We hypothesized that clinical risk factors could be identified within 2 weeks of onset of severe (stage 3 or 4) acute gut GVHD for identifying a patient population with a very poor outcome. Among 1,462 patients who had allogeneic hematopoietic cell transplantation (HCT) between January 2000 and December 2005, 116 (7.9%) developed stage 3–4 gut GVHD. The median time to onset of stage 3–4 gut GVHD was 35 (4–135) days after allogeneic HCT. Eighty-five of the 116 patients (73%) had corticosteroid-resistance before or within 2 weeks after the onset of stage 34 gut GVHD. Significant risk factors for mortality included corticosteroid-resistance (HR=2.93; p=0.0005), age >18 years (HR=4.95; p=0.0004), increased serum bilirubin (HR 2.53; p=0.0001), and overt gastrointestinal bleeding (HR 2.88; p=0.0004). Among patients with stage 3–4 gut GVHD, the subgroup with 0, 1 or 2 risk factors had a favourable prognosis, whereas the subgroup with 3 or 4 risk factors had a dismal prognosis. This information should be considered in designing future studies of severe gut GVHD and in counseling patients about prognosis.

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Umbilical cord blood (CB) is increasingly used as an alternative source of stem cells in adult unrelated transplantation. Although registry studies report similar overall outcomes in comparison with BM/PB, comparative studies focusing on severe infections and infection-RM (IRM) with a long follow-up are scarce. A total of 434 consecutive unrelated transplants (1997)(1998)(1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009) were retrospectively analyzed to compare overall outcomes, incidence and risk factors of severe viral and invasive fungal infections in CB (n = 65) vs BM/PB recipients (n = 369). The 5-year OS was 38 vs 43%, respectively (P = 0.2). CB transplantation (CBT) was associated with a higher risk of invasive aspergillosis (100-days-cumulative incidence 16 vs 6%, P = 0.04) and CMV infection without differences in RM. No statistically significant differences were found regarding NRM (NRM of 38% in CB vs 37% in BM/PB at 1 year) nor IRM (30% in CB vs 27% in BM/PB at 1 year). In the overall population, NRM and IRM improved in more recent years. In adults who receive a single CBT, the risk of severe infections is increased when compared with unrelated BM/PB recipients, but mortality from infections is similar, leading to similar NRM and survival. INTRODUCTIONInfections are a major concern after allo-HSCT, and the main cause of mortality in at least 35-45% of deaths.1-7 The use of unrelated donors (UD) in adults increases the risk of severe infectious complications, although recent reports have found similar survival with matched sibling and UD allo-HSCT in the setting of specific diseases, such as AML. 8,9 Moreover, the use of cord blood (CB) as an alternative source of HSC in adults who lack an HLA-matched UD BM or PB has shown to be a valid alternative for an allo-HSCT. Recent studies have shown that similar NRM and OS can be achieved with CB if an accurate choice of the CB unit(s) is made, in comparison with other alternative donor sources.10-15 However, slow hematologic and immune recovery after CB transplantation (CBT) still remains a concern, and a high rate of serious pre and post-engraftment infections has been reported. However, few studies have actually compared the incidence of severe infections and infection-RM (IRM) of adult CBT recipients as opposed to UD BMT/PBT.For this purpose, and as a continuation of a previously published study by our group, 16 we performed a multicenter 12-year retrospective study to analyze the impact of the source of HSC for UD transplantation, including single CBT and BM/PBT on overall transplantation outcomes, especially. We also analyzed the

Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury. We conducted an observational pilot study to provide data for the potential design of a randomized study of lithium. Twenty patients with steroid refractory intestinal GVHD meeting enrollment criteria were given oral lithium carbonate. GVHD was otherwise treated per current practice, including 2 mg/kg per day of prednisone equivalent. Seventeen patients had extensive mucosal denudation (extreme endoscopic grade 3) in the duodenum or colon. We observed that 8 of 12 patients (67%) had a complete remission (CR) of GVHD and survived more than 1 year (median 5 years) when lithium administration was started promptly within 3 days of endoscopic diagnosis of denuded mucosa. When lithium was started promptly and less than 7 days from salvage therapy for refractory GVHD, 8 of 10 patients (80%) had a CR and survived more than 1 year. In perspective, a review of 1447 consecutive adult HCT patients in the preceding 6 years at our cancer center showed 0% one-year survival in 27 patients with stage 3–4 intestinal GVHD and grade 3 endoscopic appearance in the duodenum or colon. Toxicities included fatigue, somnolence, confusion or blunted affect in 50% of the patients. The favorable outcomes in patients who received prompt lithium therapy appear to support the future conduct of a randomized study of lithium for management of severe GVHD with extensive mucosal injury.Trial Registration: ClinicalTrials.gov NCT00408681