Hairy Cell Leukemia

P1, N=27, Not yet recruiting, Luminary Therapeutics

P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2029

P1, N=30, Active, not recruiting, City of Hope Medical Center | Trial completion date: Jun 2026 --> May 2027

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=45 --> 28 | Trial completion date: Jul 2028 --> Jun 2029 | Trial primary completion date: Apr 2028 --> May 2026

Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

However, interpretation of these findings is limited by the non-randomized design and differences in rituximab exposure between groups, which may have contributed to the observed outcomes and limited definitive conclusions. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Case 1 was a 65-year-old woman diagnosed in 2017 with SMZL and treated with rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), oncovin (vincristine), and prednisone (or prednisolone) (R-CHOP), achieving complete remission, who presented nine years later with recurrent hyperlymphocytosis at 10.8 × 109/L with villous appearance, massive splenomegaly, and systemic symptoms...The patient was treated with rituximab-bendamustine and achieved complete remission...Rituximab monotherapy was followed by rapid improvement, with normalization of the lymphocyte count to 2.13 × 109/L and regression of splenomegaly from the first cycle. These observations highlight the importance of combining lymphocyte immunophenotyping and bone marrow aspiration in isolated splenomegaly with villous lymphocytes on blood smear to avoid underdiagnosis of this new histopathological entity and therefore guide therapeutic management in the absence of guidelines.

Treatment regimens included Cladribine alone or with Rituximab, yielding high response rates and minimal toxicity. In this multiethnic Middle Eastern and North African cohort, HCL predominantly affected middle-aged men and was often incidentally detected. Cladribine-based therapy achieved durable remissions with excellent survival, highlighting consistent efficacy across diverse populations.

Standard treatment with purine analogs (i.e. cladribine) induces long-term remissions, but up to 25% of patients relapse early...The functional importance of DUSP1 was corroborated by demonstrating that BMSC-induced protection from cell death could be overcome through DUSP1 inhibition. Our results might set the stage for future clinical testing of DUSP1 inhibition to eliminate minimal residual disease (MRD) and prevent disease relapse in HCL.

P1, N=18, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2025 --> Jun 2026

P2, N=15, Completed, Scripps Health | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Apr 2026 | Trial primary completion date: Dec 2026 --> Apr 2026