Cytomegalovirus-Specific Immunity Recovers More Slowly after Cord Blood Transplantation Compared with Matched Sibling Donor Allogeneic Transplantation.

BACKGROUND: Rapid quantitative recovery of NK cells but slower recovery of T-cell subsets along with frequent viral infections are reported after umbilical cord blood (UCB) compared with matched sibling donor (MSD) hematopoietic cell transplantation (HCT). However, it remains unclear whether increased propensity for viral infections is also a result of slower recovery of virus-specific immunity after UCB as compared to MSD HCT. OBJECTIVES: We examined the differences in the function of virus-specific peripheral blood mononuclear cells (PBMC) after UCB (N=17) vs. MSD (N=9) using previously collected patient blood samples at various time points after HCT. METHODS: Interferon-gamma (IFN-γ) enzyme-linked immune absorbent spot (ELISpot) assay was used to quantify the PBMC frequencies that secrete IFN-γ in response to 11 immunopeptides from 5 common viruses. We included the patients who received the same reduced intensity conditioning regimen without ATG, no systemic glucocorticoids and had no relapse or acute/chronic graft-versus-host disease within 1 year after HCT. RESULTS: The CMV-reactive PBMC frequencies were higher in CMV seropositive vs. seronegative patients after HCT. Among CMV seropositive patients, the frequency of CMV-reactive PBMC was lower after UCB compared to MSD throughout one year of HCT. We observed no differences in virus-specific PBMC responses towards HHV6, EBV, BK, and adenovirus antigens between UCB and MSD. CONCLUSION: Our data demonstrate that the reconstitution of CMV-specific immunity is slower in CMV seropositive recipients of UCB vs. MSD HCT in contrast to other viruses which had similar recoveries. These study findings support implementation of more potent prophylactic strategies for preventing CMV reactivation in CMV seropositive patients receiving UCB HCT.

MDS disease characteristics, not donor source, predict hematopoietic stem cell transplant outcomes.

Myelodysplastic syndrome (MDS) is a heterogeneous group of hematological malignancies with considerably variable prognoses and curable only with hematopoietic cell transplantation (HCT). Few studies comparing MDS HCT outcomes between sibling and umbilical cord blood (UCB) donors exist. Using the University of Minnesota Blood and Marrow Transplant (BMT) database, we retrospectively analyzed HCT outcomes among 89 MDS patients undergoing either sibling or double UCB HCT in 2000-2013. We observed similar survival, relapse and non-relapse mortality between sibling and UCB donor sources. Relapse was increased in those with monosomal karyotype (P=0.04) and with reduced intensity conditioning (P<0.01). In summary, our data highlight similar MDS HCT outcomes regardless of donor source and support the use of UCB as an alternative donor when a sibling is unavailable.

Hemorrhagic cystitis after allogeneic hematopoietic cell transplantation: risk factors, graft source and survival.

Although hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic cell transplantation (alloHCT), its risk factors and effects on survival are not well known. We evaluated HC in a large cohort (n=1321, 2003-2012) receiving alloHCT from all graft sources, including umbilical cord blood (UCB). We compared HC patients with non-HC (control) patients and examined clinical variables at HC onset and resolution. Of these 1321 patients, 219 (16.6%) developed HC at a median of 22 days after alloHCT. BK viruria was detected in 90% of 109 tested HC patients. Median duration of HC was 27 days. At the time of HC diagnosis, acute GVHD, fever, severe thrombocytopenia and steroid use were more frequent than at the time of HC resolution. In univariate analysis, male sex, age <20 years, myeloablative conditioning with cyclophosphamide and acute GVHD were associated with HC. In multivariate analysis, HC was significantly more common in males and HLA-mismatched UCB graft recipients. Severe grade HC (grade III-IV) was associated with increased treatment-related mortality but not with overall survival at 1 year. HC remains hazardous and therefore better prophylaxis, and early interventions to limit its severity are still needed.

Clinical outcomes of AML patients relapsing after matched-related donor and umbilical cord blood transplantation.

AML relapse remains the leading cause of transplant failure among Allo-SCT recipients. A single institution study was conducted on 348 patients with AML who received an Allo-SCT from an umbilical cord blood (UCB, 222) or HLA-matched-related (RD, 126) donor between 2000-2011. Relapse after Allo-SCT occurred in 72 UCB and 32 RD transplant recipients. Three patients achieved CR after withdrawal of immune suppression with no further therapy. Fifty-two patients received intensive post-relapse therapy, defined as systemic chemotherapy (22 UCB, 7 RD), second Allo-SCT (nine UCB, two RD), or DLI±systemic chemotherapy (0 UCB, 12 RD); of these, 25% achieved CR (21% UCB vs 35% RD, P=0.16). Survival at 1 year after relapse was 22% for all patients (19% UCB vs 28% RD, P=0.36). In multivariable analysis, post-relapse mortality was lower in patients receiving intensive therapy for relapse (hazard ratio (HR)=0.4; 95% confidence interval (CI) 0.2-0.6, P<0.01) and higher in patients with peripheral blood blasts above the median (HR=3.8; 95% CI 2.2-6.6, P<0.01), active infection (HR=1.9; 95% CI 1.0-3.5, P=0.05) and non-infectious medical complications (HR=2.0; 95% CI 1.2-3.5, P=0.01). In conclusion, patients with AML relapsing after Allo-SCT who were in good-enough clinical condition to receive intensive therapy had superior short-term survival.