ALBERT

Description: Stage of the disease at transplant is critical for outcome after unrelated donor umbilical cord blood transplantation (UD-UCBT). The results of UD-UCBT in adults transplanted early in the course of their disease are unclear. Thus, UD-UCBT remains as the last resort for most patients. The major aim of this report was to study the outcome of a series of adult patients with hematologic malignancies undergoing UD-UCBT early in the course of their disease in a single institution. From May 1997 to May 2004, 40 patients in early disease stages underwent UD-UCBT. All patients received thiotepa, busulfan (orally in 29, intravenously in 11), cyclophosphamide, and antithymocyte globulin (Lymphoglobulin in 24 and Thymoglobulin in 16) as conditioning, cyclosporine and prednisone for graft-versus-host disease (GVHD) prophylaxis, and filgrastim to fasten engraftment. Diagnosis were chronic myeloid leukemia in chronic phase in 14 cases, high-risk acute lymphoblastic leukemia in 14 (12 in CR1, 1 in CR2, and 1 in CR3), high-risk acute myeloblastic leukemia in 8 (7 in CR1 and 1 in CR2), and high-risk myelodysplastic syndrome in 4 (3 untreated and 1 in CR1). Median age was 27 years (range, 16–46). The degree of HLA match (HLA-A and -B by serology and -DRB1 by high-resolution DNA typing) was 6/6 in 2 (5%), 5/6 in 18 (45%), and 4/6 in 20 cases (50%). The median number of nucleated and CD34+ cells infused was 1.8 x 107/kg (range, 0.9–4) and 0.8 x 105/kg (range, 0.1–5.7) respectively. Median time to PMN above 0.5 x 109/L and to platelets above 20 x 109/L was 22 days (range, 13–44) and 69 days (range, 32–188), and the cumulative incidence of myeloid and platelet engraftment was 90% (95% CI, 81–99%) and 70% (95% CI, 57–86%), respectively. Time to myeloid engraftment showed a direct relationship with the number of CFU-GM and CD34 cells cryopreserved (P = .02 and .01 respectively) and infused (P = .0001 and .0004 respectively). Platelet engraftment was faster in patients receiving grafts with a higher number of CFU-GM (P = .005) and CD34+ cells (P = .04), in those receiving Thymoglobulin (P = .02) and in those not developing acute GVHD above grade II (P = .04). Eight patients (20%) developed acute GVHD above grade II, and 9 of 25 patients at risk had extensive chronic GVHD. Patients receiving Thymoglobulin had a lower risk of acute GVHD (P = .0003). With a median follow-up of 33 months (range, 3–87), the probability of disease-free survival (DFS) at 3 years was 48% (95% CI, 30–66%) and was related directly to age (P = .004) and inversely to the development of acute GVHD above grade II (P = .004). The probability of DFS at 3 years was 66 % for patients younger than 31 years and 54% for those not developing acute GVHD above grade II. Cell dose, degree of HLA mismatch, and diagnosis did not clearly influence DFS. These results compare to those obtained after matched unrelated donor bone marrow transplantation, and suggest that UD-UCBT is a reasonable first-line option for adults with hematologic malignancies requiring transplantation and lacking a HLA-matched sibling donor.