GCSF-Primed Allo-BMT Following Reduced Intensity Conditioning Regimen In Children with AML- Good Outcome In Patients In 1

st

Complete Remission with Rapid Neutrophil Engraftment and Low Incidence of Chronic Gvhd.
Authors: Ostronoff Fabiana , Ostronoff Mauricio , Maior ANA Patricia Souto , Calixto Rodolfo , Martins Monique , Coutinho Mariana , Sucupira Alexandre , Botelho Luis Fabio , Florencio Rodrigo 
Published: October 2019

Abstract
Abstract 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.