[Clinical features and risk factors of hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation].

Objective: To explore the relative risk factors, clinical intervention and prognosis of hemorrhagic cystitis (HC) in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: From January 1 2010 to May 31 2017, 425 patients with allo-HSCT received a retrospective analysis. Results: ①Among the 425 patients, 262 were male and 163 were female. The median age was 26 (2-56) years old. There were 138 cases of acute myeloid leukemia (AML) , 96 cases of acute lymphoblastic leukemia (ALL) , 29 cases of myelodysplastic syndrome (MDS) , 98 cases of severe aplastic anemia (SAA) and 64 cases of chronic myeloid leukemia (CML) . 221 cases of sibling match transplantation, 89 cases of unrelated donor transplantation and 115 cases of haplotype transplantation. ②108 patients (25.41%) developed HC, with the median time of onset of 32 (3-243) days and the median duration of 20 (3-93) days; 33 cases (30.56%) were grade Ⅰ, 49 cases of grade Ⅱ (45.36%) , 21 cases (19.44%) of grade Ⅲ, and 5 cases (4.63%) of grade Ⅳ. ③103 cases of HC were cured, 5 patients were ineffective, 12 patients died and died of transplantation related complications (infection, recurrence, severe acute GVHD, secondary implant failure) . ④Univariate analysis showed that age < 30, type of transplantation, CMV and acute GVHD were associated with the occurrence of HC after allo-HSCT. Multivariate analysis showed that acute GVHD was an independent risk factor for HC after allo-HSCT. Conclusion: Prognosis of HC after allo-HSCT was better after timely treatment.

[Impact on platelet recovery of recombinant human thrombopoietin in severe aplastic anemia patients with allogeneic hematopoietic stem cell transplantation].

Objective: To investigate and analyze the impact on PLT recovery of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of Hematology Division of General Hospital of Jinan Military Command was conducted in the 85 SAA cases who treated with allo-HSCT from January 2010 to March 2017. According to the administration of medicines for platelets, 85 patients were divided into rhTPO group (n=29), rhIL-11 group (n=27) and blank group (n=29), respectively. The median time of PLT ≥20×109/L, PLT ≥50×109/L, and PLT ≥100×109/L, the numbers of megakaryocytes in marrow smear (25±5) days after transplantation and the quantities of platelet transfusion were analyzed retrospectively. The adverse events of rhTPO and rhIL-11 groups were observed. Results: There were no significant differences in the recovery of granulocytes and PLT ≥20×109/L among the three groups (P>0.05). The time of PLT ≥50×109/L in rhTPO group was shorter than that in blank group [16.5 (11-39) d vs 22 (14-66) d, P<0.05], as well as the time of PLT ≥100×109/L [rhTPO: 23 (12-51) d; rhIL-11: 28 (12-80) d; blank group: 35 (18-86) d, P<0.05]. Platelet transfusions were also less in rhTPO group than in rhIL-11 and blank groups [20 (10-30) U, 30 (10-50) U, 35 (10-70) U, P<0.05]. The counts of megakaryocyte in rhTPO group, rhIL-11 group and blank group were 31.5 (0-200), 12 (0-142) and 11(0-187) (P<0.05), respectively. The difference between rhTPO group and rhIL-11 group was statistically significant (P<0.05), but no difference between rhIL-11 group and blank group (P>0.05). Multivariate analysis showed that rhTPO was an independent factor for platelet recovery [HR=4.01 (95%CI 1.81-9.97), P=0.010]. The rhTPO group had no obvious adverse events. Conclusion: rhTPO can promote platelet recovery of SAA patients after allo-HSCT, reduce platelet transfusion with safety.

[Modulation of umbilical cord blood mesenchymal stem cells on Treg cells in the patients with aplastic anemia].

