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Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.
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Platelet-derived growth factor receptor beta (PDGFRB) rearrangements play an important role in the pathogenesis of eosinophilia-associated myeloid/lymphoid neoplasms. Up to now, more than 70 PDGFRB fusions have been identified. Here, a novel PDGFRB fusion gene CSNK2A1-PDGFRB has been identified in myeloproliferative neoplasm (MPN) with eosinophilia by RNA-sequencing, which has been verified by reverse transcription polymerase chain reaction and Sanger sequencing. The new PDGFRB fusion partner gene CSNK2A1 encoded one of the two catalytic subunit of casein kinase II (CK2). To our knowledge, this is the first report on the involvement of CSNK2A1 in fusion genes, especially fusion with another kinase PDGFRB in MPN. In addition, the CSNK2A1-PDGFRB fusion retained the entire kinase domain of PDGFRB and response to imatinib at low concentration. The patient with CSNK2A1-PDGFRB was sensitive to imatinib treatment and acquired sustained complete remission.
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Objective@#To study the value of unmethylated cytosine guanine dinucleotide oligodeoxynucleotide (DSP30) and IL-2 in the conventional cytogenetic (CA) detection of the chromosomal aberrations in chronic lymphocytic leukemia (CLL) .@*Methods@#Bone marrow or peripheral blood cells of CLL patients were cultured with DSP30 plus IL-2 for 72 h, following which R-banding analysis was conducted. Fluorescence in situ hybridization (FISH) was performed in 85 patients. CA results were compared with data obtained by FISH.@*Results@#Among 89 CLL patients, the success rate of chromosome analysis was 94.38% (84/89) . Clonal aberrations were detected in 51 patients (51/84, 60.71%) . Of them, 27 (27/51, 52.94%) were complex karyotype. Among 85 CLL patients tested by FISH, chromosomal abnormalities were detected in 74 (74/85, 87.06%) patients, of which 2 (2/74) patients were complex karyotypes, accounting for 2.70%. Of the 85 CLL patients examined by FISH, 50 had abnormal karyotype analysis, 30 had normal karyotype, 5 failed to have chromosome analysis. Among them, 25 cases showed clonal aberrations by FISH assay but normal by CA, and 4 cases were normal by FISH but displayed aberrations in chromosome analysis, and totally 78 (91.76%) cases with abnormality detected by the combination of the two methods. The frequency of 13q- abnormality detected by FISH was significantly higher than that by CA analysis (69.41%vs 16.67%, P<0.001) , while the frequency of 11q-,+12 and 17p- detected by two methods showed no significant difference (P>0.05) . The detection rate of complex abnormalities in conventional karyotype analysis was higher than that in FISH (50.98%vs 2.70%) . In addition, 11 low-risk and 9 intermediate-risk patients according to FISH results showed complex karyotype by cytogenetics, and were classified into high-risk cytogenetic subgroup.@*Conclusion@#DSP30 and IL-2 are effective in improving the detection rate of CA in CLL patients (60.71%) and CA is more effective to detect complex karyotype. However, FISH had a higher overall abnormality detection rate (87.06%) than CA, especially for 13q-. The combination of CA and FISH not only enhanced the detection rate of clonal aberrations to 91.76%, but also provided more precise prognosis stratification for CLL patients, thus to provide more information for clinical implication.
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Objective@#To investigate the current basic situation of the staff of ultrasound departments in Shanghai′s medical institutions, for providing references in making management policy of these professionals.@*Methods@#Questionnaire surveys on human resource and service ability were made to all the ultrasound departments of medical institutions in Shanghai in December 2013 and November 2018 respectively. Data of the two surveys were compared and analyzed, and were descriptively analyzed by mean and percentage.@*Results@#The number of ultrasound professionals per 10 000 people in Shanghai was 1.04 in 2018. Tertiary hospitals had advantages in the number of the professionals, and the proportion of professional qualification, age, education background and professional title of the professionals. Compared to those data in 2013, the number of ultrasound professionals had increased 31.8% in 2018. The proportion of medical practitioners with medical imaging specialty was 95.6%(2 063/2 158), and had increased by 4.7 percent. The medical services workload of ultrasound was 19.82 million person-time, and had increased 45.8%.@*Conclusions@#Development of ultrasound departments was rapid, but the development of professionals was unbalanced with the development of medical services. It is suggested to strengthen training of ultrasound professionals and improve the system of hierarchical medical system.
