Combined effect of total nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematologic malignancies

Abstract

Both total nucleated cell (TNC) dose and human leukocyte antigen (HLA)-match affect the outcome of cord blood (CB) transplantation. However, how to prioritize these characteristics in unit selection is not established. Therefore, we analyzed the outcomes of 1061 patients who received single-unit myeloablative CB transplantation for leukemia or myelodysplasia. TNC dose and HLA-match each affected survival via their effect on transplant-related mortality (TRM); neither was associated with relapse. Therefore, TRM was the focus of multivariate analyses combining dose and HLA-match. Compared with our 1 HLA-mismatch (MM) reference group with TNC 2.5 to 4.9 x 10(7)/kg, recipients of 0 MM units had the lowest TRM regardless of dose (relative risk [RR] = 0.4, P = .019). TRM for recipients of 1- or 2-MM units with TNC 5.0 x 10(7)/kg or greater was similar to the reference group (RR = 0.8, P = .391 and RR = 1.0, P = .847) despite their greater dose. Recipients of 2 MM units with TNC 2.5 to 4.9 x 10(7)/kg had a greater TRM (RR = 1.5, P = .014), and those with 1 or 2 MM and TNC less than 2.5 x 10(7)/kg or 3 MM did substantially worse. These findings support new unit selection criteria that take into account both TNC dose and HLA-match and have important implications for the size of the global CB inventory needed to find an optimum CB graft.

Figure 1

The cumulative incidence (CI) of neutrophil engraftment by day 77 in patients given units with 0-MM (mean TNC, 4.4) or 3-MM (mean TNC, 3.9), or according to the TNC ×10⁷/kg in patients with 1- or 2-MM CB grafts. Note that the 4 TNC categories in this figure exclude those that had either 0 or 3 mismatches, accounting for the lower number of cases in each TNC group in the figure compared with Table 2.

Figure 2

CI of grades 3 to 4 aGVHD according to HLA-mismatch.

Figure 3

CI of relapse according to HLA-mismatch.

Figure 4

CI of 3-year TRM. Data are shown by TNC dose (A), HLA-mismatch (B), TNC dose and HLA-mismatch combined (C), and the Kaplan-Meier probability of disease-free survival (D). Recipients of units with either 1 or 2 mismatches were analyzed by separate TNC dose categories, whereas recipients of 0-MM units and 3-MM units were not.