Outcomes of haploidentical bone marrow transplantation in patients with severe aplastic anemia-II that progressed from non-severe acquired aplastic anemia / 医学前沿

Severe aplastic anemia II (SAA-II) progresses from non-severe aplastic anemia (NSAA). The unavailability of efficacious treatment has prompted the need for haploidentical bone marrow transplantation (haplo-BMT) in patients lacking a human leukocyte antigen (HLA)-matched donor. This study aimed to investigate the efficacy of haplo-BMT for patients with SAA-II. Twenty-two patients were included and followed up, and FLU/BU/CY/ATG was used as conditioning regimen. Among these patients, 21 were successfully engrafted, 19 of whom survived after haplo-BMT. Four patients experienced grade II-IV aGvHD, including two with grade III-IV aGvHD. Six patients experienced chronic GvHD, among whom four were mild and two were moderate. Twelve patients experienced infections during BMT. One was diagnosed with post-transplant lymphoproliferative disorder and one with probable EBV disease, and both recovered after rituximab infusion. Haplo-BMT achieved 3-year overall survival and disease-free survival rate of 86.4% ± 0.73% after a median follow-up of 42 months, indicating its effectiveness as a salvage therapy. These promising outcomes may support haplo-BMT as an alternative treatment strategy for patients with SAA-II lacking HLA-matched donors.

Myelodysplastic syndromes combined with mature plasmacytoid dendritic cells proliferation: report of one case and review of literature / 白血病·淋巴瘤

Objective To investigate the clinical features, diagnosis, treatment and prognosis of myelodysplastic syndromes (MDS) with mature plasmacytoid dendritic cells (PDC) proliferation. Methods The clinical data of one case of MDS with excess blasts (EB)﹣1 with mature PDC proliferation in Air Force Medical Center was retrospectively analyzed, and the literature was reviewed. Results The patient′s physical examination revealed anemia and thrombocytopenia. Bone marrow smears showed 0.064 of myeloblasts and 0.152 of dendritic cells. Immunophenotyping showed two groups of abnormal proliferation cells, namely, myeloblasts and mature PDC. Decitabine treatment was given, and the red blood cells and platelets were infused intermittently. The condition of patient was basically stable. Conclusions MDS with mature PDC proliferation is extremely rare. No special clinical manifestations are found, and the diagnosis is based on bone marrow cytology and immunophenotyping. There is no standard regimen for treatment of MDS with mature PDC proliferation, and the prognosis depends on the progression of MDS.

Heterogeneity of immunomodulatory function of exosomes derived from human umbilical cord mesenchymal stem cells / 军事医学

Objective To investigate the heterogeneity of immunomodulatory function of exosomes secreted from human umbilical cord-derived mesenchymal stem cells(hUC-MSC).Methods Five different hUC-MSCs lines were isolated and cultured.Exosomes were isolated from the supernatant.The expression of specific surface markers CD9,CD63,CD81 and CD44 was detected by flow cytometry.The protein concentration of hUC-MSCs exosomes(hUC-MSCs-ex)was evaluated by the BCA assay.Concanavalin A and rhIL-2 stimulated umbilical cord blood mononuclear cells (UBMCs) from healthy donor were co-cultured at different concentrations of hUC-MSCs-ex from different cell lines for 72 h.The growth rate of UBMCs was detected by MTT assay.ELISA was used to test the levels of IFN-γ and TNF-α of the supernatants.The UBMCs co-cultured with hUC-MSCs were co-cultured with K562 cells at the ratio of 5∶1.The cytotoxic activity was calculated by MTT assay.Results hUC-MSCs-ex expressed CD9,CD63,CD81and CD44.Different hUC-MSCs lines had different regulating activities on the proliferation,secretion and killing ability of UBMCs.Conclusion hUC-MSCs-ex has heterogeneity of immunomodulatory function on UBMCs.

Primary culture of murine spleen-derived mesenchymal stem cells by explant culture / 中国比较医学杂志

Objective This study aimed to establish a reliable primary culture protocol for preparing murine spleen-derived mesenchymal stem cells ( MSCs) by tissue explant culture.Methods Healthy mouse spleens were crushed by syringe handle to harvest spleen mesenchymal tissues.Then the tiny pieces of spleen tissue were digested by collagenase II before seeded into culture flasks.The morphological characteristics of spleen tissue-derived cells were observed under the inverted microscope.Further, the surface antigen profile of the cells was analyzed by flow cytometry (FACS).The cells were induced to differentiate into osteoblasts and adipocytes.Results The murine spleen-derived MSCs exhibited a spindle-shaped appearance.The FACS results showed that the spleen-derived MSCs highly expressed CD29, CD44, CD105 and Sca-1, but weakly expressed CD11b, CD34, CD45 and Ia. In addition, the spleen-derived MSCs steadily differentiated into osteoblasts and adipocytes in the induction medium.Conclusions A method of primary culture of murine spleen-derived MSCs by explant culture is successfully established.The harvested MSCs exhibit high purity and cell proliferation ability, and provide a reliable cell model for related researches.