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Objective:To investigate the current basic situation of the staff of ultrasound departments in Shanghai′s medical institutions, for providing references in making management policy of these professionals.Methods:Questionnaire surveys on human resource and service ability were made to all the ultrasound departments of medical institutions in Shanghai in December 2013 and November 2018 respectively. Data of the two surveys were compared and analyzed, and were descriptively analyzed by mean and percentage.Results:The number of ultrasound professionals per 10 000 people in Shanghai was 1.04 in 2018. Tertiary hospitals had advantages in the number of the professionals, and the proportion of professional qualification, age, education background and professional title of the professionals. Compared to those data in 2013, the number of ultrasound professionals had increased 31.8% in 2018. The proportion of medical practitioners with medical imaging specialty was 95.6%(2 063/2 158), and had increased by 4.7 percent. The medical services workload of ultrasound was 19.82 million person-time, and had increased 45.8%.Conclusions:Development of ultrasound departments was rapid, but the development of professionals was unbalanced with the development of medical services. It is suggested to strengthen training of ultrasound professionals and improve the system of hierarchical medical system.
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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 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 carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype.@*METHODS@#Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing.@*RESULTS@#Sixty-two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation.@*CONCLUSION@#Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.
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Humanos , Persona de Mediana Edad , Factores de Edad , Análisis Mutacional de ADN , Cariotipo , Leucemia Mieloide Aguda , Genética , Mutación , Síndromes Mielodisplásicos , Genética , PronósticoRESUMEN
OBJECTIVE@#To explore the clinical and laboratory characteristics of 5 patients with myeloid leukemia and t(12;22)(p13;q12).@*METHODS@#Bone marrow cells were cultured for 24 h and analyzed by standard R-banding. Rearrangement of the MN1 gene was detected by fluorescence in situ hybridization (FISH) using dual color break-apart MN1 probes. MN1-ETV6 and ETV6-MN1 fusion genes were detected by reverse transcription polymerase chain reaction (RT-PCR). And the products were subjected to direct sequencing.@*RESULTS@#Among the 5 patients, 2 had AML-M0, 2 had AML-M4, and 1 had CMML at the initial diagnosis. t(12;22)(p13;q12) was the primary abnormality among all patients. Rearrangements of MN1 gene were detected by FISH in all patients. MN1-ETV6 and ETV6-MN1 fusion genes were detected respectively in 4 and 3 patients.@*CONCLUSION@#t(12;22)(p13;q12) is a rare but recurrent chromosomal abnormality in myeloid leukemia, and is related to poor prognosis. allo-SCT is valuable for patients with t(12;22)(p13;q12).
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Humanos , Bandeo Cromosómico , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 22 , Citogenética , Hibridación Fluorescente in Situ , Leucemia Mieloide , Genética , Proteínas de Fusión Oncogénica , Translocación GenéticaRESUMEN
Objective@#To carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype.@*Methods@#Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing.@*Results@#Sixty two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation.@*Conclusion@#Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.
