CLL/SLL and the therapies used to treat the disease may be associated with a number of complications. Attempts to decrease the number of diseased cells in the blood may also cause problems with other components of the blood. “Penias” have been discussed in an earlier section and are associated with decreases in red cells, white cells, and/or platelets. Blood counts thus must be monitored closely during therapy.
Enormous advances have been made not only in the basic and initial treatments of CLL/SLL, but also in the management of the disease’s complications. Serious or troublesome issues of years ago are now handled in a rather routine manner with the advent of new medications. For instance, nausea from chemotherapy is now a thing of the past with the availability of potent anti-nausea/vomiting medications.
Another point of interest is that a patient who has developed a transformation to a more aggressive disease may, at the same time, still have CLL/SLL. Thus the patient has essentially two lymphomas/leukemias at the same time. And, since some aggressive lymphomas are curable, it is quite possible that, after intervention, the patient may return to having CLL/SLL only. It is also important to stress that some complications or transformations of CLL/SLL may occur without any precipitating cause.
Blood-Cell Related Effects
Conditions known as “penias,” anemia, neutropenia, and thrombocytopenia all describe decreases or reductions in the level of certain blood components.
Anemia refers to an abnormal reduction in the number of red blood cells or hemoglobin (carried by the red cells). This may be the result of ineffective, deficient, or suppressed hematopoiesis (blood production), such as from chemotherapy, and may also result from excessive loss (such as from bleeding) or excessive destruction of red cells (hemolysis). One form of hemolysis, autoimmune hemolytic anemia (AIHA), is a condition caused when the body produces antibodies that destroy its own red blood cells. “Auto” means “self”, so the antibodies do not recognize the body’s own red cells. Both CLL/SLL, as well as purine analogues such as fludarabine used to treat CLL, have been known to cause AIHA.
Treatment can consist of injections of red cell boosting medications (erythropoetins) such as Epogen, Procrit or Aranesp, which, however, are only partially helpful in AIHA. When significant drops in hemoglobin occur, blood transfusions may be necessary.
Neutropenia is an abnormally low number of neutrophils (a type of white blood cell). Neutrophils serve as the primary defense against infections by destroying invaders in the blood. The occurrence of neutropenia makes a person more susceptible to bacterial and other infections and, without prompt medical attention, the condition may become life-threatening. Administrations of Neulasta, Neupogen or Leukine can frequently improve the situation.
Thrombocytopenia is a decrease in platelets for blood clotting. Significant drops may require transfusions of platelets. Drugs to stimulate platelet production are being clinically tested.
Aplasia means the bone marrow is virtually devoid of blood cells and is a rare complication of therapy.
Myelodisplasia is also a rare complication where bone marrow production is faulty or abnormal.
Effects of Therapy on Organs
Interstitial pneumonitis - this swelling of the lungs is a condition brought on by chemotherapy but may also be seen with certain viral or protozoal infections.
Tumor Lysis Syndrome
Tumor lysis syndrome usually occurs at the start of therapy when there is a high count of cancerous cells. Rapid response to therapy can stress the kidneys, because the kidneys must clear wastes released by the dying leukemic cells. The condition is normally manageable by administration of fluids and short term drugs, and/or slowing down of the treatment. Allopurinol® is often used prophylactically in people who may be prone to tumor lysis syndrome.
Varicella-zoster virus, a member of the herpes virus family, causes chickenpox and shingles. Shingles occurs when a chickenpox virus emerges from a period of dormancy and is activated. Both the disease of CLL and the treatments for the disease hinder the immune system’s ability to fight this infection, and people with CLL are more prone to reactivation of the varicella-zoster virus. Acyclovir (Zovirax) or valcyclovir (Valtrex) are anti viral agents used for prophylaxsis and/or treatment.
A person gets shingles usually by having had chicken pox earlier in life. The first symptom of shingles is usually a tingling feeling, itchiness, or stabbing pain on the skin. This progresses to a rash that appears as a band or patch of raised dots on the side of the trunk or on the face. The rash develops into small, fluid-filled blisters that begin to dry out and crust within several days. Shingles can be very painful and itchy. The condition is most serious when it appears on the upper half of the face as the virus may cause serious damage to the eyes. The rash and pain associated with shingles usually disappear within 3 to 5 weeks, although the pain can persist much longer and be quite intense. The pain that continues after the rash from shingles has healed is called post-herpetic neuralgia (PHN).
Most people who have shingles have only one occurrence of the disease in their lifetimes; however, individuals with impaired immune systems may suffer repeated episodes. Treatment for shingles includes antiviral drugs such as acyclovir (Zovirax). The severity and duration of an attack can be significantly reduced by early treatment. Prevention with low dose antivirals is also effective. Vaccines are now available to prevent shingles, but are usually not given to people with defective immunity such as is often the case with CLL.
This occurs uncommonly in patients with CLL/SLL, and may signal the advent of a more aggressive lymphatic malignancy, such as large cell lymphoma, developing in a setting of CLL/SLL. Most experts think that the new, more aggressive malignancy, is usually a clone or outgrowth from the original CLL/SLL. Disturbed immunity and/or a virus may sometimes play a role in the transformation. (A virus known as the Epstein-Barr virus is associated with about one third of such transformations.) The transformation is difficult to treat if it occurs in patients who have received prior chemotherapies.
The abnormal lymphocytes seen in this type of leukemia (PLL) are called prolymphocytes. The diagnosis of PLL rather than CLL is made if more than about half of the leukemic cells are prolymphocytes. If there are prolymphocytes present, but these make up less than half of all the abnormal cells, this rare condition is called mixed CLL/PLL. Prolymphocytes may also be seen in advanced CLL.
Acute Lymphocytic Leukemia (ALL)
Extremely rarely, CLL can transform into the acute form of lymphocytic leukemia, requiring an aggressive treatment shift.
Acute Myeloid Leukemia (AML)
AML is another possible complication following treatment for CLL. Chemotherapy combinations, usually with chlorambucil, damage the DNA of blood-forming cells. These damaged cells may go on to become cancerous, leading to AML, which is quite aggressive and difficult to treat.