Influence of the number of high-risk cytogenetic abnormalities on the clinical characteristics and prognosis in 360 patients with newly diagnosed multiple myeloma / 中华血液学杂志

Objective: To investigate the influence of the number of high-risk cytogenetic abnormalities (HRCA) on the clinical characteristics and prognosis of patients with newly diagnosed multiple myeloma (MM) . Methods: A total of 360 patients with newly diagnosed MM admitted to Jiangsu Province Hospital between November 2013 and September 2020 were included in this study. Cytoplasmic light chain immunofluorescence with fluorescence in situ hybridization (cIg-FISH) was used to detect HRCA. Cytogenetic abnormalities were combined with clinical characteristics and outcomes for further analysis. Results: Among the 360 patients, 120 patients (33.3%) presented with no HRCAs, and 175 (48.6%) , 61 (16.9%) , and four (1.1%) patients had one, two, and three HRCA (s) , respectively. Patients were divided into three groups, including the no-HRCA group, one-HRCA group, and ≥two-HRCA group, according to the number of HRCAs. There were significant differences in the R-ISS stage, hemoglobin level, albumin level, and the proportion of bone marrow plasma cells among the three groups (P<0.05) . The COX proportional-hazards model identified extramedullary disease (P=0.018) , HRCA ≥ 2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P<0.001) as independent risk factors for progression free survival (PFS) and identified lactate dehydrogenase (LDH) level ≥ 220 U/L (P<0.001) , HRCA ≥2 (P=0.001) , and absence of autologous hematopoietic stem cell transplantation (P=0.005) as independent risk factors for overall survival (OS) . The median PFS was 28 months, 22 months, and 14 months (P=0.005) for the three cohorts, and their OS was not reached,60 months, and 30 months (P=0.001) , respectively. Conclusions: HRCA ≥ 2 is an independent risk factor for decreased survival in patients with newly diagnosed MM. More HRCAs result in heavier tumor burden, as well as a higher risk of disease progression and death.

Genetic characteristics and prognostic influencing factors of middleˉhighˉrisk multiple myeloma patients stratified based on Mayo Stratification of Myeloma and RiskˉAdapted Therapy consensus guidelines / 白血病·淋巴瘤

Objective To investigate the genetic characteristics and prognostic influencing factors of the middleˉhighˉrisk patients with multiple myeloma (MM) based on Mayo Stratification of Myeloma and RiskˉAdapted Therapy (mSMART) consensus guidelines. Methods A total of 179 hospitalized MM patients in Fujian Provincial Hospital from June 2009 to October 2017 were collected. Eventually, 49 patients were included except for the patients who were unable to perform mSMART stratification. According to the mSMART stratification criteria, the patients were divided into lowˉrisk group (24 cases) and middleˉhighˉrisk group (25 cases). The genetic characteristics of the two groups were analyzed to explore the relationship between mSMART stratification and clinical features. KaplanˉMeier method and logˉrank test were used to make survival analysis; logistic regression analysis was used to analyze the prognostic influencing factors in highˉrisk patients. Results The incidence of CSK1B gene amplification was the highest in the lowˉrisk group (41.7%, 10/24), while in the middleˉhighˉrisk group, the incidence of RB1 gene deletion was the highest (88.0%, 22/25). In the lowˉrisk group and the middleˉhighˉrisk group, there were no statistical differences in bone destruction, hypercalcemia, renal damage, anemia, β2 microglobulin abnormality, albumin abnormality, lactate dehydrogenase abnormality, and plasma cell ratio abnormality (all P> 0.05). Survival analysis showed that the median survival time of the middleˉhighˉrisk group was lower than that of the lowˉrisk group (23.19 months vs. 39.71 months, P＝ 0.043). Multivariate logistic regression analysis found that anemia and bone destruction were risk prognostic influencing factors for mSMART stratification as a middleˉhighˉrisk group (P＝ 0.044, P＝ 0.002). Conclusion mSMART stratification could indicate the poor prognosis for the patients with middleˉhighˉrisk, and the anemia and bone destruction are risk prognostic influencing factors for patients with middleˉhighˉrisk stratification.

