Aswanth Reddy

Introduction: Hemophilia A and B are among the most common inherited bleeding disorders in humans with lifelong risk of spontaneous and recurrent bleeding. While prophylaxis with clotting factors has improved outcomes, challenges like inhibitor development and treatment burden persist. We aim for a comparative effectiveness between these agents and traditional therapy with this study. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Studies were identified through PubMed, Cochrane Central, and ClinicalTrials.gov up to May 30th, 2025. Eligible studies were double-arm RCTs comparing non-clotting factor prophylaxis (emicizumab, fitusiran, concizumab) and on-demand therapy in patients with hemophilia A or B. Results: Non-clotting factor prophylaxis significantly reduced the annualized bleeding rate (ABR) for all treated bleeds [ n = 399, (RR = 0.13; 95% CI: 0.09–0.19), I ² = 63.8%, p = 0.0107], spontaneous bleeds [RR = 0.08; 95% CI: (0.06, 0.11), I ² = 0.0%, p = 0.5933)] and joint bleeds [RR = 0.09; 95% CI: (0.06, 0.14), : I ² = 26.2%, p = 0.2468 ]. Haem-A-QoL total score improved with prophylaxis [MD = −11.08 [−16.34, −5.83], I ² = 57.5%, p = 0.0949]. Prophylaxis increased the likelihood of achieving zero treated bleeds [RR = 4.11; 95% CI: (1.48%, 11.45%), I ² = 88.5%, p < 0.0001]. An exploratory network meta-analysis comparing fitusiran, emicizumab, and concizumab reported no statistically significant difference in the ABR for all treated bleeds. Conclusion: Compared to on-demand therapy, non-factor prophylactic therapies significantly reduce bleeding episodes, improve quality of life, and increase the likelihood of zero bleeds in patients with hemophilia.

Colorectal cancer (CRC) is one of the most common cancers globally and a leading cause of cancer-related deaths. Over the past decade, our understanding of CRC has significantly evolved, particularly in the areas of genomic prognostication and targeted therapies. However, surgical management beyond the initial resection of the primary tumor remains an area of ongoing discussion and research. We report a case of a 51-year-old man with metastatic CRC and liver metastases, treated with right hemicolectomy and chemotherapy, achieving complete remission. Two years later, he developed an isolated subcutaneous recurrence at the prior surgical drain site. Microsatellite instability status changed from primary to recurrent lesions. Surgical resection achieved negative margins, and the patient has since remained disease-free without additional therapy. This rare presentation challenges traditional models of CRC metastasis and highlights the potential role of lymphatic dissemination, tumor dormancy, or surgical seeding.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from adrenal medulla and extra-adrenal paraganglia. Metastatic pheochromocytomas, pose diagnostic and therapeutic challenges due to their atypical presentations and potential for malignant transformation years after primary tumor resection. We report a case of 61-year-old woman who presented with intermittent cough, shortness of breath, and elevated blood pressure 6 years after resection of primary adrenal pheochromocytoma. Imaging revealed bilateral pulmonary nodules, a retroperitoneal mass, and L4 vertebral involvement, raising suspicion for metastatic pheochromocytoma. Elevated serum metanephrines and normetanephrines, alongside tissue biopsy and MIBG imaging, confirmed diagnosis. Germline genetic testing did not reveal any pathogenic mutations. The patient underwent CT-guided cryoablation for retroperitoneal lymph nodes and scheduled for radiofrequency ablation (RFA) of metastatic lesions. This case underscores evolving understanding of PPGLs, challenging “10% rule” regarding metastasis and inheritance. While mutations in genes such as SDHB are associated with increased metastatic risk, sporadic cases like this highlight need for lifelong surveillance in all patients' post-resection of primary tumor. Ablative techniques, EBRT, and emerging systemic therapies are promising methods for managing metastatic disease. This case highlights importance of long-term follow-up and genetic testing in patients with PPGLs, even in absence of hereditary mutations, to detect and manage late-onset metastatic disease efficiently.

Maha Zafar, Manaswini Krishnakumar, Aswanth Reddy. J Cancer Prev 2025;30:41-6. https://doi.org/10.15430/JCP.25.001

Effective post-transplant immunosuppression is essential to induce tolerance to allogeneic tissues and promote long-term graft survival. However, suppression of the immune system significantly increases the risk of opportunistic infections. In addition to the ongoing challenge of balancing graft survival and preventing infections, previous gold-standard calcineurin inhibitor-based immunosuppression also posed an increased risk of nephrotoxicity, cardiac disease, and diabetes. Belatacept is approved as an alternative to calcineurin inhibitor-based regimens. Although belatacept has improved cardiovascular and metabolic adverse events in renal transplant patients’ but it carries a notably higher risk of long-term graft survival and renal toxicity, similar to calcineurin inhibitor-based regimens. However, there may be an increased risk of infections with its mechanism of action. We present a case of a 62-year-old female who developed disseminated histoplasmosis 18 months after being on belatacept-based immunosuppression after a deceased donor renal transplant for end-stage renal disease secondary to focal segmental glomerulosclerosis. Grocott Methenamine Stain (GMS) of peripheral blood smear showed intracellular yeast in neutrophils, consistent with histoplasmosis. Disseminated histoplasmosis was confirmed with positive bronchoalveolar lavage (BAL) and urine culture. The patient later developed hemophagocytic lymphohistiocytosis (HLH) secondary to immunosuppression and disseminated histoplasmosis. The patient succumbed to the disease despite maximal medical therapy. To our knowledge, there is one other published report of disseminated histoplasmosis in a patient with belatacept-based immunosuppression. The unique feature of this case is the development of HLH secondary to disseminated histoplasmosis while on belatacept. Further research is needed to evaluate the need for antifungal prophylaxis in patients on belatacept therapy.

A 63-year-old man presented to the oncology clinic reporting diffuse scalp swelling for the last 3 months. Magnetic resonance imaging of the head showed diffuse scalp swelling, calvarium destructio...

Bispecific antibodies have emerged as a promising class of therapeutics in the field of oncology, offering an innovative approach to target cancer cells while sparing healthy tissues. These antibodies are designed to bind two different antigens, enabling them to bridge immune cells with cancer cells, resulting in enhanced tumor cell killing and improved treatment responses. This review article summarizes the current landscape of bispecific antibodies in lung cancer, including their mechanisms of action, clinical development, and potential applications in other solid tumor malignancies. Additionally, the challenges and opportunities associated with their use in the clinic are discussed, along with future directions for research and development in this exciting area of cancer immunotherapy.

The abscopal effect describes tumor responses outside the irradiated field. The literature shows increased overall survival and response rates in patients receiving immunotherapy and radiation, likely from exaggerated abscopal effects. We present a 57-year-old woman with stage 4 lung adenocarcinoma who received treatment with a combination of chemotherapy and immunotherapy. She had disease progression on maintenance immunotherapy, confirming resistance. Palliative radiation to the sternal bone lesion resulted in a significant response to all areas of cancer, confirming the abscopal effect. Unfortunately, she developed severe pneumonitis; to our knowledge, this is the first case of abscopal lung toxicity.