General Information About Adult Acute Lymphoblastic Leukemia (ALL)
L3 ALL is associated with a variety of translocations that involve translocation of the c-myc proto-oncogene to the immunoglobulin gene locus t(2;8), t(8;12), and t(8;22).
Patients with ALL may present with a variety of hematologic derangements ranging from pancytopenia to hyperleukocytosis. In addition to a history and physical, the initial workup should include:
- Complete blood count with differential.
- A chemistry panel (including uric acid, creatinine, blood urea nitrogen, potassium, phosphate, calcium, bilirubin, and hepatic transaminases).
- Fibrinogen and tests of coagulation as a screen for disseminated intravascular coagulation.
- A careful screen for evidence of active infection.
A bone marrow biopsy and aspirate are routinely performed even in T-cell ALL to determine the extent of marrow involvement. Malignant cells should be sent for conventional cytogenetic studies, as detection of the Ph1 t(9;22), myc gene rearrangements (in Burkitt leukemia), and MLL gene rearrangements add important prognostic information. Flow cytometry should be performed to characterize expression of lineage-defining antigens and allow determination of the specific ALL subtype. In addition, for B-cell disease, the malignant cells should be analyzed using RT-PCR and FISH for evidence of the bcr-abl fusion gene. This last point is of utmost importance, as timely diagnosis of Ph1 ALL will significantly change the therapeutic approach.
Diagnostic confusion with AML, hairy cell leukemia, and malignant lymphoma is not uncommon. Proper diagnosis is crucial because of the difference in prognosis and treatment of ALL and AML. Immunophenotypic analysis is essential because leukemias that do not express myeloperoxidase include M0 AML, M7 AML, and ALL.
The examination of bone marrow aspirates and/or biopsy specimens should be done by an experienced oncologist, hematologist, hematopathologist, or general pathologist who is capable of interpreting conventional and specially stained specimens.
Prognosis and Survival
Factors associated with prognosis in patients with ALL include the following:
Age: Age, which is a significant factor in childhood ALL and AML, may be an important prognostic factor in adult ALL. In one study, overall, the prognosis was better in patients younger than 25 years; another study found a better prognosis in patients younger than 35 years. These findings may, in part, be related to the increased incidence of the Ph1 in older ALL patients, a subgroup associated with poor prognosis.[5,6]
CNS involvement: As in childhood ALL, adult patients with ALL are at risk of developing CNS involvement during the course of their disease. This is particularly true for patients with L3 (Burkitt) morphology. Both treatment and prognosis are influenced by this complication.
Cellular morphology: Patients with L3 morphology have improved outcomes, as evidenced in a Cancer and Leukemia Group B study (CLB-9251), when treated according to specific treatment algorithms.[8,9] This study found that L3 leukemia can be cured with aggressive, rapidly cycling lymphoma-like chemotherapy regimens.[8,10,11]
Chromosomal abnormalities: Chromosomal abnormalities, including aneuploidy and translocations, have been described and may correlate with prognosis. In particular, patients with Ph1-positive t(9;22) ALL have a poor prognosis and represent more than 30% of adult cases. Bcr-abl-rearranged leukemias that do not demonstrate the classical Ph1 carry a poor prognosis that is similar to those that are Ph1-positive. Patients with Ph1-positive ALL are rarely cured with chemotherapy, although long-term survival is now being routinely reported when such patients are treated with combinations of chemotherapy and Bcr-abl tyrosine kinase inhibitors.
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(4;11) and t(9;22), compared with patients with a normal karyotype, patients with deletion of chromosome 7 or trisomy 8 have been reported to have a lower probability of survival at 5 years. In a multivariate analysis, karyotype was the most important predictor of disease-free survival.[Level of evidence: 3iiDii]