Erdheim-Chester disease (ECD) is a rare histiocytic disorder with heterogeneous clinical manifestations. Central nervous system (CNS) involvement is associated with poor prognosis. Although targeted therapies have improved outcomes in patients with mitogen-activated protein kinase (MAPK) pathway alterations, optimal treatment strategies for adult patients with CNS ECD are still lacking. We describe a 24-year-old female with isolated CNS ECD without pathogenic genetic alterations. The disease was refractory to corticosteroids, radiotherapy, and cladribine monotherapy. Combination therapy with cladribine and cytarabine (Ara-C) led to clinical improvement and remission on radiologic imaging, and toxicities were acceptable. This case suggests that combination chemotherapy may represent an optimal therapeutic strategy for adult patients with CNS ECD. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Hairy cell leukaemia (HCL) is a B-cell malignancy whose induction chemotherapy consists of 5 days of cladribine, a purine nucleoside analogue. While there are consensus guidelines from the National Comprehensive Cancer Network (NCCN) on antifungal prophylaxis in the setting of acute myeloid leukaemia or acute lymphocytic leukaemia, there are no consensus guidelines for antifungal prophylaxis during induction treatment of HCL. We describe a case of angioinvasive Fusarium infection in a healthy, young patient who completed cladribine chemotherapy for HCL. While rare, fusariosis poses a significant morbidity and mortality risk in neutropenic patients undergoing treatment. Prevention of fusariosis requires appropriate prophylactic agents and treatment requires resolution of neutropenia and the elimination of the fungus. This case highlights early recognition and prompt start of antifungals as the cornerstone of management. Antifungal prophylaxis is not routinely recommended during HCL induction, and whether patients might benefit from prophylaxis warrants further study.

Classic hairy cell leukemia (HCL) is a rare, indolent B-cell lymphoproliferative disorder characterized by bone marrow fibrosis causing pancytopenia, splenomegaly, and a near-universal BRAF V600E mutation. Purine nucleoside analogs (PNAs) are the standard first-line therapy but are contraindicated in patients with significantly advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD) due to renal excretion and risk of prolonged myelosuppression. Data on the use of targeted therapies, such as BRAF inhibitors, in dialysis-dependent HCL patients are lacking.

Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders characterized by the identification of hairy cells, a specific immunophenotypic and genetic profile, a different clinical course and the need for appropriate treatment.

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) can be either high- or low-intensity. This study aims to examine predictors associated with high-intensity MS treatment strategies using commercial claims data.

Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder of bone marrow-derived dendritic cells that is uncommon in adults. Its clinical presentation varies depending on the organ involved. Central nervous system (CNS) involvement poses a critical therapeutic challenge because of permanent neurological dysfunction. Here, we report two contrasting cases of adult-onset LCH with distinct clinical outcomes. Case 1 involved a 36-year-old woman presenting with a persistent headache. Neuroimaging revealed a solitary osteolytic lesion in the left parietal bone with dural thickening. Surgical resection was performed, and histopathological examination revealed characteristic Langerhans cells with positive S-100 immunostaining, confirming the diagnosis of LCH limited to the calvarium. The patient was treated with bisphosphonates and remained stable without systemic involvement. Case 2 involved a 26-year-old man presenting with cognitive impairment, somnolence, polyuria, and endocrine dysfunction. Magnetic resonance imaging revealed an enhancing hypothalamic lesion. Histopathological and immunohistochemical analyses confirmed LCH with CD1a and S-100 positivity. BRAF V600E mutation was not detected via pyrosequencing. Systemic chemotherapy with cladribine resulted in partial tumor regression; however, the cognitive dysfunction persisted. These contrasting cases highlight that disease distribution, particularly CNS involvement, influences therapeutic strategies and neurological outcomes in adult LCH. Our findings emphasize that early diagnosis and proactive systemic evaluation are essential as functional recovery remains limited once neurological damage occurs, even with successful cytoreductive therapy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) are immune-mediated peripheral neuropathies that may follow a progressive course and be refractory and poorly tolerated to standard immunomodulatory treatments. Therapeutic options for such patients remain limited. We report two patients with immune-mediated neuropathies-one with typical CIDP and one with MMN-who were treated with low-dose intermittent subcutaneous cladribine. Clinical outcomes were assessed using the Medical Research Council (MRC) sum score and the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Both patients demonstrated clinically meaningful and sustained improvements in muscle strength and functional disability lasting up to 24 months after treatment completion. Cladribine was well tolerated; transient lymphopenia occurred in one patient without serious adverse events. These cases suggest that cladribine may represent a potential therapeutic option for selected patients with CIDP or MMN. Further studies are warranted to confirm efficacy and safety.

Treatment options after venetoclax-hypomethylating agent (Ven-HMA) failure in acute myeloid leukemia (AML) remain limited, with a median overall survival of 2-3 months. Cladribine targets biologically distinct leukemia stem cells, including monocytic populations implicated in venetoclax resistance. We conducted a multicenter retrospective study across six Israeli academic centers to evaluate cladribine-based salvage therapy, predominantly cladribine, low-dose cytarabine, and venetoclax (CAV), in 31 patients with relapsed/refractory AML. Median age was 70 years (range 21-81); 87% had prior venetoclax exposure, 61% had undergone prior allogeneic transplantation, and 55% were classified as ELN-2022 adverse risk. After a single treatment course, the composite complete remission rate (CRc) was 45% and the overall response rate was 52%. Median overall survival was 5 months, with a 1-year survival of 30%. Patients achieving CRc had significantly longer survival (16.2 vs. 2.9 months; p < 0.0001). Twelve patients (39%) were bridged to cellular therapy, with a median survival of 12.6 months. Toxicity was predominantly hematological; invasive fungal infection occurred in 23% and was associated with fluconazole rather than mold active prophylaxis. The 30-day mortality was 19%. Cladribine-based salvage demonstrates clinically meaningful activity after Ven-HMA failure and can bridge patients to cellular therapy.

Langerhans cell histiocytosis (LCH) is a rare clonal myeloid neoplasm. Canadian data on clinical characteristics, molecular profile, and treatment outcomes is limited. This study aims to report the initial experience of a Canadian rare diseases program, reflecting "real-world" diagnostic pathways, referral patterns, and treatment heterogeneity across multiple provinces. We conducted a retrospective review of patients managed in an adult-care cohort with histologically confirmed LCH diagnosed between 2000 and 2025 across multiple Canadian centers. Patients diagnosed as children and subsequently transferred to adult care were included. Clinical features, radiologic findings, histopathology, molecular testing, treatment approaches, and outcomes were collected and analyzed. Thirty-one patients were identified, with a median age at diagnosis of 42 years (range: 2-84) and a male predominance (65%). Bone (74%), lung (29%), and skin (16%) were the most commonly involved sites. Concomitant or subsequent malignancies were present in 19% of patients. Molecular testing found BRAFV600E mutations in 44% of tested patients. The most common first-line systemic therapy was cytarabine (n = 10), followed by other drugs such as hydroxyurea, vemurafenib, and cladribine. This series represents the initial experience of a Canadian rare disease referral program and captures the clinical heterogeneity and longitudinal adult care of patients with LCH across multiple provinces. Variability in treatment approaches highlights the need for collaborative prospective natural history studies and coordinated clinical trials.