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Regional HCL Patient Forum (NYC/NE)

June 16, 2022

The Hairy Cell Leukemia Foundation thanks Dr. Jae Park of the Memorial Sloan Kettering Cancer Center in New York for his presentation during our regional HCL patient forum. Below is a summary of the presentation and discussion.

Overview of Hairy Cell Leukemia

Hairy Cell Leukemia is rare and slow growing and is more frequently found through incidental means, usually abnormal blood work, than by presentation of symptoms. The hairy cells are called thus due to hair-like projections extruding from the cell, visible microscopically. These cells express a specific set of markers, namely CD20, CD25, CD11c, and CD103.  The presence of CD25 is a key factor in the diagnosis of classic HCL. If a patient is negative for CD25, but positive for the other markers, it is very likely that he or she has the variant form of HCL. 

These hairy cells accumulate in the bone marrow and in the spleen, sometimes causing enlargement of the spleen called splenomegaly. This doesn’t occur in all HCL patients; approximately 50% of HCL patients do not have a perceptibly enlarged spleen. Other clinical signs of HCL are low levels of the three types of blood counts, collectively called pancytopenia.  Low red blood cell count is referred to as anemia and can cause fatigue, muscle pain, and shortness of breath. Low platelet count is called thrombocytopenia and can affect the blood’s ability to clot causing bruising and bleeding. And low white blood cell count, called leukopenia, can increase a patient’s susceptibility to various infections. The hairy cells tend to gather in the bone marrow, causing it to be densely filled with fibers. As a result, it may be difficult to aspirate liquid marrow during a bone marrow biopsy.

Classic HCL carries a BRAF mutation, which is also present in many other types of cancers. This mutation is important because: 1) as almost all classic hairy cell patients have the mutation, the mutation itself may be implicated in the cause of HCL; and 2) there are therapies available that specifically target the BRAF mutation.

HCL is diagnosed through blood analysis, flow cytometry, physical examination, and bone marrow biopsy.

When is HCL Treatment Required?

Due to its slow growing nature, HCL does not always warrant treatment immediately following diagnosis. As a general rule, practitioners look at blood levels that are trending downward over time. Some patients may have blood levels that are lower than normal, but if they are not dangerously low and are not trending downward, the patient may be placed into a period known as “watch and wait”.

When blood levels fall below a generally accepted standard, called the 1, 10, 100 rule, treatment options are then considered. This rule is described further: Absolute Neutrophil count (ANC) falls below 1, Hemoglobin falls below 10, or Platelets fall below 100. These counts vary from time to time, and a one-time dip is not necessarily a cause for immediate treatment. Trends in counts are far more indicative. 

Standard Treatment

The standard treatment for HCL is Cladribine or Pentostatin, forms of chemotherapy which fall into the class of purine analogs. These treatments are very effective in restoring blood counts in almost all patients, but about 30% of patients may experience recurrence of disease requiring further treatment. Purine analogs target B and T cells and kill many good cells along with the hairy cells. 

When used in conjunction with immunotherapy such as Rituximab, the remissions are longer lasting than with purine analogs alone and may reduce a chance of disease recurrence and future treatments. The downside to using chemotherapy to treat HCL is that it leaves patients vulnerable, for a period of time, to infections of all types, and it may cause secondary cancers.  Thus, in spite of the excellent results with purine analogs, other, less risky therapies are currently being investigated and tested. 

Novel HCL Treatments

One treatment option that has been developed is an oral therapy, Vemurafenib, that targets the BRAF mutation. This therapy has been used in melanoma for some time and is now used in relapsed HCL. After initiating chemotherapy, blood counts dip then slowly rise. With Vemurafenib, however, the counts do not dip but instead immediately begin to slowly rise.  As a result, Vemurafenib doesn’t make the patient more susceptible to infection during treatment. There are some potential side effects, but they can be managed. The response with Vemurafenib alone in relapsed HCL is very good, but not complete. This means that while the blood counts do return to normal, some hairy cells remain in the bone marrow. 

Dr. Park conducted a study combining Vemurafenib with Rituximab and the results were very good. This study was done in patients with HCL who had previously been treated and relapsed. The study showed that responses are deeper and fewer patients experience disease recurrence compared to Vemurafenib alone. Dr. Park and his team then decided to do a clinical trial using Vemurafenib and Obinutuzumab, a drug similar to rituximab, as the first line of treatment for HCL to see if they could get results comparable to the Cladribine/Rituximab study. The Vemurafenib/Obinutuzumab study is now complete and the results will be published in a few months. The results are very promising and we hope that in the future we may be able to treat classic HCL without chemotherapy and without putting patients at even further risk of serious infection. 

Vemurafenib does not work in patients with variant HCL as they do not have the BRAF mutation. For those patients, Cladribine/Rituximab therapy is currently the best course of action, but there are other treatment options being studied in variant HCL, including Ibrutinib and some MEK and ERK inhibitors.