Adult acute lymphoblastic leukemia: Treatment guidelines and recommendations

This study summarized key guidelines for the diagnosis, treatment, and follow-up of adult acute lymphoblastic leukemia (ALL).

ALL is a type of cancer in which the bone marrow makes too many lymphoblasts (a type of early white blood cell).  A better understanding of ALL diagnosis, risk factors, treatment, and follow-up care can improve both treatment outcomes and quality of life. The European Society for Medical Oncology has recently summarized key guidelines on the diagnosis and management of patients with ALL.

Before treatment, it is important that ALL diagnosis is confirmed and the type of ALL be distinguished. The different types of ALL include B-cell precursor ALL, T-cell precursor ALL, and Burkitt leukemia. Patients may have a certain genetic change called the Philadelphia chromosome. These classifications can affect prognosis and treatment options.

ALL is also defined as either standard-risk or high-risk. Older age, not being able to tolerate primary treatment, and having higher white blood cell levels at diagnosis are usually associated with poorer outcomes. Minimal residual disease refers to small numbers of leukemia cancer cells that remain in the patient during or after treatment. It is a well-established risk factor and predictor to help treatment decisions. Complete molecular remission after treatment is generally the main goal of ALL treatment and is a predictor of survival and long-term remission.

Patients should undergo treatment as soon as possible. Steroid drugs are usually given for 5 to 7 days before primary treatment with chemotherapy. Standard chemotherapies include daunorubicin (Cerubidine), doxorubicin (Adriamycin), rubidazone (Zorubicine), idarubicin (Idamycin), and cyclophosphamide (Endoxan) usually with a steroid drug. Chemotherapies are often given in cycles over 2 induction protocols (with the aim to induce remission) lasting 1 to 2 months. This is then followed by consolidation cycles (to sustain remission). Another approach is to repeat 2 different intensive chemotherapy cycles, resulting in 8 cycles in total.

Maintenance therapy is recommended for 2.5 to 3 years after primary treatment. This is to improve long-term outcomes and reduce the risk of cancer spreading to the central nervous system. Maintenance therapy usually consists of daily 6-mercaptopurine (Purinethol) and weekly methotrexate (Otrexup).

6 to 16 weeks after primary chemotherapy, patients should be tested for complete remission (CR). In an analysis of 14 separate trials involving 6,617 ALL patients, the overall CR rate was 83%. The CR rate was higher for standard-risk disease (90% or higher) and lower for high-risk disease (about 75%).

ALL treatment outcomes are strongly related to the patient’s age. Cure rates range from 80 to 90% in childhood and decrease to less than 10% in elderly or frail patients. Adolescents and young adults (typically from 15 to 40 years) benefit from pediatric-inspired therapy. This involves increased drug intensity over several treatment steps. Recent studies have reported improved 5-year survival rates with pediatric-inspired therapy (67 to 78%) compared to conventional therapy (34 to 41%).

Elderly ALL patients (over the age of 70 years) may undergo less intensive therapy to avoid side effects. Treatment is often based on vincristine (Oncovin) and asparaginase (Elspar) as well as steroids. One analysis reported that older ALL patients treated with a less intensive protocol had a CR rate of 71%. The early death rate decreased to 15%.

Two new major treatment approaches for ALL include the targeted therapies. Targeted therapies can be used as a single therapy or added to chemotherapy. Studies have reported significantly improved long-term survival for specific types of ALL, such as Burkitt leukemia or Philadelphia-positive ALL. The tyrosine kinase inhibitor imatinib (Gleevec) in combination with chemotherapy is now the recommended treatment for Philadelphia-positive ALL.

After ALL patients reach their first CR, they may undergo a stem cell transplant (SCT). In an SCT, healthy stem cells (immature blood cells) are reintroduced into a patient. An SCT is recommended for all patients with poor early minimal residual disease response. Standard-risk patients with sustained response may not benefit from an SCT. It is the best post-remission option for high-risk ALL.

Once patients are in their second remission or later (after a relapse), an SCT is recommended. An analysis of 4 large trials found that second CRs were achieved in 44 to 45%. Average overall survival (time from treatment to death from any cause) was 4.5 to 8.4 months. The duration of the first remission (typically if over 18 to 24 months) was a strong predictor of SCT outcomes. Re-induction may also be considered for patients with longer first remissions. Targeted therapies are often recommended for relapsed patients and those no longer responding to standard therapies.

This study outlined the European Society for Medical Oncology treatment guidelines for ALL.