Is Cladribine Chemotherapy?
Chemotherapy is a treatment with drugs to interrupt the formation of cancer cells, either by destroying them or by preventing their multiplication. It is given by mouth, in injection, by infusion or on the skin, depending on the type of cancer and the stage.
Cladribine is a synthetic antineoplastic that has shown its effectiveness in the treatment of hairy cell leukemia.
Cladribine is the most used antineoplastic (chemotherapy) treatment. The usual dose is 0.1 mg/kg/day in continuous infusion for 7 days, although discontinuous doses are also used (infusion of 2 hours for 5 days or 3 hours once a week for 6 weeks). The most notorious undesirable effects are neutropenia and immunosuppression.
Subcutaneous administration is also being used.
Regarding cladribine side effects, the first 2 weeks after the start of treatment, the platelet count, the absolute neutrophil count and the hemoglobin concentration decrease first and then increase, normalizing on day 15, week 5 and week 8 respectively. The myelosuppressive effects of cladribine were more noticeable during the first month of treatment. A careful hematological control is recommended especially during the first 4 to 8 weeks after treatment with cladribine.
In clinical studies, fever is associated with the use of cladribine in approximately 72% of the patients. The majority of febrile episodes can occur during the first month and is not associated with infection.
Hairy cell leukemia is a chronic B-cell lymphoproliferative syndrome, comprising approximately 2 to 3% of all adult leukemias. These cells have characteristic hairy projections and infiltrate the bone marrow and red pulp of the spleen, although other organs can also be affected.
In more than half of the patients, there is anemia, leukopenia, neutropenia, monocytopenia, thrombocytopenia (low levels of blood cells), splenomegaly which refers to enlargement of the spleen (80 to 90% of cases) and infections. Hepatomegaly and autoimmune diseases (polyarthritis, erythema nodosum…) are also frequent.
Adenopathies, bone involvement, ascites, pleural effusion and neurological complications are rare.
In peripheral blood, there may be leukocytosis or monocytopenia. Hairy cells (tricholeukocytes) are small or medium-sized lymphoid cells with an oval or indented nucleus of chromatin more dispersed than in normal lymphocytes and absent or obscure nucleoli. The cytoplasm is abundant and pale blue, presenting hairy projections in all its periphery. These projections are different from those of lymphocytes of splenic lymphoma with villous lymphocytes. They show positivity for resistant-tartrate acid phosphatase.
Bone marrow aspiration can be dry due to fibrosis, with an increase in reticulin fibers. An interstitial or patchy tumor infiltrate with partial preservation of fat and hematopoietic elements are appreciated. Unlike most low-grade lymphomas, the infiltrate is characterized by a wide separation between the small oval or kidney cells of the cells, which may have a “fried egg” shape.
In the spleen, the cellular infiltrates are found in the red pulp cords, with a typically atrophic white pulp. In the liver, the infiltration is usually portal and sinusoidal. The lymph nodes may appear infiltrated, although this finding usually coincides with a high tumor mass.
Treatment for Hairy Cell Leukemia
The “watch and wait” tactic can be accepted, although it is acceptable to start treatment when there is a symptomatic disease (fatigue, discomfort due to splenomegaly) or when cytopenias appear (anemia, thrombocytopenia, neutropenia).
Other than cladribine, pentostatin is also used for treatment of hairy cell leukemia.
-Pentostatin: The dose usually used is 4 mg/m2 every 15 days for a total of 8-10 cycles. Side effects include myelosuppression, fever, infections, digestive, neurological and liver disorders.
The complete remission rate achieved with these medications ranges between 75-90% and that of long-term relapses of 30-40%.
Interferon is used in some patients who have not responded to treatment with purine analogs. Splenectomy can also achieve prolonged remissions. Monoclonal antibodies (rituximab) are showing efficacy in patients with refractory disease or relapse, as well as in the treatment of minimal residual disease.
Retreatment with the same drug may be reasonable in case of relapse when the duration of the remission was greater than one year. In case of resistance, the use of new drugs (ibrutinib, vemurafenib) should be considered.