Upfront Haploidentical Stem Cell Transplant with Post Transplant Cyclophosphamide in Children with Severe Aplastic Anemia

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Introduction In children with severe acquired aplastic anemia, although matched sibling donor (MSD) hematopoietic stem cell transplant (HSCT) is standard of care. If it's not available then usually immune suppressive therapy (IST) is offered. But the success of IST at best is 50-70% and many children only achieve partial response and still have risk of developing clonal disorders or relapse in follow up. Recent data has shown upfront matched unrelated donor (MUD) HSCT can be as good an option as MSD. However, MUD is not easily available in the developing world due to lack of registries and Non-Caucasian population and multiple ethnicities. Recently, John Hopkins group showed in a series of 14 patients of severe aplastic anemia, refractory to initial therapy with IST, that haploidentical donor HSCT with post-transplant cyclophosphamide (PTCy) can be offered as a treatment with event free survival (EFS) and overall survival (OS) of 100%. In the developing world, due to lack of funds, usually the first chance at therapy is the best chance and most people can't afford further therapy after failure of IST. So, we offered upfront haploidentical HSCT with PTCy to 4 children with severe aplastic anemia and here we describe outcomes of the same. Methods After informed consent of the parents four children (median age- 4 years, range 2-11 years and male: female = 1:3)) underwent haploidentical HSCT with PTCy from a family donor. Conditioning was Rabbit ATG 1.5 mg/kg x 3 days (day-8 to day-6), Fludarabine 40 mg/m2 × 4 days (day-5 to -2), Cyclophosphamide 14.5 mg/kg x 2 days (day-5 & -4) and total body irradiation 2 Gy (day-1). Peripheral blood stem cell was the graft in all cases (median CD34 cell dose -9 million/kg; range-5 to 11 million/kg). Donor was father in 3 cases and mother in 1. GVHD prophylaxis was PTCy 50 mg/kg on day +3 & +4 and cyclosporine and MMF. Results All children were transplanted within 2-months from diagnosis of aplastic anemia. All four children engrafted (Neutrophil engraftment on median day+17; range-16-19 and platelet median engraftment on day+16; range12-27). All were fully donor on day+30, 60 and 100. Acute GVHD grade 1 was seen in 1 child. No chronic GVHD was seen. CMV reactivation was seen in 2 children. All are alive and disease free and GVHD free at median follow up of 1 year (range 6 month to 30 months). Two are off immune suppression whilst one is on tapering dose and one with 6 months follow up is still on immune suppression. Conclusion Upfront haploidentical HSCT with PTCy is safe and effective option for children with aplastic anemia lacking a matched donor.