Influencing factors of pulmonary ventilation function and its relationship with indoor air pollution in rural areas of Gansu Province / 环境与职业医学

Background Indoor air pollution is an important risk factor affecting health of the respiratory system. Studies on indoor air pollution in China are mostly limited to the central and eastern regions, and there are few studies in the rural areas of northwest China. Objective To explore the influencing factors of lung ventilation function and its relationship with indoor air pollution in rural areas of Gansu Province based on a cross-sectional investigation. Methods A total of 399 subjects were selected from four villages in Baiyin and Yuzhong of Gansu Province. Questionnaires were used to collect demographic information, lifestyle, disease history, fuel use, and other information, and physical and functional tests were ordered such as height, weight, and lung function. The Indoor Air Pollution (IAP) exposure index was calculated based on smoking, fuel type, and weekly ventilation. IAP > 5 was defined as a high level of indoor air pollution. Lung function indexes included forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC, forced vital capacity as a percentage of predicted value (FVC%), and forced expiratory volume in the first second as a percentage of predicted value (FEV1%), which were used to determine pulmonary ventilation dysfunction. Logistic regression model was used to evaluate the relationship between indoor air pollution and pulmonary ventilation function, and subgroup analysis was further conducted according to home address and BMI , in order to identify the high-risk population of pulmonary ventilation dysfunction. Results The mean age of the subjects was (56.75±7.31) years old; 155 subjects (38.85%) had normal pulmonary ventilation function, and the other 244 subjects (61.14%) had impaired pulmonary ventilation function; about 89.97% of the subjects were exposed to high level of indoor air pollution (IAP > 5). We found that IAP > 5 (OR=2.327, 95%CI: 1.089-4.974) and use of bituminous coal as the main heating fuel in winter (OR=3.467, 95%CI: 1.197-10.037) increased the risk of pulmonary ventilation dysfunction after adjusting for age, BMI, residence, gender, smoking, drinking, and cardiovascular disease. The subgroup analysis results showed that no ventilation in the living room/bedroom (OR=3.460, 95%CI: 1.116-10.268) increased the risk of pulmonary ventilation dysfunction in Baiyin. Heating with coal stoves and Chinese Kang in the bedroom (OR=2.092, 95%CI: 1.030-4.247) and cooking in the bedroom in winter ( OR =2.954, 95% CI : 1.046-8.344) also increased the risk of pulmonary ventilation dysfunction in the residents with BMI≤24 kg·m−2. IAP > 5 (OR=3.739, 95%CI: 1.147-12.182) was associated with a significantly increased risk of pulmonary ventilation dysfunction in the BMI > 24 kg·m−2 subgroup. Conclusion The pulmonary ventilation function of rural residents in Gansu is poor, which is negatively correlated with indoor air pollution. Coal use, overweight, cooking in bedroom, and use of coal stoves and Chinese Kang for heating may increase the risk of pulmonary ventilation dysfunction, while room ventilation is a beneficial factor.

Analysis of the efficacy and influencing factors of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia in the chronic phase and accelerated phase / 中华血液学杂志

