Abstract

CBT is a curative therapy for thalassemia, with cell dosage is a critical factor for CBT. We previously showed that by combining strategies that maximize cell dose-using non-red cell reduced plasma depleted cord blood (PD CB), forego post-thaw wash, and double cord transplantation - promising results may be achieved with unrelated CBT in selected patients. Between 7/91 and 4/06, 45 unrelated CBT were performed after myeloablative therapy (Bu/Cy/ATG in all 33 patients with known regimen) in 36 pediatric patients with transfusion-dependent thalassemia and 2 SCD patients at 14 transplant centers (TC) using 80% PD CB (6 double cords & 1 re-transplant). For the thalassemics, 19 were Lucarelli class 1, 4 class 2, 1 class 3, and 14 status unknown. Median age was 6 yo (range 0.3–20 yo) and median weight was 19 kg (range 8–76 kg). Data was audited. No significant adverse events were observed despite major ABO incompatibility in 9 cases. Unadjusted ANC500, platelet 20K and 50K engraftment with donor chimerism were achieved in 81±7%, 79±8% and 76±8% of the cases, and median times to ANC500 engraftment, platelet 20K and 50K engraftment were at +16.5 (range 11–33), +37 (range 16–133) and +55 (range 26–144 days) days, respectively. 8 patients died including 2 early deaths prior to day +20 and one accidental trauma caused cerebral hemorrhage. All remaining 30 patients are alive, with 25 disease-free and 5 autologous recovery for an 1-Yr OS of 77±7% and DFS at 65±8%. With a mean and median follow up time of 392 and 257 days respectively (range 7–1,760 days), the median day to hospital discharge was day +58 (range 22–137 days). The two experienced TC (>5 cases of CBT for hemoglobinopathy) were compared with less experienced centers, and CBU that were post-thaw washed (14%) were compared with CB that were not washed (86%). Results show potential benefits with TC experience and no post-thaw wash; however, since both experienced centers do not practice post-thaw wash, these two factors cannot be distinguished. Unadjusted ANC500, platelet 20K and 50K engraftment were 87±7%, 86±8% & 86±8% and 1-Yr OS of 87±7% and DFS at 77±9% were achieved for experienced centers not performing post-thaw wash. The role of plasma depletion vs. RBC depletion was also studied by matching age, weight, TNC dose, #HLA matches, conditioning regimen, thalassemia diagnosis, and post-thaw wash between the groups at the 2 experienced TC. Outcome trended towards improvements in engraftment and thalassemia-free survival for PD CB; however, larger numbers and rigorous matched pair analysis are needed for definitive conclusions. Overall, this is the largest known study of unrelated cord blood transplantation for thalassemia and preliminary results show that when cell dose (PD CBU, double cord, and no wash) and other conditions (TC experience and judicious patient selection) are optimal, CBT may be a promising approach for the curative therapy of thalassemia major with unadjusted ANC500, platelet 20K and 50K engraftment rates of 93±7%, 91±8% & 82±8% respectively and 1-Yr OS of 86±9% and DFS at 86±9%.

Disclosures: Brian Wang, Lawrence Petz and Robert Chow are employees of StemCyte.; Brian Wang, Lawrence Petz and Robert Chow have stock options of StemCyte.; Robert Chow is a Board Director of StemCyte.

Author notes

*

Corresponding author