Primary bone lymphom:report of 7 cases and literature review / 实用肿瘤学杂志

To explore the clinic characters,treatments and prognosis of patients with primary bone lym-phoma( PLB ) .The clinical symptoms, signs, X -ray features, pathological morphology, immunophenotype and treatment of 7 patients with PLB were analyzed retrospectively and the pertinent literatures were reviewed.The re-sults showed that the main complains of 7 cases of PBL were local pain.The CT showed osteolytic bone destruc-tion and soft tissue swelling.There were 3 cases of diffuse large B cell lymphoma,1 case of Burkitt-type lympho-ma,1 case of periferal T-cell lymphoma,1 case of anaplastic large cell lymphoma,and 1 case of Hodgkins lym-phoma.2 patients presented with stageⅠ,4 with stageⅡ,and 1 with stage 3.The therapeutic procedure includes local radiotherapy combined with chemotherapy and targeted therapy.The clinical presentation of PLB is not spe-cial.The diagnosis and identification of histological type of PLB should be established by histopathological and im-munohistochemistry examinations.Early diagnosis and active therapy could improve the prognosis of PLB.Combi-nation therapy including radiotherapy and chemotherapy is the optimal treatment for PLB.

Intrathecal injection of umbilical cord mesenchymal stem cells for spinocerebellar ataxia / 中国组织工程研究

BACKGROUND:Spinocerebel ar ataxia is a inherited neurodegenerative disease with progressive cerebel ar masonic movement disorders as the main clinical manifestation. So far, no drug is available to control the disease progression. OBJECTIVE:To observe the clinical effect of umbilical cord mesenchymal stem cells in treating spinocerebel ar ataxia by intrathecal injection. METHODS:Thirty-eight cases of spinocerebel ar ataxia were given umbilical cord mesenchymal stem cells by intrathecal injection, 1×106/kg once a week, four times as a course. These 38 cases received 52 courses. Among them, 27 cases received 1 course, 8 cases received 2 courses and 3 cases received 3 courses. International Cooperative Ataxia Rating Scale (ICARS) and Activity of Daily Living Scale (ADL) were used to evaluate patients’ neural functions (the greater scores, the more severe damage) and ability of daily living (the lower score, the stronger the ability of daily living). After treatment, al patients were subjected to fol ow-up visit. RESULTS AND CONCLUSION:The total effective rate of 52 courses of treatment was 84.62%. ICARS and ADL scores were significantly decreased at 1 month after treatment (P<0.01). In most of effective patients, unstable walking and standing, slow movement, upper limb fine motor disorder, writing difficulties, dysarthria, eye movement disorders were improved. After treatment, common adverse effects were dizziness (1 case), low back pain (2 cases), headache (1 case), and fever (2 cases). Al these symptoms disappeared within 1-3 days. No treatment-related adverse events happened in the median fol ow-up of 39 months (11-59 months). The il ness of effective patients had been stable for 1-19 months, average (5.95±4.84) months. Intrathecal injection of umbilical cord mesenchymal stem cells is safe to ameliorate clinical symptoms to some extent within a certain time. It may delay the progression of spinocerebel ar ataxia. Multiple courses of treatment can help to further improve neurological function in most patients.

