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Objective To retrospectively analyze the clinical efficacy and safety of VCD (bortezomib/cyclophosphamide/dexamethason) in the treatment of multiple myeloma (MM) patients. Methods Fifty-five consecutive patients with newly diagnosed or relapsed MM were enrolled in the study retrospectively from June 2012 to June 2017. We collected and analyzed the clinical information of all patients treated with VCD.Results Firstly, the patients received therapy of VCD for median 4 cycles (Range : 2 ～8). The overall response rate (ORR) was 85.5％ (45/55). The complete response/near complete response rate (CR/nCR) , very good partial response rate (VGPR) and partial response rate (PR) were 27.3％, 23.6％ and 34.6％, respectively. The ORR of10 patients with renal inadequacy was 80.0％, while 45 cases with normal renal function was 82.2％ (P=0.627).Secondly, with a median follow-up of 13.5 months, the median progression free survival (PFS) , the median duration of response (DOR) and the median overall survival (OS) were 27 (1～61) months, 18 (1～50) months and 49 (1～64) months, respectively. Univariate prognostic analysis showed that abnormal ISS stage Ⅲ, relapse, renal dysfunction and response inferior to VGPR were negative prognostic factors for PFS, while abnormal ISS stageⅢ and renal dysfunction were negative prognostic factors for OS. Moreover, the multivariate prognostic analysis showed that abnormal ISS stage Ⅲ and response inferior to VGPR were independent prognostic factors for PFS, while ISS stage Ⅲ was independent prognostic factors for OS. Thirdly, the VCD treatment is effective and safe.The adverse events were evaluated according to International Myeloma Working Group Uniform Response Criteria.The results showed that the most common grade 3 ～4 non-hematology adverse events (AEs) were infection (20.0％) , peripheral neuropathy (5.5％) and hypertension (5.5％). The most common grade 3～4 hematology AEs were thrombocytopenia (10.9％) , neutropenia (9.0％) and anemia (5.5％). A total of 2 patients (3.6％) discontinued VCD because of serious peripheral neuropathy and 2 cases (3.65％) died of respiratory failure because of serious infection. Conclusions The VCD regimen is effective and safe in the treatment of newly diagnosed or relapsed/refractory MM patients in China. VCD is safe in patients with renal dysfunction.
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Objective@#To investigate the risk factors of poor graft function (PGF) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe aplastic anemia (SAA) .@*Methods@#Clinical data from 111 SAA patients who received allo-HSCT were analyzed retrospectively. Factors including age, gender, interval to transplantation, the level of serum ferritin before transplantation were analyzed by Cox multivariate regression analysis.@*Results@#Among the 111 patients who underwent allo-HSCT, 16 developed PGF (14.4%) . Multivariate analysis showed donor type (HR=2.656, 95%CI 1.204-5.858, P= 0.016) and the level of serum ferritin before tansplantation (HR=3.170, 95%CI 1.400-7.180, P=0.006) were significant risk factors for PGF.@*Conclusion@#Unrelated donor transplantation and the high level of serum ferritin before transplantation are risk factors for PGF.
