Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation: A retrospective multicenter study of Turkish hematology research and education group (ThREG).

Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15-71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS.

TcRαß-depleted haploidentical transplantation results in adult acute leukemia patients.

INTRODUCTION: The use of αß+ T-cell-depleted grafts is a novel approach to prevent graft failure, graft-versus-host disease (GVHD), and non-relapse mortality (NRM) in patients undergoing haploidentical hematopoietic stem cell transplantation. PATIENT AND METHOD: Thirty-four patients with acute leukemia and lacking a match donor were treated with αß T-cell-depleted allografts from haploidentical family donors. A total of 24 patients had acute myeloid leukemia (AML) and 10 had acute lymphoblastic leukemia. 84.4% of patients were in the high-risk group, and 55.9% were not in remission. The preparative regimen included thiotepa, melphalan, fludarabine, and anti-thymocyte globulin-Fresenius. Grafts were peripheral blood stem cells engineered by TcR-alpha/beta depletion. RESULTS: Neutrophil and platelet engraftment was achieved on days +12 (range, 10.5-15) and +11 (range, 10-12). All but three patients were engrafted with full donor chimerism. Grade III-IV acute GVHD occurred in two (5.9%) patients and chronic GVHD in two (6.1%). Disease-free survival and overall survival were 42 and 54% at 1 year, respectively. AML as disease type (HR: 4.87, 95% CI: 1.50-15.87) and mother as donor (HR: 1.05, 95% CI: 1.00-1.11) were found to be independent risk factors on patient survival. Mortality and NRM in the first 100 days were 5 of 34 (14.7%) and 4 of 34 (11.7%). Relapse was the main cause of death (56.3%). T-cell reconstitution appears to be faster than that reported in published data with CD3/CD19-depleted grafts. CONCLUSION: αß T-cell-depleted haploidentical transplantation may be a good alternative for high-risk patients if there are no human leukocyte antigen matched donors.

Retrospective analysis of adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation: A multicenter experience of daily practice.

Compared to pediatric age group, the prognosis of adult acute lymphoblastic leukemia (ALL) is still dismal even in patients receiving allogeneic hematopoietic cell transplantation (AHCT). We retrospectively analyzed 205 adults (male: 122; female: 83) with ALL who underwent AHCT. Median age of patients was 28 (18-59). Fifty-two patients had Ph(+) ALL. The estimated relapse-free and overall survival (OS) of the study cohort at 1, 2 and 3 years were 52.3%/63.9%, 42.9%/49.5% and 39.9%/45.6%, respectively. On multivariate analysis, first complete remission at the time of AHCT, TBI-based conditioning and development of chronic graft-versus-host disease were only factors, which were significantly associated with prolonged OS.

Ratio of metastatic to examined lymph nodes is a predictor of mortality in locally advanced gastric cancer treated chemo-radiotherapy.

BACKGROUND/AIMS: To evaluate whether the ratio between the number of metastatic lymph nodes and the number of total removed lymph nodes (MLR) is related survival in patients with locally advanced (stage 3) gastric cancer treated chemo-radiotherapy. METHODOLOGY: We included 179 patients with locally advanced lymph node-positive gastric cancer treated chemo-radiotherapy within this study. The cut-off values, area under curve (AUC), sensitivity, and specificity were calculated using the receiver operating characteristic (ROC) curve technique for MLR. RESULTS: The sensitivity and specificity of MLR for mortality were 71.54% and 51.79%, respectively, when the cutoff level was accepted as the ratio ≥ 0.3. The AUC for the predictive value of MLR with regard to mortality was 0.609 (95% confidence interval [CI]: 0.533-0.681, p: 0.0135). Overall survival rates were significantly lower in patients with high MLR than in those with low MLR (15 months vs. 35 months, p: 0.002, respectively). In multivariate analysis, overall survival rates were significantly associated with MLR status (low or high). CONCLUSION: The simple and easily obtainable MLR is an independent predictor for mortality in patients with locally advanced gastric cancer even if chemo-radiotherapy, which is known to increase local control, was given.

Is human kallikrein-11 in gastric cancer treated with surgery and adjuvant chemoradiotherapy associated with survival?

Human kallikreins (hKs) have been reported to be involved in human cancers, and several hKs are promising biomarkers of various cancers, such as prostate, ovarian, breast, and testicular cancer. In the present study, we aimed to evaluate the prognostic value of immunohistochemical expression of hK11 in patients with gastric cancer. The study included 55 (36 men and 19 women; 58 ± 10 years of mean age) patients with gastric cancer treated with surgery and adjuvant chemoradiotherapy. Tissue sections were evaluated immunohistochemically with a monoclonal anti-hK11 antibody. Of the 55 patients, 35 (63.6%) were hK11-positive and 20 (36.4%) were hK11-negative. Disease-free and overall survival rates were significantly higher in patients with hK11 positive than in those with hK-11 negative expression (24 months vs. 11 months, p: 0.043; 29 months vs. 13 months, p: 0.038, respectively). In conclusion, hK11 expression in gastric cancer appears to be associated with a better prognosis. hK11 may be a prognostic biomarker of gastric cancer. On the other hand, it is needed to elucidate the mechanisms underlying the regulation of hK11 expression in gastric cancer.