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Objective:To explore the application of venetoclax in transplantation of patients with refractory acute myeloid leukemia (AML).Methods:The diagnosis and treatment process of a patient with refractory AML who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) under venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen after induction therapy failure in the First Affiliated Hospital of Soochow University in March 2020 were retrospectively analyzed.Results:The patient was a 28-year-old female who was diagnosed with refractory AML. The patient was initially given induction chemotherapy with IA (idarubicin+cytarabine) (3+7) regimen, but the disease did not relieve, then the induction chemotherapy with CLAG (cladribine+cytarabine+granulocyte colony stimulating factor) regimen was given, but the disease still did not relieve. After chemotherapy with venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen, salvage haploid allo-HSCT was performed. Re-examination of bone marrow showed remission, and implantation was successful. The patient was followed up for 100 days and had sustained remission, and no transplantation complications occurred.Conclusion:For refractory AML patients who have failed primary induction therapy, the use of venetoclax and hypomethylating agents bridging myeloablative preconditioning regimen can be used as a preferred solution for salvage allo-HSCT.
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Objective:To investigate the incidence, risk factors and survival of cGVHD patients in combination of a haploidentical donor supported with an unrelated umbilical cord blood for hematopoietic stem cells transplantation (haplo-cord-HSCT).Methods:300 hematological malignancies individuals who received dual transplantation were enrolled in the study between January 2012 and July 2016 at the department of Hematology in the First Affiliated Hospital of Soochow University. The clinical diagnosis and scoring the severity of cGVHD syndromes according the National Institutes of Health (NIH) consensus conference in the 2014 update. Cox proportional hazards regression was used to identify risk factors associated with transplant outcomes.Results:During follow-up with a median time of 26.4 months (range 0.2-61.8) post transplantation, the 1-year, 3-year and 5-year cumulative incidence of cGVHD was 26.3 % (95 % confidence interval [CI], 23.5 %~29.1 %), 30.3 % (95 % CI, 27.3 %~33.3 % ) and 32.2 % (95 % CI, 28.7 %~35.7 %). For all 73 patients with cGVHD, first-line or second-line treatment were given. During the follow-up period, 53 patients survived, and 20 patients died. In multivariate analysis, the cGVHD overall survival (GOS) were associated with thrombocytopenia(<100×109/L)(HR=0.103, 95 % CI 3 %-36.1 %, P<0.001). Conclusions:Our data suggest that, the 5-year cumulative incidence of cGVHD was 32.2 % after haplo-cord-HSCT with hematological malignancies. Thrombocytopenia (<100×109/L)was independent risk factors for GOS.
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Objective@#To compare the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) with paroxysmal nocturnal hemoglobinuria-aplastic anemia (PNH-AA) syndrome.@*Methods@#The outcomes of 46 patients who received allo-HSCT (16 PNH patients, 30 PNH-AA patients) from July 10, 2007 to June 2, 2018 were analyzed retrospectively. The conditioning regimen was busulfan, cyclophosphoramide, and ATG in haploidentical donors and unrelated donors. Patients with matched sibling donors were treated with the fludarabine, cyclophosphamide, and ATG regimen.@*Results@#There were no differences of baseline data between the 2 groups except gender distribution and the numbers of haploidentical donor transplantation. The median values of absolute nucleated cell counts were 10.58 (3.83-13.83) ×108/kg in the PNH group and 10.81 (3.96-33.40) ×108/kg in the PNH-AA group (P=0.668) . The median doses of CD34+ cells infused were 5.00 (3.14-8.42) ×106/kg and 3.57 (1.97-6.17) ×106/kg (P=0.002) , respectively. All patients obtained complete engraftment. The median time for myeloid engraftment were 11 (7-14) days in the PNH group and 12 (10-26) days in the PNH-AA group (P=0.003) . The median time for platelet engraftment were 13 (11-16) days and 18 (12-75) days (P=0.002) , respectively, after a median follow-up of 36 (4-132) months in the PNH group and 26 (4-75) months in the PNH-AA group (P=0.428) . There were no differences of incidence rates of acute graft-versus-host disease (aGVHD) , chronic GVHD and infection between PNH and PNH-AA groups (P>0.05) . No patient occurred early death and relapse. The estimated 3-year overall survival (OS) of PNH and PNH-AA groups were (100.0±0.0) % and (85.7± 6.6) % (P=0.141) , GVHD-free and failure-free survival (GFFS) were (100.0±0.0) %, (78.7±7.7) % (P=0.067) .@*Conclusions@#allo-HSCT is effective for patients with PNH and PNH-AA syndrome. The preliminary results indicate that myeloid and platelet engraftment in PNH group were faster than PNH-AA group. There were no differences in OS and GFFS between PNH group and PNH-AA group.
