Impact of molecular response time achievement on survival of chronic phase chronic myelogenous leukemia patients treated by imatinib

Background: Chronic myelogenous leukemia (CML) is the most common myeloproliferative disorder. BCR-ABL, the CML cell, contains oncogene makes tyrosine kinase protein which causes cells to grow and reproduce out of control. Recently, a tyrosine kinase inhibitor, namely, imatinib had high efficacy in CML treatment. Importantly, quantification of BCR-ABL transcripts is the most sensitive method to monitor molecular response at deeper levels than the hematologic and cytogenetic response to achieve an excellent outcome. Objective: We described the molecular response, time achievement, and the impact on survival in CML patients. Materials and Methods: A retrospective medical record of 143 BCR-ABL positive chronic phase CML patients have been treated by imatinib 400 mg. The hematological response was determined and the molecular response was assigned by BCR-ABL quantification. The time to achieve major molecular response (MMR) was defined by ≤0.10% ratio of BCR-ABL to ABL control gene and its impact on median survival. Results: In our study, the median age at presentation was 45 years (range 12–73 years). Male to female ratio was 2:1. Patients achieved MMR on 12, 18, and 24 months were 8 (5.5%), 26 (18.2%), and 26 (18.2%), respectively. Patients achieved MMR in <24 months have longer median survival 83.8 (77.4–90.8) months compared to 58.9 (51.7–66.2) of those who failed to achieve it in 24 months, P < 0.001. Conclusion: Our data have shown time to MMR achievement had an impact on survival. The patients that did not achieve MMR had a poorer clinical outcome. Early recognition and prompt treatment of these patients can improve outcomes

Management strategy for an advanced head of pancreas carcinoma patient with obstructive jaundice

Background: Pancreatic cancer (PC) is still considered incurable, with overall survival 3–5 months and 5-year survival 3% in advanced stage. Obstructive jaundice often complicates head of pancreas carcinoma. Strategy for bile diversion and chemotherapy regimen choices is needed to prolong survival and good quality of live. Case: Male, 64 years old, with abdominal discomfort and jaundice. Abdominal CT scan showed caput pancreas mass 43 mm ×39 mm attached to common mesenteric artery. The FNAB showed adenocarcinoma pancreas well differentiated. The diagnosis of PC adenocarcinoma well-differentiated T3N1M0 Stage III was made. Metal stent placement by ERCP to diverse bile. Chemotherapy with gemcitabine and carboplatin for six cycles, results in stable disease. The patient still has good performance status (PS 0-1), so second line chemotherapy regimen with 5- fluorouracyl, folinic acid, and oxaliplatin were given for 6 cycles. In month 15, the patient wished for oral chemotherapy, and capecitabine was given. His condition deteriorated with peritoneal metastase. The patient passed away in month 26 due to pneumonia and sepsis. Discussion: In locally advanced PC, resectability assessment is important. With mesenteric artery contact, resection is impossible. Endoscopic placement of a metallic biliary stent is strongly recommended for diversion. First-line chemotherapy of gemcitabine carboplatin can be given for fit patients. In refractory stage, second-line 5 fluorouracyl, folinic acid, and oxaliplatin significantly extend overall survival. Conclusion: Management strategy in advanced pancreatic carcinoma is important due to the poor prognosis nature. Bile diversion and prompt chemotherapy regimen choice can prolong survival and improve patient’s quality of liv

Circulating Plasma miRNA-21 as a Superior Biomarker Compared to CA 15-3: Assessment in Healthy Age Matched Subjects and Different Stage of Breast Cancer Patients

BACKGROUND: Carbohydrate antigens 15-3 (CA 15-3) is a conventional tumor marker in breast cancer, with low sensitivity and specificity. MicroRNA (miRNA)-21 showed its stability in circulation and could serve as powerful biomarker. The aim of this study was to evaluate miRNA-21 as breast cancer biomarker compared to CA 15-3 in Indonesian population.METHODS: Circulating plasma miRNA-21 expression was measured using qRT-PCR in 49 patients at various stages of breast cancer and 16 healthy controls. The relative expression value of miRNA-21 was calculated using 2-ΔΔCt. Meanwhile, CA 15-3 was quantified using electrochemiluminescence immunoassay (ECLIA) methods. The results of miRNA-21 and CA 15-3 plasma circulating expression were compared with controls at each stage and between stages of breast cancer.RESULTS: CA 15-3 median level in breast cancer group was 1.60 times higher compared to control group (p=0.019), 21.00 m/mL and 13.05 m/mL, respectively. Median miRNA-21 expression in breast cancer group was elevated 4.92 folds compared to control group (p=0.001), 4.43 and 0.90, respectively. There was no significant difference of CA 15-3 level between controls and all stages of breast cancer group. CA 15-3 cut-off value was 15.05 m/mL (p=0.016) with 59.2% sensitivity and 62.5% specificity. Meanwhile, there was a significant difference of miRNA-21 expression between controls and most stages of breast cancer group. Circulating miRNA-21 expression cut-off value was 2.07 (p=0.000) with 91.8% sensitivity and 87.5% specificity.CONCLUSION: Circulating miRNA-21 expression and CA 15-3 levels were significantly increased in breast cancer group compared to control group. The miRNA-21 expression increased consistently with breast cancer stage progression. miRNA-21 could serve as superior biomarker compared to CA 15-3.KEYWORDS: biomarker, breast cancer, circulating plasma, liquid biopsy, miRNA-2

