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Significant improvements in haploidentical stem cell transplantation (haplo-SCT) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for haplo-SCT for SAA remains undefined. A recent review demonstrated haplo-SCT using NMA and RIC, engraftment between 75 to100% and OS one year of 75-100%. In our Institutions we started a double source since Jan 2017 using a RIC protocol that is the objective of this presentation. There were nine haplo-SCT in eight patients in two Brazilian centers, Hospital Santa Marcelina (n=5) and Hospital São Paulo (n=3). All patients were male, median age 26 years old (14-39), nocturnal paroxysmal hemoglobinuria clonality in five (62,5%); treated with Cyclosporine, Thymoglobulin (n=4), Eltrombopag (n=1), Eculizumab (n=2) and/or Alemtuzumab (n=1). Median time disease to transplant was 15,7 months (3.8-192). All patients submitted more than 20 RBC transfusions, and median of ferritin was 2,283 ng/mL (753-3,486). One patient had carbapenem-resistant gram-negative bacilli (CRNGB: Escherichia coli, Klebsiella pneumoniae and/or Pseudomonas aeruginosa). Panel reactive antibody was negative in all patients. The donor was a sibling in 44% (n=4), father and mother 22% each (n=2) and one patient received cells from his cousin after an early failure of engraftment from mother first transplant. The cause of this failure was a JC virus and adenovirus acute infections. The second haplo-SCT conditioning was Fludarabine, Cyclophosphamide and 600 cGy TLI. There were seven male donors. RIC was consisted of Fludarabine, Cyclophosphamide and total body irradiation (TBI) 200 cGy. The source was G-CSF primed bone marrow (G-BM) grafts in combination with PBSC no ex-vivo T cells depleted, and Cyclophosphamide 50 mg/Kg/day IV on days +3 and +4 post-transplant (PTCy), as well as graft versus host disease (GvHD) prophylaxis. The median of G-BM MNCs was 5.4 x 10⁸/Kg (2.3-8.7), and PBSC was 10 x 10⁶CD34+/Kg (4-18.7). One (11%) patient died for sepsis at day +13, he was the only with a confirmed CRGNB colonization before transplant. The ANC recovery was at day +17 (13-24). No one had Sinusoidal Obstructive Syndrome. Acute GvHD grade II and moderate chronic GvHD was observed in two patients (25%). Two patients had engrafting failure: the first at day +30 and received a successfully new haplo-SCT; the second at day +60, with a partial donor reconstitution without dependence of transfusion after immunosuppressive therapy. These two patients had female donors. The OS and DFS at two years were 87.5% and 75%, respectively. In conclusion, with a median follow-up of 30 months, haplo-SCT, PTCy with double source keep the 87.5% overall survival, with no one severe chronic GvHD. Our data suggests an excellent results for haplo-SCT, PTCy, RIC, double source in the SAA treatment. However, prospective well-designed trials need to confirm these results. Disclosures No relevant conflicts of interest to declare.

Allogeneic stem cell transplantation (allo-SCT) represents a curative option for intermediate- and high-risk acute leukemias (AL). The number of unmanipulated haploidentical allo-SCT (haplo-SCT) is increasingly used with favorable outcomes. Incidence of graft-versus-host disease (GvHD) in haploidentical bone marrow (BM) transplants using post-transplant cyclophosphamide (PTCy) is low, counterbalanced by an excess in disease recurrence; and acute GvHD using mobilized peripheral blood stem cells (PBSC) ranges between 30% and 40%. The ultimate choice of graft source depends on the design of the full transplantation package based on transplantation center experience. We conducted a retrospective analysis of 32 patients (59% male), who received an haplo-PTCy with double source of stem cells, G-CSF primed bone marrow plus G-CSF-mobilized PBSC, for high-risk or advanced acute leukemia in two Brazilian centers, Hospital Santa Marcelina (n=23) and Hospital São Paulo (n=9), from 2013 to 2019. The median age patients were 27.5 years (range 17-60 years). Median disease time before haplo-PTCy was 8.9 months (3.6-108). There were 13 acute myeloid leukemia (AML), 17 acute lymphoblastic leukemia (ALL), one mixed phenotype acute leukemia and one dendritic cell leukemia. 6/17 ALL were Ph1 positive. 34% of the patients received 2 treatment protocols to achieve CR and 12.5% had submitted to more than two treatments. So, at the time of transplant 75% (n=24) was in first CR (CR1) although one (3%) patient was minimal residual disease (MRD) positive and six (18.7%) there were no MRD available. The others patients (n=8, 25%) were on second or third CR. The HCT-CI comorbidities was ≥ 3 in two patients, and there were 15 patients (46%) with carbapenem-resistant gram-negative bacilli (CRGNB) colonization before transplant. Panel reactive antibody was positive in two patients. The donor was a sibling in 68.7% (n=22), father, mother and child in two (6%), three (9%) and five (15%) patients, respectively. The conditioning was reduced intensity (RIC) in 87.5% (n=28) patients, with fludarabine, cyclophosphamide and total body irradiation (TBI) 200 cGy. After conditioning, patients received G-CSF primed bone marrow grafts in combination with PBSC no ex-vivo T cells depleted, and cyclophosphamide 50 mg/Kg/day IV on days +3 and +4 post-transplant, as well as GVHD prophylaxis. Six (18.7%) patients died for sepsis before 60 days (10 to 58 days), all had had CRGNB before transplant, four those ones with no grafting, died from days +10 to +19. Acute GvHD grade III-IV was observed in two patients, who died at +48 and +95 days. High mortality related to transplant (TRM) was observed considering all patients. CRGNB was a determining factor in these early deaths. If we excluded all CRGNB patients of this study the mortality could be 11% (2 patients with GVHD in 17 patients transplanted). Four patients (16%) has severe cGvHD. Nine patients (37%) relapsed in two years. Two years OS and DFS were 40% and 37.5%, respectively. In conclusion, with a median follow-up of 2 years, haplo-PTCy with double source leads to 40% overall survival in 32 patients with high-risk advanced acute leukemia, with 16% (n=2) being in treatment for cGvHD. The causes of death were relapse 43% (n=7), early sepsis in patients with CRGNB colonization 37.5% (n=6), grade IV acute GvHD in 12,5% (n=2), and one patient died for pneumonia community at D+285. Our data suggests that haplo-PTCY double source is a feasible option in these cases. However, CRGNB colonization in aggressive disease is the main factor that should be considered as exclusion for haplo-SCT in development countries. Disclosures No relevant conflicts of interest to declare.