1. Induction of remission

2. consolidation/intensification of therapy

3. Maintenance.

A summary of one regimen’s entire treatment process is available.

Treatment of high-risk disease:

 Patients with high risk disease require special treatment programs that use different medications and doses from those used in patients with standard risk ALL. In addition, allogeneic stem cell transplantation is more frequently recommended in these patients.

INDUCTION OF REMISSION:

 Induction of remission takes about four weeks and is almost always performed while the patient remains in the hospital.

Treatment includes: vincristine (Oncovin) and an anthracycline along with prednisone, dexamethasone, or another steroid hormone.

Vincristine and the anthracycline drugs are anti-cancer chemotherapy drugs. These drugs work by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are less affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract.

Effects of chemotherapy on these and other normal tissues cause side effects during treatment, including anemia (lowered red blood cell count), an increased risk of infection (lowered white blood cell count) and bleeding (lowered platelet count).

Vincristine and the anthracycline drugs are given through an intravenous (IV) line. Prednisone can be given either by mouth or IV. Other medicines such as cyclophosphamide (Cytoxan, given IV) or L-asparaginase (Elspar, given as a subcutaneous, intramuscular or IV injection) may also be given.

Approximately 80 percent of newly diagnosed adults with acute lymphoblastic leukemia enter complete remission after the initial treatment, meaning that there are no detectable lymphoblasts in the blood or bone marrow and that the bone marrow is functioning normally. However, such remissions are usually short-lived unless additional chemotherapy is given.

CONSOLIDATION/INTENSIFICATION THERAPY

 once remission is achieved, additional therapy is needed to avoid relapse. Relapse probably occurs because abnormal cells are still present, even though these cells cannot be detected by routine examination of the blood or bone marrow.

Chemotherapy — some of the same medicines given during induction are also used during remission consolidation therapy, which may last for several months. Most of this treatment can take place during the day, without the need to remain in the hospital overnight.

In addition to scheduled doses of chemotherapy, many treatment programs call for preventive treatment of the central nervous system (the brain and spinal cord). Abnormal lymphoblasts in the brain often do not respond to chemotherapy given only into a vein, but must be treated directly with radiation to the head and/or injection of chemotherapy, such as methotrexate, into the fluid surrounding the spinal cord and brain through a lumbar puncture (also called a spinal tap).

Stem cell transplantation — Stem cell transplantation, also called bone marrow transplantation is a treatment in which the patient is given very high doses of chemotherapy or total body radiation, called myeloablative treatment. This kills cancer cells but also destroys all normal cells developing in the bone marrow. This means that the body's normal source of blood cells (the bone marrow) is no longer functional.

After the treatment, the patient requires a supply of healthy young blood cells (called stem cells) to be reintroduced, or transplanted. The transplanted cells reestablish the blood cell production process in the bone marrow.

Current data indicate that there is no clear advantage to stem cell transplantation as compared to chemotherapy during consolidation therapy for standard risk patients in their first complete remission, although it may shorten the overall treatment course. However, allogeneic stem cell transplantation is recommended following a second complete remission.

Allogeneic transplantation uses stem cells from a donor other than the patient, ideally a sibling with a similar genetic makeup (called a matched related donor, or MRD). If the patient does not have a sibling with similar genetic characteristics, an unrelated person with a similar genetic makeup may be used (called a matched unrelated donor, or MUD). Another possibility is to use a sibling with partially similar genetic characteristics, although this is not as well studied (sometimes called a partially matched family member donor). Umbilical cord blood can also provide a source of unrelated stem cells.

Allogeneic transplantation treats acute lymphoblastic leukemia in two ways. First, high doses of chemotherapy or total body radiation are given immediately before the transplant, which aggressively attacks and kills the leukemia cells present in the blood and bone marrow. Second, when cells from another person are injected, the donor stem cells undergo an immune response that helps destroy any remaining leukemia cells. This is called the "graft versus leukemia" or "graft versus tumor" effect. Unfortunately, this response is closely associated with a complication called "graft versus host disease", in which the immune response includes an attack on some of the patient's own organs. Symptoms can include severe skin rash, diarrhea, liver damage, and other problems. Still, allogeneic transplant is preferred over autologous transplantation in patients with acute lymphoblastic leukemia.

• Autologous transplantation, which uses the patient's own stem cells collected while the patient is in complete remission, is of no greater benefit than chemotherapy for adults with ALL. Thus, it is not recommended.

MAINTENANCE THERAPY

Remission maintenance therapy or remission continuation therapy is a standard part of acute lymphoblastic leukemia treatment, although research studies have not clearly shown its benefit for adults. It is also unclear how long therapy should continue. Depending upon the program chosen, treatment is often continued for two to two and a half years (table 1).

During maintenance treatment, oral medications (pills) are taken on certain days of the month and intravenous (IV) chemotherapy may be given into a vein once per month. Side effects during this phase of treatment are less frequent and less severe than those experienced during earlier stages of treatment. Most people are able to return to full activity during their maintenance treatment period.

RESIDUAL DISEASE AND RELAPSE RISK:

The standard two to three years of treatment, patients in complete clinical remission should have a bone marrow aspiration and biopsy repeated every three to six months for at least the next two years. This allows for early detection and treatment if relapse were to occur. Patients with acute lymphoblastic leukemia who maintain complete, continuous remission for four to five years are considered cured and no longer need routine bone marrow examination.

Unfortunately, up to 25 percent of adults with acute lymphoblastic leukemia are resistant to the initial induction of remission. Many adults with ALL who do attain an initial complete remission will ultimately suffer a relapse. Although a second remission can often be achieved, retreatment of such patients is generally unsuccessful in the long run, and most will die of their disease or of complications of treatment.

• In patients with acute lymphoblastic leukemia who received stem cell transplantation and was in complete remission at two years, the overall chance of being alive in complete remission at nine years was 82 percent. The latest relapses in this group occurred at four to seven years.

Treatment of relapse or resistant disease:

 A second remission may be attained using a similar induction regimen if the relapse occurs more than two years following initial treatment.

Salvage regimens are treatments used after all other available treatments have failed. These regimens are intended to reduce symptoms and prolong survival, but may not be able to cure the disease. Optimally, such patients should enroll onto a clinical trial specifically designed for treatment of resistant acute lymphoblastic leukemia with new agents alone or in combination.

Allogeneic stem cell transplantation is also a reasonable option for selected patients with resistant or relapsed disease. All eligible patients who achieve a second complete remission should consider allogeneic stem cell transplantation.