Serum ferritin level affects T lymphocyte CD4, CD8, and CD4/CD8 ratio in transfusion-dependent beta-thalassemia

Background: Chronic blood transfusions and hemolysis are the major causes of secondary iron overloading transfusion- dependent beta-thalassemia. Iron overload can cause several organ complications including immune alteration. Infection due to immune alteration is number two leading cause of mortality in thalassemia. Research on the correlation of ferritin as iron overload marker and T lymphocyte subsets alteration in adult thalassemia patients are still rare and require further study. Objective: The objective of the study was to study the correlation of iron overload and T lymphocyte subsets CD4, CD8, and CD4/CD8 ratio in adult transfusion-dependent beta-thalassemia. Methods: The study was cross-sectional observational analytic study conducted on 36 subjects with transfusion-dependent beta-thalassemia diagnosed by clinical examination and laboratory high-performance liquid chromatography followed up at Hematology Clinic, Dr. Soetomo Teaching Hospital Surabaya, Indonesia. Ferritin serum was measured by chemiluminescence immunoassay method, while CD4, CD8 counts, and CD4/CD8 ratio were assessed by flow cytometry with antigen for CD3/CD4/CD8. Results: There were 36 subjects, 21 males and 15 females with median age of 23 (range 18–48). The mean ferritin serum was 5137.8 ± 2433.5 ng/ml while CD4, CD8, and CD4/CD8 ratio were 695.56 ± 25.17; 822.4 ± 360; and 0.95 ± 0.42, respectively. The analysis of correlation showed that there is correlation of ferritin and CD4 (r = ‒0.34, P < 0.05), ferritin and CD8 (r = 0.43, P < 0.05), and ferritin and CD4/CD8 ratio (r = 0.34, P < 0.05). Conclusion: In this study, there was a correlation between ferritin serum and CD4, CD8, and CD4/CD8 ratio. An increase of ferritin in iron overload will decrease CD4, increase CD8, and decrease CD4/CD8 ratio

Early detection breast cancer: role of circulating plasma miRNA-21 expression as a potential screening biomarker

Background/aim: To explore the potential of the circulating plasma miRNA-21 as an early detection biomarker by comparing earlystage breast cancer (BG) and healthy control (HG) in Indonesian population. Materials and methods: The enlisted patients were 26 adult female early-stage breast cancer patients (stage 1A, 1B, 2A, and 2B) of Airlangga University Hospital from August 2019 to October 2019. Sixteen volunteers were recruited as matching healthy subjects. MiRNA-21 expression was quantified by plasma qRT-PCR. Data analysis performed using IBM SPSS Statistics v.24 (IBM Corp., Armonk, NY, USA). MiRNA-21 cut-off, sensitivity, and specificity were analyzed using receiver operating characteristic (ROC) curve. Results: The study included 26 BG and 16 HG subjects. The miRNA-21 expression in BG group was 3.933 (1.181-11.794) and 0.905 (0.164-4.532) in HG group (4.34 folds; P = 0.001), with 1.66 cut-off (92.3% sensitivity; 81.2% specificity). MiRNA-21 expression separated analysis in HG showed a 0.578 times lower expression in menopause subjects [0.651 (0.164-0.414)], compared to premenopause ones [(1.123 (0.758 - 4.532); P = 0.031]. Yet, in BG group, 1.729 times higher miRNA-21 expression was observed in menopause subjects (6.021 ± 3.583), compared to premenopause ones (3.500 ± 1.517; P = 0.022). Conclusion: Circulating miRNA-21 expression is a potential biomarker for early detection of breast cancer and might act as a breast cancer risk predictor

Hubungan Antara Kadar Feritin Serum Dengan Jumlah CD4, CD8, DAN RASIO CD4/CD8 Pada Pasien Thalassemia Beta Dewasa Tergantung Transfusi: Penelitian Observasional Cross Sectional Di Poliklinik Onkologi Satu Atap Hemato-Onkologi Medik Penyakit Dalam Instalasi Rawat Jalan RSUD Dr.Soetomo Surabaya