Objective@#To explore the efficacy and prognosis of nilotinib or dasatinib as second- or third-line treatment in patients with chronic myeloid leukemia (CML) in the chronic phase (CP) and accelerated phase (AP) .@*Methods@#From January 2008 to November 2018, the data of CML patients who failed first- or second-line tyrosine kinase inhibitor (TKI) -therapy received nilotinib or dasatinib as second-line and third-line therapy were retrospectively reviewed.@*Results@#A total of 226 patients receiving nilotinib or dastinib as second-line (n=183) and third-line (n=43) therapy were included in this study. With a median follow-up of 21 (range, 1-135) months, the cumulative rates of complete hematological response (CHR) , complete cytogenetic response (CCyR) and major molecular response (MMR) were 80.4%, 56.3%and 38.3%, respectively in those receiving TKI as second-line TKI therapy. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 78.7%and 93.1%, respectively. Multivariate analyses showed that Sokal high risk, female gender, the best response achieved <CHR on the first-line TKI-therapy, the interval from diagnosis to switching to second-line TKI ≥18 months, AP or hematologic failure, or non-specific mutation of BCR-ABL kinase domain before second-line TKI therapy, developing severe hematologic toxicity during the second-line TKI therapy were variables associated with poor responses or outcomes on second-line TKI therapy. With a median follow-up of 6 (range, 3-129) months, the cumulative CHR, CCyR and MMR were 95.7%, 29.3%, and 18.6%, respectively in those receiving the third-line TKI therapy. The 2-year PFS and OS rates were 66.8% and 93.8%, respectively. The patients with an interval from diagnosis to starting TKI ≥6 months, achieving no cytogenetic response on the second-line TKI, the interval from diagnosis to starting second-line TKI ≥60 months, and progression to AP before the third-line TKI therapy had lower probabilities of responses and unfavorable outcomes.@*Conclusions@#The efficacy of dasatinib and nilotinib as second- or third-line TKI-therapy were active in the CML patients with TKI-resistance. The best response achieved on previous TKI-therapy, the disease phase before switching TKI, and the severe hematologic toxicity developing on the current TKI-therapy were associated with the responses and outcomes.

Comparison of nilotinib vs imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase / 中华血液学杂志

Objective@#To compare the cytogenetic and molecular responses, outcomes and severe hematologic toxicity of nilotinib and imatinib as frontline therapy in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) .@*Methods@#Newly diagnosed CML-CP patients were consecutively recruited from January 2006 to December 2018 who received nilotinib and imatinib as first-line treatment. Clinical data were retrospectively analyzed.@*Results@#A total of 524 patients were classified into 439 (83.8%) receiving imatinib and 85 (16.2%) receiving nilotinib. Comparing with imatinib group, patients in nilotinib group were much younger (P=0.019) and more with intermediate and high Sokal risks (P<0.001) , WBC ≥100×109/L (P<0.001) , HGB<120 g/L (P<0.001) , blast cells in bone marrow (P=0.026) , splenomegaly (P<0.001) by physical examination at diagnosis, and longer interval from diagnosis to TKI treatment (P=0.003) . With a median TKI duration of 57 (range 3-153) months, the probabilities of complete cytogenetic response (CCyR) (P=0.011) , major molecular response (MMR) (P=0.001) and MR4.5 (P=0.046) were much higher in nilotinib group than those in imatnib according to each risk group. There is no statistical significance on probabilities of failure free survival (FFS) , progression free survival (PFS) and overall survival (OS) at 6 years between the two groups. Multivariate analyses showed that imatinib was an adverse factor associated with achieving CCyR (OR=0.6, 95% CI 0.5-0.8, P=0.001) , MMR (OR=0.6, 95% CI 0.5-0.9, P=0.032) and MR4.5 (OR=0.6, 95%CI 0.5-0.9, P=0.032) and poor FFS (OR=1.9, 95%CI 1.0-3.4, P=0.041) . In addition, Sokal score was an independent factor affecting cytogenetic and molecular responses, treatment failure, disease progression and survival. Male, WBC ≥100×109/L or HGB<120 g/L at diagnosis were significantly associated with lower cytogenetic and molecular response rates and/or poor FFS. The severe hematologic adverse events were not associated with different TKIs.@*Conclusions@#Nilotinib reaches to the faster and deeper cytogenetic and molecular responses and significantly improves FFS than imatinib in newly diagnosed patients with CML-CP.

