High Disease-Free Survival with Enhanced Protection against Relapse after Double-Unit Cord Blood Transplantation When Compared with T Cell–Depleted Unrelated Donor Transplantation in Patients with Acute Leukemia and Chronic Myelogenous Leukemia

Abstract

Double-unit cord blood (DCB) grafts are a rapidly available stem cell source for adults with high-risk leukemias. However, how disease-free survival (DFS) after DCB transplantation (DCBT) compares to that of unrelated donor transplantation (URDT) is not fully established. We analyzed 166 allograft recipients (66 8/8 HLA-matched URDT, 45 7/8 HLA-matched URDT, 55 DCBT) aged 16–60 years with high-risk acute leukemia or chronic myelogenous leukemia (CML). URDT and DCBT recipients were similar except DCBT recipients were more likely to have lower weight, non-European ancestry, and receive intermediate intensity conditioning. All URDT recipients received a CD34+ cell selected (T-cell depleted) graft. Overall, differences between the 3-year transplant-related mortality were not significant (8/8 URDT 18%, 7/8 URDT 39%, DCBT 24%, p = 0.108) whereas the 3-year relapse risk was decreased after DCBT (8/8 URDT 23%, 7/8 URDT 20%, DCBT 9%, p = 0.037). Three-year DFS was 57% in 8/8 URDT, 41% in 7/8 URDT, and 68% in DCBT recipients (p = 0.068), and the 3-year DFS in DCBT recipients was higher than that of 7/8 URDT recipients (p = 0.021). In multivariate analysis in acute leukemia patients, factors adversely associated with DFS were female gender (HR 1.68, p = 0.031), diagnosis of acute lymphoblastic leukemia (HR 2.09, p = 0.004), and 7/8 T-cell depleted URDT (HR 1.91, p = 0.037). High DFS can be achieved in adults with acute leukemia and CML with low relapse rates after DCBT. Our findings support performing DCBT in adults in preference to HLA-mismatched T-cell depleted URDT and suggest DCBT is a readily available alternative to T-cell depleted 8/8 URDT especially in patients requiring urgent transplantation.

Optimal Practices in Unrelated Donor Cord Blood Transplantation for Hematologic Malignancies

“…For example, the University of Minnesota (UMN)/Fred Hutchinson Cancer Research Center (FHCRC) reported comparable 5-year disease-free survival (DFS) after myeloablative matched related, matched URD, mismatched URD and double unit CB (dCB) transplantation 4 . Recent single center comparisons has demonstrated comparable DFS in recipients of 8/8 HLA-matched URD and CB transplants (Figures 1A/1B) 6,8 . These analyses are notable for the low rates of relapse after CBT.…”

“…Our centers frequently prioritize a CB graft over a 7/8 HLA-matched URD and this practice is strongly supported by single center analyses 4,6,8 . Knowledge of the patient’s ancestry, use of computerized programs based upon population haplotype frequencies (eg the NMDP’s Haplogic and search prognosis tool 31,32 and consultation with HLA experts can rapidly determine the likelihood of identifying an 8/8 HLA-matched URD as soon as the recipients HLA-typing and preliminary search results are obtained.…”

“…The HR for relapse in HLA-matched versus CB transplant recipients was 1.95 (95%CI: 1.16–3.27, p = 0.01), and the HR in the HLA-mismatched versus CB transplant recipients was 1.97 (95%CI: 1.04–3.73, p = 0.04). Figure 1B is a MSKCC analysis demonstrating DFS in adult acute leukemia patients (dCBT compared to T-cell depleted unrelated donor allografts) 6 . In this analysis, CBT recipients had significantly higher DFS than HLA-mismatched URD recipients.…”

Graft predominance after double umbilical cord blood transplantation: a review

“…T-cell alloreactivity towards these precursor cells may result in unit predominance but also into enhanced graft versus leukemia (GVL) (22)(23)(24). Interestingly, in adult patients suffering from hematological malignancies, dUCBT may be associated with a lower incidence of relapse (25)(26)(27)(28)(29). A possible stronger graft versus leukemia (GvL) effect might be associated with a stronger T-cell mediated GVL reactivity, due to multiple major HLA-antigen mismatches (14,29).…”

A novel reduced intensity conditioning regimen for patients with high-risk hematological malignancies undergoing allogeneic stem cell transplantation

“…4,5 Based on favorable outcomes in CBT recipients, we investigated this regimen in recipients of peripheral blood stem cells (PBSC) transplants. Twenty consecutive patients transplanted at Memorial Sloan Kettering Cancer Center between 2008 and 2013 who received Cy50/Flu150/Thio10/TBI400 were included in this retrospective analysis after obtaining approval from the center’s institutional review and privacy board.…”