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Objective@#To analyze the morbidity, clinical characteristics, therapeutic outcomes and prognosis of cardiac lymphoma.@*Methods@#Individual patient data were obtained from pathology defined 10 cases of cardiac lymphoma from Jan 2000 to Jun 2016. The patient’s general information, clinical manifestation, pathological diagnosis, laboratory examination, cardiac involvement feature, cardiac complications, treatment, therapeutic effect and prognosis were analyzed.@*Results@#Of 3 918 cases of lymphoma patients, 10 cases of cardiac involvement were identified, including primary cardiac lymphoma (PCL) in 1 case, secondary cardiac lymphoma (SCL) in 9 cases. Of the 10 patients in our analysis, the male-to-female ratio was 3∶2, with a median age of 55 (19-88) years old. The most presenting complaints were dyspnea in 7 cases, followed by chest pain in 5 cases, fatigue in 2 patients and edema in 2 cases. Pathological types included diffuse large B cell lymphoma (DLBCL) in 7 cases, T cell lymphoma (T-LBL) in 1 case, Hodgkin’s lymphoma (HL) in 1 case, and Burkitt lymphoma (BL) in 1 case. The sites of the heart affected by lymphoma in the PCL patient were right and left atriums with multiple nodules; and for SCL, the sites were mainly pericardium associated with a pericardial effusion in 5 cases, a pericardial mass in 2 cases. Congestive heart failure affects 7 patients and cardiac arrhythmias were identified in 4 cases mainly sinus tachycardia, atrial fibrillation and atrioventricular block. Except one untreated because of old age and poor performance, the rest of 9 patients were treated by either chemotherapy in 4 cases or chemotherapy combined radiotherapy (including the extracardiac sites) in 5 patients. With the median follow-up of 9 months, the one PCL patient achieved partial response (PR) , progress free survival (PFS) for 6 months and the overall survival (OS) for 21 months; in the cohort of 6 SCL patients cardiac involved at diagnosis, complete response (CR) was achieved in 1 case (16.7%) , PR in 3 cases, progressing disease (PD) in 2 cases, with the median PFS for 5 months and the median OS for 19 months; and for the other 3 SCL patients cardiac involved at progression, PR was achieved in 2 case and death in 1 case, with the median PFS for 4 months and the median OS unavailable because of censored data.@*Conclusion@#Cardiac lymphoma represents a rare subset of lymphoma, the most common type is DLBCL, and the main clinical manifestations are dyspnea and chest pain, always combined by arrhythmia and congestive heart failure. The main therapeutic regimen for cardiac lymphoma includes combined chemotherapy and the prognosis for patients with either PCL or SCL is usually poor.
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BACKGROUND:To date, there are few domestic reports about the influence of bone marrow mesenchymal stem cel s on T cel s proliferation in patients with aplastic anemia. And no study addresses the topic that if bone marrow mesenchymal stem cel s achieve immune regulation in aplastic anemia patients through inhibiting T cel s proliferation. OBJECTIVE:To explore the effects of human bone marrow mesenchymal stem cel s on T cel s immune regulation in patients with aplastic anemia. METHODS:Human bone marrow mesenchymal stem cel s were isolated, cultured and subcultivated in vitro. The morphological appearance of bone marrow mesenchymal stem cel s was observed and surface markers were measured by flow cyometry. The bone marrow mesenchymal stem cel s were co-cultured with T cel s extracted from peripheral blood of healthy volunteers and aplastic anemia patients for 7 days. The expressions of interferon-γ, interleukin-4 and interleukin-10 in the supernatants were detected with enzyme linked immunosorbent assay. RESULTS AND CONCLUSION:The levels of interleukin-2 and interferon-γin the supernatant of aplastic anemia patients were significantly higher (P<0.05), while levels of interleukin-4 and interleukin-10 were significantly lower than that in healthy controls (P<0.05). Bone marrow mesenchymal stem cel s suppressed the elevated levels of interleukin-2 and interferon-γ, and enhanced the decreased levels of interleukin-4 and interleukin-10, thus regulating the immune dysfunction of aplastic anemia patients.
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BACKGROUND: Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is an effective method for treating multiple malignant hematological diseases and hereditary diseases.However,systematic internal organs disorders,especially pulmonary complications,are commonly following allo-HSCT,How to correctly diagnose and treat the coexistence of pulmonary infectious complications and pulmonary noninfectious complications has great importance.OBJECTIVE: To report a case suffered from pulmonary Aspergillus infection coexisted with obliterative bronchiolitis at 1 year following allo-HSCT,and to discuss the prevention,clinical manifestation and treating method by reviewing related literature.METHODS: At 373 days after allo-HSCT,the patient developed fever,dry cough,shortness of breath and dyspnea on exertion A high-resolution computed tomography of chest demonstrated that there were alveolar infiltrating in the upper,middle and lower lobe of the right lung,and the focus of infection was performed further biopsy.RESULTS AND CONCLUSION: The histopathological examination of the sample showed alveolus dilatation,epithelial cells hyperplasia,fibrinous obliteration in alveolar space and peribronchiolar lymphocytes inflammation,which were CD3(+),CD45RO(+),CD20(-),CD79a(-),MPO(-),CD34(-).Aspergillus fumigatus could be seen in the cultured biopsied tissue specimen.Pulmonary function test showed that,air flow obstruction with reduction of forced expiratory volume in one second was 59.27%.The patient was diagnosed as invasive pulmonary Aspergillus infection combined with bronchiolitis obliterans and was treated by caspofungin combined with intravenous voriconazole for invasive aspergillosis,methylprednisolone,azathioprine,intravenous immunoglobulin and azithromycin for bronchiolitis obliterans.At 40 days after treatment,the CT examination showed the focus was absorbed completely.
