Q: My nephew was just diagnosed with the ALL type of leukemia. How bad is this?
A: Acute lymphocytic leukemia (ALL) occurs when lymphocytes, a type of white blood cell (WBC) that is part of the body’s immune system, develop a DNA defect that makes them multiply in an uncontrolled fashion, becoming cancerous; exposure to radiation, certain infections, certain genetic disorders and other conditions may cause the defect in some patients, but most cases occur with no identifiable cause.
About 85 percent of ALL cases are in children, the remaining 15 percent in adults usually over the age of 40. ALL represents around 30 percent of all childhood cancers; it is the most common cancer in children. ALL is diagnosed in about 3000 children (almost 3 per 100,000) and 1,000 adults per year. It has a peak incidence between 2 and 5 years of age, then drops off and slowly increases again after age 40.
The symptoms of ALL stem from the lack of normal red blood cells (RBCs), platelets or WBCs due to the cancerous cells crowding out normal cell production in the bone marrow. Fatigue, shortness of breath with exertion or weakness occurs if the RBCs (that carry oxygen around the body) become very low. Easy bruising, blood in the stool, excessive bleeding from minor trauma or little red spots especially on the lower legs (petechia) can occur with low platelets. Insufficient normal WBCs (cells that fight infection), even if the total WBC count is high from the cancerous cells, can put the patient at risk for infections. ALL cells may multiply in certain organs, especially the spleen; in 10-20 percent of patients the initial symptoms are related to an enlarged spleen and may include left upper abdominal fullness or even early satiety from the spleen squishing the stomach. Bone pain may occur due to the abnormal cells multiplying in the bone marrow.
ALL is diagnosed by identifying the abnormal cells by blood tests and bone marrow biopsy. Tests to look for disease elsewhere in the body may include examination of the cerebral spinal fluid and possibly certain imaging exams. Tests to identify the type and genetics of the abnormal cells, such as cytogenetics and immunophenotype, may help guide treatment decisions and inform prognosis.
Supportive therapy with transfusions of RBCs and/or platelets is a mainstay of treatment, as are antibiotics for infections. Since ALL progresses rapidly if untreated, specific disease treatment is initiated shortly after the diagnosis is confirmed.
Initially, individualized induction therapy with a combination of chemotherapy agents and possibly drugs that target specific abnormalities of the cancer cells is used to kill the cancer cells, allowing normal cell production to resume. ALL can invade the central nervous system, so treatment aimed at killing the cancer cells in the cerebrospinal fluid (intrathecal chemotherapy and/or radiation therapy) also may be required.
Sixty to 90 percent of adults achieve an initial remission after induction, with even higher rates up to 99 percent in children. However, 25 percent of children and up to 65 percent of adults relapse after an initial remission. Although 50 to 70 percent of children who relapse achieve a second remission, only 40 to 50 percent of adults do. In general, patients who relapse, especially patients with early relapses, have a poorer prognosis.
Page 2 of 2 - Once remission has been achieved, the next step is individualized consolidation therapy to kill any remaining cancer cells and help minimize the risk of a relapse. This phase of treatment lasts about six months. The induction and consolidation phases are the most aggressive treatment regimens.
The last treatment phase is maintenance therapy, which involves lower doses of chemotherapy agents for two to three years. This is more commonly done in children, as data on its efficacy in adults is lacking, and is intended to reduce the risk of any missed cancers cells returning.
Some patients will undergo stem cell transplantation after achieving remission. In these patients very intensive chemotherapy and possibly whole body irradiation is given to try and kill any lingering cancer cells. Stem cells, capable of dividing into and replenishing all types of blood cells, are then transfused into the patient.
The overall five-year survival for children with ALL is now more than 85 percent, with 50 percent of children disease free and the rest still alive but requiring further treatments. The prognosis is not as good for adults, with only a 20-percent to 40-percent five-year survival.
Testing for minimal residual disease (MRD) uses PCR (polymerase chain reaction), reverse transcription PCR or multicolor flow cytometry to identify even tiny amounts of remaining ALL cells that may be missed by conventional testing. Up to 70 percent of kids will have MRD detectable after induction, but this number drops during the consolidation period. Measuring MRD has been shown to be a predictor of relapse; studies are on-going to see if it may be useful to help guide treatment modifications. Treatment change can go in two directions; less aggressive therapy to decrease side effects in patients without MRD or medication changes/intensified therapy for those with significant MRD. MRD testing may possibly play a surveillance role, screening for disease relapse.
Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.