Shah, Shiv

Abstract Background Hairy cell leukemia (HCL) is a rare, indolent B-cell malignancy accounting for ~1% of all lymphoid neoplasms. While purine analogs remain the standard first-line therapy, the increasing use of combination regimens and targeted agents has expanded the therapeutic landscape. Data on long-term outcomes in real-world practice remain limited. Methods This is a retrospective, multicenter cohort study. We included 104 patients aged ≥18 years with a diagnosis of HCL who had at least one oncology visit from January 1, 2010, to July 17, 2025. Patients diagnosed prior to 2010 were left-truncated to account for survivorship bias. Data were abstracted from electronic medical records. Key outcomes included treatment patterns, response rates, overall survival (OS), and progression-free survival (PFS). Results The median age at diagnosis was 56.9 years (range 32.1–83.8), and 80% were male. Most patients (77%) were diagnosed during or after 2010. The most frequent frontline therapies were cladribine (63%), cladribine with rituximab (12%), rituximab monotherapy (9.7%), vemurafenib-based regimens (7.7%), splenectomy with or without interferon (3.8%), interferon monotherapy (2.9%), and other (1.9%). The overall complete response (CR) rate to first-line therapy was 63%, with 15% achieving a partial response (PR) and 22% having stable or no response. For patients receiving cladribine with rituximab first-line (n = 12), 92% had a CR. For patients receiving cladribine monotherapy first-line (n = 65), 63% had a CR and 12% had a PR. For patients receiving rituximab monotherapy first-line (n = 10), 50% had a CR and 20% had a PR. For patients receiving vemurafenib-based regimens first-line (n = 8), 75% had a CR. Among the 39 patients who received second-line therapy, the most common regimens included cladribine (31%), rituximab (26%), cladribine plus rituximab (18%), and vemurafenib-based regimens (13%). The CR rate after second-line therapy was 72%. For patients receiving cladribine with rituximab second-line (n = 7), 86% had a CR and 14% had a PR. For patients receiving cladribine monotherapy second-line (n = 12), 67% had a CR. For patients receiving rituximab monotherapy second-line (n = 10), 80% had a CR and 10% had a PR. For patients receiving vemurafenib-based regimens second-line (n = 5), 40% had a CR and 20% had a PR. Among the 17 patients who received third-line therapy, the most common regimens included rituximab (41%), cladribine (18%), and vemurafenib-based regimens (18%). The CR rate after third-line therapy was 50%. For patients receiving rituximab monotherapy third-line (n = 7), 43% had a CR and 14% had a PR. For patients receiving cladribine monotherapy third-line (n = 3), 33% had a CR. For patients receiving vemurafenib-based regimens third-line (n = 3), 67% had a CR and 33% had a PR. Overall, treatment-related hospitalizations for first-line therapy occurred in 27% of patients. 50% of patients receiving first-line cladribine with rituximab had treatment-related hospitalizations. 25% of patients receiving first-line vemurafenib-based treatment had treatment-related hospitalizations. 23% of patients receiving first-line cladribine monotherapy had treatment-related hospitalizations. 20% of patients receiving first-line rituximab monotherapy had treatment-related hospitalizations. Overall, after a median follow-up of 6.6 years (range 0.1–46), estimated OS was 96.6% at 5 years, 85.7% at 10 years, and 80.3% at 15 years. The median OS was 24.5 years [95% CI: 18.3, not reached]. Estimated PFS was 95.1% at 1 year, 89.9% at 3 years, 74.8% at 5 years, and 50.8% at 10 years. Median PFS was 12.2 years [95% CI: 7.0, not reached]. Estimated OS for first-line cladribine monotherapy was 100% at 5 years and 86.5% at 10 years. Estimated OS for first-line vemurafenib-based treatment was 85.7% at 5 years and 85.7% at 10 years. Conclusions This large real-world cohort provides important insights into the long-term management of HCL. Cladribine-based regimens remain the predominant first-line approach, with high response rates and durable remissions. However, treatment-related toxicity is common. Outcomes in later lines remain favorable, particularly with re-treatment using purine analogs or combination regimens. These findings underscore the importance of individualized treatment planning and the continued need for real-world evidence to inform care in rare hematologic malignancies.

Abstract BACKGROUND Leptomeningeal disease (LMD) carries poor prognosis with an average survival of 3-6 months after diagnosis. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for delivery of intrathecal chemotherapy (IC) and disease monitoring but are not widely used. Intraventricular administration of chemotherapy may be associated with superior efficacy and improved patient comfort. The purpose of this study was to assess safety and efficacy of IC and disease monitoring via OR in routine clinical practice. METHODS Patients who received at least one administration of IC via OR for LMD between 2017 and 2022 were included. Demographics, treatment type, complications and outcomes were recorded. RESULTS We identified 22 patients (17 females, 5 males) with mean age 50.9 ± 14.8 years. The primary tumors were: breast (12), leukemia (3), ovarian carcinoma (3), CNS lymphoma (1), urothelial carcinoma (1), spinal melanocytoma (1), and high-grade glioma (1). A total of 208 OR injections were performed [median was 9 OR injections per patient, interquartile range (IQR) (5, 13)]. Five patients (23%) experienced mild adverse events of grade 2 or lower by Common Terminology Criteria for Adverse Events. Overall risk of adverse event from injection was 3.4% (7/208). Eight patients (36.3%) converted into negative CSF cytology (median 1 month following first injection). Eighteen patients (82%) had clinical or radiological progression of their LMD (median 2 months following first injection). Eleven patients (50%) died of their LMD during follow-up. Median OS and PFS from the first injection were 5.3 months [95% CI 4.8-NE (not estimable)] and 4.3 months [95% CI 1.8-16.0], respectively. CONCLUSION Use of OR in routine clinical practice is a safe and feasible option and should be strongly considered for treatment and monitoring of patients with LMD. The median OS in our cohort is comparable to prior published series.

Abstract INTRODUCTION Leptomeningeal disease (LMD) is an aggressive, late-stage complication of systemic cancers that maintains a poor prognosis with an average survival of 3-6 months. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for the delivery of intrathecal chemotherapy in the treatment of LMD. However, widespread use of OR has been limited by reports of complications, limited physicians trained in their use, and the stigma of brain surgery. Here, we assess survival and complication rates for patients who received intrathecal chemotherapy through OR for LMD treatment. METHODS After IRB approval, chart review of patients who received at least one administration of intrathecal chemotherapy through OR for LMD treatment between 2017- 2020 at Mayo Clinic in Phoenix, Arizona was conducted. Charts were reviewed for demographics, treatment type, complications, and outcomes. RESULTS A total of 10 patients were included. The median overall survival from date of first OR injection was 110.5 days (95% CI: 64 – not estimable). The median time to progression from the first injection was 55.5 days (95% CI: 45 – 753). A total of 82 OR injections were conducted for an average of approximately 8 injections per patient. Two patients (20%) experienced mild adverse events – grade 2 or lower by Common Terminology Criteria for Adverse Events with a single injection. The majority of injections involved no adverse events with the overall risk of any complication at 2.4%. None of the patients experienced infection, a commonly reported complication of OR use. CONCLUSIONS Our results support the inclusion of intrathecal chemotherapy via OR into the treatment paradigm in patients with leptomeningeal malignancies. This approach is feasible, safe, and median survival is comparable with data reported in published series. The overall complication rate in patients receiving intrathecal chemotherapy through OR is very low including the risk of infection.