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Objective@#To compare the outcomes between haploidentical donor hematopoietic stem cell transplantation (haplo-HSCT) and matched-sibling donor transplantation (MSD-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH) .@*Methods@#The clinical data of 40 PNH patients received HSCT (haplo-HSCT=25, MSD-HSCT=15) from July 2007 to May 2018 were analyzed retrospectively to compare the outcomes between haplo-HSCT and MSD-HSCT groups.@*Results@#There were no differences in terms of gender, age, patients of PNH-AA and median time from diagnosis to transplantation between the 2 groups (P>0.05) . The median values of absolute mononuclear cell counts and CD34+ cells infused were 10.74 (4.80-22.86) ×108/kg and 12.19 (5.14-17.25) ×108/kg (P=0.866) , 3.57 (0.68-7.80) ×106/kg and 4.00 (3.02-8.42) ×106/kg (P=0.151) respectively, in haplo-HSCT and MSD-HSCT groups. All patients attained complete engraftment, no patient occurred graft failure. The median durations for myeloid and platelet engraftment were 12 (range, 9-26) and 11 (range, 7-15) days (P=0.065) , 19 (range, 11-75) and 13 (range, 11-25) days (P=0.027) respectively, in haplo-HSCT and MSD-HSCT groups. During a median follow-up of 26 (4-65) months in haplo-HSCT and 36 (4-132) months in MSD-HSCT groups (P=0.294) , the incidences of grade Ⅰ-Ⅳ acute graft-versus-host disease (aGVHD) were 32.0% and 20.0% (P=0.343) , grade Ⅱ-Ⅳ aGVHD were 16.0%, 13.3% (P=0.759) , chronic GVHD were 30.7% and 24.6% (P=0.418) , moderate-severe chronic GVHD were 12.7% and 7.1% (P=0.522) respectively, in haplo-HSCT and MSD-HSCT groups. The incidences of infection were 32.0% (8/25) and 26.7% (4/15) (P=1.000) respectively, in haplo-HSCT and MSD-HSCT groups. No patients occurred early death and relapse. Three-year estimated overall survival (OS) were (86.5±7.3) % and (93.3 ±6.4) % (P=0.520) , GVHD-free and failure-free survival (GFFS) were (78.3±8.6) % and (92.9±6.9) % (P=0.250) respectively, in haplo-HSCT and MSD-HSCT groups.@*Conclusion@#The preliminary results indicated that haplo-HSCT was a feasible choice for PNH with favorable outcomes, haplo-HSCT and MSD-HSCT produced similar therapeutic efficacy.
