1.Clinical analysis of 14 patients aged ≤ 50 years with high-risk multiple myeloma treated with allogeneic hematopoietic stem cell transplantation
Pan PAN ; Jiali WANG ; Weihua ZHAI ; Qiaoling MA ; Donglin YANG ; Sizhou FENG ; Mingzhe HAN ; Aiming PANG ; Erlie JIANG
Chinese Journal of Hematology 2024;45(1):28-34
Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis.Methods:In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022.Results:There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%–100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion:allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.
2.Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia
Yuyan SHEN ; Donglin YANG ; Yi HE ; Aiming PANG ; Xin CHEN ; Qiaoling MA ; Rongli ZHANG ; Jialin WEI ; Weihua ZHAI ; Mingzhe HAN ; Erlie JIANG ; Sizhou FENG
Chinese Journal of Hematology 2024;45(4):383-387
Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10 8/kg, and the number of CD34 + cells was 3.29 (2.53-6.10) ×10 6/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.
3.Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification
Hui WANG ; Runzhi MA ; Aiming PANG ; Donglin YANG ; Xin CHEN ; Rongli ZHANG ; Jialin WEI ; Qiaoling MA ; Weihua ZHAI ; Yi HE ; Erlie JIANG ; Mingzhe HAN ; Sizhou FENG
Chinese Journal of Hematology 2024;45(5):445-452
Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022.Methods:A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed.Results:① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% –80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P=0.690) . Conclusion:Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient’s OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.
4.Survival efficacy of MDS/AML patients with TP53 abnormal received allogeneic hematopoietic stem cell transplantation
Dan FENG ; Mingyang WANG ; Jia LIU ; Haixiao ZHANG ; Xin CHEN ; Rongli ZHANG ; Weihua ZHAI ; Qiaoling MA ; Aiming PANG ; Donglin YANG ; Jialin WEI ; Yi HE ; Sizhou FENG ; Mingzhe HAN ; Erlie JIANG
Chinese Journal of Hematology 2023;44(3):222-229
Objective:TP53-abnormal MDS/acute myeloid leukemia (AML) patients’ allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment’s effectiveness and influencing factors should be studied.Methods:42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed.Results:There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C ( P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS ( P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS ( P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion:Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.
5.Efficacy and safety of Venetoclax in the treatment of 25 patients with recurrent hematologic malignancies after an allogeneic hematopoietic stem cell transplantation
Xin CHEN ; Zengyan LIU ; Rongli ZHANG ; Weihua ZHAI ; Qiaoling MA ; Aiming PANG ; Donglin YANG ; Yi HE ; Jialin WEI ; Sizhou FENG ; Mingzhe HAN ; Erlie JIANG
Chinese Journal of Hematology 2022;43(7):542-549
Objegtive:To investigate the efficacy and safety of preemptive/salvage therapy with venetoclax (VEN) in patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:Retrospective analysis the clinical data of 25 patients with minimal residual disease (MRD) positive or morphological recurrence after allo-HSCT treated with VEN in the hematological Hospital of Chinese Academy of Medical Sciences from 2021.2 to 2021.11, there were 15 MRD positive patients (preemptive treatment group) and 10 morphological recurrence patients (salvage treatment group) . The dose of VEN in both groups was 400 mg/d, which was reduced to 100 mg/d when combined with azole antifungal drugs.Results:①In the preemptive group, there were 7 males and 8 females, with a median age of 32 (18-52) years; There were 13 cases of acute myeloid leukemia (AML) , 1 case of acute lymphoblastic leukemia (ALL) and 1 case of primary myelofibrosis (PMF) ; the median time from MRD positive to the application of VEN was 2.5 (0-12.5) months. The median course of treatment was 2 (1-4) . On the 7th day of the first course of treatment, the median concentration of VEN was 1945 (688-5383) μg/L. After one course of VEN treatment, MRD in 8 patients turned negative (major responses) , MRD in 4 patients decreased by 50% compared with that before treatment, 3 cases were ineffective, and the overall response rate (ORR) was 80% (12/15) . On the 7th day of treatment, 3 of the 9 patients with VEN blood