Objective: To explore the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (the rate-limiting enzyme of cholesterol synthesis) on the proliferation and apoptosis of chronic myelogenous leukemia (CML) cells. Methods: Both normal and CML bone marrow progenitor cells were assayed in semisolid methylcellulose culture after incubation for 24 hours in suspension culture with 10 mg*L－1 simvastatin. Also, sub-G1 cells and DNA end-labeling positive cells as apoptotic cells were identified by flow cytometry after being exposed to simvastatin for 72 hours. Results: Simvastatin selectively inhibited proliferation and induced apoptosis of CML cells, but had no much influence on normal bone marrow cells. Conclusion: CML cells are more sensitive to a short-term exposure to simvastatin than normal bone marrow cells. It will be a promisingly effective chemotherapeutic agent or in vitro purging agent in autologous stem cell transplantation for the treatment of CML.

Objective To discusses the effectiveness of tocilizumab in the treatment of hypomyopathic dermatomysositis (HDM) combined with interstitial lung disease (ILD) in children. Methods The clinical characteristic, treatment, and prognosis of HDM combined with ILD were analyzed in 2 patients. The related literatures were reviewed. Results Both ten-year-old girl and 8-year-old boy had shortness of breath after activities, but had no clinical manifestations of muscle damage; both of them had typical rash, but had nornal muscle strength and muscular tension. Laboratory tests showed the elevation of serum ferritin, lactate dehydrogenase, glutamate aminotransferase, and aspartate aminotransferase. Creatine kinase slightly increased in the initial test, and then was in the normal range in the following tests. The high resolution computed tomography showed that pulmonary interstitial lesions. HDM combined ILD was diagnosed clinically. The girl died after treatment with high-dose hormones, cyclophosphamide, cyclosporine, pirfenidone, and gamma globulin failed. The boy was stabled after conventional hormone treatment plus tocilizumab (240 mg twice). His laboratory indicators were in the normal range in the follow-up. Conclusions The clinical manifestations and laboratory indicators aren't typical in childhood HDM. The mortality is high. Combined with tocilizumab treatment is effective in one case.

BACKGROUND:Recent studies have found that stem cellpluripotency and differentiation is regulated by many long non-coding RNAs (LncRNAs). The expression and effect of LncRNA AK089560 during differentiation of stem cells is unclear. OBJECTIVE:To investigate the expression of LncRNA AK089560 in mesenchymal stem cells C3H10T1/2 undergoing osteogenic and adipogenic differentiation. METHODS:Osteogenic differentiation of mesenchymal stem cells C3H10T1/2 was induced by recombinant human bone morphogenetic protein-2 and evaluated using alkaline phosphatase staining. The adipogenic differentiation of mesenchymal stem cells C3H10T1/2 was induced by three factors (dexamethasone, indomethacin and insulin) and evaluated by oil red O staining. The dynamical expression of LncRNA AK089560 was detected by qRT-PCR assay. The AK089560 secondary structure was predicted using RNAfold software. The relationship between AK089560 and neighboring protein-coding genes was analyzed using UCSC genome browser and visualized by fancyGENE online software. RESULTS AND CONCLUSION:Over 70%of C3H10T1/2 cells were positive for alkaline phosphatase after osteogenic induction and more than 80%of the cells positive for oil red O staining after adipogenic induction. qRT-PCR results showed that the expression of LncRNA AK089560 at days 2, 4, 6 of both osteogenic and adipogenic differentiation was significantly decreased compared with the control group (P<0.05). Bioinformatics analysis showed that there was a stem-loop structure for AK089560 and sense overlap relationship between AK089560 and protein-encoding gene Sema3a. These findings indicate that LncRNA AK089560 expression is reduced during osteogenic differentiation and adipogenic differentiation, showing that AK089560 may be involved in regulating the multi-directional differentiation of stem cells.

OBJECTIVETo observe the antileukemic effect in relapse patients by infusion of donor immunocompetent cells with or without granulocyte colony-stimulating factor (G-CSF) mobilization.

