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OBJECTIVE@#To explore the clinical and laboratory characteristics of hematological tumors with different types of abnormalities in platelet derived growth factor β (PDGFRβ) gene.@*METHODS@#A retrospective analysis was carried out on 141 patients with abnormal long arm of chromosome 5 (5q) and comprehensive medical history data from Changhai Hospital Affiliated to Naval Medical University from 2009 to 2020, and their clinical data were collected. R-banding technique was used for chromosomal karyotyping analysis for the patient's bone marrow, and fluorescence in situ hybridization (FISH) was used to detect the PDGFRβ gene. The results of detection were divided into the amplification group, deletion group, and translocation group based on FISH signals. The three sets of data column crosstabs were statistically analyzed, and if the sample size was n >= 40 and the expected frequency T for each cell was >= 5, a Pearson test was used to compare the three groups of data. If N < 40 and any of the expected frequency T for each cell was < 5, a Fisher's exact test is used. Should there be a difference in the comparison results between the three sets of data, a Bonferroni method was further used to compare the data.@*RESULTS@#In total 98 patients were detected to have PDGFRβ gene abnormalities with the PDGFRβ probe, which yielded a detection rate of 69.50% (98/141). Among these, 38 cases (38.78%) had PDGFRβ gene amplifications, 57 cases (58.16%) had deletions, and 3 (3.06%) had translocations. Among the 98 cases, 93 were found to have complex karyotypes, including 37 cases from the amplification group (97.37%, 37/38), 55 cases from the deletion group (96.49%, 55/57), and 1 case from the translocation group (33.33%, 1/3). Analysis of three sets of clinical data showed no significant gender preponderance in the groups (P > 0.05). The PDGFRβ deletion group was mainly associated with myeloid tumors, such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (P < 0.001). The PDGFRβ amplification group was more common in lymphoid tumors, such as multiple myeloma (MM) (P < 0.001). The PDGFRβ translocation group was also more common in myelodysplastic/myeloproliferative tumors (MDS/MPN).@*CONCLUSION@#Tumors with PDGFRβ gene rearrangement may exhibit excessive proliferation of myeloproliferative tumors (MPN) and pathological hematopoietic changes in the MDS, and have typical clinical and hematological characteristics. As a relatively rare type of hematological tumor, in addition to previously described myeloid tumors such as MPN or MDS/MPN, it may also cover lymphoid/plasma cell tumors such as multiple myeloma and non-Hodgkin's lymphoma.
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Humans , Clinical Relevance , Hematologic Neoplasms/genetics , In Situ Hybridization, Fluorescence , Multiple Myeloma , Myelodysplastic Syndromes , Retrospective Studies , Translocation, GeneticABSTRACT
OBJECTIVE@#To investigate the clinical and immunological characteristics, treatment and prognosis of common variable immune deficiency (CVID) in adult patients.@*METHODS@#We retrospectively analyzed the clinical data of 13 adult patients hospitalized in our hospital for CVID diagnosed according to the criteria in International Consensus Document (2016), and analyzed their clinical manifestations, laboratory test results, imaging findings, pathological examinations and treatments.@*RESULTS@#The mean age of onset was 24.46±16.82 years in these patients, who had a mean age of 32.54±14.86 years at diagnosis with a median diagnostic delay of 5 years (IQR: 2-15 years). The main manifestation of the patients was repeated infections, including repeated respiratory tract infection (10 cases; 76.9%) and repeated diarrhea (3 cases; 23.1%). Three (23.1%) of the patients had autoimmune disease and 10 (76.9%) had chronic pulmonary disease. IgG, IgA and IgM were decreased in all the patients. The proportion of CD4+T cells decreased in 10 patients (76.9%), CD8+T cells increased in 11 patients (84.6%), and CD4/ CD8 decreased in 10 patients (76.9%). Complement C3 decreased in 58.3% (7/12) and C4 decreased in 33.3% (4/12) of the patients. Twelve patients (92.3%) were treated with intravenous infusion of gamma globulin with symptomatic treatments. One patient died due to massive gastrointestinal hemorrhage, and the other patients showed improve ments after the treatments and were discharged.@*CONCLUSIONS@#The clinical manifestations of CVID are diverse, and recurrent respiratory tract infection is the most common manifestation. Decreased IgG often accompanied by lowered IgA and IgM levels is a common finding in laboratory tests. The treatment of CVID currently relies on gamma globulin with symptomatic treatments for the complications.