concentration <1 000 μg/L or >3 000 μg/L turned negative for MRD (33.3%) , and 5 of the 6 patients with VEN blood concentration between 1000 and 3000 μg/L turned negative for MRD (83.3%) . Grade 3/4 neutropenia occurred in 5 patients (33%) and grade 3/4 thrombocytopenia occurred in 5 patients (33%) , there were no new cases of severe infection and death. ②In the salvage group, there were 7 males and 3 females, with a median age of 44 (28-59) years; there were 6 cases of AML, 2 cases of ALL, 1 case of atypical chronic myeloid leukemia (aCML) , 1 case of refractory hemopenia with multiline dysplasia (MDS-RCMD) ; the median time from relapse to application of VEN was 0 (0-1) months. The median treatment was 1 (1-2) course. The median concentration of VEN on the 7th day of the first course of treatment was 2 419 (1 200-6 155) μg/L. After one course of VEN treatment, 3 cases achieved complete remission (CR) (major responses) and 3 cases achieved partial remission (PR) , 4 cases were ineffective and the ORR was 60% (6/10) . On the 7th day of treatment, 1 of the 4 patients with VEN blood concentration >3 000 μg/L achieved CR (25%) , and 2 of the 6 patients with VEN blood concentration between 1 000 and 3 000 μg/L achieved CR (33.3%) . Grade 3/4 neutropenia and grade 3/4 thrombocytopenia occurred in 10 patients (100%) . One patient died of severe pulmonary infection. ③The median follow-up was 4.5 (1-8.5) months. The overall survival rate (OS) of the preemptive group and the salvage group were (70.2±12.7) % and (50.0± 15.8) %, respectively ( χ2=1.873, P=0.171) . The OS of patients with and without primary response to one course of VEN were (90.9±8.7) % and (36.2±14.7) % respectively ( χ2=6.843, P=0.009) . Three patients with TP53 mutation achieved the major responses after VEN treatment. Conclusion:Preemptive/salvage therapy with VEN after allo-HSCT in patients with hematological malignancies is effective and well tolerated, monitoring the concentration of VEN is expected to improve the curative effect. The prognosis of patients who fail to reach the major responses after one course of preemptive/salvage treatment with VEN is poor, so they need to switch to other treatment schemes as soon as possible.
6.A multicenter retrospective study on the etiology of necrotizing pneumonia in children
Yunlian ZHOU ; Jinrong LIU ; Qiuwei YI ; Lina CHEN ; Zhiying HAN ; Changdi XU ; Suyan LIU ; Chuangli HAO ; Jing LIU ; Qiaoling LI ; Lijun WANG ; Chao WANG ; Guanghua CHE ; Yuanyuan ZHANG ; Lin TONG ; Yeqing LIU ; Shunying ZHAO ; Yuejie ZHENG ; Shu LI ; Hanmin LIU ; Jie CHANG ; Deyu ZHAO ; Yingxue ZOU ; Xinxing ZHANG ; Guangmin NONG ; Hailin ZHANG ; Jianli PAN ; Yanni CHEN ; Xiaoyan DONG ; Yunfeng ZHANG ; Yingshuo WANG ; Dehua YANG ; Quan LU ; Zhimin CHEN
Chinese Journal of Pediatrics 2021;59(8):658-664
Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.
7.Allo-HSCT for acute myeloid leukemia with myelodysplastic-related changes: a clinical analysis
Haixiao ZHANG ; Aiming PANG ; Xin CHEN ; Rongli ZHANG ; Weihua ZHAI ; Qiaoling MA ; Donglin YANG ; Jialin WEI ; Yi HE ; Sizhou FENG ; Mingzhe HAN ; Erlie JIANG
Chinese Journal of Hematology 2021;42(10):814-822
Objective:To evaluate the outcomes and prognostic factors of adults with acute myeloid leukemia with myelodysplastic-related changes (AML-MRC) who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) . The genetic mutation lineage of patients with AML-MRC and the molecular mutation affecting the transplantation prognosis was discussed.Methods:The clinical data of 75 patients with AML-MRC who underwent allo-HACT from 2006 to 2020 were retrospectively analyzed for clinical characteristics, survival, relapse-related indicators, and risk factors affecting transplantation prognosis. Additionally, the clinical characteristics and prognosis of multilineage dysplasia (M) group, history of myelodysplastic syndrome (MDS) or myelodysplastic syndrome/myelodysplastic proliferative tumor (MDS/MPN) (H) group, and MDS related cytogenetic abnormalities (C) group were compared. The bone marrow of 43 patients underwent targeting second-generation sequencing (137 genes) .Results:①There were 41 males and 34 females with a median age of 41 (18-56) years, a median follow-up time of 35 (95% CI 30-49) months, and a median survival time (OS) of 78 (95% CI 23-) months. Three-year OS and event-free survival (EFS) were 57.1% (95% CI 45.6%-71.4%) and 52.0% (95% CI 40.8%-66.1%) . Also, the