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Purpose Myelofibrosis (MF) may serve as a poor prognostic factor in myelodysplastic syndromes (MDS). This study explored the impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of MDS patients with MF. Patients and Methods Three hundred and sixteen MDS patients were enrolled in this retrospective study. Based on the degree of MF, we divided the patients into 2 groups: grade 0–1 (MF-0/1) and grade 2–3 (MF-2/3) groups. The clinical features, treatments, and prognosis in MDS patients with MF were analyzed. Results Forty-three (13.6%) patients were diagnosed as MF-2/3. Complex karyotypes were more common in the MF-2/3 compared to MF-0/1 groups (P = 0.002). The overall response rate (ORR) of cytoreduction was 49.0%, along with 53.3% in the MF-0/1 and 16.7% in MF-2/3 groups (P = 0.017). In total, 141 patients underwent allo-HSCT, including 121 in the MF-0/1 and 20 in MF-2/3 groups. The median time to neutrophil reconstruction was 12 (range: 7–34) and 14 (range: 10–45) days (P = 0.005), and platelet reconstruction was 14 (range: 8–68) and 18 (range: 8–65) days (P = 0.045) in the MF-0/1 and MF-2/3 groups, respectively. However, the cumulative incidence of neutrophil and platelet engraftment achieved at day + 30 was not different between the two groups (P = 0.107, P = 0.303, respectively). Non-relapse mortality, relapse, and acute and chronic graft-versus-host disease were similar between the two groups (all P > 0.05). Among patients with allo-HSCT, the 2-year overall survival (OS) was 68.5% (95% CI: 60.1–76.9%) and 68.4% (95% CI: 47.4–89.4%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.636). Among patients without allo-HSCT, the 2-year OS was 49.9% (95% CI: 40.7–59.1%) and 19.2% (95% CI: 0–39.6%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.002). In multivariate cox analysis, complex karyotype was an unfavorable factor for relapse (HR, 4.16; P = 0.006), disease-free survival (DFS) (HR, 2.16; P = 0.020), and OS (HR, 2.47; P = 0.009) post-transplantation. Conclusion Patients with MF-2/3 have more complex karyotypes and lower ORR of cytoreduction in MDS. Among patients without allo-HSCT, patients with MF-2/3 have a worse prognosis than those with MF-0/1. However, the adverse impact of MF on prognosis may be overcome by allo-HSCT.

To compare the outcomes between peripheral blood stem cell (PBSC)+cord blood and PBSC+bone marrow (BM) grafts in the setting of haploidentical donor (HID) transplantation, 110 patients were enrolled in this retrospective study, including 54 recipients of haplo-PBSC+cord transplants and 56 recipients of haplo-PBSC+BM transplants. Chimerism analyses revealed that by day 30 post-transplantation, 94.3% of surviving patients in the haplo-PBSC+cord group had achieved full haploidentical chimerism and 5.7% had10% cord chimerism, whereas 100% of surviving patients in the haplo-PBSC+BM group had achieved full donor chimerism. The cumulative incidence of platelet engraftment at 30 days was 92.6% in the haplo-PBSC+cord group versus 89.3% in the haplo-PBSC+BM group (P =.024), that of grade II-IV acute graft-versus-host disease (GVHD) at 100 days was 31.5% versus 48.2% (P =.060), and 1-year relapse was 13.0% versus 25.0% (P =.027), nonrelapse mortality was 9.3% versus 12.5% (P =.76), disease-free survival (DFS) was 77.7% versus 62.5% (P =.028), and overall survival (OS) was 81.4% versus 69.6% (P =.046). Multivariate analysis identified haplo-PBSC+cord transplantation as a protective factor for relapse (hazard ratio [HR], .31; P =.007), DFS (HR, .40; P =.007), and OS (HR, .44; P =.016). Overall, haplo-PBSC+cord transplantation led to faster platelet engraftment, lower relapse, and superior DFS and OS compared with haplo-PBSC+BM transplantation and thus might be a better transplant mode in the setting of HID transplantation.