Subject(s)
Adolescent , Adult , Child , Humans , Middle Aged , Young Adult , Autoimmune Diseases , Common Variable Immunodeficiency , Delayed Diagnosis , Immunoglobulins, Intravenous , Retrospective StudiesABSTRACT
Objective To investigate the diagnosis, treatment and prognosis of acute promyelocytic leukemia (APL) with NPM_RARα fusion gene positive. Methods One APL patient with NPM_RARα fusion gene positive who was diagnosed by using morphology, immunology, cytogenetics, molecular biology and multiplex fluorescence in situ hybridization in Changhai Hospital in November 2014 was retrospectively analyzed, and the patient was induced with retinoic acid and treated with DA (daunorubicin + cytarabine) regimen, followed by 4 courses of cytarabine consolidation therapy. Results Abnormal promyelocyte accounted for 0.64 by morphology. And the group of cells expressed myeloperoxidase (MPO), CD13, CD15, CD117, and CD7, CD11c, CD79a, CD123 weakly expressed or not by immunophenotype analysis; karyotype analysis showed 45, XY, t(5;17), 7p-,-16[8]/46, idem,+20[5]/45, idem,-8,+20[2]/46, XY[5]; the fusion gene screening showed that the expression level of NPM_RARα was 416.98% compared with that of APL; molecular complete remission was obtained after the consolidation therapy, but the patient relapsed after 34 months. Finally, the patient died of abnormal coagulation and respiratory failure, with overall survival of 35 months. Conclusion APL with NPM_RARα fusion gene positive is a rare type of acute leukemia, and the main treatment method is retinoic acid combined with myeloid chemotherapy regimen, which has a favorable efficacy but a poor prognosis.
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Objective@#To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) .@*Methods@#In this study we retrospectively analyzed 158 Ph+ ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy.@*Results@#Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ2=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ2=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ2=7.908, P=0.005) .@*Conclusions@#Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph+ ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.
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Objective To investigate clinical and hematological features of myeloid neoplasms with eosinophilia and abnormal PDGFRA/B and the effect of imatinib. Methods The data of three eosinophilia patients with abnormal PDGFRA/B fusion gene in Changhai Hospital, the Second Military Medical University and 22 Chinese cases reported in Chinese medical journals were analyzed. Thirty-one cases of idiopathic hypereosinophilic syndrome from Changhai Hospital, the Second Military Medical University were used as the controls. Results Compared with idiopathic hypereosinophilic syndrome, no differences were found in age, percentage of bone marrow eosinophils and counts of platelets in peripheral blood in myeloid neoplasms with eosinophilia and abnormal PDGFRA/B (all P ＞0.05), but statistical differences were found in gender (χ2＝5.080, P ＝ 0.016), peripheral blood white blood cell count (t ＝ 4.908, P ＝ 0.001), eosinophilic granulocyte absolute value (χ2＝ 17.230, P ＝ 0.001) and hemoglobin concentration (t ＝ 2.770, P ＝ 0.013). The median follow-up time was 17 months (3-108 months) in 24 myeloid neoplasms patients with eosinophilia and abnormal PDGFRA/B from Chinese report. Complete hematopoietic remission (CHR) rate was 91.7 % (22/24) after the treatment of imatinib. The total complete molecular remission (CMR) rate was 75.0 % (18/24). The median time of remission was 3 months (1-8 months). CMR in patients with PDGFRA and with PDGFRB was 76.5 % (13/17) and 85.7 % (6/7), respectively. Only one patient (4.2 %) died of disease relapse. Conclusion Imatinib has a favorable effect on myeloid neoplasms with eosinophilia and abnormal PDGFRA/B featured by distinct hematologic and clinical manifestations.
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Objective To analyze the application of quality control cycle (QCC) in reducing the false negative rate of minimal residual disease (MRD) of flow cytometry in patients with acute myeloid leukemia (AML). Methods In AML patients with abnormal fusion gene detected in hematology laboratory of Changhai Hospital during the year of 2014, the prevalence of AML-MRD detected both by flow cytometry (FCM) and real-time fluorescence quantitative polymerase chain reaction (FQ-PCR) were analyzed retrospectively. The possible causes of false negative rate of flow cytometric MRD referring to PCR were further deeply analyzed, and the improvement measures were adapted from January 2015 to December 2015 and further judged all according to the QCC methods. Results Pareto diagram showed that the dilution and coagulation of the specimen, the improper analysis strategy and the incomplete combination of the MRD index [composition ratio:83.3 % (60/72)] were the main factors leading to the leakage of FCM MRD in 2014. The QCC group devised measures to reduce the dilution probability of bone marrow and develop a standard operating procedures (SOP) for sampling and testing, strengthen the maintenance of the flow instrument and more importantly, focused on optimizing the antibody panels and gated strategies referring to the current two main kinds of MRD detection combination modes on the basis of the latest advances published in 2015. Finally, the undetected rate of AML-MRD was reduced by FCM from 14.8 % (72/486) in 2014 to 2.6 % (16/620) in 2015. Conclusions The QCC can effectively reduce the leakage rate of flow cytometric AML MRD, improve the ability of laboratory quality control and the ability to solve problems. Solving problems with QCC is thus worthy of being popularized.
