[Efficacy of Oral Cyclophosphamide for Treatment of Refractory T-cell Large Granular Lymphocytic Leukemia Accompanied with Pure Erythrocyte Aplastic Anemia].

OBJECTIVE: To explore the clinical effects of oral small dose of cyclophosphamide (CTX) in the treatment of T-cell large granular lymphocytic leukemia (T-LGLL) accompanied with pure red cell aplasia (PRCA). METHODS: The clinical features, characteristics of laboratory examinations and the process of oral small dose of CTX treatment after the ineffective treatment of cyclosporine A combining with prednisone in 1 case of T-LGLL with PRCA were reported and discussed with related references. RESULTS: The elderly female patient had indolent process, mainly presenting with anemia and significant low hyperplasia of bone marrow erythrocyte cells. Peripheral blood smear showed mainly with characteristic large granular lymphocytic morphology. The results of immunophenotypic analyses and genetic reassortment were compatible with T-LGLL. No effects were shown after 5 months of cyclosporine A combining with prednisone treatment and the patient still needed recurrent blood transfusion. CTX was prescribed as a second-line medication and the dose was 100 mg/d. Hemoglobin could returned to normal level and the efficacy remained for 1 year even after the medication was stopped. CONCLUSION: T-LGLL accompanied with PRCA is a rare disease and oral small dose CTX can be an effective therapeutic regimen.

The effect of imatinib therapy on the outcome of allogeneic stem cell transplantation in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

OBJECTIVE: To evaluate the efficacy of imatinib administration before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). METHOD: Patients with imatinib therapy time exceeding 30 days pre-/post-transplant were screened in our data. Imatinib was used in induced or consolidated chemotherapy pre-transplant, or maintenance therapy after 60 days post-transplant (therapy time was less than 180 days) regardless of the molecular status of the disease. RESULTS: Sixty-nine patients with Ph+ ALL were enrolled in the retrospective analysis. Forty-four patients received imatinib therapy, including 24 pre-transplant, 9 post-transplant, and 11 both pre- and post-transplant. With a median follow-up time of 395 days (range, 55-2762 days) post-transplant, 3-year estimated overall survival was 62.3 ± 16.6, 40.0 ± 21.9, 41.7 ± 22.2, and 25.9 ± 11.4%, respectively (P = 0.221), and disease-free survival (DFS) was 53.6 ± 17.9, 20.0 ± 17.9, 33.3 ± 25.5% and 23.6 ± 11.4%, respectively (P = 0.421), in patients with imatinib therapy pre-transplant, post-transplant, both pre- and post-transplant, neither pre- nor post-transplant. The incidence of relapse at 3 year for patients with imatinib therapy post-transplant (n = 20) was 63.6%, comparing with 24.2% (P = 0.018) in patients without imatinib therapy post-transplant (n = 49). The ratio of CD4+CD25+Foxp3+ cells in blood was significantly higher at 30 and 60 days after imatinib therapy than that at the time of pre-imatinib in 20 patients (P = 0.019 and 0.001, respectively). CONCLUSIONS: Application of imatinib pre-transplant might have benefited for patients with Ph+ ALL. Whether administration of imatinib, regardless of the molecular status of the disease post-transplant increases relapse, is a worthy goal for further study.

[Effect of granulocyte colony stimulating factor on myeloid-derived suppressor cells in the bone marrow and peripheral blood: a preliminary study].

OBJECTIVE: To investigate the effect of granulocyte colony stimulating factor (G-CSF) on myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood, and explore the relationship between MDSC and graft-versus-host disease (GVHD). METHODS: Bone marrow, peripheral blood and peripheral blood stem cells were obtained from 12 healthy hemopoietic stem cell donors before and on day 5 after G-CSF mobilization. Flow cytometry was employed to examine the number of MDSC, and the relationship between MDSC number and the incidence of GVHD was analyzed. RESULTS: In normal physiological conditions, MDSC could be detected in the peripheral blood and bone marrow with a cell percentages of (1.35±0.35)% and (2.44±1.11)%, respectively, showing a significantly higher cell percentage in the bone marrow (P=0.015). On the 5th day after G-CSF mobilization, the percentage of MDSCs increased to (4.01±1.82)% in the peripheral blood and to (4.38±2.19)% in the bone marrow, showing no significant difference between them (P=0.083). The mobilization caused a significant increase in the number of MDSCs in the peripheral blood (P=0.047) but not in the bone marrow (P=0.761). The number of MDSCs in the collected samples showed a significant inverse correlation to the incidence of GVHD (P=0.048). CONCLUSIONS: MDSCs are present in the peripheral blood and bone marrow of healthy donors, with a greater number in the bone marrow. G-CSF can mobilize the MDSCs from the bone marrow to the peripheral blood to increase number of MDSCs in the peripheral blood, which may contribute to a lowered incidence of GVHD in hematopoietic stem cell transplantation (HSCT).

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis.

In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.

[Clinical implications of HLA-G protein expression in acute leukemia].

OBJECTIVE: To detect the expression of membrane-bound HLA-G (mHLA-G) and serum HLA-G (sHLA-G) in acute leukemia patients and investigate the correlation between HLA-G expression and the occurrence and development of acute leukemia. METHODS: Enzyme-linked immunosorbent assay and flow cytometry were used to detect the expression levels of sHLA-G and mHLA-G in 40 newly diagnosed leukemia cases, 10 refractory and relapsed leukemia cases, and 30 leukemia cases receiving chemotherapy. Ten normal individuals served as the normal control group. RESULTS: The mean serum level of sHLA-G in normal individuals was 5.87±2.07 ng/ml, as compared to 10.05±6.58 ng/ml in newly diagnosed leukemia patients and 12.32±5.85 ng/ml in refractory and relapsed cases. The mean level of mHLA-G in normal individuals, newly diagnosed cases, and refractory and relapsed cases were (0.29±0.20)%, (0.60±0.44)%, and (0.77±0.41)%, respectively. The mean levels of sHLA-G and mHLA-G were significantly higher in the newly diagnosed cases than that in the normal controls (P<0.05), and significantly higher in patients before chemotherapy than in those with complete remission after chemotherapy (P<0.05). CONCLUSION: HLA-G expression levels might influence the treatment outcomes and can serve as a prognostic factor for acute leukemia.