G-CSF-Primed Allogeneic-BMT Following Reduced Intensity Conditioning (RIC) Regimen for Patients with AML. Rapid Engraftment, Low Incidence of Chronic Gvhd (cGVHD) and Good Outcome for Patients In 1

st

Complete Remission (CR), but Not for More Advanced Cases
Authors: Ostronoff Mauricio , Maior ANA Patricia Souto , Ostronoff Fabiana , Florencio Rodrigo , Martins Monique , Botelho Luis Fabio , Sucupira Alexandre , Coutinho Mariana , Calixto Rodolfo 
Published: October 2019

Abstract
Abstract 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.