Integrated Multimodal Diagnostic Validation in Hematological Disorders: First Prospective Study from a Conflict-Affected, Resource-Limited Setting in Yemen

Background and objectives: Hematological disorders pose significant diagnostic challenges, particularly in conflict-affected, resource-limited regions like Yemen, leading to delays, misdiagnoses, and suboptimal patient care. This study aimed to prospectively validate an integrated multimodal diagnostic approach for hematological disorders in Yemen, assessing its diagnostic accuracy, clinical utility, prognostic value, and cost-effectiveness compared to conventional morphology-based diagnosis. Methods A prospective study enrolled 420 patients with suspected hematological disorders. A comprehensive algorithm, integrating peripheral blood film morphology, flow cytometry, molecular genetics, bone marrow trephine biopsy with immunohistochemistry, and targeted ancillary tests, was employed. The final integrated diagnosis, established by a multidisciplinary team, served as the gold standard. Diagnostic accuracy, agreement, malignancy prediction, survival analysis, and cost-effectiveness were assessed. Results The cohort showed a diverse spectrum, predominantly malignancies. PBF achieved 87.5% overall accuracy but had low sensitivity (41.5%) for lymphoma infiltration, highlighting its limitations. The integrated approach achieved 96.8% combined diagnostic accuracy. Flow cytometry was crucial for acute leukemias, chronic lymphocytic leukemia, and lymphomas. Molecular testing confirmed BCR-ABL1 in 94% of CML and JAK2 V617F in 89% of BCR-ABL1-negative myeloproliferative neoplasms. Bone marrow trephine biopsy combined with IHC provided 100% definitive diagnosis for lymphoma. Prognostic factors included age > 40 years, hemoglobin < 8 g/dL, WBC > 50,000/µL, platelet < 50,000/µL, splenomegaly, and lymphadenopathy. Poor survival was predicted by age > 60 years, high WBC (> 100,000/µL), low hemoglobin (< 6 g/dL), blast percentage > 50%, and delayed diagnosis. The complete integrated panel ($245/patient) demonstrated superior diagnostic accuracy and improved Quality-Adjusted Life Years, showing a favorable economic profile. Conclusion This pioneering study in a conflict-affected, resource-limited setting establishes that an integrated multimodal diagnostic approach substantially improves diagnosis of hematological disorders, overcoming morphology-based limitations. These findings emphasize the critical need for implementing comprehensive diagnostic capabilities to optimize patient outcomes and inform public health strategies.