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Objective@#To evaluate the clinical characteristics and prognosis of 3q26 rearrangements in chronic myeloid leukemia (CML) patients. @*Methods@#The clinical and laboratory data of 1 075 patients with CML diagnosed from 2010 to 2016 were retrospectively analyzed, and they were divided into 3q26 rearrangement positive group (n=19) and 3q26 rearrangement negative group (n=1 056). The expression of EVI1, ABL kinase region mutation and survival time between the two groups were compared. Meanwhile, the prognostic effects of three treatment methods, including tyrosine kinase inhibitors (TKIs), TKIs combined with chemotherapy and allogeneic hematopoietic stem cell transplantation, on the patients with 3q26 rearrangements were compared. @*Results@#Most of the patients with 3q26 rearrangements were in the advanced phase (χ 2 =181.233, P＜0.01), and the median time to enter the acute phase was shorter (9.5 months). The mutation ratio of ABL kinase region and expression levels of EVI1 in 3q26 rearrangement positive group were significantly higher than that in the negative group (χ 2 =16.758, P＜0.01; Z/U=-0.331 9, P＜0.01). After treatment with TKIs, the median survival time of the 3q26 rearrangement positive group was significantly shorter than that of the negative group (χ 2 =313.229, P＜0.01). The prognosis of the patients treated with hematopoietic stem cell transplantation was better than that with TKIs (P=0.049). @*Conclusion@#The CML patients with 3q26 rearrangements have a higher risk of sudden change, shorter survival time and poor prognosis. Hematopoietic stem cell transplantation may improve their prognosis.
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Objective@#To investigate the prognosis of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) for patients with acute myeloid leukemia and MLL rearrangement.@*Methods@#From September 2009 to May 2016, the clinical data of 47 patients with MLL-rearranged AML undergoing allo-HSCT in the First Affiliated Hospital of Soochow University were retrospectively analyzed.@*Results@#Among 47 MLL-rearranged AML patients, 24 were male and 23 female. The median age was 30 (15-58) years old. There are 36 (76%) patients were FAB-types M4/M5. Two-year overall survival (OS), disease-free survival (DFS), relapse incidence and transplant-related mortality (TRM) were (64.4±8.4)%, (47.3±9.3)%, 41.0% and 17.9%, respectively. Of them, 45 patients were detected with 11q23 translocations, and 2 patients with normal karyotype were MLL partial tandem duplication. According to different chromosome karyotype, 47 patients were divided into three groups: 16 cases of t (6; 11), 15 cases of t (9; 11) and 16 cases of other types. Overall survival was compared between the three groups, there was no significant difference (χ2=1.509, P=0.472). On multivariate analysis, independent risk factor on OS was transplant age >45 years [HR=4.454(95%CI 1.314-15.099), P=0.016]. The multivariate analysis also confirmed the higher TRM in patients at non-CR state when transplanted [HR=10.370(95%CI 1.043-103.110), P=0.046]. Positive minimal residual disease (MRD) before transplantation was a negative prognostic factor on DFS [HR=4.236(95%CI 1.238-14.495), P=0.021] and relapse incidence (RI) [HR=5.491(95%CI 1.371-21.995), P=0.016].@*Conclusion@#Transplant age (>45 years), allo-HSCT in non-CR state adn positive MRD before transplantation were negative prognostic factors in allo-HSCT for MLL-rearranged AML patients.
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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 explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) for paroxysmal nocturnal hemoglobinuria (PNH).@*Methods@#A total of 17 patients with PNH who received Haplo-HSCT from January 2013 to September 2017 were analyzed retrospectively.@*Results@#Of them, 4 patients had de novo PNH, 13 patients had aplastic anemia-PNH syndrome (AA-PNH). All patients received modified busulfan and Cytoxan (BuCy)-based regimens combined with anti-thymocyte globulin (ATG). Granulocyte colony-stimulating factor-mobilized bone marrow and peripheral blood stem cells were transplanted as graft. Prophylaxis for graft-versus-host disease (GVHD) was ciclosporin A+ mycophenolate mofetil (MMF)+short-term methotrexate (MTX). All patients were engrafted successfully. The median time of neutrophils to 0.5×109/L and platelets to 20×109/L was 12(10-15) days and 14(11-45) days, respectively. All of the 17 patients achieved full donor chimerism at 30 d after Haplo-HSCT. Seven patients developed grade Ⅱ-Ⅳ acute GVHD, and 4 chronic GVHD. Median follow-up time was 27.1 (8.6-60.4) months. Of the 17 patients, 15 survived and 2 died of severe pulmonary infection and transplant associated thrombotic microangiopathy. Three-year overall survival was (77.8±15.2)%.@*Conclusion@#Haplo-HSCT may be effective and safe for PNH patients who did not have matched donor.
