JAK2 mutation and treatment of JAK2 inhibitors in Philadelphia chromosome-negative myeloproliferative neoplasms

ABSTRACTThe Philadelphia chromosome-negative (Ph-negative) myeloproliferative neoplasms (MPNs) polycythaemia vera (PV), essential thombocythaemia (ET) and primary myelofi brosis (PMF) are clonal disorders of multipotent haematopoietic progenitors. The genetic cause of these disorders was not fully defi ned until a somatic activating mutation in the JAK2 non-receptor tyrosine kinase, JAK2V617F, was identifi ed in most patients with PV and a considerable proportion of patients with ET and PMF. The discovery of JAK2 mutation has changed the molecular reclassification of MPNs and served as a genomic target for therapeutic implication. A number of JAK2 inhibitors have been developed and tested for MPNs. Several JAK2 inhibitors have reached the phases of clinical trial and included patients with intermediate-risk or high-risk MF. This population of MF is the best candidate for trials because currently it has no effective therapy besides patients’ poor survival. Considering all clinical data on Ph negative MPNs, JAK2 inhibitors have shown a clinical benefi t and reduced symptoms in the vast majority of MF cases. The most developed among JAK2 inhibitors is Ruxolitinib, which has demonstrated clinical improvement with well tolerated toxicities. However, JAK2 inhibitor was equally active in patients with and without JAK2 mutation. Other JAK2 inhibitors are less developed, but showed a similar clinical benefi t. Furthermore, its effect on the natural course of MPNs in treating patients needs to be investigated.Keywords: myeloproliferative neoplasms – JAK2 mutation – JAK2 inhibitors

Long-Term Predictors of Disease Free Survival (DFS) in Ovarian Cancer Sensitive to Platinum Based Chemotherapy

Until now, there has been progress in the treatment of ovarian cancer, but ovarian carcinoma is still a cause of high mortality. Various factors have been known to be associated with a poor prognosis, such as the absence of symptoms, lack of an effective screening tool, diagnosis of the disease that was only detected after an advanced stage, high recurrence of disease resistant to chemotherapy. There are more than 70% of cases detected in advanced stage, with long-term survival of only 15-30%; while those detected in early stages, the survival reaches 90%. The recurrence risk of IIIC stage disease is as high as 40% -50%. However, there is a small group of patients who can recover after standard therapy. There is variability in the recurrence-free period and survival, so it is difficult to predict the outcome with certainty. Ovarian cancer patients with the same characteristics can show a different prognosis, related to high molecular heterogeneity of tumor genetics. We report a rare case that is a 56-year-old woman who has experienced a 5-year free disease after complete remission after standard chemotherapy from stage IIIC ovarian cancer. The disease-free period of up to 5 years after therapy may be related to factors that can be predictors of prognosis, such as age at diagnosis, body mass index, physical performance, cancer cell biology, and the success of surgical response and chemotherapy in these patients

THE COGNITIVE FUNCTION OF ANTHRACYCLINE-BASED ADJUVANT CHEMOTHERAPY IN WOMEN WITH BREAST CARCINOMA

Objective: The objective of this study was to determine the changes in cognitive function of anthracycline-based adjuvant chemotherapy in women with breast carcinoma. Method: The study design was prospective longitudinal study. The breast cancer patients who received anthracycline-based adjuvant chemotherapy were recruited from Internal Medicine Department wards and TULIP cancer outpatient clinic Sardjito General Hospital Yogyakarta. Subjects eligible with inclusion and exclusion criteria were examined for cognitive function by mini-mental state examination (MMSE) nd before chemotherapy (T0 ) at 3 weeks after 2nd adjuvant chemotherapy (T1 ), 3 weeks after 4 th adjuvant chemotherapy (T2), and 3 months after 4th adjuvant chemotherapy (T3 ). The mean difference of 3 MMSE scores were analyzed with Wilcoxon-signed rank test and

Validation of the Palliative Prognostic Score (PaP score) in Patients with Metastatic Cancers in Dr. Sardjito General Hospital Yogyakarta