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Objective To investigate the monitoring significance of WT1 gene level in the prognosis of acute myeloid leukemia (AML) patients with normal karyotype after hematopoietic stem cell transplantation (HSCT). Methods The clinical data of 115 AML patients with normal karyotype who were treated with HSCT from July 2009 to March 2017 in the First Affiliated Hospital of Soochow University were retrospectively analyzed. The dynamic detection of bone marrow WT1 gene was carried out by using reverse transcription_polymerase chain reaction (RT_PCR). According to the relative expression level median of WT1 gene before transplantation, the whole patients were divided into the two groups (<median group and ≥median group) for survival analysis. Results There were 52 males and 63 females in 115 patients. The average age was (39± 10) years old. The median white blood cell count at initial diagnosis was 20.45×109/L [(0.5-355.9)×109/L], the ratio of blast cells in the bone marrow was 0.60±0.28, and the relative expression level median of WT1 gene was 87×104, while the median time of the follow_up was 24 (3-79) months. Among 115 patients, 19 cases relapsed. Remission group (96 cases) and relapse group (19 cases) were followed up. The WT1 gene level was monitored by using bone marrow puncture in 1 month, 3 months, 6 months, 12 months after transplantation. It was found that the WT1 gene relative expression level of relapse group was higher than that of remission group, and the differences between the two groups at 6 month_point [remission group (187±50)×104, relapse group (871±211)×104, t ＝ 2.519, P＝ 0.014] and 12 month_point [remission group (51±9)×104, relapse group (1 797±312)×104, t ＝ 4.000, P< 0.05] were statistically different. The overall survival (OS) rate of 2_year, progression_free survival rate in WT1 gene relative expression level < 87×104 group were higher than those in WT1 gene relative expression level ≥87×104 group, the relapse rate in WT1 gene relative expression level <87×104 group was lower than that in WT1 gene relative expression level ≥87×104 group, and the differences were statistically different (all P<0.05). Multivariate analysis showed that the level of WT1 gene at 12 months after transplantation was an independent factor affecting OS ( HR＝4.12, P＝0.046) and PFS ( HR＝5.95, P＝0.001). There were 19 cases of recurrence (16.5%), with a median relapsed time of 11 (1-60) months. When WT1 gene relative expression level was significantly increased in 19 patients, firstly immunosuppressive agents were reduced, of which 6 patients were not influenced by this intervention; in other 13 cases, only 5 cases were influenced by intervention. Conclusions For CN_AML patients, the expression level of WT1 gene before transplantation has a negative correlation with the prognosis. The expression level of WT1 gene at 12 months after transplantation is an independent factor for affecting the survival. The relapsed patients have a higher WT1 expression level, and clinical interventions for relapsed patients have a favorable effect.
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Objective@#To investigate the efficacy of first-line administration of generic dasatinib or first-generation TKI (imatinib) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) treated by hematopoietic stem cell transplantation (HSCT).@*Methods@#Clinical features and prognoses of 63 newly diagnosed Ph+ ALL patients from Jan 2014 to June 2017 treated by HSCT combined with first-line administration of generic dasatinib or imatinib were retrospective analyzed.@*Results@#Of 63 Ph+ ALL patients, 31 cases were administered generic dasatinib, and the other 32 ones imatinib. Complete remission (CR) rates at the fourth week of induction therapy in generic dasatinib and imatinib groups were 96.8% and 93.8% (P=1.000) , respectively. Meanwhile major molecular response (MMR; BCR-ABL/ABL reduce 3log) rates were 41.9% and 43.8% (χ2=0.021, P=0.884), respectively. Relapse rates before transplantation were 6.5% and 12.5% (P=0.672), respectively. MMR rates before HSCT were 83.9% and 68.8% (χ2=1.985, P=0.159), respectively. The 20-monthes overall survival (OS) rates of generic dasatinib and imatinib groups were 95.5% and 76.5% (χ2=0.990, P=0.320) respectively; 20-monthes event-free survival (EFS) rates were 93.5% and 61.4% (χ2=5.926, P=0.015), respectively. Statistically significant differences of EFS were reached. Multiple factors analysis showed that generic dasatinib (HR=0.201, 95% CI 0.045-0.896, P=0.035) and MMR before transplantation (HR=0.344, 95% CI 0.124-0.956, CI=0.041) could improve EFS.@*Conclusions@#First-line administration of generic dasatinib could improve EFS for Ph+ALL patients treated by HSCT when compered with imatinib.
