Cancer | Leukemia | Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is a cancer of lymphocytes that live in the bone marrow, lymph nodes and spleen. ALL accounts for 20 percent of acute leukemia in adults, but is also the most common type of acute leukemia in children.

ALL usually causes illness suddenly, within days or weeks. Most problems are related to the replacement of normal bone marrow and diminished normal blood counts. ALL causes anemia, which leads to:

In addition to these signs of bone marrow failure, ALL sometimes can cause enlarged lymph nodes, an enlarged liver or spleen, or pain in the bones or joints.

Acute lymphoblastic leukemia (ALL) usually is suspected because a test finds abnormal blood counts and the appearance of leukemic cells, or blasts, in the blood. Then, the diagnosis is established by examination of the bone marrow. It usually is difficult to be certain of a diagnosis of ALL simply by the appearance of cells under the microscope. Therefore additional laboratory tests normally are needed.

One important test is immunophenotyping (also called flow cytometry), which determines whether the cells are lymphoid (ALL) rather than myeloid (AML). Immunophenotyping will also determine whether they are T or B lymphocytes. In addition, chromosome testing, called cytogenetics, is a critical part of the evaluation that also will help determine the appropriate course of treatment.

The treatment of acute lymphoblastic leukemia (ALL) varies according to one's age, general condition at diagnosis and the results of the cytogenetic testing. Standard therapy for ALL has not changed in approximately 15 years, for the current strategy has been very effective at curing adults. Treatment can be divided into four phases:

The initial two phases use intensive chemotherapy medications designed to kill cells that grow quickly, like leukemia cells. Therapy for ALL typically continues for two to three years. Complete remission is achieved in approximately 90 percent of patients, with 25 percent to 40 percent enjoying long-term survival. Approximately 5 percent of patients die of treatment-related complications during their initial therapy and another 5 percent fail to ever achieve an initial remission.

Treatment of ALL is usually urgent and needs to be given within days and sometimes the same day as the diagnosis is made. Normally, patients are treated with chemotherapy. The first phase in treatment, called induction chemotherapy, requires that patients remain in the hospital for approximately four weeks.

The most common drugs used for induction treatment of ALL are daunorubicin, vin-cristine, prednisone, asparaginase and sometimes cyclophosphamide (Cytoxan). Intensive supportive care accompanies the chemotherapy, including transfusion of red blood cells and platelets. Antibiotics are needed both preventatively and as treatment for both bacterial and fungal infections. The agent G-CSF (Neupogen) can be useful in reestablishing a normal white blood count. Although the likelihood of mouth sores and disruption of the intestinal tract is rare, complete but temporary hair loss does occur.

Once blood counts have returned to normal, a repeat bone marrow biopsy is performed to determine whether the patient has entered complete remission. A complete remission is achieved when the blood and bone marrow show no evidence of persistent leukemia and blood counts have returned to normal.

Consolidation chemotherapy typically includes multiple cycles of intensive chemotherapy given over a six to nine month period. Frequent hospitalizations are required and intensive supportive care is still needed, including red blood cell and platelet transfusions. Stem cell transplantation is not typically performed to treat ALL unless abnormal cytogenetics are present.

Once patients have completed intensive chemotherapy, they need to take oral chemotherapy pills for an additional 18 to 24 months. These oral chemotherapy pills are usually well-tolerated with only minimal side effects. Patients need to have their blood tests checked once a month while taking chemotherapy pills. Most patients with ALL can return to work during maintenance therapy.

ALL frequently can recur in the spinal fluid (the fluid that bathes the spinal column and brain). To prevent relapse at this location, chemotherapy must be infused directly into the fluid that bathes the spinal column. This is done by inserting a needle between the vertebrae of the lower back and infusing chemotherapy directly into the clear spinal fluid, which is called intrathecal chemotherapy. Patients are routinely given 6 to 12 injections of intrathecal chemotherapy to prevent recurrence of ALL. More injections may be necessary if leukemia cells are detected in the spinal fluid.

Most people complete intrathecal therapy within two to four months of starting their treatment. Headaches and nausea are the most common side effects.

Stem cell transplantation, also called bone marrow transplantation, is only performed in patients who have abnormal cytogenetics, chromosome testing, or other high risk ALL features. Cytogenetics is the most important component of deciding whether or not a person should have a bone marrow transplant for ALL. Patients with the Philadelphia chromosome or with the translocation involving chromosomes 4 and 11, should go on to bone marrow transplantation.

At UCSF Medical Center, allogeneic transplantation -- which uses stem cells or bone marrow from a matched brother or sister -- is preferred and considered the standard therapy for ALL. Young patients with very high-risk ALL who need an allogeneic transplant but lack a matched sibling donor are sometimes appropriately treated with allogeneic transplant using a matched unrelated donor located though the National Marrow Donor Program (NMDP).

At UCSF we also offer autologous transplantation -- which uses cells collected from the patient's own bone marrow after they have achieved complete remission -- for patients with high risk ALL who lack compatible donors. The autologous stem cell transplantation protocol is an experimental therapy. Following successful induction therapy, patients with high-risk ALL are given one cycle of intensive consolidation chemotherapy.

When the blood counts begin to return to normal after consolidation therapy, stem cells are collected from the blood using a technique called apheresis. A large IV catheter called a Quentin catheter is inserted into one of the large veins in the neck. This catheter is connected to an apheresis machine, which acts as a centrifuge that separates the blood into individual components allowing the collection of only the white blood cells. All the other cells, including red blood cells and platelets, are given back to the patient. Each apheresis procedure takes four hours, and two to three procedures are usually necessary to collect enough stem cells. A monoclonal antibody, called CAMPATH, is added to the stem cell collection bag in attempt to "clean" the stem cells of any contaminating leukemia cells.

High-dose therapy in the ALL protocol includes both radiation therapy and chemotherapy. The hospitalization for the high-dose radiation, chemotherapy and re-infusion of autologous peripheral blood stem cells lasts approximately four weeks. The side effects are severe and aggressive supportive care measures are needed.