Leukemia is an uncontrolled and unregulated growth of immature white cells. Eventually, the leukemia population crowds out all the normal cell lines in the bone marrow, causing severe anemia, infections and bleeding.
Chronic leukemias have a slow rate of growth, but are difficult to eradicate. Often they are diagnosed during routine blood work for other reasons, and do not cause any symptoms till the normal blood counts drop.
There are two kinds of chronic leukemias:
Chronic lymphocytic leukemia (CLL): This causes a rising lymphocyte count. There are 4 stages of disease, ranging from Stage 0, with an elevated lymphocyte count only, to full fledged disease with anemia, low platelet count, enlarged lymph glands and spleen. Additional tests that predict for faster progression are chromosomal abnormalities, e.g. deletion of 17 p and 11 q, and trisomy 12.
Decision to start treatment depends on the advent of symptoms, e.g. low grade fevers, fatigue and weight loss.
Treatment options have increased in the last decade. Many new drugs are entering the armamentarium. New combinations are achieving long term remissions.
These include
Chemotherapy agents like Fludarabine, Pentostatin, Cladribine, Cyclophosphamide, Vincristine, older agents as Chlorambucil, and Steroids, as single agents or in combination.
Antibody treatments, e.g. Rituximab and Alemtuzumab.
Bone Marrow Transplants: mainly autologous, i.e. patients own marrow reinfused after achieving remission. For more information on transplants, please refer to the blog pages.
Complications of CLL include
repeated infections,
autoimmune (antibody against self proteins) destruction of red blood cells and platelets, and
transformation into more aggressive forms, e.g. prolymphocytic and acute lymphocytic leukemia, and large cell lymphoma, aka Richter’s transformation.
Chronic Myelgenous Leukemia is a chronic leukemia affecting the “non lymphocytic” cell lines. It is characterized by a rise in the white cell count, and an enlargement of the spleen.
The disease presents in 3 phases:
Chronic Phase, often discovered incidentally, with an elevated count, and sometimes, fatigue and left upper abdominal pain, due to spleen enlargement. This can last for almost 5 years
Accelerated phase is ill defined, with increasing symptoms of fevers, sweats, weight loss, and increasing numbers of immature cells. This can last for up to 18 months.
Blastic phase, is the evolution into an acute leukemia.
Chromosomal abnormality: commonly seen is a translocation (exchange) between chromosome 9 and 22, called Philadelphia chromosome. This translocation creates a fusion protein, which leads to leukemic transformation.
Treatment in the chronic phase is directed against this fusion protein, with an inhibitor. This newer modality of treatment has given long term remissions. The drugs available in this category are imatinib, nilotinib and dasatinib. For people who are not candidates for this treatment, and the goal is only to decrease the counts, without attempting remissions, hydroxyurea remains a useful choice.
Allogeneic bone marrow transplants are potentially curative treatments. The marrow is obtained from a matched donor, and is delivered after a conditioning treatment to suppress the recipient’s immunity.
Accelerated and Blastic phases require more intensive chemotherapy. Imatinib still has a response, but of limited duration. Induction chemotherapy will be required, with combinations of drugs e.g. Ara-C and daunorubicin. These stages carry a poorer prognosis, with a more limited life expectancy.