Biological sex and gender factors significantly influence the pathogenesis, progression, and treatment response in hematologic malignancies. This comprehensive review examines sex-specific differences in acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and multiple myeloma through systematic analysis of the peer-reviewed literature published between 2014–2024 and identified through structured searches of PubMed, Web of Science, and MEDLINE databases. Epidemiological data demonstrate higher disease incidence (57% male vs. 43% female in MM, 63% male vs. 37% female in AML hospitalizations for ages 18–39) and inferior outcomes in male patients across malignancy types (5-year relative survival rates of 48.8% vs. 60.4% in females with AML), while female patients exhibit superior survival despite experiencing greater treatment-related toxicities. Our analysis reveals consistent sex-specific patterns in molecular mechanisms, including distinct mutational profiles, differences in immune system function, and sex-based pharmacokinetic variations that collectively suggest the necessity for sex-differentiated treatment approaches. The review identifies reproducible patterns across diseases, particularly in cytogenetic and molecular characteristics, with females demonstrating favorable prognostic mutations in leukemias and higher rates of chromosomal abnormalities in multiple myeloma. Despite these identifiable patterns, significant knowledge gaps persist regarding the underlying mechanisms of sex-based outcome differences. Incorporating sex and gender considerations into precision medicine frameworks represents a critical advancement toward optimizing treatment strategies and improving clinical outcomes for patients with hematologic malignancies.

A patient with acute myeloid leukemia (AML) presented with a cardiac mass of unknown nature. This case underscores the importance of careful monitoring and a multidisciplinary approach in managing and differentiation of rare cardiac complications in leukemia patients. It aims to improve diagnostic accuracy and therapeutic outcomes in similar challenging scenarios. This case report discusses a 33-year-old male who was initially diagnosed with Acute Myeloid Leukemia (AML). During medical check-ups before allogeneic hematopoietic stem cell transplant (allo-HSCT), cardiac ultrasound revealed several mobile and homogenous masses of unidentified nature in his right atrium and right ventricle. The lesions presented gradually increasing calcification of the capsule, the nature of these masses remains unknown. The patient was diagnosed with Acute Myeloid Leukemia and achieved complete remission following multiple chemotherapy cycles. From a leukemia treatment perspective, an allo-HSCT was needed as soon as possible. However, several masses were found in his right heart before the transplant. A series of tests were performed to determine the nature of the cardiac mass. His echocardiograms and MRI revealed persistent mobile and nodular masses with a calcified capsule in the right atrium and right ventricular lateral wall, and no signals changes of the mass between MRI first-pass perfusion and delayed enhancement. Which complicated the differential diagnosis. Finally, considering the need for leukemia treatment, allo-HSCT was performed after extensive workup, including echocardiography, MRI, and PET/CT, which ruled out leukemic infiltration, typical infectious vegetation, and primary or metastatic cardiac tumors. The cardiac masses were first discovered during pre-transplant screening in April 2022, approximately 5 months after initial AML diagnosis in November 2021. At present, more than 2 years after transplantation, follow-up imaging examination of the masses revealed gradually increasing calcification, but of a still unknown nature. The case of this 33-year-old male with AML and concomitant cardiac masses highlights a complex challenge in his diagnosis and treatment. Despite extensive imaging and multidisciplinary consultations, including echocardiography, MRI, and PET/CT, the exact nature of these calcified, mobile nodular masses in the right atrium and right ventricular lateral wall remains elusive. Their persistence and atypical imaging characteristics underscore the need for continued research and collaboration to elucidate their underlying pathology.