PF774 EXCELLENT OUTCOME OF MATCHED DONOR AND HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTATION WITH TARGETED BUSULFAN‐BASED MYELOABLATIVE CONDITIONING IN PATIENTS WITH NONMALIGNANT GENETIC DISEASES
Authors: Hong K.T. , Kang H.J. , Ahn H.Y. , Choi J.Y. , Song S.H. , Yu K.‐S. , Jang I.‐J. , Shin H.Y. 
Published: June 2019

Background:T‐cell replete Haploidentical stem cell transplantation (Haplo‐SCT) with high dose post‐transplant cyclophosphamide (PT‐Cy) is being increasingly used for patients when a HLA identical sibling or a matched related donor is not available. With regard to inborn errors of metabolism (IEM) or primary immunodeficiency which need a hematopoietic stem cell transplantation (HSCT) for cure, haplo‐SCT could be an alternative option. However, there is insufficient data on the efficiency and safety of the procedure of haplo‐SCT with PT‐Cy in patients with nonmalignant genetic diseases.Aims:The aim of the present study is to evaluate the feasibility and safety of haplo‐SCT with PT‐Cy in patients with nonmalignant genetic diseases compared with HLA matched donor transplantation.Methods:We retrospectively analyzed 16 patients (Haplo group) receiving Haplo‐SCT with PT‐Cy from peripheral blood graft source, and 20 patients (Matched group) receiving HSCT from related matched (n = 4), unrelated 9–10/10 matched donors (n = 16) between Jan 2014 and Feb 2018 at Seoul National University Children's Hospital. Three chronic granulomatous disease (CGD), 5 adrenoleukodystrophy (ALD), 4 Krabbe disease, and 4 others were included in Haplo group, whereas 11 CGD, 1 ALD, 1 Krabbe disease, 3 congenital neutropenia, and 4 other diseases in Matched group. We used an intensive daily pharmacokinetic monitoring method for busulfan dosing for effective myeloablation and to reduce toxicity. The total target area under the curve (AUC) of busulfan was set at 74,000 to 76,000 μg × h/L. Targeted busulfan, fludarabine were used in both groups for the conditioning regimen, while cyclophosphamide was included in Haplo group, and anti‐thymocyte globulin in Matched group.Results:The outcomes of haplo group and Matched group, respectively, are discussed. The median follow‐up time were 27.6 months (range, 11.9–60.8), and 34.2 months (range, 12.5–59.9), respectively. The cumulative incidence (CI) rates of neutrophil engraftment in haplo and control groups were 93.8% and 95.0%. The median days of neutrophil engraftment were 14 days and 11 days, and those of platelet engraftment were 34 days and 17 days, respectively. The both groups did not differ in terms of transplantation‐associated complications (hepatic veno‐occlusive disease, CMV reactivation, hepatic toxicity, hemorrhagic cystitis). For 13 patients with IEM, the post‐HSCT brain MRI findings were reported as similar to the pre‐HSCT one. In particular, 2 ALD patients in Haplo group who did not showed neurologic symptom before HSCT (pre‐HSCT Loes scores were 0 and 2, respectively) are still normal with regard to neurologic status at median follow‐up time 41 months and 18 months, respectively. The CI rates of grade II–IV, grade III‐IV acute and extensive chronic graft versus host disease were 45.0% versus 40.0% (P = 0.68), 6.0% versus 20.0% (P = 0.263) and 13.3% versus 26.7% (P = 0.335), respectively. The event‐free survival rates at 2 years (93.8% versus 95.0%, P = 0.856) were similar and the overall survival rates were 100% in both groups.Summary/Conclusion:The present study shows that haplo‐SCT using PT‐Cy, along with a targeted busulfan‐based myeloablative conditioning regimen, is a safe and promising therapeutic option for patients with nonmalignant genetic diseases. In particular, it could be useful for patients in urgent need of HSCT who lack a sibling donor or do not have enough time to find a suitable unrelated donor.