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^stComplete Remission (CR), but Not for More Advanced Cases

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 1^st CR and 13 pts in ≥ 2^nd CR. FAB classification: AML M1 (3 cases); AML M2 (18); AML-M4 (5); AML M5 (1) and AML M7 (1). Among the pts in 1^st 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 1^st 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 2^nd 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 1^st CR who are not eligible for myeloablative conditioning regimens can be successful, offering low incidence of cGVHD and rapid neutrophil engraftment.