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Objective@#To evaluate the outcome of combination of haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) with an unrelated cord blood unit for severe aplastic anemia (SAA).@*Methods@#The clinical data of 127 SAA patients [including 74 male and 53 female patients, 65 very severe aplastic anemia (vSAA), the median age as 23.5(3-54) years] received HID-HSCT from September 2011 to April 2017 were analyzed retrospectively. The median interval from SAA diagnosis to transplantation was 2 (0.5-180) months. The conditioning was modified Bu/Cy+ATG/ALG-based (Busulfan + cyclophosphamide + antithymocyte immunoglobulin/antilymphocyte immunoglobulin) regimen. Cord blood units were selected based on the results of HLA typing and cell doses evaluated before freezing. Units with at least 4/6 matched HLA loci became the candidates. Prophylaxis for graft-versus host disease (GVHD) was by cyclosporine (CsA), mycophenolate mofetil (MMF) plus short-term methotrexate (MTX).@*Results@#The median values of absolute nucleated cell counts were 10.87 (3.61-24.00)×108/kg in the haploidentical grafts and 2.22 (1.10-7.30)×107/kg in the cord blood units, respectively. The median doses of CD34+ cells infused were 3.49(1.02-8.89) ×106/kg in the haploidentical grafts and 0.56 (0.16-2.27) ×105/kg in the cord blood units, respectively. Of the 127 patients, 5 patients occurred early death, one patient occurred primary graft failure. All 121 surviving patients attained complete haploidentical engraftment. The median durations of myeloid engraftment were 11 (9-28) days and 15 (9-330) days for platelets, with a cumulative platelet engraftment incidence of 96.1%. The incidence of infection was 58.27% (74/127). During a median follow-up of 20.5 (4-60) months, the incidence of grade Ⅱ-Ⅳ acute GVHD was 24.79% (30/121), moderate-severe chronic GVHD was 14.15% (15/106), 4-year estimated overall survival was (78.5±4.3) %, 4-year estimated failure-free survival was (77.4±4.3) %, respectively.@*Conclusion@#Combination of HID-HSCT and an unrelated umbilical cord blood unit was a feasible choice with favorable outcome for SAA patients without matched donors.
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Objective@#To probe the feasibility of decitabine (DAC) combined with micro-transplantation as consolidation treatment for older patients with acute myeloid leukemia (AML).@*Methods@#Between November 2012 and September 2015, 37 consecutive patients with AML ≥60 years of age were analyzed. Of them, 19 patients received consolidation therapy with DAC followed by micro-transplantation (microtransplant group). Another 18 ones (chemo group) were treated with DAC plus priming regimen as consolidation chemotherapy in the same period.@*Results@#There were no significant differences in terms of age, WBC count, and disease status of onset between the microtransplant and chemo groups (P>0.05). The two regimens were well tolerated. There was no difference of CTC grade 3-4 nonhematologic toxicities between the microtransplant and chemo groups (36.8% vs 27.8%, χ2=0.347, P=0.728). The median recovery durations for neutrophil and platelet in the microtransplant group were similar to those in the chemo group (12 vs 13 days, z=1.599, P=0.110; 14 vs 12 days, z=-1.314, P=0.189, respectively). No graft-versus-host disease was observed in the microtransplant group. The 2-year leukemia-free survival and overall survival were better in microtransplant group (50.7% and 54.9%, respectively) than in chemo group (24.3% and 30.0%, respectively) (P=0.047 and P=0.071, respectively).@*Conclusion@#DAC combined with micro-transplantation as a consolidation regimen may be a safe and promising option for older patients with AML.
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Objective@#To study the specific killing effect of CD4 membrane protein targeted chimeric antigen receptor modified T (CAR-T) cell.@*Methods@#The second generation CD4 targeted chimeric antigen receptor containing 4-1BB costimulation domain was insert into lentiviral vector through recombinant DNA technology. Lentivirus was prepared and packaged by 293T cells with four plasmids. Beads activated T cells were transduced with lentivirus and the transduction efficiency was checked with Protein L and flow cytometry. T cell subsets and IFN-γ concentrations were detected with probe-tagged antibody and cytometric bead assay.@*Results@#①The transduction efficiency of activated T cells with prepared lentivirus were 50.0%-70.0%. A subset of CD8+ T cell acquired dim expression of CD4 membrane protein after activation. CD4+T cell and CD8+CD4dim T cell were gradually killed by CD4 targeted CAR-T post lentivirus transduction. ②The kill efficacy of CD4 targeted CAR-T cell and control T cell toward KARPAS 299 T cell at an E∶T ratio of 8∶1 for 24 h was (96.9±2.1)% and (11.2±3.1)%, CAR-T cell has a higher killing efficacy than control T cell (t=7.137, P=0.028). The IFN-γ concentrations in culture supernatant of CAR-T cell with K562-CD4 cell, CAR-T cell with K562 cell and CAR-T cell alone were (15 648±2 168), (1 978±354) and (1 785±268) pg/ml, CAR-T cell cocultured with K562-CD4 cell produced more IFN-γ than the other two controls (P<0.01).@*Conclusions@#CD4 targeted CAR-T has an immunophenotype of CD8+CD4-T cell. CD4 targeted CAR-T cell has killing efficacy toward normal CD4+T cell and CD4+T lymphoma cell. CD4 targeted CAR-T cell also has a killing efficacy toward CD4dim target cell.