Fertility and disease outcomes in patients with chronic myeloid leukemia / 中华血液学杂志

Objective@#To explore Fertility and disease outcomes in patients with chronic myeloid leukemia (CML) .@*Methods@#Clinical and fertility outcomes of male (from Jul. 1998 to Feb. 2018) and female CML (from Sep. 2009 to Feb. 2018) patients were retrospectively analyzed at Peking University People’s Hospital.@*Results@#A total of 49 male CML patients and their spouses were enrolled. Before their spouses conceived, 34 patients were receiving tyrosine kinase inhibitor (TKI) imatinib, 9 with nilotinib, and 6 with dasatinib. At the time of conception, the median age of these male patients was 32 years (range, 25-48 years) , and the median TKI treatment duration was 36 months (range, 0.2-198 months) . One male patient having achieved complete hematologic response yet discontinuing TKI for a year developed a disease progression to blast crisis. The other 48 patients sustained stable disease. The total conception times were 61 and finally 55 infants were born including one with premature birth, two with low birth weight, and one with hypospadias receiving surgery. The other 18 female patients after pregnancy were enrolled. Two patients developed spontaneous abortions. Two received induced abortions. Fourteen gave birth to healthy infants without congenital malformation. The interval from diagnosis of CML to initiation of TKI was 4 months (range, 0.3-16 months) . During a median follow-up of 45 months (range from 7-114 months) , the estimated complete cytogenetic response (CCyR) rate, major molecular response (MMR) rate and molecular response4.5 (MR4.5) rate by 5 years were 88.9%, 85.3% and 35.1%, respectively. The estimated failure-free survival, progression-free survival and overall survival were 64.2%, 90.9% and 90.9%, respectively. All 14 babies developed as normal.@*Conclusions@#It seems that TKIs do not affect pregnancy outcome in the spouses of male CML patients, suggesting that withdrawal of TKIs is not necessary. Female CML patients have good pregnancy and disease outcomes in the TKI era.

Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia / 中华血液学杂志

Objective@#To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) .@*Methods@#A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients.@*Results@#A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×109/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3-CD56+ cell number was 5.0 (1.4-6.4) ×109/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3+ CD56+ cells was 0.55 (0.24-1.74) ×109/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ2=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ2=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ2=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ2=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ2=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively.@*Conclusion@#The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Philadelphia chromosome-negative myeloid neoplasms in patients with Philadelphia chromosome-positive chronic myeloid leukemia during tyrosine kinase inhibtor-therapy / 中华血液学杂志

Objective@#To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph- MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph+ CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph-) during tyrosine kinase inhibtor (TKI) - therapy.@*Methods@#We retrospectively analyzed Ph+ CML patients who developed CCA/Ph- during TKI-therapy from May 2001 to December 2017.@*Results@#Data of CCA/Ph- 63 patients, including 7 progressing to Ph- MDS/AML and 56 remaining disease stable were collected. Compared with those with stable disease, patients with Ph-MDS/AML had lower hemoglobin (P=0.007) and platelet (P=0.006) counts, and higher proportion of peripheral blasts (P<0.001) when the first time CCA/Ph- was detected, and more mosonomy 7 abnormality (5/7, 71.4%) when MDS or AML was diagnosed; meanwhile, trisomy 8 (32/56, 57.1%) was more common in those with stable disease. Outcome of the patients with Ph- MDS/AML were poor. However, most of those with CCA/Ph- and stable disease had optimal response on TKI-therapy.@*Conclusions@#A few patients with Ph+ CML developed CCA/Ph- during TKI-therapy, most of them had stable disease, but very few patients developed Ph- MDS/AML with more common occurrence of monosomy 7 or unknown cytopenia. Our data suggested the significance of monitoring of peripheral blood smear, bone marrow morphology and cytogenetic analysis once monosomy 7 or unknown cytopenia occurred.

