3. Cord blood transplants for adults using myeloablative conditioning

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Cord blood transplantation (CBT) from unrelated donors has comparable efficacy to bone marrow transplantation (BMT) from unrelated donors and can restore hematopoiesis with acceptable toxicities in adults. We studied the clinical outcomes of 92 adult patients with hematological malignancies who received CBT from unrelated donors after myeloablative conditioning. Overall rate of high-risk patients was 58% and median follow-up was 22 months (range: 1 to 82 months). Three patients died within 28 days of CBT and primary graft failure occurred in 3 of 89 evaluable recipients. A median time of neutrophil (>500/μL) and platelet (> 20,000/μL) engraftment were 22 and 40 days. The cumulative incidence of grades II to IV and grades III and IV acute GVHD were 52% and 8%. The number of patients suffered from any type of chronic GVHD was 67 of 73 evaluable recipients (92%). Twenty-two was extensive type (30%). Despite using human leukocyte antigen (HLA)-mismatched cord blood graft in all cases, rapid tapering of immunosuppressants after transplantation and the low incidence to treat severe acute GVHD with steroid, GVHD-related death was only 2 of all 23 deaths (9%). The 1-year probability of transplant-related mortality (TRM) was 20% and the 2-year probability of relapse was 18%. The 2-year probabilities of disease-free survival (DFS) were 95% in standard-risk patients (N = 39) and 60% in high-risk patients (N = 53). We speculated that the immune reconstitution process over a period of several months after CBT might have contributed to those promising clinical results. Circulating T cell counts normalized after 3 months for CD8⁺ and 4 months for CD4⁺ in our CBT recipients, both of which were significantly faster than in previously published studies. After T cell recovery, peripheral blood T cells moved from the naive to the central memory fraction immediately, and then moved to the effector memory fraction. A naive subset of CD4⁺ T cells remained (median: 38 cells/μL on day 90, n = 12) during the first 3 months, which was significantly higher than in the BMT control (median: 9 cells/μL on day 90, n = 5, p = 0.015). To investigate whether these T cells with memory phenotype are functional, we analyzed antigen-specific T-cell recovery using cytomegalovirus (CMV) as a specific antigen. CMV-responsive CD4⁺ T cells were detected within the first 4 months in all recipients with positive CMV antigenemia (n = 13), but CD8⁺ T cells were detected only in 5 out of 13 cases. To conclude, naive cord blood T cells rapidly increased in number and adopted a memory phenotype showing cytokine-production and antigen-recognition capacity in the early phase after CBT. These data suggest that mature T lymphocytes in cord blood have unique properties and contribute to the favorable clinical outcome of CBT.