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Objective To observe the therapeutic effect and adverse effect for chemthrombocytopenic of rhIL-11 in chemotherapy for acute myeloid leukemia. Methods We adopted a randomized, blank-control, crossover trial of rhIL-11 in 16 newly diagnosed patients with acute myeloid leukemia. The treatment group were accepted chemotherapy by DA or TA. rhIL-11 (25μg·kg-1·d-1, subcutaneously) was administered from 24 h after chemotherapy and continued for seven to fourteen days. The changes of platelet counts were observed. Results The group by chemotherapy had higher platelet counts than control after rhIL-11 treatment and platelet transfusion frequency was reduced. The adverse effect of rhIL-11 was light, including fatigue, muscular soreness and low-grade fever. Conclusion rhIL-11 is safe and effective in reducing chemotherapy thrombocytopenia.
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BACKGROUND:Hematopoietic reconstruction of malignant tumor in hematopoietic system is related to disease itself,pretreatment program and therapeutic tool after transplantation;especially,mobilization.collection and cryopreservation of auto-peripheral blood stem cell play a key role in successful reconstruction of hematopoietic system after transplantation.OBJECTIVE:To investigate the reconstruction of hematopoietic system through mobilization, collection and cryopreservation of auto-peripheral blood stem cell in patients with malignant tumor and analyze the effective factors on quantity and quality of auto-peripheral blood stem cell.DESIGN:Case analysis based on malignant tumor in hematopoietic system.SETTING:Department of Blood,Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA;Department of Blood,Zhujiang Hospital,Nanfang Medical University.PARTICIPANTS:A total of 18 patients with malignant tumor in hematopoietic system were selected from Department of Blood,Guangzhou General Hospital of Guangzhou Military Area Command of Chinese PLA.Their ages ranged from 1 6to 56 years.Among them,2 patients had acute myelogenous leukemia(AML),1 acute lymphoblastic Ieukemia(ALL),2 lymphoblastic Ieukemia (LL),2 chronic granulocytic leukemia(CGL),4 multiple myeloma(MM),and 7 non.Hodgkin lymphoma.Granulocyte colony-stimulating factor(G-CSF)was made by Chugai Pharmaceutical Company Limited (batch number:N3G31).METHODS:①All patients were mobilized with associated chemotherapy+G-CSF.Associate chemotherapy:Patients with leukemia were given 2 g/m2 arabinosyl cytosine every 12 hours from lhe first to the third days and 200 mg/m2 etoposide or 50 mg/m2 fludarabine from the first to the fifth days. In addition patients with MM were treated with arabinosyl cytosine as the same way mentioned above and with 1 g/m2 cyclophosphamide from the first to the second days. And patients with lymphoma were given 2 g/m2 cyclophosphamide from the first to the second days. When numbers of leucocyte of all patients decreased below 1.0×109L-1 after chemotherapy.G-CSF started mobilization and the collection was stopped with 5μg/(kg·d)subcutaneous injection.②When numbers of leucocyte increased to (4.0-10.0)×109 L-1,hemopoietic stem cells of peripheral blood were collected till the amount of mononuclear cells≥4.0×108/kq or numbers of CD34+ cells≥2.0×108/kg.And then,the samples were dealt with cooling device.maintained in liquid nitrogen at-196℃ and defrosted in water bath at 37-40℃.③Focal sites of patients were pretreated with local irradiation with 200 cGy/time and 5 times/week for 4 successive weeks.The total dosage was 40 Gy.At 48 hours later,(55.3±28.7)mL hemopoietic stem cells of peripheral blood were transfused back. And the duration from transfusion to collection was about(56.5±22.3)days.300 μg/d G-CSF was subcutaneously injected into all patients at 1 day after transplantation and the reaction was stopped at the phase of neutrophil≥0.5×109L-1. Finally. Refusing-staining rate of trypan blue of peripheral blood stem cell, amount of mononuclear cells, number of granulation-monophyly progenitor cell colony and percentage of CD34+ cells