Effect of clonal hematopoiesis in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia after chemotherapy / 中华血液学杂志

Objective: To investigate the effect of clonal hematopoiesis (CH) in remission on hematopoiesis recovery in patients with NPM1 mutated acute myeloid leukemia (AML) after chemotherapy. Methods: Retrospective analysis was performed on 86 patients with NPM1(mut) AML newly diagnosed and treated in the First Affiliated Hospital of Soochow University between July 2016 and June 2019. Their clinical data and NGS test results at diagnosis were analyzed. Moreover, bone marrow samples in remission were tested using Sanger sequencing. The log-rank test was used to analyze the difference in hematopoietic recovery, and Cox proportional hazard models were used to analyze the prognostic factors affecting hematopoietic recovery. Results: The median age of the 86 NPM1(mut) AML patients was 50 years (15-69 years). There were 39 males and 47 females. Forty-one patients were induced with intensity chemotherapy ("7 + 3"), whereas 45 patients were treated with low-dose cytarabine-based induction chemotherapy. At diagnosis, The most common mutations in the patients were FLT3, DNMT3A, TET2, and IDH1/IDH2 mutations. CH-associated mutations persisted in 21 patients during remission, and the mutations were DNMT3A, TET2, ASXL1, and IDH1/IDH2. The recovery time of neutrophils in patients with CH-associated mutations in remission was consistent with that in patients without CH in remission (P=0.282) but the recovery time of platelets in patients with CH in remission was significantly longer[26 (95% CI 21-32) days vs 25 (95% CI 23-26) days, P=0.032]. Furthermore, univariate analysis indicated that age, induced chemotherapy program, and CH in remission were risk factors for platelet recovery, whereas multivariate analysis indicated that induced chemotherapy program and CH in remission were independent risk factors for platelet recovery (HR=0.454, P=0.001 and HR=0.520, P=0.027, respectively) . Conclusion: CH in remission delays the hematopoietic recovery of patients with NPM1(mut) AML after chemotherapy.

Clinical research on influence of auto or allo-mesenchymal stem cells transplantation on hematopoietic recovery / 肿瘤研究与临床

Objective To investigate the impact of auto and allogenic mesenchymal stem cells (MSC) transplantation on hematopoietic reconstitution. Methods MSC from auto, donor bone marrow or embryonic tissue were cultured and expanded in vitro in the serum culture system. Five patients received hematopoietic stem cell transplantation (HSCT) were investigated. Case 1 of systemic lupus erythematosus and Case 2 of non-hodgkin' s lymphoma (NHL) received auto MSC transplant before auto-HSCT. Case 3 of paroxysmal nocturnal hemoglobinuria received HLA-identical allogenic MSC transplant before HLA-identical allo-HSCT.Case 4 of chronic myelocytic leukemia and Case 5 of NHL had delayed hematopoietic reconstitution (129th and 78th day, respectively) after allo- and auto-HSCT, respectively, and received MSC from embryonic tissue.Results Case 1, 2 and 3 had no manifested side effects after MSC transplantation combined with HSCT.Neutrophil count of case 1, 2, and 3 were over 0.5 ×109/L at 1st, 10th and 10th day, respectively, platelet count were over 20 ×109/L at 1st, 8th and 33th day, respectively, and agranulocytosis at Ost, 7th and 12th day, respectively. The treatment of embryonic tissue MSC transplant was confirmed to fail for Case 4 and 5.Conclusion The time of MSC transplant has a great impact on hematopoietic reconstitution. MSC transplantation and HSCT performed simultaneously can improve hematopoietic reconstitution. However, the impact of MSC on patients with delayed hematopoietic reconstitution after HSCT needs further study.

Effects of allogenic intra-bone marrow bone marrow transplantation on the hematopoiesis in mice / 基础医学与临床

Objective To investigate the effects of allogenic intra-bone marrow bone marrow transplantation (IBM-BMT) on re-establishing hematopoiesis in mice. Methods Bone marrow mononuclear cells (BMNCs) from BALB/ c mice were transplanted into the C57BL/6 mice treated with a lethal dose of ~(60)Coγ-ray radiation through intra-bone marrow injection or intravenous injection. Sixty of the C57BL/6 mice were randomly divided into three groups as higher dose intra-bone marrow injection group (IBM1 group), lower dose intra-bone marrow injection group (IBM2 group) and intravenous injection group (IV group). The nucleated cell numbers of whole bone marrow from the tibia of each recipient mouse were counted respectively at the day 1, day 3, day 6 and day 9 after the transplantation. The donor-derived total nucleated cells and myeloid cells were quantified by flow cytometry. Results At 6th day after transplantation, more total bone marrow nucleated cells, total donor-derived nucleated cells and donor-derived myeloid cells in the tibia of injected side in both IBM1 group and IBM2 group were found than that in IV group (P<0.05 or P<0.01). Conclusion Compared with traditional bone marrow transplantation (IV-BMT),IBM-BMT improves the bone marrow hematopoiesis in the early hematopoietic re-establishing stage in allogenic bone marrow transplantation.