METHODSTwenty patients with leukemia in relapse after allogeneic bone marrow transplantation (allo-BMT) were treated with chemotherapy followed by donor-derived lymphocytes (DDL) without G-CSF mobilization (Group A, n = 11), or donor peripheral blood progenitor cells (PBPCs) with G-CSF mobilization (Group B, n = 9).

RESULTSFive patients in Group A were in hematologic relapse. After DDL infusion, 3 of 5 patients had a temporary complete remission (CR) and relapsed after 3, 7 and 10 months, respectively. One achieved partial remission and died of interstitial pneumonia; and the other one showed no response. Another 6 patients in Group A were in cytogenetic relapse or central nerve system (CNS) leukemia, and all achieved CR and remained in disease free survival (DFS) for 10 to 98 months after DDL infusion. All 9 patients in group B were in hematologic relapse. Three patients with chronic myeloid leukemia (CML) had cytogenetic and molecular remission for 16, 35 and 51 months, respectively after PBPC infusion; and 5 patients with acute lymphoid leukemia (ALL) had CR and were still in CR for 10 to 18 months except 1 patient relapsed soon. And the other one with AML showed no response to the therapy.

CONCLUSIONDonor immunocompetent cells infusion is an effective therapy for relapsed leukemia after allo-BMT, especially for the patients with early (molecular and cytogenetic) or CNS relapse. Infusion of donor PBPC mobilized by G-CSF seems to have more potentiated graft-versus-leukemia (GVL) effect than DDL infusion.

Adolescent ; Adult ; Bone Marrow Transplantation ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Hematopoietic Stem Cell Mobilization ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; therapy ; Male ; Middle Aged ; Recurrence

OBJECTIVETo investigate the application of allogeneic peripheral blood stem cell transplantation (allo-PBSCT) in the treatment of hematologic malignancies.

METHODSBetween October 1995 and August 2001, fifty-one patients with hematologic malignancies (median age 34 years, range 5.5 approximately 52 years) received allo-PBSCT from HLA-identical (50) or 1-antigen mismatched sibling donors with conditioning regimens of TBI + CY or modified BU/CY2. Thirty-one patients were acute leukemia (AL) (15 in CR(1), 7 in CR(2) or greater, 10 in relapse including 2 relapse after allo-BMT and the other one never achieved remission); 12 chronic myeloid leukemia (CML) (CP 5, AP 2, BC 4 and relapse after allo-BMT 1); 7 MDS (RAEB 1, RAEB-T 1, AL secondary to MDS 5); Burkitt's lymphoma 1. A combination of cyclosporine and methotrexate was administered for GVHD prophylaxis.

RESULTAll patients were engrafted. The median time (range) to neutrophil >/= 0.5 x 10(9)/L and platelet >/= 20 x 10(9)/L was 14 (10 approximately 20) and 11 (7 approximately 45) days post-transplant, respectively. Grade II approximately IV acute GVHD occurred in 20/51 (39%) and grade III approximately IV aGVHD in 2 patients. Clinical chronic GVHD was diagnosed in 23 of 44 (52%) evaluable patients. Fourteen patients died: 8 died of transplant related complications, 6 of relapse. Thirty-seven patients are alive with a median follow-up of 399 (75 approximately 2 176) days, and among them 34 are in continuous complete remission, the other 3 relapsed. The 2-year probability of overall survival, disease-free survival (DFS) and relapse is 64%, 61% and 24%, respectively.

CONCLUSIONAllogeneic PBSCT is safe for both donors and recipients, and results in a rapid and stable engraftment without increase in incidence or severity of acute GVHD.

Acute Disease ; Adolescent ; Adult ; Child ; Female ; Follow-Up Studies ; Graft vs Host Disease ; etiology ; Hematologic Neoplasms ; mortality ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Male ; Middle Aged ; Survival Analysis ; Survival Rate ; Transplantation, Homologous ; Treatment Outcome

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.