General Information
Sixty percent to 80% of adults with acute lymphoblastic leukemia (ALL) can be
expected to attain complete remission status following appropriate induction
therapy. Approximately 35% to 40% of adults with ALL can be expected to
survive 2 years with aggressive induction combination chemotherapy and
effective supportive care during induction therapy (appropriate early treatment
of infection, hyperuricemia, and bleeding). A few studies that use intensive
multiagent approaches suggest that a 50% 3-year survival is achievable in
selected patients, but these results must be verified by other
investigators.[1-4]
As in childhood ALL, adult patients with ALL are at risk of developing central
nervous system (CNS) involvement during the course of their disease. This is
particularly true for patients with L3 histology.[5] Both treatment and
prognosis are influenced by this complication. 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. Diagnostic
confusion with acute myelocytic leukemia (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 and M7 AML as well as ALL.
Appropriate initial treatment, usually consisting of a regimen that includes
the combination of vincristine, prednisone, and anthracycline, with or without
asparaginase, results in a complete remission rate of up to 80%. Median
remission duration for the complete responders is approximately 15 months.
Entry into a clinical trial is highly desirable to assure adequate patient
treatment and also maximal information retrieval from the treatment of this
highly responsive, but usually fatal, disease. Patients who experience a
relapse after remission can be expected to succumb within 1 year, even if a
second complete remission is achieved. If there are appropriate available
donors and if the patient is younger than 55 years of age, bone marrow
transplantation may be a consideration in the management of this disease.[6]
Transplant centers performing 5 or fewer transplants annually usually have
poorer results than larger centers.[7] If allogeneic transplant is considered,
transfusions with blood products from a potential donor should be avoided if
possible.[4,8-13]
Patients with L3 morphology have improved outcomes when treated according to
specific treatment algorithms.[14,15] Age, which is a significant factor in
childhood ALL and in AML, may also 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 those younger than 35
years. These findings may, in part, be related to the increased incidence of
the Philadelphia chromosome (Ph1) in older ALL patients, a subgroup associated
with poor prognosis.[1,2] Elevated B2-microglobulin is associated with a poor
prognosis in adults as evidenced by lower response rate, increased incidence of
CNS involvement, and significantly worse survival.[16] Patients with Ph1-positive ALL are rarely cured with chemotherapy. Many patients who
have molecular evidence of the bcr-abl fusion gene, which characterizes the Ph1
, have no evidence of the abnormal chromosome by cytogenetics.
Because many patients have a different fusion protein from the one found in
chronic myelogenous leukemia (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 prognoses 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.[17] 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).
Long-term follow-up of 30 patients with ALL in remission for at least 10 years has demonstrated 10 cases of secondary malignancies. Of 31 long-term female survivors of ALL or acute myeloid leukemia under 40 years of age, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, 2 congenital problems occurred.[18]
References
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- Zhang MJ, Hoelzer D, Horowitz MM, et al.: Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee. Ann Intern Med 123 (6): 428-31, 1995.
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