were detected before and after thaw.MAIN OUTCOME MEASURES:①Collection of auto-peripheral blood stem cell;②survival rate and related markers of auto-peripheral blood stem cell after cryopreservation;③hematopoietic reconstruction of auto-peripheral blood stem cell after transplantation.RESULTS:All 18 patients with malignant tumor in hematopoietic system were involved in the final analysis.The mean collection time of auto-peripheral blood stern cell was 12.6 days after chemotherapy.the collection times were 1.9.total number of leucocyte was(8.93±1.27)×1 0.L-1 on the first day,and collection rate of mononuclear cell was (138.33±28.61)%. ②Refusing-staining rate of trypan blue of auto-peripheral blood stem cell was similar before and after cryopreservation[(96.26±1.33)%, (92.75±2.04)%,P＞0.05].in addition,after cryopreservation,recovery rates of mononuclear cells,CD34+ cells and granulation-monophyly progenitor cell were(91.96±1.37)%, (85.94±0.64)%and (87.69±4.53)%,respectively.Collection rate of mononuclear cells,number of granulation-monophyly progenitor cell colony and percentage of CD34+ cells were lower in patients with myeloma than in those with leukemia and lymphoma (t=2.524-3.268.P＜0.05).③At 15 days after transplantation,15 patients had the neutrophil≥0.5× 109L-1;at 20 days after transplantation,blood platelet was≥20 × 100 L-1.granulation-monophyly progenitor cells[(18.67-26.82)× 105/kg] of 5 patients grew poorly if the course of chemotherapy was more than 10 times.Among them,3 patients had delayed hematopoietic reconstruction after transplantation of auto-peripheral blood stem cell.CONCLUSION:①High-dose chemotherapy combined with G-CSF can shorten collection time of peripheral blood stem cell and improve collection rate of mononuclear cells.②Increase of chemotherapy times before transplantation can affect quantity and quality of auto-peripheral blood stem cell and cause delayed hematopoietic reconstruction.
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To explore the effect of recombinant human interleukin 11(rhIL-11), granulocyte-colony stimulating factor (rhG-CSF) combined with cyclophosphamide (CTX) on mobilizing peripheral blood stem/progenitor cells in C57BL/6 mice. A total of 48 C57BL/6 mice were randomized into four groups. CTX (200mg/kg) was injected intraperitonealy on the first day (d0) in the treatment group. rhIL-11 alone or in combination with rhG-CSF was administered subcutaneously, beginning from 24 hours after CTX for 15 consecutive days in two other groups. The changes in peripheral blood white cell counts, platelet counts and the percentage of hematopoietic stem/progenitor cells of the mice were observed. It was shown that rhIL-11 or/and rhG-CSF could increase the numbers of WBC, PLT, CFU-GM, CFU-E, CFU-MK progenitor cells, and the percentage of CD34 positive cells in peripheral blood of myelosupressed mice. The results demonstrated that rhIL-11 alone or in combination with G-CSF and CTX could mobilize bone marrow haematopoietic stem/progenitor cells into peripheral blood.
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To investigate the role of vascular endothelial growth factor (VEGF) in occurrence and progression of acute myeloid leukemia (AML), enzume linked immunosorbent assay(ELISA) was used for detection of VEGF concentration in plasma from AML patients and normal bone marrow donors.The mean VEGF concentration in the plasma from refractory (558 90pg/ml) and non refractory (392 54pg/ml) AML patients was higher than that from normal donors (57 27pg/ml) and AML patients post Allo BMT (77 31pg/ml).There were significant differences between refractory and non refractory AML group. The baseline VEGF level (196 14pg/ml) of patients in complete remission (CR) after a median follow up of 6 months was significantly lower than that of patients with newly diagnosed or relapsed AML, but significantly higher than that of patients with Allo BMT AML and normal donors. Therefore, abnormal VEGF expession may play an important role in development of AML, and VEGF might be used to evaluate prognosis of AML.