Objective: To research the modulation of Umbilical cord blood mesenchymal stem cells on the number and function of Treg cells in the patients with aplastic anemia, as well as the expression of LFA-1 on Treg cells. Methods: A total of 20 newly diagnosed NSAA patients were collected from May 2015 to Jun 2016 in Department of Hematopathy, General Hospital of Jinan Military, and 10 healthy volunteers were recruited as controls. Separation of the patients and controls with peripheral blood mononuclear cells were divided into two groups, including PBMCs culture alone, PBMCs co-culture with UC-MSCs, application of flow cytometry detect respectively the proportion of the Treg cells and the expression of LFA-1 on Treg cells under different culture conditions. The Treg cells and CD4(+) CD25(-)T lymphocyte were separated by magnetic cell sorting (MACS) system, CFSE label CD4(+) CD25(-)T lymphocyte, comparing the inhibitive function of Treg cells on CD4(+) CD25(-)T lymphocyte with or without co-culture with UC-MSCs. Results: The intensity of fluorescence expression of LFA-1 on T lymphocyte in aplastic anemia increased obviously((71.4±10.1)vs(52.5±8.7) , P=0.002), but the LFA-1 expressed on Treg cells had no significant difference(P=0.199). After co-cultured with UC-MSCs, the proportion of LFA-1 on Treg cells in aplastic anemia reduced greatly ((20.96±1.76)% vs(44.26±1.19)%, P=0.012), at the same time, UC-MSCs increased the proportion of Treg cells obviously ((5.33±1.14)%vs(1.94±0.65)%, P=0.003), but the effect of Treg cells on the mean frquency of dividing CD4(+) CD25(-)T lymphocyte had no significant difference with or without co-culture with UC-MSCs(P=0.290). Conclusions: The intensity of fluorescence expression of LFA-1 on lymphocyte in aplastic anemia increases obviously, indicating the possible pathogenesis of AA. UC-MSCs inhibit the expression of LFA-1 on Treg cells and enhance the proportion of Treg cells, but UC-MSCs doesn't directly improve the immunosuppression of single Treg cells.

Dysregulated module approach identifies disrupted genes and pathways associated with acute myelocytic leukemia.

OBJECTIVE: To identify disrupted genes and pathways involved in acute myelocytic leukemia (AML) by systematically tracking the dysregulated modules across normal and AML conditions. MATERIALS AND METHODS: In this study, we firstly integrated the protein interaction data and expression profiles to infer and reweight the normal and AML networks using Pearson correlation coefficient (PCC). Next, clustering-based on maximal cliques (CMC) approach and a maximum weight bipartite matching method were implemented to infer the condition-specific modules and capture the disturbed modules, respectively, from two conditional networks. Then, the gene compositions and functional enrichment analysis were performed to identify the dysregulated genes and pathways. Finally, reverse transcription polymerase chain reaction (RT-PCR) was implemented to study the expression level of several key genes in AML patients. RESULTS: In two conditional-specific networks, universal changes of gene correlations were revealed, making the differential correlation density among disrupted module pairs. In this work, a total of 84 altered modules were identified by comparing modules in normal and AML networks. Functional enrichment analysis showed that genes in altered modules mainly involved in cell cycle, nucleic acids and cancer signaling process, and differentially expressed genes (DEGs) and changed gene correlations were mainly participated in natural killer cell-mediated cytotoxicity and acute myeloid leukemia pathway. The key genes, such as MYC, EGFR, MAPK1 and CCNA1, were all significantly differentially expressed in AML patients. CONCLUSIONS: This module approach effectively identifies dysregulated pathways and genes associated with AML. The considerable differences of gene correlations yield to these dysfunctional modules, and the coordinated disruption of these very modules contributes to leukemogenesis.

High-dose immunosuppressive therapy combined with cord blood infusion and non-myeloablative peripheral blood stem cell transplantation for patients with severe aplastic anemia.

OBJECTIVES: The aim of this study was to compare the clinical effective rates of high-dose immunosuppressive therapy combined with cord blood infusion (IS + CBI) and non-myeloablative peripheral blood stem cell transplantation (NSCT) for severe aplastic anemia (SAA). PATIENTS AND METHODS: Human leukocyte antigen (HLA)-mismatched patients received immunosuppressive therapy combined with IS + CBI, whereas those with HLA matches received NSCT. Clinical effective rates, hematopoietic recovery, and prevalence of complications were compared between the two groups. RESULTS: No significant difference in total effective rate or 2 years long-term survival was observed between the two groups. The total effective treatment in the NSCT, IS + CBI group was 80%, 68.75%, and the 2 years long-term survival rate in two groups was 2 years 76.66%, 68.75%, respectively. The median times of WBC > 1.0×109/L in the NSCT group was faster than that of IS + CBI group (13 vs 19 days) (p = 0.027). The median recovery times of PLT and Hb in the NSCT group was significantly faster than that of IS + CBI group (19 vs 50 days) (p = 0.00), (27 vs 57 days) (p = 0.001). The SAA group and the very SAA (VSAA) group did not show a significant difference in effective rate (76.74% vs 68.42%) (p = 0.490). In the NSCT group, two preparative regimens did not show a significant difference in effect (70.59% vs 92.31%) (p = 0.141). CONCLUSIONS: IS + CBI is applicable to HLA-mismatched patients with SAA. NSCT is the treatment of choice for patients with HLA matching alleles. Both treatment methods are effective on VSAA.