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Objective@#To investigate the efficacy of sequential treatment with first-line administration of second-generation tyrosine kinase inhibitors (TKI) and first-generation TKI (imatinib) in patients with Ph+ acute lymphoblastic leukemia (Ph+ ALL) followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#Retrospective analysis of clinical features and prognosis of 76 newly diagnosed Ph +ALL patients from June 2011 to December 2015 treated by allo-HSCT combined with first-line administration of second-generation or first-generation TKI was performed and the efficacy compared.@*Results@#Of 76 Ph+ ALL patients, first-generation TKI was administered in 57 cases, second-generation TKI in 19 cases, including 10 cases of nilotinib and 9 cases of dasatinib. There was no significant difference in age, WBC counts, additional chromosomal abnormalities, time form diagnosis to transplantation, transplantation type, conditioning regimen or TKI initiation time between the two groups. Complete remission (CR) rates at the fourth week of induction therapy in first-generation TKI group and second-generation TKI group was 93.0% and 94.7% (P=1.000), respectively. Major molecular response (MMR, BCR-ABL/ABL reduce 3 log) rates meanwhile were 46.0% and 40.0% (χ2=0.169, P=0.681). Relapse rates before transplantation were 14.0% and 10.5% (P=1.000). MMR rates before transplantation were 54.4% and 68.2% (χ2=1.152, P=0.283). The 2-year overall survival (OS) rates of first-generation and second-generation TKI group were 62.0% and 94.7% (χ2=5.765, P=0.016), 2-year event-free survival (EFS) rates were 46.3% and 84.2% (χ2=5.644, P=0.018), respectively. Univariate analysis showed that second-generation TKI could improve OS (HR=0.126, 95%CI 0.017-0.939, P=0.043). Multiple factors analysis showed that second-generation TKI (HR=0.267, 95%CI 0.081-0.873, P=0.029) and MMR before transplantation (HR=0.496, 95%CI 0.254-0.968, P=0.040) were good independent prognostic factors of EFS.@*Conclusions@#There was significant difference in the efficacy of second-generation TKI and first-generation TKI for Ph+ ALL patients treated by allo-HSCT. First-line administration of second-generation TKI showed better efficacy than that of first-generation TKI for Ph+ ALL patients.
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Objective To examine the value ofprocalcitonin (PCT) in differential diagnosis of bloodstream infections (BSI) caused by coagulase-negative Staphylococcus (CNS) from contamination in Department of Hematology.Methods One hundred and fifty-six patients with bloodstream or intravenous catheter-related CNS infection were included in this study.The patients were treated in Department of Hematology,the First Affiliated Hospital of Soochow University during the period from January 2013 to December 2015.The patients were divided into CNS bloodstream infection group (n=66) and blood culture contamination group (n=90).The two groups were compared in terms of sex,age,diagnosis,length of hospital stay,duration of neutropenia,neutrophil count and lymphocyte count,peak fever,C-reactive protein (CRP) and PCT.The receiver operating characteristic (ROC) curve was plotted with SPSS 21.0 software to analyze the value of PCT in differential diagnosis.Results Age,sex,clinical diagnosis,length of hospital stay,duration of neutropenia,neutrophil count and lymphocyte count did not show significant difference between bloodstream infection group and contamination group (P＞0.05),while peak fever (P＜0.001),CRP (P=0.002) and PCT (P=0.018) were significantly higher in bloodstream infection group than in contamination group.ROC analysis indicated that PCT provided optimal discrimination between these two groups at cnt-offvalue of 0.374 μg/L,with sensitivity of 54.5％ and specificity of 94.4％.The area under the curve (AUC) was 0.830±0.032 (95％ CI:0.767-0.893,P＜0.001).Conclusions PCT may be a good marker for differentiating CNS bloodstream infection from contamination with higher specificity than the commonly used marker CRP.This finding may help clinicians reduce the overuse of antibiotics.