three-year cumulative recurrence rate (CIR) and transplant-related mortality rate (TRM) were 26.8% (95% CI 16.6%-30.0%) and 22.7% (95% CI 13.2%-33.8%) , respectively. Furthermore, multivariate analysis revealed that pre-transplant non-CR1 status was an independent risk factor for OS and EFS. Other independent risk factors for OS included abnormal karyotype of -5/5q- chromosome and the absence of chronic graft-versus-host disease (cGVHD) after transplantation. ②Among the 75 patients, 59 (78.7%) were in group H, 20 had received demethylation drugs before turning to AML and nine cases (12.0%) in group C and seven cases (9.3%) in group M. There was no significant difference in the three-year OS and EFS among the three groups[group M vs H vs C: OS: 71.4% (95% CI 44.7%-100.0%) vs 55.0% (95% CI 41.8%-72.5%) vs 55.6% (95% CI 31.0%-99.7%) , P=0.700; EFS: 71.4% (95% CI 44.7%-100.0%) vs 46.5% (95% CI 34.0%-63.8%) vs 55.6% (95% CI 31.0%-99.7%) , P=0.600]. Compared with primary and secondary AML-MRC, there was no statistically significant difference in the three-year OS and EFS[61.9% (95% CI 41.9%-91.4%) vs 55.0% (95% CI 41.8%-72.5%) , P=0.600; 61.9% (95% CI 41.9%-91.4%) vs 46.5% (95% CI 34.0%-63.8%) , P=0.400]. Furthermore, there was no significant difference in the time to AML between patients who received demethylation treatment before (20 cases) and those who did not (39 cases) [195 (16-937) d vs 162 (9-3167) d, P=0.804]. Moreover, there were no statistically significant differences in the three-year OS and EFS between the two groups ( P=0.400, P=0.700) . ③ NGS test was performed on bone marrow samples of 43 patients (57.3%) , and 73 mutation types were found. Additionally, U2AF1 had the highest mutation incidence (11 cases, 25.6%) , and more than 10% were found: RUNX1 (ten cases, 23.3%) , NRAS (ten cases, 23.3%) , ASXL1 (six cases, 14.0%) , PTPN11 (five cases, 11.6%) , TET2 (five cases, 11.6%) . Univariate analysis showed U2AF1[ P=0.875, HR=1.110 (95% CI 0.295-4.195) ], RUNX1[ P=0.685, HR=0.728 (95% CI 0.157-3.375) ], NRAS[ P=0.919, HR=0.923 (95% CI 0.196-4.334) ] mutation did not affect OS. Conclusion:Chromosome abnormality of -5/5q-, cGVHD, and non-CR1 status before transplantation were independent risk factors for OS in patients with allo-HSCT and AML-MRC. Additionally, the MHC subgroup classification was not a factor affecting the prognosis of transplantation. Treatment with demethylated drugs may not delay MDS turning to AML and prolong the OS after transplantation.
8.The effect of CYP3A5 gene polymorphism on tacrolimus concentration and adverse events in patients undergoing allogeneic hematopoietic stem cell transplantation
Xin CHEN ; Rongli ZHANG ; Weihua ZHAI ; Qiaoling MA ; Aiming PANG ; Donglin YANG ; Yi HE ; Jialin WEI ; Erlie JIANG ; Sizhou FENG ; Mingzhe HAN
Chinese Journal of Hematology 2021;42(10):828-833
Objective:To investigates the relationship between CYP3A5 gene polymorphism, tacrolimus concentration, and acute graft versus host disease (GVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A retrospective analysis of the clinical data of 35 Chinese adult patients who received allo-HSCT from July 2019 to February 2020 was conducted. Also, bone marrow samples were collected before transplantation for CYP3A5 genotyping, and intravenous infusion of tacrolimus and a short course of methotrexate (MTX) ± mycophenolate were used to prevent GVHD. The initial concentration was monitored on the second or third day of tacrolimus administration, followed by 2-3 times a week. The drug dose was adjusted according to the target blood concentration (10-15 ng/ml) .Results:In 16 allo-HSCT patients with CYP3A5 *3/*3 gene, the initial concentration of tacrolimus (9.82 ng/ml vs 8.53 ng/ml) , the initial concentration/dose (C/D) ratio (5.72 ng·ml -1·mg -1vs 4.26 ng·ml -1·mg -1) , and the median C/D ratio in the first two weeks after HSCT (5.29 ng·ml -1·mg -1vs 4.61 ng·ml -1·mg -1, 5.65 ng·ml -1·mg -1vs 4.56 ng·ml -1·mg -1) were significantly higher than in 19 patients with at least one CYP3A5 * 1 allele ( P=0.028, 0.001, 0.037, 0.045) . The incidence of Ⅲ-Ⅳ aGVHD in patients with CYP3A5*1 alleles was higher than in patients with CYP3A5*3/*3 gene[ (26.3±10.1) % vs (6.2±6.1) %, P=0.187]. Conclusion:CYP3A5 genotype-directed administration may help achieve the target blood concentration of tacrolimus after HSCT more quickly, reduce the incidence of severe aGVHD, and improve the efficacy of transplantation.
