Objectives

To compare double unrelated umbilical cord blood and HLA-mismatched (haploidentical) related donor transplantations for the treatment of leukemia and lymphoma in adults.

Background

Earlier studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for Reduced-Intensity Conditioning (RIC) hematopoietic cell transplants (HCT) in patients that do not have access to either an HLA-matched sibling or suitably HLA-matched unrelated donor. Both haplo-BM and dUCB grafts are more accessible for patients lacking an HLA-matched donor.

This study assessed the hypothesis that progression-free survival at two years after haplo-BM transplantation is similar to the progression-free survival after dUCB transplantation.

Participants

Patients aged 18 to 70 years with chemotherapy-sensitive lymphoma or acute leukemia in remission were assigned to undergo double unrelated umbilical cord blood (n = 186) or HLA-mismatched (haploidentical) related donor transplantation (n = 182). Of the 186 patients randomized to the dUCB arm, 172 received the treatment as assigned. Of the 182 patients randomized to the haplo-BM arm, 153 received the treatment as assigned.

Enrolled patients had a Karnofsky score greater than or equal to 70% and adequate physical function of the cardiac, hepatic, renal, and pulmonary systems. Furthermore, subjects had one of the following: Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR); Acute Myelogenous Leukemia (AML) in CR1; Acute Leukemias in 2nd or subsequent CR; Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR; adult T-cell leukemia/lymphoma in first or subsequent CR; Burkitt's lymphoma: second or subsequent CR; chemotherapy-sensitive Lymphoma.

Design

Participants were enrolled in the study between June of 2012 and June 2018 and randomized 1:1 using random block sizes stratified by transplant centers (n=33). The primary end point was 2-year progression-free survival (PFS).

The donor and recipient in the haplo-BM arm were HLA identical for at least one antigen (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1.

Patients enrolled in the dUCB arm had to have two UCB units with a minimum of 1.5 x 10^7/kg pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units, the minimum pre-cryopreserved total nucleated cell dose of each unit was at least 2.0 x10^7/kg. Furthermore, units were HLA matched at a minimum of 4/6 to the recipient at HLA -A, HLA-B (at low resolution using DNA based typing), and HLA -DRB1 (at high resolution using DNA based typing).

All participants received a conditioning regimen/preparative regimen prior to transplant as well as a GVHD prophylaxis regimen.

Participants randomized to the dUCB arm received the following conditioning regimen: fludarabine cyclophosphamide, and either 200 or 300 cGy total-body irradiation (TBI). GVHD prophylaxis started 3 days prior to transplantation and included 15 mg/kg mycophenolate mofetil three times daily (with a maximum daily dose of 3 g) through day 35 and cyclosporine adjusted to maintain a trough level of 200 to 400 ng/mL through day 100 and tapered by 10% weekly until discontinued between days 180 and 200.

Participants randomized to the haplo-BM received the following conditioning regimen: cyclophosphamide, fludarabine, and 200 cGy TBI. GVHD prophylaxis consisted of 50 mg/kg cyclophosphamide IV daily on days 3 and 4, 15 mg/kg mycophenolate mofetil three times daily from days 5 through 35, and tacrolimus adjusted to maintain a concentration of 5 to 15 ng/mL from day 5 through day 180.

Conclusions

There were no significant differences seen in progression-free survival between double unrelated umbilical cord blood and HLA-mismatched (haploidentical) related donor transplantations for leukemia or lymphoma. Analyses of secondary end points, including overall survival, favored haploidentical BM donors.

Fuchs EJ, O'Donnell PV, Eapen M, et al. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021;137(3):420-428. doi:10.1182/blood.2020007535

Request Data

Please note that researchers must be registered on this site to submit a request, and you will be prompted to log in. If you are not registered on this site, you can do so via the Request button. Registration is quick, easy and free.