Integrative Analysis of Clinicopathological Features Defines Novel Prognostic Models for Mantle Cell Lymphoma in the Immunochemotherapy Era: A Report from The North American Mantle Cell Lymphoma Consortium

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. RESULTS: In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p \u3c 0.0001) and progression-free survival (PFS, p \u3c 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p \u3c 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort. CONCLUSIONS: The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL

A Dose-Response Relationship to Radiotherapy for Cutaneous Lesions of Langerhans Cell Histiocytosis

Langerhans cell histiocytosis (LCH) is a rare disease, afflicting approximately 4.6 and 1-2 per 1 million children and adults, respectively. While LCH can involve numerous organ systems such as the lung or bone, it is uncommon for the disease to be limited to the skin. Radiotherapy has an established role for osseous lesions. However, the efficacy and dose for nonosseous manifestations of the disease are not well described. In the current case report, we detail a 49-year-old adult male with skin-limited LCH requiring palliative radiotherapy (RT) to numerous sites for pain control. The patient was initially diagnosed and treated with single agent cytarabine for approximately 6 months. Despite treatment, he had little symptomatic response of his cutaneous lesions. We delivered a single dose of 8 Gray (Gy) to 3 separate skin lesions, including the bilateral groin, right popliteal region, and right axillary lesion, which resulted in pain reduction and partial response at four-month follow-up. Subsequently, we decided to treat the left axillary untreated lesion to a higher dose of 24 Gy in 12 fractions. At four-month follow-up, the left axilla RT resulted in complete clinical response and improved pain control compared to the right axilla. Following RT treatments, the patient was found to have a BRAF mutation, and vemurafenib was initiated. Further follow-up with positron emissions tomography demonstrated complete metabolic response in numerous disease areas, including both axillae. Based on this case report’s findings, a higher radiotherapy dose may be more effective for treating cutaneous LCH