TY - JOUR
T1 - Busulfan/melphalan/antithymocyte globulin followed by unrelated donor cord blood transplantation for treatment of infant leukemia and leukemia in young children
T2 - The Cord Blood Transplantation study (COBLT) experience
AU - Wall, Donna A.
AU - Carter, Shelly L.
AU - Kernan, Nancy A.
AU - Kapoor, Neena
AU - Kamani, Naynesh R.
AU - Brochstein, Joel A.
AU - Frangoul, Haydar
AU - Goyal, Rakesh K.
AU - Horan, John T.
AU - Pietryga, Daniel
AU - Wagner, John E.
AU - Kurtzberg, Joanne
N1 - Funding Information:
We thank the COBLT banks for the banking and storage of cord blood for transplantation and the many individuals at the transplant institutions who supported the children through their transplantations and participated in this trial. Supported by a contract from the National Heart, Lung and Blood Institute (N01-HB-67132 [S.L.C.], N01-HB 67135 [N.K.], N01-HB 67139 [J.E.W.], and N01-HB-67138 [J.K.]).
PY - 2005/8
Y1 - 2005/8
N2 - 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 × 107 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 × 105 CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/μL) 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.
AB - 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 × 107 nucleated cells per kilogram (range, 4.6-29.2) and 2.6 × 105 CD34+ cells per kilogram (range, 0.7-8.3). The cumulative incidence (CINC) of neutrophil recovery (absolute neutrophil count >500/μL) 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.
KW - Acute leukemia
KW - Busulfan
KW - Children
KW - Cord blood
KW - Melphalan
KW - Transplantation
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U2 - 10.1016/j.bbmt.2005.05.003
DO - 10.1016/j.bbmt.2005.05.003
M3 - Article
C2 - 16041314
AN - SCOPUS:22344435686
SN - 1083-8791
VL - 11
SP - 637
EP - 646
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 8
ER -
