Pattern of Cytogenetic Abnormality by Fluorescence in Situ Hybridization (FISH) in Multiple Myeloma Patients in a Tertiary Hospital

Background: Multiple myeloma is a plasma cell neoplasm with acquired genetic abnormalities of clinical and prognostic importance, with survival duration ranging from a few months to more than 10 years. Cytogenetic abnormalities (CA) detected by fluorescence in situ hybridization (FISH) are of major prognostic significance since e.g. patients with del(17p), t(4;14) or gain 1q21 show dismal outcome. Objective: To evaluate the cytogenetic patterns by fluorescence in situ hybridization (FISH) of clinically diagnosed cases of multiple myeloma.Methods:This cross-sectional study was conducted in Department of Haematology, Dhaka Medical College Hospital, Dhaka, from January 2018 to December 2018. A total number of 30 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 10.0.Results:Out of 30 diagnosed Multiple Myeloma cases the mean age was 56.37±10.38 years and male to female ratio was almost 3:1. Sixteen (56.7%) of 30 patients. Among 30 cases of 8 cases were thyrogenicity positive of 7(23.3%) patients was detected del 13q positive. Isolated del 13q was found in 4 cases. 2 cases were found coexistence of del 13q and del 17p positive ;1 case was found coexistence of del 13q and t(4;14) positive and rest of 1 case had del 17 p positive. There was no detectable t (11; 14) and t(14;16) in any of 30 cases.Conclusion:FISH panel for Multiple Myeloma including del (13q); t(11;14); t(4;14), del(17p), t(14;16) is very important molecular test for the prognosis , risk stratification, treatment modality of the patient. On the basis of cytogenetic abnormality Multiple Myeloma risk stratification is modified now a day. This Revised International Staging system R-ISS is a simple and powerful prognostic staging system.

Immunophenotypic challenges in diagnosis of CD79a negativity in a patient with B acute lymphoblastic leukemia harboring intrachromosomal amplification of chromosome 21: a case report

Background Being expressed in all stages of B-cell development and having a significant value on the European Group for the Immunological Characterization of Acute Leukemias scoring system, CD79a is considered as an excellent pan-marker for lineage assignment of B cells by flow cytometry. Therefore, any lack or decrease in CD79a expression makes the diagnosis of B acute lymphoblastic leukemia cases very challenging, especially in developing country laboratories where flow cytometry analyses are not always available and, when they are, they are limited in the number of markers used for lineage assignment. Since this case is potentially interesting, we report a B acute lymphoblastic leukemia case with a lack of expression CD79a associated with intrachromosomal amplification of chromosome 21 genetic abnormality. We further discuss the practical challenges in the diagnosis of this case. Case presentation We present the case of an 8-year-old Caucasian boy from eastern Morocco who was initially hospitalized for a hemorrhagic syndrome. Peripheral blood smear examination showed a significant number of blasts suggesting acute leukemia. Bone marrow was studied for morphology, cytochemistry, immunophenotyping, and cytogenetics. Flow cytometry analyses showed expression of CD19, CD22, CD10, CD34, and HLA-DR markers by leukemic blasts. The expression of CD79a, which was checked with two different monoclonal antibodies, confirms that this marker was severely decreased in this case. Cytogenetic study performed by fluorescence in situ hybridization revealed the presence of intrachromosomal amplification of chromosome 21, a cytogenetic abnormality that is specific for B acute lymphoblastic leukemia. Conclusion CD79a is one of the critical markers in the assignment of B acute lymphoblastic leukemia. In our case, we were lucky enough to be assisted by a few other markers of the B lineage that were positive in this case. Also, we mention the importance of proceeding to cytogenetic study, which in our case helped us to confirm the diagnosis made by flow cytometry by highlighting a cytogenetic abnormality that is specific to B acute lymphoblastic leukemia.

P190BCR-ABL1 in a Patient with Philadelphia Chromosome Positive T-Cell Acute Lymphoblastic Leukemia: A Rare Case Report and Review of Literature

T-acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) is rare and aggressive leukemia. Philadelphia chromosome positive (Ph+) is the most common cytogenetic abnormality in chronic myeloid leukemia (CML) and B-acute lymphoblastic leukemia (B-ALL). Ph+ T-ALL is exceeding rare and has a therapeutic and prognostic significance. The incidence and outcome of Ph+ T-ALL are unknown. Differentiation between Ph+ T-ALL/LBL and T-cell lymphoblastic crises of CML may be difficult. We report a rare case of adult de novo T-ALL with significant monocytosis, having Ph+ with (P190 <i>BCR-ABL1</i>) as a cytogenetic abnormality. He was treated with ALL induction chemotherapy and imatinib and achieved complete remission, then relapsed twice and expired shortly after the last CNS relapse.

