Abstract 23: Umbilical Cord Blood (CBU) Source as First Choice or as Rescue for Bone Marrow Transplant in Primary Immunodeficiencies (PID): A Single Center Experience

Abstract Introduction Cord blood represents a rich source of stem cells to be used for bone marrow transplant. Thanks to new manipulation techniques, haploidentical transplant has received new impetus while the use of cord blood stem cells has declined in recent years. The advantages of cord blood cells are immediate availability, lower level of compatibility required between donor and recipient and reduced risk of GVHD compared with other sources. The disadvantages are the limited cellularity, risk of posttransplant viral reactivation given the immaturity of the immune system and nonrepeatable use. Objectives Describe our experience of using CBU in 10 patients affected by Primary Immunodeficiecy (PID). Methods CUB was used as first choice in 7 of them and as rescue after graft failure of a first alpha/beta depletion haplotransplant in 3 patients affected by Chronic Granulomatous disease (CGD). Results Median age at transplant was 16 months. Median of total nucleated cell was: 0.551 x 108 /kg (0.24 – 1.26); 10/10 patients engrafted; median day of recovery of neutrophils (PMN) >500×109/L and platelets (PLT) >20 000×109/L was: D+19 (12-37) and D+35 (16-70) days respectively. Only one patient with CGD died on Day +20 because of Scedosporium disseminated infection. In this case PTCy was administered on day +3 and +5 because of 5/8 degree of mismatch. Acute GVHD incidence/severity was grade 0-I=55.5%, II=33.3%, III- IV=11.2%. Chronic GVHD was not attended. A median 2.7 years of long term follow up (1- 12) shows complete immune reconstitution, with normal response to mitogens, polyclonal repertoire in T cells (TRECs) and (KRECs) and full recovery from Immunoglobulin Replacement Therapy (IgRT). All patients present full donor chimerism on PMN while 2/10 present mixed chimerism on PBL (>80% donor). Discussion In our experience, CBU is a viable source of stem cells for pediatric patients with urgent need for a transplant, it is associated with good and complete immunologic reconstitution, low risk of complications and no case of graft failure. The opportunity to use cord units with low degree of compatibility as rescue with PTCy post infusion is an attractive option that needs to be considered in further studies. Pt 1 2 3 4 5 6 7 8 9 10 Disease IL10RA deficiency IL-2RG deficiency fHLH DOCK8 deficiency fHLH IL10RA deficiency WAS CGD CGD CGD Status Alive Alive Alive Alive Alive Alive Alive Alive Alive Dead WBC /kg 0.427x 10^8 1.26 x 10^8 0.605 x 10^8 0.4 x 10^8 0.572 x 10^8 0.74 x 10^8 0.48 x 10^8 0.53 x 10^8 0.9 x 10^8 0.24 x 10^8 CD34 + /KG 0.167 x 10^6 0.35 x 10^6 0.552 x 10^6 0.11 x 10^6 0.14 x 10^6 0.26 x 10^6 0.15 x 10^6 0.2 x 10^6 0.6 x 10^6 0.105 x 10^6 Conditioning Treo/Flu/TT Treo/Flu Bu/Flu Treo/Flu/TT Bu/Cy Bu/Flu Treo/FluTT Treo/Cy/Flu Treo/Flu TBI/FluPT-Cy Match 6/6 8/8 10/10 10/10 10/10 8/8 5/8 6/8 8/8 5/8 Last chimerism PBL (%) 100 100 91,7 100 100 100 100 100 82,8 100 Last chimerism PMN (%) 100 100 100 100 100 100 100 100 100 100 Response to mitogens normal normal normal normal normal normal normal normal normal / stop IgRT (months) 7 6 13 10 6 10 12 ongoing 13 / GVHD Acute / / Acute Acute Acute Acute Acute Acute / Grade I / / I II II II III I / CMV reactiation Yes No No Yes No Yes Yes Yes Yes /