Severe hematologic toxicity and its impact on treatment response in newly diagnosed patients with chronic myeloid leukemia receiving tyrosine kinase-inhibitor therapy / 中华血液学杂志

Objectives@#To explore the incidence and factors of severe leukopenia and/or thrombocytopenia in newly diagnosed patients with chronic myeloid leukemia (CML) to probe their impacts on cytogenetic and molecular responses, progression free survival (PFS) and overall survival (OS) .@*Methods@#Data of newly diagnosed patients with CML in the chronic phase (CP) and/or accelerated phase (AP) were retrospectively collected and analyzed.@*Results@#855 CML patients [including 744 (87%) in the CP and 111 (13.0%) in the AP] were included in this study. 523 (61.2%) patients were male with a median age of 39 years (range, 14-87 years) . 749 (87.6%) patients received imatinib, 93 (10.9%) nilotinib, and 13 (1.5%) dasatinib, respectively as front-line therapy. At a median treatment of 1 month (range, 0.1-7.0 months) , 137 (16.0%) developed ≥grade 3 leukopenia and/or thrombocytopenia and recovered 0.6 month (range, 0.3-6.5 months) . Multivariate analysis showed that female gender (OR=1.5, 95%CI 1.0-2.2, P=0.033) , WBC ≥100×109/L (OR=1.9, 95%CI 1.3-2.8, P=0.001) , CP in Sokal high-risk (OR=2.2, 95%CI 1.2-3.9, P=0.005) , AP with ≥15% blast cells in blood or bone marrow (OR=5.1, 95%CI 1.9-13.3, P=0.001) were factors associated with higher incidence of ≥grade 3 leukopenia and/or thrombocytopenia. Severe leukopenia and/or thrombocytopenia with time of drug discontinuance >2 weeks was associated with lower probabilities of achieving complete cytogenetic (OR=0.4, 95%CI 0.3-0.6, P<0.001) , severe leukopenia and/or thrombocytopenia, no matter the time of drug discontinuance >2 weeks or ≤2 weeks, were associated with lower probabilities of achieving major molecular responses (OR=0.3, 95%CI 0.2-0.5, P<0.001; OR=0.7, 95%CI 0.5-1.0, P=0.036) and MR4.5 (OR=0.2, 95%CI 0.1-0.5, P=0.002; OR=0.7, 95%CI 0.4-1.1, P=0.110) ; however, those had no impacts on PFS and OS.@*Conclusions@#Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×109/L at diagnosed, CP in Sokal high-risk, CML-AP with ≥15% blast cells in blood or bone marrow were at high risk for higher incidence of severe leukopenia and/or thrombocytopenia. Those severe adverse events had impacts on lower cytogenetic and molecular response.

Comparison of the efficacy and safety of Chinese generic imatinib and branded imatinib in patients with chronic myeloid leukemia in consideration of demographic characteristics / 中华血液学杂志

Objectives@#To compare the efficacy and safety of Chinese generic imatinib with branded imatinib as frontline therapy in adults with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) (Frontline group) , and to explore the efficacy and safety of Chinese generic imatinib in CML-CP patients switching from branded imatinib (Switching group) .@*Methods@#Frontline group: Data of adults with newly diagnosed CML-CP receiving Chinese generic imatinib (Xinwei®) or branded imatinib (Glivec®) between October 2013 and August 2018 were retrospectively collected and analyzed. Switching group: Data of adults diagnosed with CML-CP who received branded imatinib and then switched to Chinese generic imatinib after achieving at least complete cytogenetic response (CCyR) were retrospectively collected and analyzed.@*Results@#Frontline group: In total, 409 adult patients receiving Chinese generic imatinib (n=201) or Glivec (n=208) were included in this study. Median age was 42 years (range, 18-83 years) . Comparison of baseline showed significant difference on demographic characteristics among two cohorts: lower education level (P<0.001) , and divorced or widowed status (P=0.004) and rural household registration (P<0.001) were more common in the generic imatinib cohort than those in the Glivec cohort. There was no significant difference on age, gender, Sokal risk score, WBC and HGB between the 2 cohorts. With a median follow-up of 25 months (range, 3-62 months) , there was no significant difference on the 3-year cumulative incidence of achieving CCyR (97.5% vs 94.5%, P=0.592) , major molecular response (MMR) (84.3% vs 93.1%, P=0.208) , molecular response4.0 (MR4.0) (42.7% vs 41.7%, P=0.277) , molecular response4.5 (MR4.5) (25.4% vs 33.0%, P=0.306) as well as the 3-year probabilities of failure free survival (FFS) (76.7% vs 81.0%, P=0.448) , progression free survival (PFS) (91.8% vs 96.3%, P=0.325) and overall survival (OS) (95.8% vs 98.5%, P=0.167) between the generic and branded imatinib cohorts. Multivariate analysis showed the type of imatinib was not associated with treatment responses and outcomes. The incidences of adverse effects were comparable in the 2 cohorts. Switching group: In total, 39 patients switching from branded imatinib to Chinese generic imatinib after achieving at least CCyR were included in this study. Median age was 42 years (range, 23-80 years) . With a median follow-up of 39 months (range, 6-63 months) , molecular responses were maintained in 23 (58.9%) patients and improved in 12 (39.8%) patients. Adverse effects were tolerable.@*Conclusion@#Demographic characteristics might influence the choice of the type of TKI used in CML-CP patients. There was a comparable efficacy and safety between the Chinese generic imatinib and the branded imatinib in adults with newly diagnosed CML-CP under standard management and closely monitoring. Patients could safely switch from the branded imatinib to the Chinese generic imatinib.