Myeloid sarcoma: experience from a hematology care centre of Eastern India

Objectives: To describe the case series of patients with myeloid sarcoma with their clinicopathological characteristics, cytogenetics, molecular markers, prognosis, and outcome. Material and Methods: Retrospective retrieval of data of myeloid sarcoma cases in acute myeloid leukemia was done from the electronic health records of our hospital and this case series includes the data of three years starting from January 2018 and the follow-up information was assimilated until December 2020. Results: We present twelve patients in this case series with myeloid sarcoma and all these patients had bone marrow involvement at presentation. Most of the cases were less than 20 years of age and orbit (66.7%) was the commonest site of presentation in this series. Aberrant CD 19 expression on immunophenotyping was a common associate (66.9%) and t(8;21) was the commonest cytogenetic abnormality reported in our case series. Despite of high dose intensive therapy with daunorubicin and cytarabine followed by high-dose cytarabine (HiDAC) consolidation, patients had a median relapse-free survival and median overall survival of 160 days and 299.5 days respectively. Local radiotherapy for consolidation in two of our patients had no additional benefit. Conclusion: Myeloid sarcoma is extramedullary collection of myeloid blasts with or without bone marrow involvement. They were commonly seen in young patients and t(8;21) being a common cytogenetic abnormality associated with it. The treatment outcome of patients with myeloid sarcoma seems dismal and systemic therapy remains the modality of choice.

Clinico-Hematological and cytogenetic spectrum of adult myelodysplastic syndrome: The first retrospective cross-sectional study in Iranian patients

Background Myelodysplastic syndrome (MDS), a heterogeneous group of hematopoietic malignancy, has been shown to present different cytogenetic abnormalities, risk factors, and clinico-hematological features in different populations and geographic areas. Herein, we determined the cytogenetic spectrum and clinico-hematological features of Iranian MDS patients for the first time. Methods This prospective cross-sectional study was conducted on 103 patients with MDS in Ahvaz, southwest of Iran, from 2014 to 2018. Clinical presentations, complete blood counts (CBC), and bone marrow (BM) biopsy samples were assessed. Perls' staining was used to evaluate BM iron storage. The cytogenetic evaluation was performed using the conventional G banding method on the BM. Results Patients’ median age was 62.3 (ranged from 50–76), and the majority were male (72.8%). The most common clinical symptom at the time of admission was fatigue (n = 33) followed by pallor (n = 27). The most common subgroup was MDS-Multi Lineage Dysplasia (MDS-MLD) (n = 38, 36.8%), followed by MDS-Single Lineage Dysplasia (MDS-SLD) (n = 28, 18.4%). A normal karyotype was observed in 59 patients (57.3%), while 44 patients (42.7%) had cytogenetic abnormalities. Trisomy 8 (+ 8) was the most common cytogenetic abnormality (n = 14) followed by del 17p (n = 9) and monosomy 7 (− 7) (n = 7). Twelve patients (11.65%) were transformed to AML. Conclusion Our data betokened that among our MDS patients, Trisomy 8 is the predominant cytogenetic abnormality, and MDS-MLD and MDS-SLD are the most common of subtypes. Noteworthy, the male: female ratio was slightly higher in Iran than in previous reports from other parts of the world. Our study is the first report of the clinical, hematological, and cytogenetic spectrum of MDS patients in Iran

Clinico-Hematological and cytogenetic spectrum of adult myelodysplastic syndrome The first retrospective cross-sectional study in Iranian patients

Background Myelodysplastic syndrome (MDS), a heterogeneous group of hematopoietic malignancy, has been shown to present different cytogenetic abnormalities, risk factors, and clinico-hematological features in different populations and geographic areas. Herein, we determined the cytogenetic spectrum and clinico-hematological features of Iranian MDS patients for the first time. Methods This prospective cross-sectional study was conducted on 103 patients with MDS in Ahvaz, southwest of Iran, from 2014 to 2018. Clinical presentations, complete blood counts (CBC), and bone marrow (BM) biopsy samples were assessed. Perls' staining was used to evaluate BM iron storage. The cytogenetic evaluation was performed using the conventional G banding method on the BM. Results Patients’ median age was 62.3 (ranged from 50–76), and the majority were male (72.8%). The most common clinical symptom at the time of admission was fatigue (n = 33) followed by pallor (n = 27). The most common subgroup was MDS-Multi Lineage Dysplasia (MDS-MLD) (n = 38, 36.8%), followed by MDS-Single Lineage Dysplasia (MDS-SLD) (n = 28, 18.4%). A normal karyotype was observed in 59 patients (57.3%), while 44 patients (42.7%) had cytogenetic abnormalities. Trisomy 8 (+ 8) was the most common cytogenetic abnormality (n = 14) followed by dell 17p (n = 9) and monosomy 7 (-7) (n = 7). Twelve patients (11.65 %) were transformed to AML. Conclusion Our data betokened that among our MDS patients, Trisomy 8 is the predominant cytogenetic abnormality, and MDS-MLD and MDS-SLD are the most common of subtypes. Noteworthy, the male: female ratio was slightly higher in Iran than in previous reports from other parts of the world. Our study is the first report of the clinical, hematological, and cytogenetic spectrum of MDS patients in Iran

