Raising Awareness of HCL Variant
Hairy Cell Leukemia (HCL) Variant, called HCL variant or HCLv, is a rare type of HCL that differs from the classic form in its presentation and biology. Understanding the characteristics that distinguish the rare variant of an already rare disease is critical to diagnose a patient accurately and select the most effective treatment.
To raise awareness of HCL variant, we hosted a webinar with guest speaker Dr. Farhad Ravandi from the University of Texas MD Anderson Cancer Center.
Differences in presentation
The variant form of HCL accounts for about 10% of HCL cases. While classic HCL is characterized by low blood counts, patients with HCL variant typically have higher white and lymphocyte counts. Both types of HCL involve abnormal lymphocytes with "hairy" projections.
The distinction between classic and variant HCL can be confirmed by specific surface markers and the presence of a BRAF V600E mutation, which is found in almost 100% of patients with classic HCL, but not in the variant form.
Poor response to purine nucleoside analog therapy
Dr. Ravandi noted that HCL variant shows less response to single-agent nucleoside analog therapy (cladribine or pentostatin) and has a poorer prognosis with shorter remission duration compared to classic HCL.
The combination of cladribine (or pentostatin) and rituximab has become the standard treatment for patients with HCL variant, with better outcomes than single-agent therapy. In variant HCL, concomitant administration of cladribine and rituximab is recommended to improve treatment response.
It is important to note that cladribine plus rituximab is an immunosuppressive regimen that leads to temporary blood count decreases and increased susceptibility to infections, particularly viral infections. Dr. Ravandi recommended close monitoring to prevent serious complications..
Therapy decisions can depend on many factors, including blood count features and symptoms like fatigue, night sweats, and weight loss.
Taking precautions
Dr. Ravandi advises patients to be up to date on their vaccinations, including for COVID-19, pneumonia, and flu, before starting therapy. Therapy for HCL may not need to be initiated immediately, which allows time for vaccination.
Shingles can be a concern, and prophylactic treatment with valacyclovir may be considered for unvaccinated patients.
More than one ‘variant’ of HCL
We now understand that there is more than one atypical form of HCL.. We understand that HCL expressing the IGHV4-34 immunoglobulin rearrangement is a variant form of HCL.
IGHV4-34+ HCL is considered to be less responsive to cladribine, especially when used as a single agent. It is often found to be negative for the BRAF V600E mutation, but in some cases, it can still be BRAF mutated.
Due to the resistance of IGHV4-34+ HCL to standard treatments, combination therapy (cladribine or pentostatin plus rituximab) is recommended, with the potential inclusion of BRAF inhibitors if a BRAF V600E mutation is present. For relapsed patients, treatment decisions are based on the duration of the first remission. Treatment options include B-cell receptor inhibitors like Ibrutinib, acalabrutinib, or pirtobrutinib, and possibly venetoclax as a last resort.
Conclusion
Dr. Ravandi concluded his presentation by emphasizing the significance of clinical trials and research, especially for HCL variant where treatment options are limited. These trials play a crucial role in testing new treatments, improving patient outcomes, and ultimately finding a cure for this rare disease. Participating in a trial benefits current patients and has the potential to impact future generations.
We want to thank Dr. Ravandi for shining a light on HCL Variant.