Delayed T-cell recovery and restricted T-cell receptor (TCR) diversity after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with increased risks of infection and cancer relapse. Technical challenges have limited faithful measurement of TCR diversity following allo-HSCT. Here we combined 5′-RACE PCR with deep sequencing, to quantify TCR diversity in 28 allo-HSCT recipients using a single oligonucleotide pair. Analysis of duplicate blood samples confirmed that the frequency of individual TCRs was accurately determined. After 6 months, cord blood graft recipients approximated the TCR diversity of healthy individuals, whereas recipients of T-cell-depleted peripheral blood stem cell grafts had a 28-fold and 14-fold lower CD4+ and CD8+ T-cell diversity, respectively. After 12 months, these deficiencies had improved for the CD4+, but not the CD8+ T-cell compartment. Overall, this method provides unprecedented views of T-cell repertoire recovery after allo-HSCT and may identify patients at high risk of infection or relapse.

The influence of cell dose and human leukocyte antigen (HLA) match on doubleunit cord blood (CB) engraftment is not established. Therefore, we analyzed the impact of cell dose and high-resolution HLA match on neutrophil engraftment in 84 double-unit CB transplant recipients. The 94% sustained engraftment rate was accounted for by 1 unit in nearly all patients. Higher CD3 ؉ cell doses (P ‫؍‬ .04) and percentage of CD34 ؉ cell viability (P ‫؍‬ .008) were associated with unit dominance. After myeloablative conditioning, higher dominant unit total nucleated cell (TNC), CD34 ؉ cell, and colony-forming unit doses were associated with higher sustained engraftment and faster neutrophil recovery (P ‫؍‬ .07, P ‫؍‬ .0008, and P < .0001, respectively). Total infused TNC (P ‫؍‬ .0007) and CD3 ؉ cell doses (P ‫؍‬ .001) also significantly influenced engraftment. At high-resolution extensive donor-recipient HLA disparity was frequent, but had no influence on engraftment (P ‫؍‬ .66), or unit dominance (P ‫؍‬ .13). Although the unit-unit HLA match also did not affect sustained engraftment (P ‫؍‬ 1.0), recipients of units closely (7-10 to 10-10) HLA-matched to each other were more likely to demonstrate initial engraftment of both units (P < .0001). Our findings have important implications for unit selection and provide further insight into double-unit biology. (Blood. 2011;117(12): 3277-3285)

In women with a history of RT for HL, breast cancer is diagnosed at an earlier stage, but these women are at greater risk for bilateral disease and are more likely to die as a result of causes other than breast cancer. Our findings support close follow-up for contralateral tumors in these patients and ongoing primary care to manage comorbid conditions.

Cord blood transplantation (CB-T) is increasingly used as a treatment alternative for hematologic malignancies. However, how CB-T compares to related (RD-T) and unrelated donor transplantation (URD-T) is not established. We compared survival of 75 double unit CB-T, 108 RD-T, and 184 URD-T recipients transplanted over the same period for the treatment of hematologic malignancies. Patients had similar ages and disease-risk, and a similar percentage had acute leukemia. The incidence of day 180 transplant-related mortality (TRM) of 21% (95%CI:12-31) after CB-T was higher than that of RD-T recipients. However, this was compensated for by a low risk of TRM after day 180, and a relatively low incidence of relapse. Hence, the 2 year progression-free survival (PFS) of 55% (95%CI:45-68) after CB-T was similar to that after RD-T or URD-T (p = 0.573). In multivariate analysis, donor source had no influence on PFS, with the only significant factors being recipient age and disease-risk. In a sub-analysis of 201 patients with acute leukemia, CB-T, RD-T and URD-T recipients also had similar 2 year disease-free survival (p = 0.482). These data provide strong support for the further investigation of double unit CB grafts as an alternative hematopoietic stem cell source.

Manifestations and risk factors of graft-versus-host disease (GVHD) after double-unit cord blood transplantation (DCBT) are not firmly established. We evaluated 115 DCBT recipients (median age 37 years) transplanted for hematologic malignancies with myeloablative or non-myeloablative conditioning and calcineurin-inhibitor/ mycophenolate mofetil immunosuppression. Incidences of day 180 grade II–IV and III–IV acute GVHD (aGVHD) were 53% (95%CI: 44–62) and 23% (95%CI: 15–31), respectively, with a median onset of 40 days (range 14–169). Eighty percent of patients with grade II–IV aGVHD had gut involvement, and 79% and 85% had day 28 treatment responses to systemic corticosteroids or budesonide, respectively. Of 89 engrafted patients cancer-free at day 100, 54% subsequently had active GVHD with 79% of those affected having persistent or recurrent aGVHD or overlap syndrome, whereas late GVHD in the form of classical chronic GVHD was uncommon. Notably, grade III–IV aGVHD incidence was lower if the engrafting unit human leukocyte antigen (HLA)-A,-B,-DRB1 allele match was > 4/6 to the recipient (HR 0.385, p = 0.031), whereas engrafting unit infused nucleated cell dose and unit-unit HLA-match were not significant. GVHD after DCBT was common in our study, predominantly affected the gut, had a high therapy response, and late GVHD frequently had acute features. Our findings support the consideration of HLA- A,-B,-DRB1 allele donor-recipient (but not unit-unit) HLA-match in unit selection, a practice change in the field. Moreover, new prophylaxis strategies that target the gastrointestinal tract are needed.