High Disease-Free Survival and Enhanced Protection Against Relapse after Double-Unit Cord Blood Transplantation (DCB-T) When Compared to Unrelated Donor Transplantation (URD-T) in Patients with Acute Leukemia, MDS and CML

Background: DCB-T is an immediate alternative to URD-T for patients with high-risk acute leukemia, MDS, or advanced CML. Retrospective analyses in adult DCB-T recipients also suggest that double-unit CB grafts may be associated with a protection against relapse. However, given there are no randomized trials comparing survival after URD-T and DCB-T, this question is a subject of ongoing controversy. Methods: We evaluated 211 consecutive adult allograft recipients (153 URD-T and 58 DCB-T) aged 16-60 years transplanted 10/2005-12/2012 for acute leukemia in morphologic remission (115 AML/ biphenotypic, 52 ALL), MDS with ≤5% bone marrow blasts at work-up (n = 32), or advanced CML (n = 12). URD were 8-10/10 HLA-matched (89 10/10, 52 9/10, 12 8/10). CB grafts were 4-6/6 donor-recipient HLA-matched (6 6/6, 53 5/6, 57 4/6). All patients received either myeloablative or reduced intensity conditioning. GVHD prophylaxis was calcineurin-inhibitor/MMF based in DCB-T recipients whereas the majority of URD-T recipients (n = 138, 90%) received T-cell depleted (TCD) grafts. Results: The median ages of URD-T (46 years) and DCB-T (42 years) recipients were similar (p = 0.22) and distribution of diagnoses was also similar. Neutrophil engraftment was inferior in DCB-T (95%, median 24 days) as compared to URD-T (100%, median 11 days) recipients (p <0.001), and GVHD rates were significantly higher in DCB-T as compared to TCD URD-T recipients (data not shown). Survival end-points are shown in the Table. The median (range) follow-up of survivors are similar in URD-T (46 months, 9-96) and DCB-T (42 months, 11-88) groups. While the 6-month transplant-related mortality (TRM) was higher in DCB-T (21%) versus URD-T (8%) recipients, the 3-year TRM were similar (p = 0.860). Moreover, the 3-year relapse risk was significantly decreased in DCB-T recipients (7%, p = 0.009). DCB-T recipients had a 70% 3-year DFS (p = 0.08, Figure). Conclusions: These results provide highly encouraging preliminary data. In the absence of a large randomized trial in adult patients which will be extremely challenging to conduct in the U.S., further investigation of larger patient populations controlled for possible confounding factors is needed. However, in the interim, this data supports DCB-T (performed in centers with a strong interest in the optimal conduct of CB-T) as an immediate alternative to URD-T given the strong protection against relapse in patients with acute leukemia and other high-risk myeloid malignancies such as CML and MDS.

 

Outcome	URD-T (n = 153)	DCB-T (n = 58)	P Value
3-year TRM	25% (95%CI: 18-33)	22% (95%CI: 13-34)	0.860
3-year Relapse	22% (95%CI: 16-29)	7% (95%CI: 2-17)	0.009
3-year DFS	53% (95%CI: 45-62)	70% (95%CI: 59-83)	0.080