Purpose: Somatic mutations are common in myelodysplastic syndrome (MDS), but its risk stratification is mainly based on cytogenetics. This study was to explore the prognostic significance of somatic mutations in MDS patients with normal karyotypes. Patients and Methods: Three hundred and four patients with MDS were enrolled in this retrospective study. A genomic panel of 127 gene targets were detected by next-generation sequencing. Results: Two hundred and Eighty-one (92.4%) patients carried at least one somatic mutation, while cytogenetics identified abnormalities in 140 (46.1%) patients. The 5 most frequently mutated genes were TET2, ASXL1, EZH2, TET1, FAT1, and TET2, TP53, TET1, EP300, SF3B1 in the patients with normal karyotypes and aberrant karyotypes, respectively. When mutations detected in >5% of the whole cohort, they were included in analysis and the results showed that the frequency of TET2, TP53, ASXL1, CD101, KDM6A, SH2B3 and IL-3RA mutations was different between two groups(all P Conclusion: FAT1, IL-7R and DNMT3A mutations pretict poor prognosis in MDS patients with normal karyotypes. Key words: Somatic mutation, Next-generation sequencing, Prognosis, Myelodysplastic syndrome Disclosures No relevant conflicts of interest to declare.

SummaryLeprosy is an infectious chronic granulomatous disease caused by Mycobacterium leprae. The disease mainly affects the skin, peripheral nerves, mucosa, and viscera. The World Health Organization has reported that most countries with high endemicity have reached the goal of eliminating leprosy (defined as reaching a prevalence of

To investigate the efficacy of liposomal doxorubicin together with etoposide and high dose methylprednisolone (DEP) as a salvage therapy for adult refractory hemophagocytic lymphohistiocytosis (HLH).Total 41 patients with refractory HLH were enrolled in this study. The efficacy of treatment with DEP regimen after 2 and 4 weeks were evaluated according to the United States Midwest Cooperative HLH Group.Of 41 refractory HLH patients, 28 were males and 13 females. The median age was 31(18-62) years old. The overall response rate (ORR) was 78.1%(32/41), including 12 patients (29.3%) achieved complete remission (CR) and 20 (48.8%) achieved partial remission (PR). The underlying disease of HLH were identified in 33 patients, including 1 case of primary HLH (CR), 20 cases of lymphoma associated HLH and 12 cases of EBV associated HLH. There were still 8 cases with unknown underlying disease. The 9 patients who had no response to DEP died within 2 to 4 weeks after salvage therapy. Twenty of the 32 patients who achieved PR or CR survived to undergo subsequent chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) or splenectomy.The single-arm study suggested that DEP regimen appeared to be an effective salvage protocol for adult patients with refractory HLH.

To analyze the clinical manifestations, laboratory data, therapy, and prognosis in patients with hemophagocytic lymphohistiocytosis (HLH).A retrospective study was carried out in 192 adult patients with HLH between 2003 and 2013.Of the 192 cases, 70 cases were secondary to cancer and 64 cases secondary to infection. According to HLH-2004 criteria, the coincidence rate of indices were: fever (98.96%), high level of serum ferritin (94.27%), increased level of soluble interleukin- 2 receptor(sCD25) (94.79%), decreased or absent activity of NK cells (94.27%), cytopenias (80.73%), splenomegaly (80.21%), emophagocytosis in bone marrow, spleen or lymph nodes (74.48%), hypofibrinogenemia (50.52%), hypertriglyceridemia (37.50%). In addition, 94.27% of patients were presented with liver dysfunction, 96.35% with infections, and 75.52% with coagulopathy. Incidences of central nervous system symptoms and rash were 19.27% and 20.31%, respectively. Among cancer, infection and rheumatic group, there were statistically differences on white blood cells (WBC), platelet (PLT), sCD25, alanine aminotransferase, aspartate aminotransferase, total bilirubin and globulin(GLO) (P0.05). The differences of WBC, PLT, albumin (ALB), GLO, brain natriuretic peptide, creatinine, urea nitrogen between survival group and death group had statistical significance.The secondary HLH occurs from various underlined diseases. Cancer, especially T- cell lymphoma, is the main cause, Secondly, it is EB virus infection. The diagnostic sensitive indicators are Persistent fever, higher level of serum ferritin, low or absent NK-cell activity, and increased sCD25 were the most valuable parameters for diagnosis. Cytopenias were not common in early phase of HLH secondary to rheumatic diseases. WBC, PLT, ALB, GLO could be used as the preliminary parameters for diagnosis. Cardiac insufficiency, renal insufficiency and coagulation dysfunction play important roles in prognosis.