Background. The mortality burden of cancer continues to increase in developing countries, most likely because of a late-stage at diagnosis. Identify the terminal stage is important in patients with advanced cancer because no longer aggressive therapy in patients with terminal cancer. Palliative prognostic score (PaP score)is a scoring system to predict the probability of survival within 30 days in patients with advanced cancer. PaP score divided into the heterogeneous patient sample into three iso-prognostic groups related to the chance of 30-days survival. Group A, score: 0 to 5.5 (the probability of survival within 30 days > 70%); Group B, score: 6-11 (the probability of survival in 30 days 30-70%) and group C, the score: 11.5 to 17.5 (the probability of survival in 30 days <30%).Aims. The aim of this study was to validate and to evaluate the prognostic accuracy of the palliative prognostic (PaP score) to predict 30-days survival in patients with metastatic cancers in Dr. Sardjito   General Hospital Yogyakarta.Methods. The design of this prognostic study was cohort, including patients with metastatic cancers who were visited in Tulip Hematology and Medical Oncology Clinic, inpatient and outpatient care in Dr. Sardjito General hospital during May 2015 until May 2016. The PaP score calculated in 159 consecutive patients with metastatic cancers. The positive predictive value of the PaP score was evaluated and survival analysis was performed to compare the survival of the three prognostic groups.Results. PaP score tested on 159 subjects with overall median survival was 90 days, 76 subjects categorized into group A, 22 subjects into group B and 61 patients into group C. The 30-day survival probability was 98.7% for group A (median survival could not be assessed), 63.6 % probability of 30-day survival for the group B with median survival was 35 days and for group C with 3.3% probability of 30-day and median survival was 6 days. These survival differences were highly significant (log-rank test of trends, X =203.97; P<0.0001).The positive predictive value of the PaP score in predicting 30-day mortality was 96.7% with an accuracy of PaP the score was 93.1%.Conclusion. PaP score was a valid test tool in determining prognosis in patients with metastatic cancers with high accuracy and precision in predicting 30-days survival.Keywords:  PaP score,  validation,  survival,  prognostic,  metastatic cancers

Comparison of Prognostic Scores in Chronic Myeloid Leukemia (Cml) Patients with Bcr-Abl Mutation Types B3a2 and B2a2 in Dr. Sardjito General Hospital

Background. Chronic Myeloid Leukemia (CML) is a myeloproliperative malignancy that is caused byreciprocal translocation between chromosomes 9 and 22 which form the BCR-ABL fusion gene. Most CML patients have a major type of BCR-ABL mutation. There are b3a2 and b2a2 types, which produce different oncoproteins in 25 amino acid elements. The expression of different proteins is thought to cause differences in clinical manifestations, laboratory, and prognosis. In CML, there are several prognostic scoring systems, including Sokal, Hasford, andEUTOS scores which combine clinical and laboratory parameters. The effect of this genomic breakpoint location on clinical and biological characteristics is still controversial.Aims. The aim of this study was to determine the comparison of prognostic scores between CML patients with b3a2 and b2a2 BCR-ABL mutation types in Dr. Sardjito General Hospital.Methods. This study was a cross sectional retrospective study used secondary data from medical records of Dr. Sardjito General Hospital, from March 2014 to April 2016. The prognostic score of Sokal, Hasford, and EUTOS was calculated in the BCR-ABL mutation type groups b3a2 and b2a2. Data were analyzed by Chi Square test.Results. A total of 113 CML patients were analyzed with 74 (65.5%) b3a2 mutation type groups and 39 (34.5%) b2a2 mutation type groups. Hemoglobin levels, leukocytes, platelets, basophils, and eosinophils did not differ significantly between the two groups of mutation types. Meanwhile, the statistical test for the phase of disease when the patient was first diagnosed in both types of mutations showed a significant difference (p = 0.005). More patients with types of b2a2 mutations came in the acceleration and blast crisis phases than b3a2 types. However, Sokal, Hasford, and EUTOS prognostic scores in the b3a2 mutation type group were not significantly different from the b2a2 group (p> 0.05).Conclusions. There was no significant difference in prognostic scores of CML patients with the b3a2 BCRABL mutation type compared with the b2a2 mutation type in Dr. Sardjito General Hospital Yogyakarta

Telomere and telomerase in hematological disorders Focusing on bone marrow failure syndromes and hematological malignancies

ABSTRACTWe review the present knowledge of telomeres and telomerase with special attention to their role in hematological disorders especially bone marrow failure syndromes including acquired aplastic anemia and myelodysplastic syndromes, as well as acute and chronic myeloid leukemia. The current understanding on the role of telomere and telomeres dysfunctions in hematological disorders leads us to a better understanding on the pathology of the diseases as well as considering some possibilities to employ the measurement of telomere length and telomere activity in disease prognostication. Several treatment options targeting telomere and telomerase being developed are also reviewed.Keywords: telomere- telomerase- bone marrow failure syndromes- hematological malignancie

Secondary acute myeloblastic leukemia after adjuvant chemotherapy and radiotherapy in breast cancer: A case report

A rising number of long-term survivors and potential long-term outcome related to the treatment isone of the most important issue due to the advances of management in cancer. The development ofsecondary malignancy has been reported in a number of cohorts. We present a case of breast cancerpatient developing acute myeloid leukemia (AML)- M5 within a relatively short interval of two and ahalf years from her primary treatment with adjuvant chemotherapy with 4 cycles of doxorubicin andcyclophosphamide, followed by 4 cycles of three weekly paclitaxel (AC-T) and radiotherapy. Whatcould be attributed to the occurrence of secondary leukemia in this patient will be discussed

