Treatment option overview of ALL

Successful treatment of acute lymphoblastic leukemia (ALL) consists of the control of bone marrow and systemic disease as well as the treatment (or prevention) of sanctuary-site disease, particularly the central nervous system (CNS). The cornerstone of this strategy includes systemically administered combination chemotherapy with CNS preventive therapy. CNS prophylaxis is achieved with chemotherapy (intrathecal and/or high-dose systemic) and, in some cases, cranial irradiation.

Treatment is divided into 3 phases: remission induction, CNS prophylaxis, and remission continuation or maintenance. The average length of treatment of ALL varies between 1.5 and 3 years in the effort to eradicate the leukemic cell population. Younger adults with ALL may be eligible for selected clinical trials for childhood ALL.

It has been recognized for many years that some patients presenting with acute leukemia may have a cytogenetic abnormality that is morphologically indistinguishable from the Philadelphia (Ph) chromosome. The Ph chromosome occurs in only 1% to 2% of patients with AML, but it occurs in about 20% of adults and a small percentage of children with ALL. In the majority of children and in more than one half of adults with Ph chromosome-positive (Ph+) ALL, the molecular abnormality is different from that in Ph+ chronic myelogenous leukemia (CML).

Ph+ ALL has a worse prognosis than most other types of ALL, although many children and some adults with Ph+ ALL may have complete remissions following intensive ALL treatment clinical trials. If a suitable donor is available, allogeneic bone marrow transplantation should be considered because remissions are generally short with conventional ALL chemotherapy clinical trials. Many patients who have molecular evidence of the bcr-abl fusion gene, which characterizes the Ph chromosome, have no evidence of the abnormal chromosome by cytogenetics. Because many patients have a different fusion protein from the one found in CML (p190 versus p210), the bcr-abl fusion gene may be detectable only by pulsed-field gel electrophoresis or reverse-transcriptase polymerase chain reaction (RT-PCR). These tests should be performed whenever possible in patients with ALL, especially those with B-cell lineage disease. Two other chromosomal abnormalities with poor prognosis are t(4;11), which is characterized by rearrangements of the MLL gene and may be rearranged despite normal cytogenetics, and t(9;22). In addition to t(9;22) and t(4;11), patients with deletion of chromosome 7 or trisomy 8 have been reported to have a lower probability of survival at 5 years compared to patients with a normal karyotype. In multivariate analysis, karyotype was the most important predictor of disease-free survival. L3 ALL is associated with a variety of translocations which involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus (t(2;8), t(8;12), and t(8;22)). Unlike bcr-abl-positive ALL and t(4;11) ALL, there is some evidence that L3 leukemia can be cured with aggressive, rapidly cycling lymphoma-like chemotherapy regimens.

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.