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Objective To investigate the clinical and laboratorial characteristics of patients with myelodysplastic syndrome ( MDS) and erythroid hyperplasia.Methods MDS patients whose bone marrow was hypercellular with erythroid lineage more than 50% and blasts account for less than 20% of non-erythroid cells were enrolled in this study.The ratio of mature erythrocytes to nucleated erythrocytes was no more than 20, namely MDS patients with erythroid hyperplasia ( MDS-E ).The retrospective analysis comprised 102 patients with MDS-E from the First Affiliated Hospital of Suzhou University.Clinical characteristics , karyotype , and the prognostic significance of erythroid hyperplasia were evaluated.Results A total of 48 MDS-E patients (47.1%) presented a variety of cytogenetic abnormalities.The most frequently involved chromosomes were chromosome 8 (39.5%of all abnormal karyotypes ), chromosome 7 (22.9%), followed by chromosome 5 ( 18.8%) , chromosome 1 ( 16.7%) and chromosome 20 ( 16.7%) .Hemoglobin ( Hb) level affected the prognosis by survival analysis.The overall survival ( OS) of MDS-E patients with Hb equal or more than 70 g/L was longer than that of patients less than 70 g/L ( P<0.001).Allogeneic hematopoietic stem cell transplantation (HSCT) significantly improved the OS compared with best supportive care (P<0.001) and chemotherapy (P<0.001).The extent of erythroid hyperplasia in bone marrow did not impact on prognosis ( P=0.187 ).Conclusions Compared with previous reports of MDS patients, MDS-E patients have higher level of erythroid hyperplasia , more common erythroid dyshematopoiesis , more frequent 8 and 1 chromosome abnormalities .The degree of erythroid hyperplasia is not correlated with prognosis.Allogeneic hematopoietic stem cell transplantation improves the prognosis.
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Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.
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Objective@#To investigate the characteristics of the essential thrombocythemia (ET) cases transformed to the acute myeloid leukemia (AML) and the role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of this disease.@*Methods@#The clinical and laboratory characteristics of 3 ET cases before and after transformation and after allo-HSCT were retrospectively analyzed, meanwhile the related literatures were reviewed and discussed.@*Results@#Case 1 was a male patient of 44 years old, whose PLT was 500×109/L when firstly diagnosed ET. After 3 years the disease progressed into myelodysplastic syndrome (MDS) while WT1 expression increased from 77 (first visit) to 13 171 copies/10 000 ABL copies, at the same time chromosome changed dramatically. During the period of decitabine treatment the disease processed into AML. Case 2 was a male of 58 years old whose PLT was 2 100×109/L when firstly diagnosed ET. The disease progressed to AML after 9 years, whose WT1 expression increased from 130 (first visit) to 3 222 copies/10 000 ABL copies, and he relapsed shortly after intensive chemotherapy. Case 3 was a male of 60 years old whose PLT was 900×109/L when firstly diagnosed ET. The disease progressed to AML after 5 years, whose WT1 increased from 56 (first visit) to3 696 copies/10 000 ABL copies. Moreover leukemia spread to central nervous system (CNS) during chemotherapy. Before allo-HSCT, cases 1 did not achieve remission; case 2 relapsed after a short time of remission and case 3 transferred to CNS leukemia. All of the 3 cases underwent allo-HSCT successfully, and they all achieved completely remission, whose chromosome and gene mutation recovered negative. At the same time, CNS leukemia of case 3 disappeared. The median WT1 decreased to 50 copies/10 000 ABL copies. There was no severe complication during the median time of 5 months after allo-HSCT.@*Conclusions@#The patients transformed to AML had poor prognosis, allo-HSCT was the only method that can cure the disease now.
