively 3.5×106 cells/kg (2.5 - 5.0), 32 ×106 cells/kg (29 - 59) and 13×106 cells/kg (12- 25). All patients received GCSF 10 micrograms/kg/day SC from day +1 until neutrophil engraftment. Only 8/12 pts had neutrophil counts ≤ 500/mm3 for a short interval: median 3 days (2-8). There were no infectious complications and all CMV antigenemias were negative. The transfusion requirement was low for all patients. One patient rejected the graft on day+30 and 3 patients had mix chimerism on day +30 and relapsed few weeks later. All the other patients had complete chimerism on day +30 and continue to have stable complete chimerism thereafter. Grade >=II acute GVHD occurred in 2 patients (16.5%). Only one patient who underwent unrelated donor transplantation had steroid-resistant GVHD which responded to alemtuzumab. There were no deaths related to the transplant. Five patients died due to relapsed leukemia 2,3,3,4 and 19 months after the transplant the savage therapy was very difficult: 2 of these pts had chemotherapy refractory leukemia, 2 pts were refractory to conventional BMT and one pt had aspergilosis after the second conventional BMT. This pt had a previous history of aspergilosis. Seven of the 12 patients (58%) are alive and in complete remission of their leukemia 1,2,3,3,4,6 and 7 years after BMT. None of the patients developed extensive chronic GVHD. Among the patients who survived, there were5/7 (71%) is first CR including one case of secondary AML, the case of AML-M7 and one pt who had failed induction chemotherapy. RIC in children who are not eligible for myeloablative SCT can be well tolerated and successful specially in patients who are in first complete remission. In addition, primed-GCSF BMT can be a good strategy to achieve rapid neutrophil engraftment with low rate of chronic GVHD. Disclosures: No relevant conflicts of interest to declare.
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