Background: Chronic blood transfusions and hemolysis are the major causes of secondary iron overload in transfusion dependent Thalassemia Beta. Iron overload can cause several organ complication including immune alteration. Infection due to immune alteration is number two leading cause of mortality in thalassemia. Research on the correlation of ferritin as iron overload marker and T lymphocyte subsets alteration in adult transfusion are still rare and requires further study Objective: To study the correlation of iron overload and T lymphocyte subsets CD4, CD8 and CD4/CD8 ratio in adult transfusion dependent beta thalassemia. Methods: The study was cross sectional observational analytic study conducted on 36 subjects with transfusion dependent beta thalassemia diagnosed by clinical examination and laboratory High Performance Liquid Chromatography followed up at Hematology Clinic, dr Soetomo Teaching Hospital Surabaya, Indonesia. Ferritin serum were measured by chemiluminiscence immunoassay (CLIA) method, while CD4, CD8 counts and CD4/CD8 ratio were assessed by flowcytmetry with antigen for CD3/CD4/CD8 Results: There were 36 subjects, 21 males and 15 females with median age of 23 (range 18- 48). The mean ferritin serum was 5137,8 + 2433,5 ng/ml while CD4, CD8 and CD4/CD8 ratio were 695, 56+ 251,17; 822,4+ 360 and 0,95 +0,42 respectively. Analysis of correlation showed there’s correlation of Ferritin and CD4 (r = -0,34, p< 0.05), ferritin and CD8 (r = 0,43, p <0.03) and ferritin and CD4/CD8 ratio (r = 0,34, p< 0.05) Conclusion: In this study there were correlation of ferritin serum and CD4, CD8 and CD4/CD8 ratio. An increase of ferritin in iron overload will decrease CD4, increase CD8 and decrease CD4/CD8 rati

Profile of Predictive Factors of Response to Therapy in Patients with Diffuse Large B-cell Lymphoma in dr Soetomo General Teaching Hospital Surabaya

Despite the use of rituximab as a substantial treatment for Diffuse Large B-Cell Lymphoma (DLBCL), the survival rate remains low due to high incidences of relapse. Several predictive factors for relapse have been investigated however, still expensive and not applicable. Lymphocytemonocyte ratio (LMR) reported as a predictor factor for treatment responses of DLBCL patients. The aims of this study to know the profile of predictor factors include age, LDH, Ann Arbor stage, extranodal involvement and lymphocyte-monocyte ratio (LMR), with the treatment response of LNH type Diffuse Large B-Cell Lymphoma (DLBCL) patients in dr. Soetomo Surabaya.A retrospective observational descriptive study of 203 subjects undergoing R-CHOP chemotherapy during 2015- 2017. Predictor variables were age, LDH, Ann Arbor stage, extranodal involvement and LMR. Elderly > 60 more unresponsive to chemotherapy 24 (46,2%) vs 28 (19%), high LDH more unresponsive 49 (94,2%) vs 3 (5, 8%). Ann Arbor stage III-IV more responsive to chemo than stage I-II, 24 (15,9%) vs 127 (84,155). In LMR< 2,6 subgroup, 84 (55,6%) subjects showed response to chemotherapy, while in LMR < 2,6 subgroup only 67 (44,4%) subgroups showed response. The conclusion of this study are subjects ≥60 years old, high LDH ≥200 U/l, early stage of disease, extranodal involvement and LMR<2.6 had a higher risk of unresponsiveness to chemotherapy

Cytokines, Autoantibodies, and Complements in Active Systemic Lupus Erythematosus Patients from Javanese Population

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that has various clinical manifestations. The SLE pathogenesis involves both innate and adaptive immunological components. The system is essentially determined by genetic factors that control certain clinical and serological manifestations. Genetic traits that determine the roles of cytokines, autoantibodies, and complements in SLE vary among ethnicities. The roles of TNF-α, IL-6, anti-C1q, anti-dsDNA, C3, and C4 towards SLE activity need to be evaluated in the Javanese population. This study aimed to determine the correlation of TNF-α, IL-6, anti-C1q antibodies, anti-dsDNA, C3, and C4 with SLE activity. Forty SLE patients were diagnosed based on the American College of Rheumatology (ACR) criteria. Disease activity was measured by the Systemic Lupus Activity Measure (SLAM) index. TNF-α, IL-6, Anti-C1q, and anti-dsDNA levels were measured by ELISA, while MINIMEPH measured C3 and C4. Thirty-nine female and one male patient with SLE were diagnosed according to ACR criteria. The mean of SLAM score, anti-dsDNA, C3, and C4 levels was 20.98±6.7, 224.96±298.6, 68.70±37.08 mg/dL, and 18.75±10.69 mg/dL, respectively. Spearman's correlation test showed a positive correlation between TNF-α (r = 0.971, p<0.001), IL-6 (r=0.835, p<0.001), anti-C1q (r=0.399, p=0.01), and disease activity (SLAM score) by using. The linear regression test for TNF-α, IL-6, anti-C1q, and SLAM showed the strongest association for TNF-α (r=0.891, p<0.000). TNF-α, IL-6, and anti-C1q were correlated to disease activity in SLE patients from the Javanese population

Diagnostic Problem of Facial Malignancy in The Elderly: A rare case

Introduction: Lymphoma can occur in adults and the elderly, this will affect the condition of both diagnosis and therapy. Plasmablastic lymphoma (PBL) is a subtype of diffuse large B-cell lymphoma (DLBCL), the case is rarely found and often overlaps the anatomical pathology picture similar to plasmacytoma. It is aggressive and often relapses

Cardiac Tamponade: A Rare Manifestation of Lung Cancer. A Case Report

Background: Malignancy is the most common cause of non-inflammatory pericardial effusion that is usually neglected. Metastatic involvement of the pericardium is reflecting the advanced stage of the disease and generally associated with poor outcomes