Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies

Abstract

As the threshold nucleated cell dose for one-unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared one- vs two-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematological malignancies. Study design specified one-UCB unit if the cryopreserved total nucleated cell (TNC) dose was 2.5 × 10(7)/kg recipient weight, otherwise two units matched at minima of 4/6 HLA loci to the patient and 3/6 to each other were infused. A total of 27 patients received one unit; 23 patients received two units. Median time to ANC >500/μL was 24 days (95% confidence interval 22-28 days), 25 days for one unit and 23 days for two units (P=0.99). At day 100, ANC >500/μL was 88.4 and 91.3% in the one- and two-unit groups (P=0.99), respectively. Three-year EFS was 28.6% and 39.1% in the one- and two-unit groups (P=0.71), respectively. Infusion of two units was associated with a significantly lower relapse risk, 30.4% vs 59.3% (P=0.045). Infused cell doses (TNC, CD3(+), CD34(+) and CD56(+)CD3(neg)) did not impact on engraftment, OS or EFS. Taken together, one-unit UCB transplantation with a threshold cell dose 2.5 × 10(7)/kg recipient weight after RIC is a viable option for adults, although infusion of two units confers a lower relapse incidence.

Trial registration: ClinicalTrials.gov NCT00003335.

Figures

Figure 1. Donor Chimerism

Percentage donor chimerism obtained by day of transplantation. Gray squares represent 1-unit transplant recipients and black diamonds represent the dominant unit in the 2-unit transplant recipients.

Figure 2. Engraftment of ANC >500

A) Comparison of the cumulative engraftment rate (predominant chimerism as defined >60%) between the 1-unit and 2-unit groups estimated, accounting for competing risks. B) Cumulative incidences of platelet recovery between the 1-unit and 2-unit groups estimated, accounting for competing risks. C) Cumulative incidence of neutrophil recovery (ANC >500) estimated, accounting for competing risks in the one vs two unit groups.

Figure 2. Engraftment of ANC >500

A) Comparison of the cumulative engraftment rate (predominant chimerism as defined >60%) between the 1-unit and 2-unit groups estimated, accounting for competing risks. B) Cumulative incidences of platelet recovery between the 1-unit and 2-unit groups estimated, accounting for competing risks. C) Cumulative incidence of neutrophil recovery (ANC >500) estimated, accounting for competing risks in the one vs two unit groups.

Figure 2. Engraftment of ANC >500

A) Comparison of the cumulative engraftment rate (predominant chimerism as defined >60%) between the 1-unit and 2-unit groups estimated, accounting for competing risks. B) Cumulative incidences of platelet recovery between the 1-unit and 2-unit groups estimated, accounting for competing risks. C) Cumulative incidence of neutrophil recovery (ANC >500) estimated, accounting for competing risks in the one vs two unit groups.

Figure 3. OS and EFS

Kaplan-Meier estimate for OS (A, C) and EFS (B, D) for all patients (A, B), and according to number of units transplanted for all pts (C, D), respectively. Hashed line indicates 95% CI (A & B).

Figure 3. OS and EFS

Kaplan-Meier estimate for OS (A, C) and EFS (B, D) for all patients (A, B), and according to number of units transplanted for all pts (C, D), respectively. Hashed line indicates 95% CI (A & B).

Figure 3. OS and EFS

Kaplan-Meier estimate for OS (A, C) and EFS (B, D) for all patients (A, B), and according to number of units transplanted for all pts (C, D), respectively. Hashed line indicates 95% CI (A & B).

Figure 3. OS and EFS

Kaplan-Meier estimate for OS (A, C) and EFS (B, D) for all patients (A, B), and according to number of units transplanted for all pts (C, D), respectively. Hashed line indicates 95% CI (A & B).