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Objective@#To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment.@*Methods@#Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed.@*Results@#The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) .@*Conclusions@#Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.
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Objective@#To explore the impact on prognosis in favorable-risk acute myeloid leukemia (AML) patients with different consolidation regimens after first complete remission (CR1).@*Methods@#A total of 107 cases of non-refractory adult AML from January 2010 to June 2015 in single center were enrolled in the study. HD-Ara-C group (38 cases) as the control group, we explore the prognosis in three consolidation regimens, including micro-transplantation (16 cases) , autologous transplantation (auto-PBSCT, 14 cases) , allogeneic transplantation (allo-HSCT, 39 cases).@*Results@#Of 107 patients (59 males and 48 females) , with a median age of 33 (16-59) years old and a median follow-up of 36.5 (5.3-79.1) months, the overall relapse rate was 20.6% (22/107) , and overall mortality rate was 18.7% (20/107). The 5 years cumulative relapse rate (CIR) of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 39.7%, 6.2%, 14.3% and 5.6%, respectively (P<0.001). The CIR of the observed group was lower than the HD-Ara-C group. The 5 years progression-free survival (PFS) rate of HD-Ara-C, micro-transplantation, auto-PBSCT and allo-HSCT group were 44.7%, 93.8%, 85.7% and 78.1%, respectively (P=0.011). The PFS of observed groups were similar, but superior to that in HD-Ara-C group. The 5-year overall survival (OS) in four groups was 54.9%, 100%, 92.9% and 77.4%, respectively (P>0.05). Multiple factors analysis showed that compared to HD-Ara-C regimen, allo-HSCT could improve PFS (HR=0.376, P=0.031) , but not OS (P>0.05) ; micro-transplantation and auto-PBSCT could not improve the PFS or OS (P>0.05).@*Conclusion@#As compared with HD-Ara-C regimen, allo-HSCT could obviously decrease CIR, improve PFS, but treatment-related mortality is high. These results show that auto-PBSCT and micro-transplantation have similar outcomes, compared to HD-Ara-C regimen, so both can be used as a option of consolidation treatment for favorable-risk AML.
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Objective@#To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group.@*Methods@#The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing.@*Results@#① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] (P<0.001) , but not for patients with CALR[57 (17-89) y] or MPL mutation[59 (22-71) y] (P>0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level (P<0.05) when compared with patients with CALR mutation or without mutations, or only significantly higher white blood cell count when compared with patients with MPL mutation (P=0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×109/L vs 800 (198-3 730) ×109/L, P<0.001]. ③Karyotype analysis was conducted in 1 160 patients with MPNs, the rates of karyotype abnormality of patients with and without CALR mutation were 9.8% (8/82) and 7.4% (80/1 078) (P=0.441) respectively; The rates of karyotype abnormality of patients with and without JAK2V617F mutation were 7.7% (75/971) and 6.9% (13/189) (P=0.688) respectively. The incidence of karyotype abnormality of patients with CALR mutation was higher than of with JAK2V617F[9.8% (8/82) vs 7.7% (75/971) ] without statistically significant difference (P=0.512) . The karyotype analysis of 7 cases of JAK2 exon12 mutation and 6 ones with MPL gene mutation revealed normal karyotype.@*Conclusions@#Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter lead to unique clinical phenotype.