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. Epstein-Barr virus (EBV) is the most frequent infection associated with HLH. Some studies revealed that rituximab containing regimens is an effective treatment for EBV- HLH. But we didn’t make the similar observation in Chinese adult patients. This study was aim to describe the outcomes and tried to explain the possible causes. Methods: We performed an investigation involving 46 EBV-HLH patients. Eleven of them received treatment with rituximab plus HLH-94 protocol. The other 35 patients were only treated with HLH-94 protocol. The EBV-DNA load and survive rate of patients were used to evaluated curative effective. We identified the lineage of EBV-infected cell by immunohistochemistry (ICH) in combination with in site hybridization (ISH) in Epstein-barr Virus Encoded Rnas (EBER) for cell type-specific markers. Result: The eleven patients received 3 rituximab infusions on average (range 2-4) at a dosage of 375mg/m2 every week. We found no significant difference in EBV-DNA load between the rituximab containing regimens group and conventional HLH-94 group at diagnosis (median load was 3.2×105copies/ml vs 2.8×105copies/ml) and 4 weeks after therapy (median load 6.4×103copies/ml vs 5.5×103copies/ml). The survive rates of the two groups on 2 months, 6 months and 12 months respectively were 45.5% vs 42.9%, 27.3% vs 28.6%, 18.2% vs 20.0%. The pathological examination of tissue biopsy in the patients from rituximab containing regimens group revealed that EBER was positive in all patients. We identified the lineage of EBV-infected cell by double staining——ICH in combination with ISH. Nine of them were CD3+/EBER+, and only two of them were CD20+/EBER+. Conclusion: It suggested that rituximab may be not suitable for EBV-HLH patients in China. Most probably, EBV predominantly infects T cells in Chinese, which could explain the nonsuperiority of rituximab in Chinese adult EBV-HLH. It is necessary to make further research to demonstrate it. Disclosures No relevant conflicts of interest to declare.

Purpose: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome. It occurs as a primary or acquired disorder in a condition of chaotic and uncontrolled immune system stimulation. Recent studies showed that HLH occurs not only in children, but also in adult. Here we presented the data gathered from Chinese HLH Workgroup in order to make further understanding about the disease. Methods: We performed a multi-center study involving 613 cases of HLH patients. We analyzed the clinical features, laboratory tests, diagnosis, treatments and clinical outcomes of them. All the date came from 46 hospitals, between Jan 2006 to June 2014. Results: The median age was 29 years old (Range 1 month to 82 years old). Forty-nine cases of them were primary HLH, 489 cases were acquired HLH and the other 75 case had unknown underlying disease. Among the acquired HLH group, 211 cases were malignancy-associated HLH (M-HLH),207 cases were infection- associated HLH (I-HLH), 58 cases were macrophage activation syndrome (MAS), 9 cases were associated with pregnancy, 3 patients developed HLH after autologous hematopoietic stem cell transplantation, and one case was associated with hemolytic anemia. Over ninety percent (93.3%) of the patients had hepatic function damage. We found significant difference in some diagnostic criteria among M-HLH, I-HLH and MAS group. The mean leukocytes was (9.50±8.46)×109/L, and the mean thrombocytes was (100.69±87.61)×109/L , which were significantly higher in MAS group than the other. The brain natriuretic peptide (BNP) was higher in patients with M-HLH (5477.31±6048.08 pg/ml). The aspartate aminotransferase (AST) was and bilirubin were significantly higher in patients with I-HLH. The median survival time of 613 cases is 7 months. Until now, 258 cases of patients were still survived, 297 cases were died, and the other was lost. We observed 45 cases who underwent allogenic hematopoietic stem cell transplantation (allo-HCT), including 22 cases of primary HLH, 12 cases of M-HLH, 8 cases of EBV-HLH and 3cases with unknown underlying disease. In these allo-HCT patients, 26 cases were achieved complete remission (CR), 12 cases died from transplantation related mortality (TRM), and the other died from tumor relapse or refractory EBV infection. The dead exhibited much higher level in bilirubin, lactate dehydrogenase (LDH), creatinine, and urea nitrogen. On the contrary, they had lower leukocytes and thrombocytes counts, and hypoalbuminemia. Thrombocytopenia and hypoalbuminemia play an important role in poor prognosis. Conclusion: HLH is not only a childhood disease but also occurs in adult. It associated with many underlying conditions. Lymphoma and EBV infection were two major causes of acquired HLH. Hepatic function damage is one of the most typical HLH clinical manifestations, and it tends to be more serious for patients with I-HLH. In addition, the blood cells of the patients with MAS may not reduce in the early phase; and the patients with M-HLH are easy to catch cardiac dysfunction. Acquired HLH is still a high mortality disease, and allo-HCT is one of the effective means of treatment for acquired HLH. Thrombocytopenia and hypoalbuminemia play an important role in poor prognosis. Disclosures No relevant conflicts of interest to declare.