9.Analysis of risk factors of relapse after allogeneic hematopoietic stem cell transplantation in patients with t (8;21) acute myeloid leukemia
Wenwen GUO ; Xin LIU ; Aiming PANG ; Weihua ZHAI ; Donglin YANG ; Xin CHEN ; Qiaoling MA ; Yi HE ; Rongli ZHANG ; Sizhou FENG ; Mingzhe HAN ; Erlie JIANG
Chinese Journal of Hematology 2021;42(12):998-1004
Objective:To investigate the risk factors of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with t (8;21) acute myeloid leukemia (AML) .Methods:The clinical features of patients with t (8;21) AML who received allo-HSCT between January 2008 and October 2020 in the Hospital of Blood Disease and the Chinese Academy of Medical Sciences were retrospectively analyzed. Univariate and multivariate analyses were performed on the factors that might influence relapse.Results:A total of 73 patients were enrolled. The analysis revealed that, out of the 73 cases, 10 had relapses, with a 3-year cumulative incidence of relapse (CIR) of 15.7% (95% CI 7.3%-26.8%) . The median time of relapse was 9.2 (2.0-47.6) months. Furthermore, 19 cases died, with a 3-year overall survival (OS) of 68.9% (95% CI 56.4%-81.4%) . Compared with the RUNX1-RUNX1T1 at first diagnosis, a ≥ 3-log reduction within 3 months and/or 4-log reduction within 3-12 months can significantly decrease 3-year CIR after HSCT (13.3% vs 57.1%; 5.1% vs 25.0%, both P<0.001) . Cox multivariate analysis showed that high levels of RUNX1-RUNX1T1 (≥1.58%) on the day of transplantation (day 0) [ P=0.006; HR=28.849 (95% CI 2.68-310.524) ] and the flow cytometric analysis of blasts ratio in bone marrow ≥60% at first diagnosis [ P=0.015; HR=6.64 (95% CI 1.448-30.457) ] were independent risk factors for relapse. Furthermore, no significant difference in the effect of c-Kit and Flt3 gene mutations on relapse after transplantation was observed ( P=0.877 and P=0.773, resp) . The flow cytometric analysis of blasts ratio in bone marrow ≥60% at first diagnosis [ P<0.001; HR=8.925 (95% CI 2.702-29.476) ] and the number of courses to achieve complete remission ≥ 2[ P=0.013; HR=4.495 (95% CI 1.379-14.649) ] were independent risk factors for OS. Conclusion:Both high levels of RUNX1-RUNX1T1 (≥1.58%) on the day of transplantation (day 0) and the ratio of flow cytometric analysis of blasts in bone marrow at first diagnosis increase the chance of t (8;21) AML relapse after allo-HSCT. Detection of the transcription levels of RUNX1-RUNX1T1 after allo-HSCT at different times could help predict the hazard of relapse.
10.Optimization of Ultrafiltration Technology of Enzymatic Hydrolysate from Eucommia ulmoides Peel
Ling XIE ; Han TAO ; Xuejun ZHANG ; Lingli ZHANG ; Yangjie HE ; Yunxia TIAN ; Qiaoling WU ; Chun JI
China Pharmacy 2021;32(13):1557-1564
OBJECTIVE:To optim ize the ultrafiltration technology of enzymatic hydrolysate from Eucommia ulmoides peel. METHODS:The single factor test was adopted to investigate the effects of molecular weight of ultrafiltration membrane ,liquid temperature,operating pressure ,operating frequency ,membrane filtration time ,liquid concentration and pH on transfer rates of aucubin,geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel. Setting the molecular cut off of fixed ultrafiltration membrane of 100 000,liquid concentration of 7 g/L,and pH value of 7,the ultrafiltration technology was optimized by Box-Behnken design response-surface methodology and validated with liquid temperature ,operating pressure,operating frequency and membrane passing time as factors ,using comprehensive scores calculated from transfer rates of aucubin,geniposide and chlorogenic acid as well as solid removal rate as indexes. RESULTS :The optimal ultrafiltration technology of enzymatic hydrolysate from E. ulmoides peel was as follows as liquid temperature of 35 ℃,operating pressure of 0.5 MPa,operating frequency of 35 Hz and membrane passing time of 42 min. Results of validation tests showed that the comprehensive scores of the transfer rates of aucubin ,geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel was 78.06%(RSD=1.43%,n=3),and its relative error with the predicted value (77.18%) was 1.14%. CONCLUSIONS :The optimized ultrafiltration technology is stable and reliable ,and can be used for the ultrafiltration purification of enzymatic hydrolysate from E. ulmoides peel.

Result Analysis
Print
Save
E-mail