Improving detection rate of cytogenetic abnormalities of monoclonal plasma cells through quality control cycle activities / 第二军医大学学报

Objective To improve the detection rate of cytogenetic abnormalities of monoclonal plasma cells through quality control cycle (QCC) activities. Methods A QCC team was established to collect the bone marrow samples of patients suspected with multiple myeloma, who undergoing plasma cell-associated fluorescence in situ hybridization (FISH) in Department of Hematology, Changhai Hospital of Navy Medical University (Second Military Medical University) from Jun. 2014 to Dec. 2014. The detection rate of cytogenetic abnormalities of monoclonal plasma cells was analyzed and compared with literatures to find out the difference and related causes, and then the improvement measures were formulated and practiced to evaluate the improvement effect. Results We found that low tumor load in the initial specimen and the detection result could not be judged due to that value is very close to the critical value were the two key points to be improved in the QCC activity. Based on the brainstorming and the existing laboratory conditions, the QCC team chose to sort abnormal cells by flow cytometry to increase tumor cell density and reduce background value before genetic testing. Finally, the detection rate of cytogenetic abnormalities of monoclonal plasma cells increased from 61.3% (95/155) to 92.1% (174/189) in our hospital. Conclusion The FISH detection process of bone marrow of patients suspected with multiple myeloma is optimized through QCC activities, and the detection rate of cytogenetic abnormalities of monoclonal plasma cells is effectively improved.

Progress of cytogenetic abnormalities and prognosis in multiple myeloma / 白血病·淋巴瘤

Multiple myeloma (MM) is a kind of incurable malignant tumors in blood system. With the advance of cytogenetics detection technology, the cytogenetic abnormalities occurred in almost MM patients. Cytogenetic abnormalities not only reveals the essence of MM, but can be served as the most important influencing factor of MM. This paper reviews the cytogenetics abnormalities and the different prognostic significances of MM.

Retrospective analysis of cytogenetic abnormalities detected by fluorescence in situ hybridization in pa-tients with multiple myeloma / 实用医学杂志

Objective To investigate the relationship of the cytogenetic abnormalities detected by FISH in patients with MM and their clinical features. Methods FISH on bone marrow (BM) cells was performed in 57 enrolled MM patients. Relationships between cytogenetic abnormalities and clinical features were analyzed. Results By statistical analysis , both D13S319 deletion and RB1 deletion were associated with high level of serum LDH (P = 0.024; P = 0.018) and BM plasma cells index (P = 0.027; P = 0.013). 1q21 amplification was significantly associated with high level of LDH (P = 0.030 ) and the occurence of light chain type myeloma (P = 0.023). IgH rearrangement was associated with renal function damage (P = 0.009). There were correlations among D13S319 deletion, RB1 deletion, 1q21 amplification and IgH rearrangement (P<0.01). Conclusion The genetic abnormalities detected by FISH in patients with MM were correlated with various clinical poor prognostic indicators, which can evaluate the condition and prognosis of patients more efficiently.

New insights into the biology and clinical progress of multiple myeloma : reports from the 56th American Society of Hematology annual meeting / 白血病·淋巴瘤

Multiple myeloma (MM) is a unique cancer paradigm for investigating the mechanisms involved in the transformation from a premalignant condition (unknown monoclonal gamma globulin,MGUS) into a malignant disease (MM).In its pathogenesis,genotype characteristics of tumor clones which are highly complex and heterogeneous,as well as the dialogue between plasma cells and their microenvironment are equally important and both play a key role in the outcome of the disease.MM will soon no longer be considered as a single disease.A large number of new drug emergence and applications will increase the need for monitoring minimal residual disease (MRD) in prognosis and treatment of MM.New drugs and high-dose chemotherapy with autologous stem cell transplantation applications have been significantly improving the prognosis of MM in the past 20 years.Re-examining the early MM diagnostic criteria and the possibility of early intervention will open up a new therapeutic approach.It is important to find a balance of efficacy,toxicity and cost in order to achieve a cure for this disease.

