Unmanipulated, G-CSF-Primed Bone Marrow Transplantation From Haploidentical Donor for Patients with High-Risk Acute Myeloid Leukemia.
Authors: Arcese William , Cerretti Raffaella , Santarone Stella , De Angelis Gottardo , Bavaro Pasqua , Testi Manuela , Cudillo Laura , Picardi Alessandra , Pennese Elsa , Papalinetti Gabriele , Dentamaro Teresa , Ceresoli Eleonora , Mariotti Benedetta , Piazza Fabio Di , Bartolomeo Paolo Di 
Published: October 2019

Abstract
Abstract 3122
The outcome of high-risk acute myeloid leukemia (AML) patients not undergoing an allogeneic transplantation is extremely poor. Therefore transplantation from haploidentical donor represents an alternative option for these patients on urgency to be transplanted. We report the results of a study on unmanipulated, G-CSF primed, haploidentical bone marrow (BM) transplantation in patients with high-risk AML lacking a suitable HLA-identical donor.

Materials and methods:
Between August 2005 to December 2011 58 patients (median age: 44 yrs, range 5–71) with very high-risk AML (CR1=32; CR2=16; advanced stage=10) underwent BM transplant from haploidentical donor. As pretransplant regimens, 43 patients were conditioned with a myeloablative regimen (MAC), while 15 patients received a reduced intensity conditioning (RIC). Of the 58 patients, 43 received the chemotherapy based regimen consisting of Thiotepa, i.v. Busulphan and Fludarabine (TBF MAC or RIC protocol). All 42 patients received an identical GvHD prophylaxis consisting of pretransplant ATG combined with CSA, MTX, MMF and Basiliximab, an anti-CD25 monoclonal antibody. Donors were primed with G-CSF at 4 microgr/Kg/d for 7 consecutive days. BM was harvested on day 0 and infused unmanipulated.

Results:
The median number of total nucleated, CD34+ and CD3+ cells infused was 7.2 (1–28)x108/kg, 2.04 (0.8–11)x106/Kg and 2.9 (0.9–6.7)x107/Kg, respectively. Five patients died early. All 53 evaluable patients engrafted at a median of 21 (13–29) days and the cumulative incidence (CI) of neutrophil engraftment was 100% at 30 days. For 53 evaluable patients, acute GVHD was absent or just grade I in 25 (47%). The 100-day CI of II-IV and III-IV grade acute GVHD was 34+/−0.4% and 12+/−0.2% respectively. Extensive chronic GVHD occurred in 4 (8%) out of 49 evaluable patients and the 2-year CI of extensive chronic GVHD was 13+/−0.4%. The 1 and 5-year CI of transplant-related mortality (TRM) was 32+/−0.4% and 34+/−0.4% respectively. The overall CI of relapse was 20+/−0.4% at 1-year and 34+/−0.7% at 5-year. The overall and disease-free survival probability was 61+/−6% and 54+/−7% at 1 year, 49+/−7% and 42+/−7% at 5 years. For patients in early stage of disease (CR1+CR2: n=48) the 1 and 3-year probability of overall survival was 70+/−7% and 58+/−8%.

Conclusions:
Haploidentical transplant using G-CSF primed, unmanipulated BM is correlated with high engraftment rate, low incidence of acute and chronic GVHD, acceptable TRM and favorable outcome. This approach represents a valid and feasible alternative to transplant from matched unrelated donor or cord blood for high-risk AML patients particularly on urgency to be transplanted.

Disclosures:
No relevant conflicts of interest to declare.