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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 overexpression frequencies of BRE and EVI1, the correlation between BRE and EVI1 expressions and their possible clinical implications in 11q23/MLL rearrangement acute leukemia.@*Methods@#Cytogenetic examination of bone marrow cells was performed by short-term culture method. R-banding technique was used for karyotype analysis. 47 patients were detected by interphase fluorescence in situ hybridization (FISH) with dual-color break apart MLL probe. The expressions of EVI1 and BRE genes were detected by real time quantitative reverse transcription polymerase chain reaction (RQ-PCR) . The correlation and prognostic significance were statistically tested.@*Results@#11q23/MLL rearrangements were confirmed by karyotyping and FISH, respectively in 47 patients. According to immunophenotypic analyses of 37 patients, 5 patients showed positive for CD19, CD79a or CD10, 1 for CD7; the others for CD33, CD13, CD14 and CD15, and 16 of them for CD34. Of the 47 patients, 18 patients showed EVI1 overexpression and most of them presented with t (6;11) and M4/M5. The EVI1 expression was high in t (6;11) or t (9;11) subgroup comparable with levels observed in normal subgroup (P=0.038, 0.022, respectively) . 15 patients showed high BRE expression, and most of them presented with t (9;11) and M4/M5. High BRE expression was found in t (4;11) , t (6;11) , t (9;11) and t (11;19) subgroups, respectively by comparing with normal subgroup. The BRE expression was higher in t (4;11) (P=0.004) or t (9;11) (P=0.012) subgroup than in t (6;11) subgroup. Patients with EVI1 overexpression had a short survival compared with those with low EVI1 expression (P=0.049) and it also did in t (9;11) subgroup (P=0.024) . Patients with t (9;11) and high BRE expression had a long survival compared with those with t (9;11) and low BRE expression (P=0.024) .@*Conclusion@#The EVI1 overexpression was significantly frequent in acute leukemia patients with 11q23/MLL rearranged, especially within t (6;11) subgroup and M4/M5, which was associated with an inferior outcome. High BRE expression was observed frequently in 11q23/MLL-rearranged acute leukemia especially within t (9;11) subgroup and M5.
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<p><b>OBJECTIVE</b>To report on clinical and laboratory features of myeloid neoplasms with double del(20q).</p><p><b>METHODS</b>Cytogenetic examination of bone marrow was performed on 13 cases of myeloid neophasms with double del(20q) after 24 hours of cell culture. R-banding was used to analyze the karyotypes. Interphase fluorescence in situ hybridization (FISH) was performed using dual-color probes for 20q11/20q12.</p><p><b>RESULTS</b>Double del(20q) was found to be the sole abnormality in 9 cases, double del(20q) and trisomy 9 was found in 1 case, trisomy del(20q) was found in 1 case, and sole del(20q) clone and double del(20q) clone were found to coexist in 2 cases. In 10 cases, interphase FISH showed one green and one red signal in cells with del(20q), which indicated deletion of both 20q11 and 20q12. Immunophenotyping of the leukemia cells showed positiveness for CD13 and/or CD33, CD117 in all 9 cases. Among these, co-expression of CD34 and/or HLA-DR was found in 6 cases, and coexpression of CD3 and CD7 was found in 1 case. Of the 13 cases, there were one AML-M6, nine MDS, one pure amegalokaryocye aplastic thrombocytopenia, one with normal morphology of bone marrow, and one undetermined due to dilution of the bone marrow by blood. Cytopenia were found in all cases. 9 of 13 cases died, and 4 survived with a median survival of 9 months.</p><p><b>CONCLUSION</b>Double del(20q) is a rare but recurrent chromosomal abnormality derived from del(20q). It has unique clinical and laboratory features, and the prognosis is poor.</p>
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Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Bandeo Cromosómico , Métodos , Deleción Cromosómica , Síndromes Mielodisplásicos , Genética , Neoplasias , GenéticaRESUMEN
