PB2338 LONG‐TERM OUTCOMES OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION IN SEVERE APLASTIC ANEMIA: PNH CLONES MATTER

Abstract

Background:Severe aplastic anemia (SAA) is a disease of young people, in which allogeneic hematopoietic cell transplantation (HCT) provides curative therapy. Recent studies have investigated the role of peripheral grafts, complement inhibition in patients with paroxysmal nocturnal hemoglobinuria (PNH) clones and long‐term complications.Aims:We aimed to investigate long‐term outcomes and prognostic factors in HCT for SAA.Methods:We retrospectively reviewed charts from consecutive patients transplanted for SAA in our center and analyzed: age, gender, ECOG performance status, time from diagnosis to transplant, pre‐transplant lines of treatment, pre‐transplant transfusions, hemoglobin and neutrophils at transplant, PNH (paroxysmal nocturnal hemoglobinuria) clone, graft source (bone marrow/peripheral), donor type (sibling/unrelated), HLA matching, conditioning (Cyclophospamide/Anti‐thymocyte globulin with/without fludarabine), days of neutrophil and platelet engraftment, acute (grade 2‐4) and extensive chronic GVHD (graft‐versus‐host disease), TMA (thrombotic microangiopathy), post‐transplant lymphoproliferative disease (PTLD), infections, relapse, late complications and survival. Multivariate analyses were performed to determine independent predictors of outcomes.Results:We studied 24 patients aged 20 years (range 9‐46) with severe (18) or very severe (6) AA. PNH clones (≥60%) were detected in 3 patients without signs of hemolysis or thrombosis. The majority of patients (14/24) were transplanted at refractory disease following a median of 2 (range 1‐4) previous lines of immunosuppression according to current recommendations. Bone marrow grafts (19/24) and sibling donors (15/24) were preferred when available. Matched unrelated donors were chosen in 7 patients without sibling donors; while 2 patients were transplanted with mismatched unrelated donors before the era of alternative transplantations. Fludarabine was added to the conditioning in 13/24 patients.Regarding complications, TMA developed in 3 patients and resolved in 2/3 with cyclosporine cessation; whereas PTLD in 2: one involving the central nervous system with a fatal outcome and one that resolved after Rituximab treatment. With a follow‐up of 59 months (0.9‐245), CI (cumulative incidence) of acute GVHD was 22.2% and was independently predicted by peripheral grafts and TMA (p<0.001). Ten‐year CI of chronic GVHD was 31.6% and was independently predicted by hemoglobin at transplant (p = 0.007), HLA mismatch (p<0.001), PNH clones (p<0.001) and TMA. Lastly, 10‐year OS reached 70.6% and was independently associated with a PNH clone (p = 0.034, Figure). No secondary malignancy or fatal long‐term complication was observed.Summary/Conclusion:Our study confirms that high cure rates are achieved in heavily immunosuppressed refractory SAA patients, even in older ones or post unrelated transplants. Peripheral grafts increase morbidity but not mortality in HCT for AA. More than that, our data suggest that novel approaches are needed in patients with PNH clones in order to improve morbidity and mortality in the era of effective complement inhibition.image