Abstract
Background: Combining 2 cord blood products overcomes the total nucleated cell (TNC) dose limitation and may improve clinical outcomes following allogeneic cord blood (CB) transplantation in adults. We performed a retrospective case-control study in adult patients with acute leukemia receiving myeloablative conditioning and 1 or 2 cord blood units to identify potential causes for differences in clinical outcomes following SCT and DCT and product characteristics predictive of long-term engraftment in DCT recipients.
Study Design: To evaluate 20 DCT cases, we selected 20 SCT with the largest TNC dose as controls from a cohort of 103 adult SCT patients. SCT and DCT were matched for age, sex, diagnosis, disease status, ethnicity and body weight (0.11 ≤ p ≤ 0.78) excluding patients with graft failure or previous transplants.
Results: Administered TNC dose for DCT (3.7x10e7/kg) was nearly 2-fold greater than SCT (1.9x10e7/kg, p < 0.0001) with no significant differences in post-thaw TNC recovery (p=0.13). Time to ANC > 500/uL for DCT was 17 days compared to 20 days for SCT (p<0.02). For SCT, there were 9 and 11 pts. with 1 or 2 Ag mismatch (molecular) at HLA-A,B or DRB1, respectively, (mean = 1.6 Ag mismatch). Three-way comparison of both donors and recipient for DCT also gave mean = 1.6 Ag mismatch (molecular). Overall survival (OS) at 12 months was 18% for SCT and 72% for DCT (p<0.0001) with median duration of follow-up of > 18 mos. for both groups. OS was significantly correlated with post-thaw TNC dose for SCT (p<0.04) but not for DCT (p=0.88). In the first 100 days post-transplant, infection rates for SCT (65%) and DCT (50%) were similar with no significant differences in frequency of viral, fungal or bacterial infections (p=0.74). Most importantly, infection was the primary cause of death at 100 days for SCT (9/20 patients) whereas for DCT, there were no infection-related deaths! TNC and CD34+ cell dose did not differ between engrafting and non-engrafting units, however, we found that the engrafting units had a lower absolute lymphocyte count (ALC) in 8/10 evaluable cases.
Conclusion: DCT is an effective approach to overcome the TNC dose-limiting therapeutic benefit of CB transplantation. Although 100-day post-transplant infection frequency remains high, deaths from infection are markedly reduced and OS is significantly improved in DCT recipients, however, additional studies are needed to define the mechanism. For DCT, the engrafting unit does not have a higher TNC or CD34 cell dose but paradoxically; a lower ALC dose may be predictive.
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