Clinical Course of High-Risk Multiple Myeloma Patients in Korea: A Multicenter Retrospective Study

Introduction: Increased understanding of the pathophysiology of multiple myeloma (MM) and the introduction of new drugs has led to considerable survival improvements in recent years. The International Myeloma Working Group consensus recently updated the definition for high-risk MM based on cytogenetic abnormalities. Moreover, the recent introduction of new therapeutic agents and the revision of insurance reimbursement policies have changed the clinical characteristics of MM patients in Korea. Yet, current epidemiology and the clinical characteristics of MM patients in Korea have not been fully investigated. Therefore, we aimed to understand the characteristics and management of Korean MM patients in a real-world setting by analyzing patients with high-risk cytogenetic abnormalities in the Korean Myeloma Registry. Methods: This is a retrospective observational study using the Korean Myeloma Registry, the web-based multicenter patient registry system established by the Korean Multiple Myeloma Working Party. Patients who are newly diagnosed with MM from 2010 to 2017 with at least one high-risk cytogenetic abnormality [t(4;14), t(14;16), or del(17p)] were included. Primarily, patients were classified by cytogenetic abnormality into three groups: Group 1, t(4;14) or t(14;16); Group 2, del(17p); and Group 3, t(4;14)/del(17p) or t(14;16)/del(17p). These patients were also stratified by the revised International Scoring System (R-ISS) and transplantation history for detailed analysis. We also used the number of cytogenetic abnormalities in an explanatory analysis; in this case, we included gain(1q). Progression-free survival (PFS) and overall survival (OS) were estimated, and the Hazard Ratio with the log-rank test was used for statistical comparison. Results: 391 out of 2170 MM patients from seven hospitals were identified as high-risk patients (men, 49.6%; median age, 63 years old). Median PFS for all patients was 18.9 months (95% CI 17.27-20.33), and the median OS was 44.6 months (95% CI 36.5-60.1). PFS (P&lt;0.001) and OS (P=0.012) between the cytogenetic abnormality groups were significantly different after stratification by transplant history. Patients with t(4;14)/del(17p) or t(14;16)/del(17p) amongst transplant recipients showed the worst outcome, with median PFS 15.5 (95% CI 8.7-20.5) months and median OS 35.6 (95% CI 14.9-N/A) months. Without stratification, there were no significant between-group differences in PFS and OS. OS was also significantly different between cytogenetic abnormality groups stratified by the revised International Staging System (R-ISS) (P=0.003). The lowest median OS durations were 16.9 months (95% CI 6.5-33.6) for del(17p) with R-ISS III, and 21.7 months (95% CI 9.3-N/A) for t(4;14)/del(17p) or t(14;16)/del(17p) with R-ISS III. Patients with higher R-ISS staging in the presence of del(17p) showed worse survival outcomes. Finally, PFS and OS were significantly inversely correlated with the number of cytogenetic abnormalities (P&lt;0.001). Conclusion: In real-world data from the Korean Myeloma Registry, we were able to observe the association of poor prognosis of MM patients with the number of cytogenetic abnormalities (PFS and OS) and R-ISS (OS). Moreover, we were also able to find the association of cytogenetic abnormality del(17p) and poor prognosis in MM patients. Lastly, we believe that this study provides the characteristics and management of MM patients needed to understand the real-world clinical course of high-risk MM patients in South Korea. Disclosures Kim: Amgen, BMS, Janssen, Sanofi, Takeda: Consultancy, Honoraria, Research Funding. Kim:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Yoon:Novartis: Consultancy, Honoraria; Janssen: Consultancy; F. Hoffmann-La Roche: Other: All authors received support for third-party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland., Research Funding; YuhanPharma: Research Funding; Kyowahako Kirin: Research Funding; Amgen: Consultancy, Honoraria. Yoon:Celltrion: Honoraria; Samyang: Research Funding; Amgen, Chongkundang, Celgene, Astrazeneca: Consultancy. Lee:AMGEN: Current Employment.