Prognostic effects of novel agents on cytogenetic abnormalities of multiple myeloma / 白血病·淋巴瘤

Multiple myeloma (MM) is a heterogeneous disease with certain cytogenetic abnormalities [1q21 gains,t(4;14),del 17p] associated with worse outcome.The extensive use of thalidomide,lenalidomide and bortezomib has dramatically improved the outcome for patients with MM and some cytogenetic abnormalities.It is also widely proved that bortezomib can partly overcome the harmful affects of t (4;14).However,till now,there are many controversies about the effects of some novel agents worked on certain cytogenetic abnormalities.In this review,the effects of novel agents in cytogenetic abnormalities were summaried to provide new information on clinical treatment of this disease.

Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV) and C viruses (HCV). Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0 percent (n = 17) and 9.0 percent (n = 14), respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3 percent vs. 25.0 percent). The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0 percent vs. 12.0 percent, and hyperbilirubinemia, 20.0 percent vs. 1.6 percent, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months). The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

A Case of Adult B Lymphoblastic Leukemia with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3) / 대한진단검사의학회지

In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.

Association of loss of heterozygosity with cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome

Deletions on chromosomes 5 and 7 are frequently seen in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It is assumed that these deletions indicate loss of tumor suppressor genes on these chromosomes and until these tumor suppressor genes are identified, the functional consequences of these deletions and the molecular basis of these myeloid disorders cannot be completely understood. We evaluated loss of heterozygosity (LOH) in 44 patients (18 MDS and 26 AML, diagnosed according to WHO classification criteria) at diagnosis, using a four-microsatellite marker panel: an intragenic marker on the 7th intron of gene IRF-1 of the 5q31.1 region and three markers located inside the 7q31.1 region and correlated the LOH with karyotype abnormalities. The microsatellites chosen corresponded to chromosome regions frequently deleted in MDS/AML. The samples with Q (peak area) less than or equal to 0.50 were indicative of LOH. The percent of informative samples (i.e., heterozygous) for the intragenic microsatellite in gene IRF-1 and in loci D7S486, D7S515 and D7S522 were 66.6, 73.7, 75.5, and 48.8 percent, respectively. Cytogenetic abnormalities by G-banding were found in 36 percent (16/44) of the patients (2 of 18 MDS and 14 of 26 AML patients). We found a significantly positive association of the occurrence of LOH with abnormal karyotype (P < 0.05; chi-square test) and there were cases with LOH but the karyotype was normal (by G-banding). These data indicate that LOH in different microsatellite markers is possibly an event previous to chromosomal abnormalities in these myeloid neoplasias.

Correlation of Chromosomal Aberrations with Prognostic Markers in Multiple Myeloma Patients- A Single Institution Study / 대한진단검사의학회지

BACKGROUND: Immunoglobulin heavy chain (IGH) gene rearrangement, 13q14 deletion and trisomy 1q are frequently observed in Korean patients with multiple myeloma. The purpose of our study was to analyze the statistical correlation between chromosomal aberrations and routine laboratory test results as prognostic markers and to evaluate the potential of chromosomal aberrations for the indirect assessment of prognosis in multiple myeloma patients. METHODS: We investigated the prevalence of cytogenetic aberrations in 41 patients with newly diagnosed multiple myeloma. Cytogenetic analysis was conducted by conventional karyotyping and FISH for the presence of IGH/CCND1 translocation, 13q14 deletion, and trisomy 1q using bone marrow aspirates. The records of routine laboratory tests were reviewed and their correlation with cytogenetic abnormalities was investigated. RESULTS: Sixteen (39.0%) of 41 patients had at least one cytogenetic abnormalities in conventional karyotyping or FISH. In FISH analysis of 37 patients, 8 (21.6%) showed positive result for IGH/CCND1 translocation, 8 (21.6%) for trisomy 1q, and 5 (13.5%) for 13q14 deletion. Cytogenetic abnormalities, especially trisomy 1q, were associated with significantly lower hemoglobin level and significantly higher bone marrow plasma cell percentage and beta2-microglobulin level. CONCLUSIONS: Statistical correlation between the presence of trisomy 1q and prognostic markers suggests that the evaluation of trisomy 1q in multiple myeloma patients may be used for the indirect assessment of prognosis in these patients.

