Busulfan/Melphalan/Antithymocyte Globulin Followed by Unrelated Donor Cord Blood Transplantation for Treatment of Infant Leukemia and Leukemia in Young Children: The Cord Blood Transplantation Study (COBLT) Experience

Abstract

A non-total body irradiation-containing preparative regimen was studied in young children (<4 years old) undergoing unrelated donor cord blood transplantation as part of the Cord Blood Transplantation trial for the treatment of acute lymphoblastic leukemia (n = 14), acute myeloid leukemia (n = 13), undifferentiated leukemia (n = 1), juvenile myelomonocytic leukemia (n = 2), and myelodysplastic syndromes (n = 2). Donor/recipient HLA matching based on low-/intermediate-resolution molecular typing for HLA-A and -B and high-resolution HLA-DRB1 typing was 5/6 or 6/6 (n = 21) or 4/6 (n = 11). The preparative therapy consisted of busulfan, melphalan, and antithymocyte globulin, with cyclosporine and corticosteroids for graft-versus-host disease (GVHD) prophylaxis. The median age was 1.6 years (range, 0.5-3.9 years), and the median weight was 10.5 kg (range, 5.8-19.5 kg). Cord blood grafts contained a median of 10.7 x 10 7 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 x 10(5) CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/microL) at day 42 was 0.59 (95% confidence interval [CI], 0.44-0.78) at a median of 31 days (range, 23-55 days). The CINC and Kaplan-Meier estimates of platelet engraftment at day 180 were 0.53 (95% CI, 0.34-0.69) and 0.82 (95% CI, 0.61-1.00), respectively. CINC estimates of grade III/IV acute GVHD at day 100 and chronic GVHD at 1 year were 0.25 (95% CI, 0.09-0.41) and 0.26 (95% CI, 0.09-0.44), respectively. The CINC estimate of relapse was 0.31 (95% CI, 0.16-0.47) at 2 years. With a median follow-up of 27.8 months (range, 23.4-46.7 months), the probability of survival at 1 year was 0.47 (95% CI, 0.30-0.64). A preparative regimen containing a busulfan/melphalan/antithymocyte globulin preparative regimen is well tolerated in the setting of unrelated donor cord blood transplantation for childhood leukemia and can serve as a platform preparative regimen for intensifying host immunosuppression and antileukemic therapy to allow for improved engraftment and improved relapse-free survival.

Outcome following unrelated cord blood transplant in 136 patients with malignant and non-malignant diseases: a report from the Australian and New Zealand children's haematology and oncology group

“…2,10,11,21,23,36 However, data comparisons between studies are difficult as there is heterogeneity in eligibility criteria, underlying diagnosis, treatment, supportive care plans and definitions of end points. OS in our study was 61% at 1-year post transplant and 45% at 5-years post transplant, which is comparable to earlier reports.…”

“…TRM for our entire study cohort was 25% at day 100 and 32% at 2 years, which is comparable to other studies. 2,10,11,21,23,34,36 TRM in adult recipients of UCB after a myeloablative regimen has been reported to be as high as 60%. 7,10,14,17,19,[30][31][32][33] Comparing UCBT to BMT, Rocha et al 22 compared the outcomes of 541 children transplanted for the treatment of acute leukaemia receiving a UCBT (n ¼ 99), unmanipulated BMT (n ¼ 262), or T-cell-depleted BMT (n ¼ 180).…”

Optimal management of chronic graft‐versus‐host disease in children

“…In vivo depletion of the graft with serotherapy (anti-thymocyte globulin) does appear to reduce chronic GVHD (Bacigalupo et al, 2006). In children, though, ATG is often used in the setting of unrelated cord blood transplantation, which is associated with less chronic GVHD than other alternative sources, making it difficult to determine the actual impact of ATG on chronic GVHD (Wall et al, 2005).…”

Future of cord blood for oncology uses

“…The early encouraging results led to significant growth of experience with UCB transplantation in children. [2][3][4][5][6][7][8][9][10][11] Studies comparing UCB with adult donor HSCs show that outcomes are similar, suggesting an important role for UCB as a source of stem cells in this patient population. 8,9,[12][13][14] In children, where UCB units with cell doses of 2.0 Â 10 7 /kg at cryopreservation are frequently found, engraftment has been consistently above 90% despite the number of nucleated or CD34 þ cells being about 1 log lower than in adult donor grafts.…”