Unrelated Cord Blood Transplants in Children/Adolescents in Multi-Racial Singapore.
Authors: Tan Poh-Lin , Tan Ah-Moy , Chan Mei-Yoke , Villegas Mariflor , Yeoh Allen , Quah Thuan-Chong 
Published: October 2019

Abstract
Alternative donor choices are limited in multi-racial, multi-ethnic societies with small families such as Singapore. Unrelated cord blood transplant (UCBT) provides a feasible alternative to patients lacking adult stem cell donors. We reviewed the Singapore experience in UCBT for 29 children/adolescents with malignant (N = 19) and non-malignant diseases (N = 10) from 1998 – 2006. A significant 25% of patients were of varied South-East Asian (SEA) descent with majority being SEA-Chinese. The median age at UCBT was 6.7 (0.5 – 17.7) years with younger patients in the non-malignant compared to the malignant group (4.7 versus 8.8 years). Malignant indications for UCBT included acute lymphoblastic leukemia (ALL, N = 12), acute myeloid leukemia (N = 4), chronic myeloid leukemia (N = 2) and hemophagolymphohistiocytosis (N = 1); and non-malignant indications severe combined immunodeficiency disease (N = 3), CD40 ligand deficiency (N = 2), chronic granulomatous disease (N = 1), leukocyte adhesion disease (N = 1), thalassaemia (N = 2) and Fanconi anemia (N = 1). Seventeen patients received myeloablative conditioning (MAC), 12 received reduced intensity conditioning (RIC). Of the 12 RIC patients, 8 received dual UCBT with a median total nucleated cell dose (TNC) of 7.2 (3.4 – 12.2) x 10(7)/kg, CD34 cell dose of 1.7 (0.7 – 3.7) x 10(5)/kg compared to a median 6.2 (2.4 – 21.8) x 10(7)/kg, CD34 of 3.1 (0.2 – 297.6) x 10(5)/kg in MAC patients who received single UCBT.All except 3 patients received 1 – 2 HLA antigen mismatched cords. Sixteen of 19 and 6 of 10 patients in the malignant and non-maligant groups engrafted at a median of 19.5 (2 – 21) days and 20 (14 – 41) days, respectively. Nine and 2 of 17 malignant patients and none of non-malignant patients developed grade 1- III aGVHD and chronic GVHD, respectively. Thirteen of 19 patients and 8 of 10 patients in the malignant and non-malignant groups are alive at a median follow-up of 23 (9 – 48) months and 31 (14 – 73) months, respectively. The main cause of death was disease relapse in the malignant group (5 of 6 patients). In the malignant group, a select group of ALL patients (ALL-RIC, N = 6) was given dual UCBT after RIC with the aim to reduce transplant-related morbidity/mortality while preserving chances of engraftment, graft-versus-leukemia effects and long-term neuro-endocrine outcome. These patients received a median total nucleated cells (TNC) dose of 7.2 (3.4 – 12.2) x 10(7)/kg and CD34 cell dose of 2.0 (0.8 – 3.7) x 10(5)/kg recipient BW and were discharged at a median of 17 (12 – 16) days. Compared to another 6 ALL patients who received single UCBT after MAC (ALL-MAC), these received a median TNC of 5.4 (2.6 – 8.1) x 10(7)/kg and CD34 of 2.8 (0.6 – 297.6) x 10(5)/kg recipient BW and were discharged at a median of 59 (31 – 118) days. ALL-RIC and ALL-MAC patients engrafted at a median of 6 (2 – 28) days and 21 (14 – 37) days, respectively, with one primary graft failure in the ALL-MAC group. There were 4 relapses, 2 in each group at a median follow-up of 23 (12 – 30) months and 16 (3.5 – 48) months, respectively. More patients in ALL-RIC group developed acute GVHD compared to the ALL-MAC (83% versus 33%). All patients except 1 from each group are alive as of last follow-up, with death occurring from a road-traffic accident while in complete remission and one from relapse in the ALL-RIC and ALL-MAC groups, respectively. UCBT successes in children/adolescent is high in multi-racial Singapore using conventional and novel approaches.