'FLT3-ITD Mutation Does Not Influence Survival Outcome in Adult Acute Promyelocytic Leukemia Patients Treated With ATO and ATRA-Based Therapeutic Regimen: Experience From a North Indian Tertiary Care Centre'.

INTRODUCTION: NPM1 and FLT3-ITD are frequently mutated genes in acute myeloid leukemia. We studied clinico-hematological profile and survival outcome of adult acute promyelocytic leukemia (APL) patients harboring these mutations. MATERIALS AND METHODS: De novo APL cases (> 12 years), enrolled between January 2019 and June 2020, were evaluated for FLT3-ITD and NPM1 mutations (A, B, D mutations) by conventional and real-time qualitative PCR respectively. RESULTS: FLT3-ITD mutation was detected in 12 of 36 (33.3%) de novo APLs cases while NPM1 mutation was not detected. FLT3-ITD was more frequently associated with Sanz high-risk category as compared to the intermediate-risk category (75% vs. 29%, P = .02), with BCR3 transcript type (P = .08) and higher median WBC count [22.7 × 109/L)(range 1.3-184), P = .018]. One and half-years overall survival (OS) and event-free survival (EFS) were not significantly altered by the presence/absence of FLT3-ITD mutation (OS 86% vs. 70%, P = .32; EFS 86% vs. 70%, P = .33), between genders (OS, EFS both 89% in males vs. 69% in females, P = .15) and between adolescent and younger adults (AYA) (≤ 30 years) and older adult APL cases (> 30 years) (OS 86% vs. 78%, P = .55; EFS 85% vs. 77%, P = .55), however were significantly lower with BCR3 transcript as compared to BCR1 transcript (OS 56% vs. 91%, P = .019; EFS 56% vs. 91%, P = .016) in univariate analysis, although not in multivariate analysis. One and half-year OS and EFS was 57% (6/14, P = .009 for each) in high-risk APL. CONCLUSION: FLT3-ITD mutation did not influence survival outcome in adult APL treated with ATO and ATRA-based therapeutic regimen.

Characterization of Immunophenotypic Aberrancies with Respect to Common Fusion Transcripts in B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 986 Indian Patients

Objective: Based on the immunophenotype, acute lymphoblastic leukemia (ALL) can be categorized into B-cell or T-cell lineages. B-cell precursor ALL (BCP-ALL) cases show various genetic/molecular abnormalities, and varying frequencies of chimeric fusion transcripts in BCP-ALL cases are reported from different parts of the world. We studied the immunophenotypic aberrancy profiles of a large number of BCP-ALL cases with respect to various common chimeric fusion transcripts. Materials and Methods: Flow cytometric immunophenotyping and multiplex reverse-transcription polymerase chain reaction assays were performed for 986 BCP-ALL cases. Results: Among 986 BCP-ALL cases, the incidence of various fusion transcripts was 38.36% in adult cases and 20.68% in pediatric cases. Adult BCP-ALL patients with t(9;22)(BCR-ABL1) fusion transcripts and expression of aberrant myeloid markers were significantly older at presentation (p=0.0218) with male preponderance (p=0.0246) compared to those without aberrant myeloid expression. In pediatric patients with the t(12;21)(ETV6-RUNX1) chimeric fusion transcript, aberrant expression of CD13 was observed in 39.13%, CD33 in 36.95%, and CD117 in 8.69% of patients, respectively. Pediatric BCP-ALL patients with the ETV6-RUNX1 fusion transcript and expression of aberrant myeloid markers were not significantly different compared to those without with respect to demographic and clinical/hematological characteristics (p=0.5955). Aberrant myeloid markers were rarely or never expressed in pediatric and adult BCP-ALL patients with the t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts. Conclusion: Aberrant myeloid markers were frequently expressed among BCP-ALL patients with the t(9;22)(BCR-ABL1) and t(12;21) (ETV6-RUNX1) fusion transcripts. However, BCP-ALL patients with the t(4;11)(KTM2A-AF4) and t(1;19)(TCF3-PBX1) fusion transcripts rarely or never expressed aberrant myeloid markers. Aberrant myeloid CD markers can be used in predicting chimeric fusion transcripts at baseline so as to plan appropriate tyrosine kinase inhibitor therapy in cases of BCP-ALL with specific chimeric fusion transcripts. This study has delineated the relationship of chimeric fusion transcripts with the aberrant expression of myeloid markers in a large cohort of BCP-ALL cases.

PHi-RACE: PGIMER in-house rapid & cost effective classifier for the detection of BCR-ABL1-like acute lymphoblastic leukaemia in Indian patients.

For the detection of BCR-ABL1-like ALL cases, two methodologies, specifically Gene expression profiling (GEP) or Next-generation targeted sequencing (NGS) and TaqMan based low-density (TLDA) card, are being used. NGS is very costly and TLDA is not widely commercially available. In this study, we quantified the expression of 8 selected overexpressed genes in 536 B-ALL cases. We identified 26.67% (143/536) BCR-ABL1-like ALLs using hierarchical clustering and principal component analysis. BCR-ABL1-like ALL cases were significantly older at presentation (p = 0.036) and had male preponderance (p = 0.047) compared to BCR-ABL1-negative ALL cases. MRD-positivity and induction failure were more commonest in BCR-ABL1-like ALL cases (30.55 vs.19.35% in BCR-ABL1-negative ALL cases). Lastly, we built a PHi-RACE classifier (sensitivity = 95.2%, specificity= 83.7%, AUC= 0.927) using logistic regression to detect BCR-ABL1-like ALL cases promptly at diagnosis. This classifier is beneficial for hematologists in quick decision making at baseline to start tailored treatment regimes.