Outcomes After Related and Unrelated Umbilical Cord Blood Transplantation for Congenital Bone Marrow Failure Syndromes Other Than Fanconi Anemia.
Authors: Bizzetto Renata , Bonfim Carmen , Socie Gerard , Locatelli Franco , Chan Ka Wah , Ramirez Oscar , Stein Jerry , Nabhan Samir Kanaan , Miranda Eliana C.M. , Passweg Jakob R. , Gluckman Eliane , De Souza Carmino Antonio , Rocha Vanderson 
Published: October 2019

Abstract
Abstract 2300
Poster Board II-277
Allogeneic stem cell transplantation is the only curative option for congenital bone marrow failure syndromes (CBMFS). Umbilical cord blood cells from related or unrelated donor are an alternative source of stem cell for allotransplantation. We studied 64 patients with CBMFS who underwent umbilical cord blood transplantation (CBT), from related (RCBT) (n=20) and from unrelated donor (UCBT) (n=44) who were registered in Eurocord.
In the RCBT group, 13 (65%) patients had Diamond Blackfan anemia (DBA), 3(15%) amegakaryocytic thrombocytopenia (Amega), 2(10%) dyskeratosis congenita (DC), 1(5%) Schwachman Diamond syndrome (SDS) and 1(5%) Kostmann's disease (KD). The median age was 5.7 years, 60% were male, 52% were CMV positive and 52% had received more than 20 red blood cell (RBC) and/or platelet transfusions. The median time from diagnosis to transplant was 64 months. Ninety five percent received a HLA matched sibling transplant. Conditioning regimens varied by centers: 25% received reduced intensity conditioning regimens (RIC) and 75% received myeloablative conditioning regimens (MAC). All patients received graft-versus-host disease (GVHD) prophylaxis that included Cyclosporine; most patients also received additional agents. The median number of infused nucleated cells was 5×107/kg and median CD34+ cell count was 1.7×105/kg. Median follow up is 40 months. The cumulative incidence of neutrophil recovery was 95% by day 60 and platelet recovery was 85% by day 180. The cumulative incidence of acute GVHD (II-IV) was 5% at day 100 and chronic GVHD was 11% at 2 years. The 3-year overall survival was 95%.
In the UCBT group, 8 (18%) patients had DBA, 13 (29%) had Amega, 6 (14%) DC, 1(2%) SDS, 13(29%) KD, 2(5%) congenital agranulocytosis, and 1(2%) had unclassified aplastic anemia. The median age was 5 years, 64% were male, 64% were CMV positive, and 49% had received more than 20 RBC and/or platelet transfusions. The median time from diagnosis to transplant was 29 months. Eighty six percent of patients received grafts mismatched at 1 or 2 HLA loci and 3 patients received double UCBT. Conditioning regimens also varied by center: 38% received RIC and 62% MAC. GVHD prophylaxis included Cyclosporine in 91% patients. The median infused nucleated cell count was 6.1×107/kg and median CD34+cell count was 3.0×105/kg. The median follow up was 32 months. The cumulative incidence of neutrophil recovery was 55% by day 60 and platelet recovery was 50% by day 180. The cumulative incidence of acute GVHD (II-IV) was 24% at day 100 and chronic GVHD was 53% at 2 years. Two-year overall survival was 61%. Younger patients (<5 year) and number of infused nucleated cell count ≥6.1×107/kg were associated with improved survival rates. In fact, 2 year overall survival was 81% for patients transplanted with a higher cell dose versus 37% for the others (p=0.02) and it was 82% for younger patients versus 39% for older patients (p=0.01).
We conclude that CBT from a related donor is a feasible procedure for patients with non-Fanconi CBMFS. Outcomes of unrelated CBT are better in younger patients and in patients transplanted with CB units containing higher cell doses.

Disclosures:
No relevant conflicts of interest to declare.