Deep sequencing reveals the spectrum of BCR-ABL1 mutations upon front-line therapy resistance in chronic myeloid leukemia: An Eastern-Indian cohort study.

The course of clinical management in chronic myeloid leukemia (CML) often faces a road-block in the form of front-line (imatinib) therapy resistance. Subsequently, several hotspot mutations were clinically validated in the kinase domain (KD) of BCR-ABL1, in deterring imatinib sensitivity and further, made targeted by next-generation tyrosine-kinase-inhibitor (TKI) drugs. Identifying KD mutations, occurring even at low frequencies, became pertinent here. Globally, cohorts from different origins were tested and the mutational spectra were mapped to categorize clinical management as well as related pathological features of CML. Moreover, targeted deep sequencing could reveal the mutational landscape more efficiently than the less sensitive Sanger sequencing method. However, no such efforts were reported from Eastern Indian cohorts of imatinib-resistant CML-sufferers. This study assessed a prospective study cohort of imatinib-resistant CML cases from Eastern India. Following dissecting the molecular and clinical parameters, the mutational spectrum was comparatively examined using conventional Sanger and next-generation deep sequencing method. This cohort showed a prevalence of e14a2-p210 variant of BCR-ABL1 and acquired resistance against imatinib, while the disease was mostly confined in its chronic phase. Together with a few common hotspot mutations identified in this cohort, deep sequencing revealed cases with a candidate mutation, otherwise undetermined by Sanger method. Also, cases with a second low frequency mutation were identified upon applying deep sequencing. Along with highlighting a few aspects of CML biology employing an Eastern-Indian cohort, this data could mark the immense importance of deep sequencing to contribute in the clinical management of CML upon front-line therapy resistance.

Long-Term Outcome of Philadelphia Chromosome Positive Leukemia From Eastern Indian Subcontinent: An Experience in the Era of Tyrosine Kinase Inhibitor (TKI) Therapy.

INTRODUCTION: Philadelphia chromosome (Ph) marks a group of leukemia with almost all cases of chronic myeloid leukemia (CML), a subset of acute lymphoid leukemia (ALL) and rare cases of acute myeloid leukemia (AML). In the era of precision medicine, such cases are successfully managed with tyrosine kinase inhibitor (TKI) drugs. This study examined the features and long-term outcome of Ph+ve cases from a tertiary cancer care center from Eastern Indian subcontinent. MATERIALS AND METHODS: Reviewing retrospective case-records registered between 2005 and 2015, cases of CML and ALL were documented under Ph+ve category; while no instance of Ph+ve AML was found. RESULTS: In CML cohort, adult and juvenile incidences were 95.2% and 4.8% respectively; in ALL cohort, the same was found for 66.67% and 33.33% cases. Among the CML cases, 10-year overall survival (OS) and progression-free survival (PFS) were significantly affected upon the phase of disease at time of detection. Furthermore, both OS and PFS significantly dropped whenever non-TKI-based treatment was applied prior to TKI-commencement. Long-term (10-year) sensitivity to 1st generation TKI, imatinib, was noted 88.51% and 83.33% for adult and juvenile CML cohorts, respectively. For Ph+ ALL cohort, the OS was benefitted upon combinatorial TKI and chemotherapy. However, large fractions of affected individual from CML as well as ALL cohorts were found to discontinue follow-up. CONCLUSION: Together with differences in outcome on the basis of drug-use from onset, age (juvenile versus adult) and stage at diagnosis, our analyses bring forward the real-world scenario of Ph+ve leukemia managed with precision medicine.

Life-threatening Episodes of Malignant Hyperthermia Following Halothane Anesthesia in Three Children: A Case Series and Review of Literature.

Malignant hyperthermia (MH) is an inherited, pharmacogenetic disorder of the skeletal muscle, characterized by dangerous hypermetabolic state after anesthesia with succinylcholine and/ or volatile halogenated anesthetic agents, clinically manifested as hyperpyrexia and related complications like tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, rigid muscles, rhabdomyolysis and disseminated intravascular coagulation (DIC). Here we present a series of three cases of MH, admitted in our hospital in a span of 8 months for three different operative procedures to be done under general anesthesia (cleft lip repair, Duhamel's operation for Hirschsprung's disease and surgical repair of development dysplasia of hip), who developed probable hyperthermia owing to Halothane being used as an anesthetic agent. HOW TO CITE THIS ARTICLE: Laha S, Giri PP, Saha A, Gupta PP, De A. Life-threatening Episodes of Malignant Hyperthermia Following Halothane Anesthesia in Three Children: A Case Series and Review of Literature. Indian Journal of Critical Care Medicine, January 2019;23(1):47-50.

A comparative study of Hasford score and Sokal index in prognostication of the novo chronic myeloid leukemia patients and a search for new prognostic markers.

INTRODUCTION: Chronic myeloid leukemia (CML) is a common myeloproliferative disorder. Based on clinical and hematological parameters, two prognostic scoring systems, i.e., Hasford and Sokal index scoring systems are available to predict survival duration of CML patients on imatinib therapy. AIMS AND OBJECTIVES: Our study's objective is to compare Hasford score with Sokal index for the prognostication of de novo CML patients on therapy and find out new prognostic markers. MATERIALS AND METHODS: This is a retrospective study. The study population comprised 66 patients who were followed up for 60 months. For each patient, at presentation, scoring was performed as per Hasford and Sokal index and Philadelphia chromosome analysis was carried out by conventional cytogenetics. Thereafter, hematological parameters were assessed 3 monthly and conventional cytogenetics was done yearly. RESULTS: Out of these 66 patients, the number of patients belonging to low, intermediate and high risk categories are 21, 33 and 12 respectively by Hasford score and 12, 32 and 22 respectively by Sokal index. Eight patients, who had been categorized into high risk group by Sokal index but intermediate risk group by Hasford score, have shown better survival possibility as monitored by hematological and cytogenetic parameters. Ten cases, categorized into intermediate risk group by Sokal index but low risk group by Hasford score, is doing well till date. CONCLUSIONS: This study shows that Hasford score predicts survival of the patients better than Sokal index. However, multicentric study over a large population is needed to give the final verdict.