Differential analysis of blood flow parameters of ophthalmic artery by color Doppler imaging in patients with diabetes with or without retinopathy / 中国基层医药

Objective To explore the differences of blood flow parameters of ophthalmic artery by color Doppler imaging in patients with diabetes mellitus with or without retinopathy.Methods 120 patients with diabetes mellitus were collected.According to whether the patients with retinal lesions,the patients were divided into the lesion group and the non lesion group,60 cases in each group.The pulsatility index,systolic blood peak,diastolic blood peak and resistance index in posterior ciliary artery(PCA),ophthalmic artery(OA),central retinal artery(CRA) were compared between the two groups.Results (1)PCA parameters:the pulsatility index[(1.93±0.38) vs.(1.26±0.32),t=10.447],resistance index[(0.92±0.01) vs.(0.58±0.06),t=43.297]of the lesion group were higher than those of the non lesion group(all P＜0.001),and systolic blood peak,diastolic blood peak were lower,the differences were statistically significant(t=11.735,10.762,all P＜0.001).(2)OA parameters:the systolic blood peak[(27.33±8.72)cm/s vs.(35.64±6.88)cm/s,t=5.795],diastolic blood peak[(7.44±3.57)cm/s vs.(10.28±2.92)cm/s,t=4.770]of the lesion group were less than those of the non lesion group(all P＜0.001),resistance index was higher[(1.97±0.34) vs.(1.39±0.18),t=11.678,P＜0.001],but the pulsatility index had no significant difference between the two groups(t=1.732,P=0.086).(3)CRA parameters:the systolic blood peak[(7.91±2.37)cm/s vs.(10.81±2.76)cm/s,t=6.175]and diastolic blood peak[(3.17±1.99)cm/s vs.(5.04±0.66)cm/s,t=6.909]of the lesion group were less than those of the non lesion group(all P＜0.001),the pulsatility index and resistance index were higher than those of the non lesion group(t=54.222,34.293,all P＜0.001).Conclusion The analysis of the parameters of the blood flow parameters in the patients with diabetic retinopathy by fundus artery ultrasound imaging has a certain reference value.

