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Targeted Inhibition of FLT3 Mutations in Acute Myeloid Leukemia: Clinical Outcomes and Resistance Mechanisms

Posted onDecember 20, 2020February 25, 2025

Research Article

Journal of Global Hematology

Volume 1, Issue 1, 2020, Pages 1-17 10.18081/JGH/2020.1/1

Sambit Singh ¹, Ramasamy Bhatnagar, Kamaldeep Tveito, Chethana Kumar, Mathew Nagaraja *

¹ Department of Hematology and Oncology, Melaka Manipal Medical College, Karnataka, India.

Received 10 October 2020; revised 09 November 2020; accepted 20 December 2020; published 11 December 2020

Abstract

Background: FLT3 mutations represent one of the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. This study evaluates the efficacy, safety, and resistance patterns of targeted FLT3 inhibition in AML patients.

Methods: A cohort of 200 AML patients with confirmed FLT3 mutations (FLT3-ITD and FLT3-TKD) was enrolled in this prospective, multi-center clinical trial. Patients received FLT3 inhibitor therapy according to standardized protocols. Primary endpoints included complete remission (CR) rate and overall survival (OS). Secondary endpoints encompassed molecular response, safety profile, and characterization of resistance mechanisms through sequential molecular assessments.

Results: The median age of patients was 52 years (range: 18-75) with a male-to-female ratio of 1.2:1. The overall CR rate was 68%, with differential responses observed between FLT3-ITD (65%) and FLT3-TKD (72%) mutations. Median OS reached 14.5 months (95% CI: 12.3-16.7), with 1-year and 2-year survival rates of 58% and 35%, respectively. Molecular response was achieved in 60% of patients and significantly correlated with improved survival (p < 0.05). Grade 3 or higher adverse events occurred in 20% of patients, predominantly myelosuppression and gastrointestinal disturbances. Sequential molecular analyses identified emerging secondary mutations in 25% of relapsed patients, with functional studies confirming their role in reduced sensitivity to FLT3 inhibitors. Multivariate analysis identified molecular response and baseline blast percentage as independent prognostic factors.

Conclusions: FLT3 inhibition demonstrates promising efficacy in AML patients with FLT3 mutations, though response varies by mutation subtype. The identification of resistance mechanisms through clonal evolution highlights the need for continuous molecular monitoring and potential combination strategies. These findings provide a foundation for optimizing treatment approaches in FLT3-mutated AML and developing strategies to overcome resistance.

Keywords: Acute myeloid leukemia, FLT3 mutations, targeted therapy, resistance mechanisms, survival analysis

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More citation

Thalassemia in Developing Countries: Bridging the Gap in Care and Access

Posted onJanuary 5, 2020February 25, 2025Leave a comment

Research Article

Journal of Global Hematology

Volume 1, Issue 1, 2020, Pages 1-17 10.18081/JGH/2020.1/1

Sambit Singh ¹, Ramasamy Bhatnagar, Kamaldeep Tveito, Chethana Kumar, Mathew Nagaraja *

Author Affiliations

¹ Department of Hematology and Oncology, Melaka Manipal Medical College, Karnataka, India.

Received 10 October 2020; revised 09 November 2020; accepted 20 December 2020; published 11 December 2020

Abstract

Background: Thalassemia remains a significant global health challenge, particularly in developing countries where healthcare infrastructure and access to specialized care are limited. This study investigates the multifaceted barriers to thalassemia care and evaluates potential interventions for improving patient outcomes in resource-limited settings.

Methods: A mixed-methods approach was employed, analyzing data from multiple developing countries (n=1,250 patients) across different socioeconomic strata. Quantitative analysis included healthcare accessibility metrics, treatment compliance rates, and clinical outcomes. Qualitative assessment involved structured interviews with healthcare providers (n=150) and focus groups with patients/caregivers (n=200). Regional variations in care delivery were evaluated using standardized healthcare infrastructure assessment tools. Statistical analysis was performed using multivariate regression models and chi-square tests for categorical variables.

Results: Significant disparities were observed in healthcare access across socioeconomic groups (30% access in low-income vs. 95% in high-income groups, p<0.001). Regional analysis revealed marked variations in blood transfusion service availability (25% in Sub-Saharan Africa vs. 70% in Latin America, p<0.001). Treatment compliance showed gender-specific patterns (female: 88% vs. male: 85% in 0-10 age group, p=0.03) and declined with age (58% in 41+ age group, p<0.001). Quality of life scores demonstrated a significant negative correlation with age (r=-0.78, p<0.001) and positive correlation with treatment adherence (r=0.82, p<0.001). Healthcare provider distribution showed substantial urban-rural disparities (3:1 ratio, p<0.001).

Conclusions: This comprehensive analysis identifies critical gaps in thalassemia care delivery in developing countries, highlighting the need for targeted interventions. The study demonstrates that socioeconomic factors, geographical location, and healthcare infrastructure significantly impact patient outcomes. Findings suggest that implementing integrated care models, strengthening rural healthcare infrastructure, and developing cost-effective treatment protocols could substantially improve care delivery and patient outcomes in resource-limited settings.

Keywords: Thalassemia; developing countries; healthcare access; treatment compliance; socioeconomic disparities; quality of life; healthcare infrastructure; blood transfusion services