97080 Würzburg, Abbreviations used in this paper: 2D, two-dimensional; 3D, three-dimensional; ALCAM, activated leukocyte adhesion molecule; MMP, matrix metalloproteinase; MT-MMP, membrane-type MMP; NCAM, neural cell adhesion molecule; ROCK, Rho-associated serine/threonine kinase substrate; uPA, urokinase-type plasminogen activator; uPAR, receptor of uPA.

The impact of early human cytomegalovirus (HCMV) replication on leukemic recurrence was evaluated in 266 consecutive adult (median age, 47 years; range, 18-73 years) acute myeloid leukemia patients, who underwent allogeneic stem cell transplantation (alloSCT) from 10 of 10 high-resolution human leukocyte Agidentical unrelated (n ‫؍‬ 148) or sibling (n ‫؍‬ 118) donors. A total of 63% of patients (n ‫؍‬ 167) were at risk for HCMV reactivation by patient and donor pretransplantation HCMV serostatus. In 77 patients, first HCMV replication as detected by pp65-antigenemia assay developed at a median of 46 days (range, 25-108 days) after alloSCT. Taking all relevant competing risk factors into account, the cumulative incidence of hematologic relapse at 10 years after alloSCT was 42% (95% confidence interval [CI], 35%-51%) in patients without opposed to 9% (95% CI, 4%-19%) in patients with early pp65-antigenemia (P < .0001). A substantial and independent reduction of the relapse risk associated with early HCMV replication was confirmed by multivariate analysis using time-dependent covariate functions for grades II to IV acute and chronic graft-versus-host disease, and pp65-antigenemia (hazard ratio ‫؍‬ 0.2; 95% CI, 0.1-0.4, P < .0001). This is the first report that demonstrates an independent and substantial reduction of the leukemic relapse risk after early replicative HCMV infection in a homogeneous population of adult acute myeloid leukemia patients.

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As the threshold nucleated cell dose for single unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared single vs. 2-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematologic malignancies. Study design specified one UCB unit if the cryopreserved total nucleated cell (TNC) dose was ≥2.5×10 7 /kg recipient weight, otherwise 2-units matched at minimum 4/6 HLA loci to the patient and 3/6 to each other were infused. Twenty-seven patients received 1 unit; 23 patients received 2 units. Median time to absolute neutrophil count (ANC) >500/μL was 24 days (95% CI 22–28 days), 25 days for 1-unit and 23 days for 2-units (p=0.99). At day 100, ANC >500/μL was 88.4% and 91.3% in the 1 and 2-unit groups (p=0.99), respectively. Three-year event free survival (EFS) was 28.6% and 39.1% in the 1 and 2-unit groups (p=0.71), respectively. Infusion of 2 units was associated with significantly lower relapse risk, 30.4% vs. 59.3% (p=0.045). Infused cell doses (TNC, CD3 + , CD34 + , CD56 + CD3 neg ) did not impact engraftment, overall survival (OS), or EFS. Taken together, single unit UCB transplantation with threshold cell dose ≥2.5×10 7 /kg recipient weight after RIC is a viable option for adults, although infusion of 2 units confers a lower relapse incidence.

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