Dasatinib treatment based on BCR- ABL mutation detection in imatinib- resistant patients with chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To evaluate the efficiency of dasatinib as the second- or third-line tyrosine kinase inhibitor (TKI)in imatinib-resistant patients with chronic myeloid leukemia (CML)based on BCR-ABL mutation detection.</p><p><b>METHODS</b>122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib- and nilotinib-resistance, 55 in the chronic-phase (CP), 21 in the accelerated- phase (AP)and 46 in the blast- phase (BP). Those harboring dasatinib highly- resistant mutations (T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival (PFS)and overall survival (OS)were analyzed. BCR- ABL mutation detection was performed once the patients failed on dasatinib.</p><p><b>RESULTS</b>In the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR)and molecular response 4.5 (MR4.5)were 92.7%, 53.7%, 29.6% and 14.8%, respectively. 4-year PFS and OS rates were 84.4% and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0% and 35.0%; and 3-year PFS and OS rates were 56.1% and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0% and 21.4%; and 1-year PFS and OS rates were 43.6% and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second- line TKI or the third-line TKI. Of the 75 patients who were resistant to dasatinib, 37 (48.7%)developed new mutation(s), and T315I (59.5%)was the most common mutation type. The patients who already harbored mutation(s)before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib (65.7%vs 34.1%,P=0.006).</p><p><b>CONCLUSIONS</b>Dasatinib was proved to be effective in the treatment of imatinib- or/and nilotinib-resistant CML patients, especially in both CP and AP cohorts. The significance of BCR-ABL mutation screening and monitoring should be highlighted before and during dasatinib therapy.</p>

A comparison of efficacy and safety between Chinese generic imatinib versus branded imatinib in patients with newly-diagnosed chronic myeloid leukemia in the chronic phase: a single-center prospective cohort study / 中华内科杂志

Objective To compare the efficacy and safety between Chinese generic imatinib (Xinwei(R),Jiansu Hansoh Pharmaceutical Group Co.,Ltd.) versus branded imatinib (Glivec(R),Novartis) in patients with newly-diagnosed chronic myeloid leukemia in chronic phase (CML-CP).Methods Patients with newly diagnosed CML-CP were enrolled and assigned to receive either Xinwei or Glivec at an initial dose of 400 mg/d according to patients' financial capability.The efficacy and adverse effects were evaluated.Results From January 2014 to September 2015,145 eligible patients were assigned to Xinwei (n =89) or Glivec (n =56) group.All patients were treated and followed up at least 3 months.At 3 months,the complete response rates were 95.5％ (85/89) and 100％ (56/56),major cytogenetic response rates were 74.2％ (66/89) and 80.4％ (45/56),and the proportions of achieving BCR-ALBIS ≤ 10％ were 76.1％ (67/88) and 82.1％ (46/56) in Xinwei and Glivec groups respectively (all P ＞0.05).With a median follow-up of 12 months,2 patients in each group progressed to accelerate or blast phase.Hematologic and non-hematologic side effects were similar between the 2 groups.Conclusions Early hematological,cytogenetic and molecular responses between Xinwei and Glivec are comparable in newly-diagnosed CML-CP patients.The progression rate and side effects are also similar between the 2 groups.

Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Significant efforts have been made to identify factors that differentiate patients treated with novel therapies, such as bortezomib in multiple myeloma (MM). The exact expression pattern and prognostic value of the cancer/testis antigen preferentially expressed antigen of melanoma (PRAME) in MM are unknown and were explored in this study.</p><p><b>METHODS</b>The transcript level of PRAME was detected in bone marrow specimens from 100 newly diagnosed MM patients using real-time quantitative polymerase chain reaction, and the prognostic value of PRAME was determined through retrospective survival analysis. PRAME expression higher than the upper limit of normal bone marrow was defined as PRAME overexpression or PRAME (+).</p><p><b>RESULTS</b>Sixty-two patients (62.0%) overexpressed PRAME. PRAME overexpression showed no prognostic significance to either overall survival (n = 100) or progression-free survival (PFS, n = 96, all P > 0.05) of patients. The patients were also categorized according to regimens with or without bortezomib. PRAME overexpression tended to be associated with a lower two-year PFS rate in patients treated with non-bortezomib-containing regimens (53.5% vs. 76.9%, P = 0.071). By contrast, it was not associated with the two-year PFS rate in patients with bortezomib-containing regimens (77.5% vs. 63.9%, P > 0.05). When the patients were categorized into PRAME (+) and PRAME (-) groups, treatment with bortezomibcontaining regimens predicted a higher two-year PFS rate in PRAME (+) patients (77.5% vs. 53.5%, P = 0.027) but showed no significant effect on two-year PFS rate in PRAME (-) patients (63.9% vs. 76.9%, P > 0.05).</p><p><b>CONCLUSION</b>PRAME overexpression might be an adverse prognostic factor of PFS in MM patients treated with non-bortezomib-containing regimens. Bortezomib improves PFS in patients overexpressing PRAME.</p>