Status gizi awal berdasarkan Patient Generated Subjective Global Assessment (PG-SGA) berhubungan dengan asupan zat gizi dan perubahan berat badan pada penderita kanker rawat inap di RSUP DR. Mohammad Hoesin Palembang

Background: Weight loss is commonly detected among cancer patients in their early stages. This presumably happens due to low calory intake and increasing energy requirements which finally lead to malnutrition in cancer patients. Early detection to identify nutrition problems of cancer patients is through screening so as to maximize nutrient intake through nutrition therapy and diet modification and to improve nutrition status as well as quality of life of cancer patients. Objective: The study aimed to identify the relationship between nutrition status based on PS-SGA and nutrient intake and weight loss of cancer patients hospitalized at Dr. M. Hoesin Hospital of Palembang. Methods: The study was observational with prospective cohort study design. In this study the group that had fulfilled inclusion criteria were screened during their early hospitalization (within 24 hours) using patient-generated subjective global assessment score to identify their nutrition problem. Next, the group was divided into 2 smaller groups consisting of one group with malnutrition and another group without malnutrition. Analysis of nutrient intake obtained from foods provided by the hospital and outside the hospital was made to the two groups within 2 weeks of hospitalization using visual comstock and food record. Anthropometric measurement was made to find weight loss the subject of the study. Results: The results of the study showed that there was significant relationship between nutrition status and intake of energy and protein with p=0.000. The result of logistic regression test to nutrition status based on weight changes indicated that there was significant relationship between risk of nutrition and weight changespatients with risk of nutrition had 7.016 times greater probability for weight loss than those without risk of nutrition (95% C5 2.896-16.997). Conclusion: There was significant relationship between nutrition status and nutrient intake among cancer patients and there was greater probability for weight l

Prognostic Value Of Chemotherapy-Induced Neutropenia In Metastatic Colorectal Cancer At Rsup Dr Sardjito Yogyakarta

Background: Colorectal cancer is the third largest incidence of cancer in the world and is the third most common cause of death in women and men . Five-year overall survival (OS) in colorectal cancer who have undergone metastasis was 10 % . Hematologic toxicity may be a marker of biological activity of cytotoxic drug on various types of cancer . Neutropeniaafter chemotherapy known to be associated with increased patient survival .Objective : To establish whether chemotherapy-induced neutropenia is predictive of better outcome in patients with metastatic colorectal cancer (mCRC).Methods: This research was a case-control study. Subjects were patients with metastatic colorectal cancer in the Cancer Instalation Center Tulip RSUP dr. Sardjito who meet the inclusion and exclusion criteria. Data were analyzed by bivariate analysis using chi square test and multivariate analysis with logistic regression.Results: Neutropenia present in 26 patients (32.5%) of the total 80 patients of the study. Neutropenia were significantly affect OS ( p = 0.001 and OR 7.73, 95% CI: 2.51-23.80). Multivariate logistic regression analysis showed neutropenia and the number of metastases affect OS with p <0.001 and p <0.003.Conclusion: Neutropenia occurring during the two first lines of chemotherapy for metastases colorectal cancer is associated with better survival. Variables that affect OS is the number of metastases and incidence of neutropenia after chemotherapy

Prognostic Value of Albumin Levels before Therapy on Survival of Nasopharyngeal Carcinoma Patients

Nasopharyngeal cancer (NPC) is a type of cancer in Southeast Asia, with 30-80 cases annually per 10,000 population. Based on the data, about 80% of patients with advanced-stage are diagnosed first, while 20% develop metastases after therapy. A prognostic assessment is essential for the optimization of treatment. Malnutrition is one of the consequences of decreased response to treatment, quality of life, and survival. The patient's albumin determines nutrition. This study was a retrospective study to evaluate the ability of pre-therapy albumin levels to predict long-term mortality in 227 NPC patients at Dr. Sardjito Hospital. Univariate analysis identified albumin as a statistically significant predictive factor for survival (P 0.021). Albumin (ALB) 3.50 was significantly associated with shorter survival. Median Overall Survival showed (OS) ± SE ALB 3.50 vs. ALB 3.50: 9.40 ± 2.56 vs. 17.63 ± 1.51 months, P 0.021, Hazard Ratio (HR) 1.368; 95% CI (1.049–1.783). However, multivariate analysis showed low serum albumin levels before therapy on survival in NPC patients (P 0.778, HR 1.050, 95% CI (0.75–1.469). Treatment was identified as the only independent predictive factor for survival. Albumin before therapy was a potential predictive biomarker to evaluate survival in NPC patients but not an independent predictor