Cytogenetic abnormalities in patients with reproductive dysfunction / 대한산부인과학회지

OBJECTIVE: The aim of this study was to investigate the relationship between chromosome abnormalities and male or female reproductive dysfunction and to be convinced of the role of pericentric inversion of chromosome 9 (inv (9)) on human phenotypes. METHODS: Between Jan. 1995 and Dec. 2003, results of 1713 chromosomal analyses which were referred to our cytogenetic laboratory were analyzed. Study groups consisted of 658 cases of men and 18 cases of women with unexplained infertility, 65 cases of men and 109 cases of women with history of recurrent spontaneous abortion, 78 cases of women with primary amenorrhea, 61 cases of women with secondary amenorrhea and, 382 cases of men and 342 cases of women with no reproductive dysfunction (control group). The incidence of inv (9) among each group was compared with control group. RESULTS: Chromosomal abnormalities were found in 110 cases (16.7%), 2 cases (11.1%), 3 cases (4.6%), 15 cases (13.8%), 29 cases (37.2%) and 10 cases (16.4%) in each group. The incidence of chromosomal abnormalities in male infertility was higher than previous reports, and 10 cases of inv (9) were detected in male infertility group. In cases of women with infertility and secondary amenorrhea, we couldn't find the relevance between reproductive dysfunction and chromosomal abnormality. In cases of women with recurrent spontaneous abortion, 6 cases (5.5%) had autosomal translocation and 7 cases (6.42%) had inv (9). In cases with primary amenorrhea, most chromosomal abnormalities found were related to sex chromosome such as Turner's syndrome, similar to other investigations. Thirty three cases of inv (9) was detected among the whole 1713 chromosomal analyses (1.93%). In cases of male infertility, 10 cases (1.52%) had inv (9), not significantly different with male control group. But 7 cases (6.42%) of inv (9) in women with recurrent spontaneous abortion were significantly higher than female control group (p<0.05). CONCLUSION: Because considerable proportion of patients with reproductive dysfunction had various cytogenetic abnormalities, the chromosomal analysis should be considered as a diagnostic tool in the evaluation of reproductive dysfunction such as infertility, recurrent spontaneous abortion, and amenorrhea. We also found that Inv (9) had a significantly increased incidence in female recurrent spontaneous abortion.

Cytogenetic Abnormalities in Patients with Acute Myelogenous Leukemia with Lymphoid Markers / 대한임상병리학회지

BACKGROUND: Immunologic marker studies and cytogenetic studies as well as morphological studies are frequently performed for the differential diagnosis of acute leukemia. We investigated the relationship of between immunophenotyping and cytogenetic abnormalities in acute myelogenous leukemias (AMLs). METHODS: Total 153 cases of AMLs were included. Morphological, cytochemical, immunophenotypic, and cytogenetic studies were performed. We classified the AML cases according to immunophenotyping and investigated the association between cytogenetic results and immunophenotype. And we compared differences between the AML group with lymphoid markers and that without them. RESULTS: In 153 cases of AMLs, lymphoid markers (CD2, CD5, CD7, CD19, CD10) were coexpressed in 59 cases (38.6%). Cytogenetic abnormalities were in 106 cases (69.3%). No significant difference in cytogenetic abnormalities was observed between the group with lymphoid markers and without them (76.3% vs. 64.9%, P>0.05). t(8;21)(q22;22) was significantly more frequent in CD19+AMLs (78.3% vs. 7.7%, P<0.0001), compared to CD19-AMLs. In CD2+AMLs, t(15;17)(q24;q21) was significantly more frequent than in CD2-AMLs (81.8% vs. 8.5%, P<0.0001). CD7+AML cases showed fewer cytogenetic abnormalities than AML with other lymphoid markers and various chromosomal abnormalities. CONCLUSIONS: In AML, cytogenetic abnormalities were different in relation to aberrant lymphoid markers. CD19 vs. t(8;21) and CD2 vs. t(15;17) were closely associated with each other. It is thought that CD7+AML cases are heterogeneous group. We need the study for response to therapy and prognosis in AMLs with lymphoid markers so that the data of this study can be helpful for the diagnosis and treatment.