Effect of polysaccharide from spirulina platensis on hematopoietic recovery and related cytokines in mice with transplant tumor after treated by chemotherapy / 中国临床药理学与治疗学

AIM: To evaluate the effect of polysaccharide from spirulina platensis (PSP) on hematopoietic recovery and related cytokines in mice with transplant tumor after treated by chemotherapy. METHODS: The tumor cells were subcutaneously injected in the right forefoot to induce transplant solid tumor in mice. The mice were ig with PSP for 10 d and injected intraperitoneally with cyclophosphamide (CTX) for 3 d. On d 11, the count of peripheral blood cell, nucleated cell in bone marrow and CFU-S (Colony Forming Unit-Spleen) was observed; The content of DNA in bone marrow was inspected by UV-spectrophotometer; The cytokines in serums were inspected by double antibody sandwich ELISA. RESULTS: CTX could induce evident myelosuppression. But PSP could elevate the level of peripheral blood cell, increase nucleated cell and DNA in bone marrow, and promote CFU-S formation. In addition, PSP could also increase the content of IL-1, IL-3, GM-CSF, and TNF-? in serum. CONCLUSION: It is probably that PSP accelerates the hematopoietic recovery in mice with transplant tumor treated by chemotherapy by promoting endogenous cytokines secretion.

The absolute number of CD34+ cells predicts optimal timing of progenitor cell collection and posttransplant hematopoietic recovery / 대한임상병리학회지

BACKGROUND: Recently, the commercial kits for measurement of the absolute number of CD34+ cells have been introduced as a standard method. The aims of this study was to investigated optimal timing of peripheral blood progenitor cell(PBPC) collection and optimal CD34+ cells dose transplanted by measurement of the absolute CD34+ cells. METHODS: We measured total leukocyte count, mononuclear cell count and the absolute number of CD34+ cells using ProCOUNT(Becton Dickinson, USA) in peripheral blood from 54 patients and 7 normal donors who underwent 101 leukapheresis for PBPC collection. We studied correlations among the absolute number of circulating CD34+ cells, other predictors and harvesting yields. We investigated relationships between the posttransplant hematopoietic recovery and CD34+ cells dose in 30 patients. RESULTS: The total number of CD34+ cells in harvesting products could be mostly predicted from the absolute number of circulating CD34+ cells. From 4 to 6 day after G-CSF mobilization, the absolute number of circulating CD34+ cells was peaked. A number of circulating CD34+ cells more than 20/microliter ensured 2.5x106 CD34+ cells/Kg in harvesting products. The patients received CD34+ cells dose >3.5x106/Kg led to a significantly faster recovery of platelets, compared with the patients receiving <3.5x106 CD34+ cells/Kg(P<0.05). CONCLUSIONS: These results suggest that PBPC collection should be started at day of circulating CD34+ cells more than 20/microliter or 4-6 days after G-CSF mobilization for successful leukapheresis and the CD34+ cell dose more than 3.5x106/Kg for PBPC transplantation could predicted rapid hematopoietic recovery.

The Enhancing Effects of Fibroblast-Mediated G-CSF Gene Therapy on the Recovery of Hematopoiesis / 中国肿瘤生物治疗杂志

In the present study, the effects of G-CSF gene therapy was investigated on the recovery of murine hematopoietic suppression induced by high dose of cyclophosphomide (Cy) . The results showed that G-CSF gene therapy could slow down the Cy-induced decreasing of peripheral WBCs and platelets, and accerelate their recovery.It also could increase the CFU-GM, CFU - MK, CFU-S derived from the splenocyte and bone marrow cells in the chemotherapy-treated mice. The data demonstrated that fibroblast-mediated G-CSF gene therapy could significantlyreduce the hematopoietic damage to less extent, and accerelate hematopoietic recovery after chemotherapy.

Peripheral Blood Stem Cell Collection in Pediatric Donors with Malignancies and Its Significance on Hemato-poietic Recovery of Recipients / 实用儿科临床杂志

Objective Data on the leukapheresis from 26 pediatric patients with hematologic or solid malignancies was retrospectively evaluated to screen predictive factors affecting the efficacy of peripheral blood stem cell(PBSC) collection from donors,as well as hematopoietic recovery in recipients.Methods We present our experience with 49 apheresis from 26 granulocyte-colory Stimulating factor mobilized donors and analyzed the correlations between the mobilization,the leukocyte count in the donor peripheral blood and the MNC and CD_(34)~+ cell yields in collecting products and the neutrophil and platelet recovery of recipients.Results The process of mobilization and apheresis were well tolerated by our pediatric donors.The median numbers for harvested MNCs and CD_(34)~+ cells were 4.5?10~8/kg and 1.9?10~6/kg of recipient body weight,respectively.Mobilizing dose positively affected the number of mononuclear ceus(MNC) but not CD_(34)~+ cells in the apheresis products.The CD_(34)~+ cell number in the apheresis product was influenced significantly by donor circulating MNC on the day of harvest and correlated with recipient′s engraftment after PBSC was reinfused.Conclusions The MNC yield was stable and met with the demand for autologous stem cell transplantation while the CD_(34)~+ cell number varies obviously from each donor.Since a rapid engraftment was associated with a high number of CD_(34)~+ cells collected,which was in turn predicted by the level of the pre-apheresis CD_(34)~+ cells in the peripheral blood of donors,it is necessary to monitor the donors′ CD_(34)~+ cell during mobilization to determine the optimal time for apheresis.J Appl Clin Pediatr,2006,21(3):148-150