The efficacy and safety of donor lymphocyte infusion to treat Epstein-Barr virus associated lymphoproliferative diseases after allogeneic hematopoietic stem cell transplantation / 中华内科杂志

Objective To analyse our series patients' data to assess its efficacy and safety of donor lymphocyte infusion (DLI) for Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorders (PTLD) after allogeneic hematopoietic stem cell transplantation (HSCT). Methods Patients received HSCT from November 2006 to November 2009 and diagnosed as EBV associated PTLD by pathological or clinical methods were enrolled in this study. Lymphocyte was prepared by COBE collector.Related haplo-donors were the alternative if the original donors was unavailable. A range of mononuclear cell (MNC) dose of (0.5-1.0) × 108/kg was designed and the expected number of T lymphocyte included was at level of 107/kg. Cyclosporine (CsA) trough concentration was kept in a therapeutic level. Results Nine patients with PTLD received DLI 13 times, the median number of PBMC infused was 0.8 (0.16-1.03) ×108/kg, CD3+T cell number was 4.2 (1.6-5.7) × 107/kg. Seven patients received peripheral blood mononuclear cells (PBMC) from original haplo-identical donors, with 7 response and 6 complete remission.Defervescence occurred after 2 ( 1-5 ) d, and adenopathy began to recover in 6 ( 1-14 ) d after the initial infusion of leukocytes. Graft versus host diseases (GVHD) occurred in 6 recipients out of 7 evaluable patients, and all were controlled successfully. Three patients survived for 38, 23 and 3 months after PTLD.Conclusion In this small series cases, infusion of controlled dose of lymphocyte from primary donor is an effective and safe therapy for EBV associated PTLD after mismatched/haploidentical HSCT while the optimal regimen needs to be further studied.

Allogeneic bone marrow transplantation for the treatment of Bruton disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the efficacy of allogeneic bone marrow transplantation (allo-BMT) for the treatment of Bruton disease.</p><p><b>METHODS</b>HLA-matched sibling bone marrow transplantation was performed for the treatment of 2 cases of X-linked agammaglobulinemia. One of them received allo-BMT twice.</p><p><b>RESULTS</b>Recovery of hematopoiesis was gained at day 20 and day 13 after allo-BMT in the two cases respectively. Serum immunoglobin rose gradually to normal level in three months. Their humoral immuno-system was reconstituted and life quality improved. These two patients are still in disease-free survival for 13 and 2 years respectively. There was no serious graft-versus-host-disease.</p><p><b>CONCLUSION</b>Stem cell transplantation is a choice for the treatment of Bruton disease.</p>

The Role of Calcium Ion in Apotopsis of HL-60 Cells Induced by VP-16 / 中国实验血液学杂志

To study the significance of calcium in the apoptosis of HL-60 cells induced by VP-16, the technology of flow cytometry, confocal laser scanning microscopy and Western blot were used. The results showed that VP-16 could induced the apoptosis of HL-60 cells and transient increase of intracellular calcium concentration; EGTA [ethylene glycol-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid], that could combine the extracellular calcium, did not prevent the apoptosis of HL-60 cells. BAPTA-AM [1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxy-methyl) ester], however, a chelating agent of intracellular calcium ions, could prevent apoptosis and the release of cytochrome C from HL-60 cells. It was concluded that the calcium plays an important role in apoptosis and the release of cytochrome C.