<p><b>OBJECTIVE</b>Todelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements.</p><p><b>METHODS</b>Clinical data of the patient was collected. Conventional cytogenetics, fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient.</p><p><b>RESULTS</b>The patient has featured recurrent rash, joint pain, and intermittent fever. Laboratory tests showed hyperleukocytosis and marked eosinophilia. Physical examination revealed splenomegaly. His karyotype was 46,XY,t(3;5)(q26;q15)[6]/46,XY[10]. FISH assay showed that both PDGFRA and EVI1 genes were rearranged. Molecular studies of the mRNA suggested that there was a in-frame fusion between exon 12 of the PDGFRA gene and exon 9 of the FIP1L1 gene. Imatinib was initiated at a dosage of 200 mg, and after 10 months, the signal of the FIP1L1-PDGFRA fusion gene was undetectable in bone marrow sample. However, the expression of EVI1 mRNA was stable, with no significant difference found between the patient and 10 healthy controls.</p><p><b>CONCLUSION</b>MPN in association with PDGFRA and EVI1 genes rearrangements have unique clinical and genetic features. Genetic testing is helpful for early diagnosis. Imatinib may be effective for the treatment.</p>
Asunto(s)
Humanos , Masculino , Adulto Joven , Antineoplásicos , Usos Terapéuticos , Secuencia de Bases , Bandeo Cromosómico , Cromosomas Humanos Par 3 , Genética , Cromosomas Humanos Par 5 , Genética , Proteínas de Unión al ADN , Genética , Reordenamiento Génico , Mesilato de Imatinib , Usos Terapéuticos , Hibridación Fluorescente in Situ , Cariotipificación , Proteína del Locus del Complejo MDS1 y EV11 , Trastornos Mieloproliferativos , Quimioterapia , Genética , Proto-Oncogenes , Genética , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas , Genética , Factores de Transcripción , Genética , Translocación Genética , Resultado del TratamientoRESUMEN
Objective@#To analyze the incidence and microbiological features of blood stream infections (BSI) of patients with hematopoietic stem cell transplantation (HSCT) and to provide laboratory data for empirical use of antibiotic for the HSCT patients with BSI.@*Methods@#The incidence of bloodstream infection, the positive rate of blood culture, bacterial spectrum and drug resistance were analyzed in 1 265 HSCT recipients during 2013 and 2015 were retrospectively studied.@*Results@#Of 1265 patients undergoing HSCT, 1 422 cases of suspected BSI occurred in 784 patients (61.98%) , and 464 patients (59.2%) were in the stage of agranulocytosis (ANC<0.5×109/L) . The detection rate of pathogens in 2013-2015 was about 20% and increase year after year. Of the 401 strains detected, 221 were Gram-negative (G-) bacteria (55.1%) , 165 Gram-positive (G+) bacteria (41.2%) and 15 fungi (3.7%) . Escherichia coli (16.0%) , Staphylococcus epidermidis (15.5%) and Klebsiella pneumoniae (11.2%) were listed the top three. The proportion of multidrug resistant Acinetobacter Bauman and Stenotrophomonas maltophilia was 64.70% and 63.64% respectively, and methicillin resistant Staphylococcus aureus (MRSA) was more than half (57.14%) . The ratio of vancomycin resistant Enterococci (VRE) and carbapenem resistant Enterobacteriaceae (CRE) was 14.29% and 6.78% respectively. More than 40% Enterobacteriaceae bacteria were resistant to three or four generation cephalosporin antibiotics, and less were resistant to the carbapenems (6.4%) . However, many non-fermentating bacteria were highly resistant to these antibiotics and showed diversity among different strains, with a rate of 47.8% resistance to carbapenems. All the Staphylococcus were sensitive to vancomycin, teicoplanin and linezolid.@*Conclusions@#The incidence of BSI in patients with HSCT was high, and the pathogens were mainly G- bacteria. In addition to Enterobacteriaceae, the proportion of non-fermentative bacteria was quite high. No Staphylococcus detected were resistant to vancomycin, teicoplanin and linezolid.