Evolving concepts in prognostic scoring of chronic GvHD.

Chronic GvHD (cGvHD) remains one of the most complex and challenging complications after allogeneic hematopoietic cell transplantation. Emerging knowledge about the clinical manifestations and associated organ involvement of cGvHD has led to the establishment of prognostic parameters for post-transplant survival among affected allograft recipients. Studies employing the pre-National Institutes of Health (NIH) consensus data on cGvHD incidence and its risks have led to development of the CIBMTR's cGvHD risk stratification, which serves as the most refined and validated prognostic tool for estimating survival of patients with cGvHD. However, cGvHD global severity scoring has recently evolved as a powerful prognostic tool for patient survival in the post-NIH consensus era. Current use of the substantially redefined NIH criteria of cGvHD diagnosis and measurements of its severity makes it challenging to interpret prognostic scoring systems generated in the pre-NIH era. Some of the pre-NIH prognostic parameters, however, appear to retain their significance in predicting survival independently from the NIH global severity score. Thus, future analyses of prospective cohorts of patients with cGvHD defined by NIH consensus criteria will be critical in reconciling and integrating various prognostic scoring systems of cGvHD.

Improving outcomes after allogeneic hematopoietic cell transplantation for Hodgkin lymphoma in the brentuximab vedotin era.

Allogeneic hematopoietic cell transplantation (alloHCT) remains a valuable treatment alternative for relapsed/refractory (R/R) Hodgkin lymphoma (HL). Data on alloHCT outcomes in the era of new HL therapies are needed. We evaluated 72R/R HL patients who received reduced intensity conditioning alloHCT and compared the time periods 2009-2013 (n=20) with 2000-2008 (n=52). Grafts included HLA-matched sibling (35%), unrelated donor (8%) and umbilical cord blood (56%). In the recent period, patients more often received brentuximab vedotin (BV, 60% vs 2%), had fewer comorbidities (Sorror index 0: 60% vs 12%) and were in complete remission (50% vs 23%). Median follow-up was 4.4 years. Three-year PFS improved for patients treated between 2009 and 2013 (49%, 95% CI 26-68%) as compared with the earlier era (23%, 95% CI 13-35%, P=0.02). Overall survival (OS) at 3 years was 84% (95% CI 57-94%) vs 50% (95% CI 36-62%, P=0.01), reflecting lower non-relapse mortality and relapse rates. In multivariate analysis mortality was higher among those with chemoresistance (HR 3.83, 95% CI 1.38-10.57), while treatment during the recent era was associated with better OS (HR for period 2009-2013: 0.24, 95% CI 0.07-0.79) and PFS (HR 0.46, 95% CI 0.23-0.92). AlloHCT in patients with R/R HL is now a more effective treatment than previously.

GvHD after umbilical cord blood transplantation for acute leukemia: an analysis of risk factors and effect on outcomes.

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, we analyzed 1404 umbilical cord blood transplantation (UCBT) patients (single (<18 years)=810, double (⩾18 years)=594) with acute leukemia to define the incidence of acute GvHD (aGvHD) and chronic GvHD (cGvHD), analyze clinical risk factors and investigate outcomes. After single UCBT, 100-day incidence of grade II-IV aGvHD was 39% (95% confidence interval (CI), 36-43%), grade III-IV aGvHD was 18% (95% CI, 15-20%) and 1-year cGvHD was 27% (95% CI, 24-30%). After double UCBT, 100-day incidence of grade II-IV aGvHD was 45% (95% CI, 41-49%), grade III-IV aGvHD was 22% (95% CI, 19-26%) and 1-year cGvHD was 26% (95% CI, 22-29%). For single UCBT, multivariate analysis showed that absence of antithymocyte globulin (ATG) was associated with aGvHD, whereas prior aGvHD was associated with cGvHD. For double UCBT, absence of ATG and myeloablative conditioning were associated with aGvHD, whereas prior aGvHD predicted for cGvHD. Grade III-IV aGvHD led to worse survival, whereas cGvHD had no significant effect on disease-free or overall survival. GvHD is prevalent after UCBT with severe aGvHD leading to higher mortality. Future research in UCBT should prioritize prevention of GvHD.

Predictors of clinical outcomes of resected ampullary adenocarcinoma: a single-institution experience.

BACKGROUND: In the absence of prospective data, the use of adjuvant therapy in ampullary adenocarcinoma is contingent upon the clinicopathological features which can correlate to 5-year post-operative survival and disease relapse. METHODS: We investigated the factors associated with clinical outcomes among 72 patients who underwent pancreatoduodenectomy at the Cleveland Clinic from 1995 to 2007 for histologically confirmed adenocarcinoma of the ampulla of Vater. RESULTS: R0 resection was achieved in 96% of patients (median age, 72 years; 58% males, 89% Caucasians). Nineteen patients experienced disease relapse after surgery and 61% were alive within 5 years of follow up. Thirty five percent of patients received some form of adjuvant therapy. Perineural tumor invasion (p < 0.01) and presence of ulcerated tumor on histopathology (p < 0.01) were associated with higher rates of tumor relapse and poor 5-year overall survival in multivariable analysis. Lymph node involvement (p = 0.02) also portended poor overall survival after adjustment for other covariates. Although adjuvant therapy was associated with poor clinical outcomes in univariate analysis, it demonstrated a favorable albeit non-significant trend in multivariable analysis. CONCLUSIONS: Factors associated with poor clinical outcomes in this contemporary single-institution study, included perineural invasion, tumor ulceration, and lymph node involvement. No definite conclusion could be made in regards to adjuvant treatment.