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<p><b>OBJECTIVE</b>To report an acute promyelocytic leukaemia (APL) case with translocation of rob (13;21) t(15;17) (q22;q21) and review its clinical and laboratory characteristics.</p><p><b>METHODS</b>Based on routine karyotype analysis and bone marrow morphology, we further used double color double fluorescent in situ hybridization (DCDF-FISH) and reverse transcriptase PCR (RT-PCR) to examine the patient's abnormities on cytogenetic and molecular biology, and reveal the clinical characteristics of this rare translocation also from the related literatures.</p><p><b>RESULTS</b>The clinical manifestation and bone marrow morphology examination of this patient were in accordance with pathologic feature of APL. On first visit, immunophenotyping analysis showed positive myeloid markers. Through R-banding, the patient's karyotype was confirmed as 45, XX, rob(13;21) t(15;17) (q22;q21) [6]/45, XX, rob(13;21) [14]. FISH results showed that 68.9% cells were typical t(15;17) pattern. The positive rates of fusion gene of PML-RARα detected by RT-PCR was 25.8%. Patient was treated by induction and consolidation therapy, the karyotype was 45, XX, rob(13;21 )[20] after complete remission. The positive rate of fusion gene of PML-RARα by FISH and its level were 2.5% and 0.003% respectively.</p><p><b>CONCLUSION</b>APL with rob (13;21) t(15;17) (q22;q21) was very rare, which was accorded with clinical and laboratory characteristics of APL. The value of chromosome abnormality as a prognostic marker in APL needs to be further observed..</p>
Subject(s)
Humans , Chromosome Aberrations , Chromosome Banding , Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 17 , Chromosomes, Human, X , In Situ Hybridization, Fluorescence , Karyotype , Leukemia, Promyelocytic, Acute , Oncogene Proteins, Fusion , Remission Induction , Translocation, GeneticABSTRACT
Objective To investigate the detection methods of atypical bcr-abl rearrangement with b3a3 fusion transcript,and to describe the characteristics of this fusion gene.Methods Karyotype analysis,FISH and RT-PCR were applied to detect the break point of bcr-abl fusion gene in a patient who was diagnosed as acute lymphoblastic leukemia.Results The karyotype of the patient was expressed as 45,XY,-7,t(9;22)(q34;q1 1).The translocation event in chromosome 9 and 22 could be successfully detected by FISH,and a rare bcr-abl rearrangement with b3a3 fusion transcript was detected by RT-PCR with specific primers.Conclusions The rare e14a3 (b3a3) fusion of bcr-abl gene is present in this patient.Clinical laboratories using commercial kits that do not cover such rare fusions are likely to generate false result,thereby declaring combination of various methods to detect fusion genes is necessary.More studies are needed to explore the function and significance of rare bcr-abl fusion genes.
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<p><b>OBJECTIVE</b>To investigate the patients' characteristics and efficacy of prognosis evaluation by International Prognosis Scoring System (IPSS) and Revised International Prognosis Scoring System (IPSS-R) in patients with myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>Prognostic value of IPSS and IPSS-R was evaluated on clinical data from 159 MDS patients, according to WHO classification.</p><p><b>RESULTS</b>With a median age of 44 years (range:15-80 years), MDS patients had the frequency of 38.56% with abnormal karyotype, including the most common abnormality +8 (20/153, 12.6%). 34 of 142 patients transformed into leukemia. Age and the level of β2 micro-globulin were the prognostic factors by multivariate analysis and IPSS-R had a better prognostic significance. The differences in cumulative survival between IPSS subgroups were significant (P<0.05) except that between low- and intermediate I-risk group (P>0.05). There were statistical differences for IPSS-R low risk group vs high or very high risk group, and intermediate risk group vs high or very high risk group (P<0.05). IPSS-R enables IPSS subgroups re-stratification and split IPSS intermediate I-risk group into two subgroups with different prognosis.</p><p><b>CONCLUSION</b>There were significant differences in age of onset, distribution of prognosis scoring system subgroups and abnormal karyotype compared with those in Europe and America. The proportion of higher risk (worse than good karyotype) in IPSS-R was higher than that in Europe and America. Age and the level of β2 micro-globulin were prognostic factors. Both IPSS and IPSS-R were applicable in Chinese MDS patients and the latter performed better. Applying IPSS-R to re-stratify IPSS subgroups helps evaluate prognosis more accurately and improve treatment outcomes.</p>