Effect of BU and CY versus TBI and CY as conditioning regimens on the efficacy of haploidentical stem cell transplantation in patients with hematologic malignancy / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of the conditioning regimen with busulfan plus cyclophosphamide (BU+CY) or total body irradiation plus cyclophosphamide (TBI+CY) on haploidentical stem cell transplantation (HSCT) in hematologic malignancy.</p><p><b>METHODS</b>The clinical outcomes of 77 HSCT recipients with hematologic malignancy from January 2001 to December 2010, including 21 AML, 33 ALL, 19 CML and 4 MDS were retrospectively evaluated. Among them, 65 patients obtained complete remission (CR) and 12 non-remission (NR) before transplantation; 39 patients received conditioning regimen with BU+CY, and 38 with TBI+CY.</p><p><b>RESULTS</b>There were no statistically significant differences in hematopoietic reconstitution, disease free survival (DFS), and transplant- related mortality (TRM) between two groups. The estimated 3- years overall survival (OS) was 56.4% for BU+CY and 31.6% for TBI + CY (P=0.0283). The overall relapse rate was similar between two groups (15.4% vs 34.2%; P=0.1538). However, the accumulative probability of relapse at 1-year was significantly lower in BU+CY than that in TBI+CY group (2.56% vs 26.67%; P=0.0116). The incidence of grade II-IV graft-versus-host disease (GVHD) was similar between two regimens (20.5% in BU+CY group and 18.4% in TBI+CY group; P=0.8168). The incidence of chronic GVHD (cGVHD) was higher in the TBI+CY group than that of BU+CY group (84.6% vs 41.1%; P=0.0007). The extensive GVHD obtained the similar outcome (30.8% vs 10.5%; P=0.0416).</p><p><b>CONCLUSION</b>Patients using BU+CY as conditioning regimen before transplant could obtain a better 3 year OS and lower short-term relapse rate. The TBI+CY conditioning regimen could significantly increase the incidence of cGVHD without increasing the acute GVHD. BU+CY conditioning regimen could be used for HSCT, but the attention should be paid to prevent the related hemorrhagic cystitis.</p>

Efficacy of rituximab-containing regimens on post-transplantation lymphoproliferative disorder following haploidentical hematopoietic stem cell transplantation: a report of 3 cases / 中华器官移植杂志

Objective To evaluate the efficacy of rituximab-containing regimens on post-transplantation lymphoproliferative disorder (PTLD) following haploidentical hematopoietic stem cell transplantation (HSCT). Methods The clinical data of 3 cases of PTLD after haploidentical HSCT were analyzed retrospectively. Time to development of PTLD ranged from 57 to 164 days after HSCT.The main symptoms included fever, superficial lymph node enlargement. Epstein-Bart virus (EBV)-positive B-cell PTLD was diagnosed by biopsy of lymph node. Management of 3 patients consisted of withdraw of immunosuppressive treatment, anti-viral therapy, rituximab (375 rng/m2 , per week for four weeks) monotherapy or chemotherapy plus rituximab. Results All the patients had complete remission after treatment. Conclusion PTLD is a serious complication of HSCT especially haploidentical HSCT. Rituximab-containing regimens are potentially effective, well-tolerated with mild toxicity and improve the prognosis of PTLD following haploidentical HSCT.

Basiliximab for prophylaxis of graft-versus-host disease in mismatched bone marrow transplantation / 中华器官移植杂志

Objective To investigate the effects of Basiliximab on alloreactive T lymphocytes precursors, hematopoietic progenitor cells by ex vivo assay and prophylaxis of graft-versus-host disease (GVHD) in mismatched bone marrow transplantation.Methods Two groups were set up: (1) Basiliximab group including 72 leukemia patients subject to haploidentical bone marrow transplantation (BMT) with Basiliximab for prophylaxis of GVHD without ex vivo T-cell depletion. (2) Control group having 15 patients receiving the same regimen before Nov. 2000, without Basiliximab for GVHD prophylaxis. Limiting-dilution method was used to determine the effect of Basiliximab on reactivity of cytotoxic T lymphocyte precursors (CTLP). In the semi-solid hematopoietic culture system, the effect of Basiliximab on the colony proliferation of CFU-GM, BFU-E and CFU-Meg was measured. Results In Basiliximab group, 72 patients established trilineage with full donor hematopoietic reconstitution. Engraftment rate showed no statistical difference between the two groups. The incidence of grade Ⅱ-Ⅳ GVHD was 12.5 % (9 cases) in Basiliximab group and 33.3 % (5 cases) in control group respectively (P

Effect of anti-CD25 monoclonal antibody for prophylaxis and therapy of acute GVHD and immune reconstitution following HLA haplotype related T-cell undepleted allogeneic bone marrow transplantation / 中华器官移植杂志

(0.05)).It was noted that the number of CD4~(+) T cells was less significantly throughout the 18 months after BMT in two groups.The time to reach 200 CD4~(+)cells/ ?l was 6 months,and that to reach normal number of CD4~(+)was 18 months.Median time to reach normal CD3~(+) CD8~(+) and CD19~(+) was 9-12 months,and there was no significant difference between two groups.Conclusions The incidence of severe lethal aGVHD and GVHD-related deaths tended to be less in patients with Basiliximab group than un-treated group in haploidentical BMT.It is useful to use Basiliximab to treat sever GVHD.CD4~(+) reconstitution appeared significantly delayed in two groups.CD4~(+) reconstitution is crucial to control post-transplant opportunistic infections and leukemia relapse.Nevertheless,there was no significant difference in immune reconstitution and the incidence of infection and relapse between the two groups.

