Patients who are treated should have a bone marrow biopsy performed following treatment to determine if a complete response (eradication of all evidence of hairy cell leukemia) has been achieved. Among patients who have achieved a complete response by viewing the bone marrow under the microscope, it is not unusual to find minimal residual leukemia if more sophisticated studies are done to detect a small amount of hairy cells not visible under the regular microscope.

This may be one reason that some patients ultimately relapse. The question as to the need for additional therapy to eradicate minimal residual disease is a topic under current investigation. Some studies have shown that, for example, if the antibody Rituximab is given minimal residual disease may be eradicated, but it is not clear at all that this improves the long-term overall outcome for patients since patients can live for many years if not decades with a small amount of minimal residual disease and still have normal or near normal blood counts. Therefore, in general Rituximab is not given for this purpose.

Patients are usually followed quarterly after they have completed therapy. Routine blood counts are obtained to insure that the remission is being maintained. If blood counts show a decline, a repeat bone marrow may be obtained to see if the disease is relapsing by identifying a small amount of recurrent hairy cells. Immunophenotyping studies (looking for certain markers on the surface of the lymphocytes to identify hairy cells) may be done to look for a small amount of recurrent hairy cells. In addition, there are laboratory studies that can measure soluble factors or chemicals in the blood that may herald a relapse, but these are generally not often done routinely.

If relapse has been documented, careful consideration is given to decide when to re-initiate treatment. Just as there is a watchful waiting approach at the time of initial diagnosis, a similar strategy may be followed in patients who have a small amount of recurrent hairy cells, but are totally without symptoms. A small decline in the blood counts may not be sufficient to warrant re-treatment since often this disease is so slow-growing that patients can live for many years with a small amount of hairy cell leukemia in the bone marrow and it not affect the blood counts to a significant degree. However, there is an advantage to re-starting therapy before the counts deteriorate to very low dangerous levels.