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Objective To investigate the frequency of c-kit mutation and prognosis in t (8;21) acute myeloid leukemia (AML) patients with trisomy 4. Methods A total of 145 de novo t(8;21) AML patients from February 2005 to January 2013 were analyzed retrospectively. Detection of exons 8 and 17 mutation of c-kit by PCR and cytogenetic analysis by R-banding technologies were performed on bone marrow samples of all patients at diagnosis. Clinical data were collected and analyzed statistically. Results Among 145 t (8;21) AML patients, 12 cases (8.3 %) were trisomy 4, 91.7 % (11/12) of them were identified with c-kit mutation, which was significantly higher than that without trisomy 4 [26.3 % (35/133), P< 0.01]. The follow-up data showed that the patients with trisomy 4 were correlated with the lower overall survival (OS) rate (15 % vs 56 %, P< 0.01) and disease-free survival (DFS) rate (0 vs 51 %, P< 0.01) when compared with patients without trisomy 4. Furthermore, the subgroup of patients with both trisomy 4 and c-kit mutation had a worse OS and DFS (P< 0.05). Conclusions Trisomy 4 is associated with high frequency of c-kit mutation and demonstrates poor prognosis in t(8;21) AML patients. Trisomy 4 or it combined with c-kit gene mutation is the main influencing factor on the survival of the patients with t(8;21) AML.
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Objective To compare the efficacy and safety between flumatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML). Methods A multi-center, randomized and parallel comparison clinical trial was conducted in 24 newly diagnosed patients with Philadelphia chromosome-positive CML-chronic phase (Ph+ CML-CP) who were treated by flumatinib 400 mg/d, 600 mg/d or imatinib for 6 cycles (24 weeks). The hematology was evaluated at pre-medication and the 2nd, 4th, 6th, 8th, 10th, 12th, 16th, 20th, 24th week of post-medication. The morphology, cytogenetics and molecular biology were evaluated at pre-medication and 12th, 24th week of post-medication. Results In terms of efficacy, the main molecular remission (MMR) rate of flumatinib 600 mg/d group was higher than that of imatinib group after 24 weeks [44.44 % (4/9) vs. 14.29 % (1/7), P=0.017]. The rate of bcr-ablIS≤10 % in flumatinib 600 mg/d group was significantly higher than that in imatinib group (P=0.002). PK/PD analysis also hinted that patients treated by flumatinib 600 mg/d was more likely to get molecular reaction in the early stage compared with those treated by flumatinib 400 mg/d. In terms of safety, there was no significant difference in grade Ⅲ-Ⅳ of adverse events among flumatinib 400 mg/d group, flumatinib 600 mg/d group and imatinib group (P >0.05). The common adverse events in flumatinib group included skin toxicity, gastrointestinal reactions and diarrhea.There was no heart and cardiovascular toxicity in flumatinib group, and incidence of edema in flumatinib group was lower than that in imatinib group. Conclusions Flumatinib is a safe and effective drug for newly diagnosed patients with Ph+ CML-CP, and 600 mg/d is the appropriate clinical starting dose. Flumatinib and imatinib have similar safety in clinic.
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Objective To summarize the clinical features of graft failure (GF)after non-T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HCT), and to investigate the causes and treatment. Methods A retrospective analysis was carried out on 174 patientswho accepted the non-T-cell depleted Haplo-HCT from Jan 2012 to Dec 2013. The patients′ donor specific anti human leukocyte antigen antibodies (DSA) from the peripheral blood serum were detected and those DSA positive patients were treated by immunoglobulin or plasma exchange before transplatation. Results A total of three patients with acute myeloid leukemia got GF, the incidence rate was 1.72%. The patient with primary GF was given a secondHaplo-HCT, but did not get implanted with leukemia remission and three lineages persistently low , he was died of pulmonary infection eight monthes after the second transplant. One of the secondary GF patients was given peripheral blood mononuclear cells(PBMNCs) mobilized by granulocyte colony stimulating factor (G-CSF) from the donor, and got full donor chimerism on day 16 after infusion. The disease-free survival has been for 18 months. The other case was found that DSA was positive, the mean fluorescence intensity (MFI) value was 15000, then Rituximab and PBMNCs mobilized by G-CSF were administrated successively. On day 14 after infusion the partient got full donor chimerism , and MFI turned negative. The patient has been disease-free survival for 41 months. Conclusion Graft failure is a rare but fatal complication after non-T-cell depletedHaplo-HCT, Rituximab followed by PBMNCs are effective measures for DSA related GF, as were worthy of further study.