Homoharringtonine Induces Apoptosis of K562 Cells through Inhibition of P210(bcr/abl) / 中国实验血液学杂志

In this study, the underlying antileukemic mechanisms of homoharringtonine (HHT) were investigated. K562 cell line was used to observe the effects of HHT on the induction of apoptosis and on the expression of the specific chimeric protein P210(bcr/abl), as evaluated by flow cytometric annexin V-PI dual labeling technique and Western blot. The results showed that HHT induced K562 cells to apoptotic death at the concentrations of 5 - 20 ng/ml, and some of the cells became necrotic when exposed to a higher concentration. The amount of P210(bcr/abl) oncoprotein was decreased by approximately 70% when the cells were exposed to HHT for 48 hours, however, that of its partner P145(c-abl) proto-oncoprotein was not affected. It is clear from the study that HHT is an inhibitor of P210(bcr/abl) oncoprotein and therefore promotes the apoptosis of CML cells. It could be promising that HHT be used extensively in the chemotherapy of patients with CML.

A study on non-T-cell depleted haploidentical bone marrow transplantation using Basiliximab for GVHD prophylaxis / 中华器官移植杂志

Objective To explore the effects of Basiliximab (Simulect) on reducing the incidence of severe acute GVHD in haploidentical bone marrow transplantation (BMT). Methods Nine patients with leukemia received haplotype Allo-BMT from HLA two or three loci mismatched related donor. Most patients were classified as high risk category. The donors of patients were administrated with G-CSF 250 ?g/day for 7 doses prior to marrow harvest. In addition to combination of CsA, MTX, ATG and Mycophenolate mofetil for GVHD prophylaxis, Simulect was administered to prevent severe GVHD. A total 40 mg Simulect was given in two doses of 20 mg each by 30 min intravenous infusion on 2 h before transplantation and day 4 after transplantation.Results All patients were engrafted. 100 % donors hematopoietic cells after transplantation was determined by cytogenetic evidence analysis. None developed the Ⅱ-Ⅳ acute GVHD. Eight patients could be evaluated for chronic GVHD. All experienced chronic GVHD confined to the skin. The median follow-up duration was 14 months (range 12～20 months). One patient died from CMV infection on 3 months and one patient died from disease relapse on 14 months. The remaining 7 patients were survived in disease free situation.Conclusion The use of Simulect in haploidentical bone marrow transplantation is effective on preventing acute severe GVHD and improving disease-free survival.

Antibiotic Combined Therapy as an Empirical Treatment for Febrile Patients with Neutropenia / 中华医院感染学杂志

OBJECTIVE To assess the clinical effectiveness of antibiotic combined therapy for febrile neutropenia as an empirical treatment.METHODS We analyzed bacterial epidemiology form Jan 2001 to Feb 2003 and performed a study in 202 neutropenic febrile patients after chemotherapy or(HSCT).Three groups were divided.In first group(84 cases) carbapenems and vancomycin were used.In second group(78 cases)and in third group(40(cases)) used cephalosporin or quinolone.RESULTS Carbapenems plus vancomycin were with response rate of 93%,and(without) vancomycin were only 66%.Cephalosporin or quinolone was with response rate only of 30%.(CONCLUSIONS) Strong antibiotic with vancomycin is effective for treating patients with neutropenia and fever(under) limited bacterial epidemiology.

ALLOGENEIC BONE MARROW TRANSPLANTATION USING G-CSF MOBILIZED MARROW / 解放军医学杂志

20?10 9 /L was (18 1?3 0) days in the recipients.The incidences of grade I GVHD and II GVHD were 28 6% and 5 7%, respectively. Furthermore, the percentages of CD34 + and CD4 + cells in G CSF stimulated bone marrow increased, concomitant with a significant decline in CD8 + cell count. These data demonstrated that G CSF mobilization remodeled the density of hematopoietic progenitors and T lymphocyte subsets in the bone marrow, which in turn accelerated hematopoietic reconstitution and minimized the incidence of severe acute GVHD after allogeneic transplantation.Transplantation of marrow harvests from donors who are pretreated with G CSF might be a feasible measure for a successful allogeneic bone marrow transplantation.