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Traditionally, the 4 components of ALL treatment are induction,
consolidation, maintenance, and CNS prophylaxis. Other aspects of treatment are also discussed.
Standard induction therapy typically involves either a 4-drug regimen of vincristine, prednisone, anthracycline, and cyclophosphamide or L-asparaginase or a 5-drug regimen of vincristine, prednisone, anthracycline, cyclophosphamide, and L-asparaginase given over the course of 4-6 weeks.
Using this approach, complete remissions are obtained in 65-85% of patients. The rapidity with which a patient's disease enters complete remission is correlated with treatment outcome.
In a large French study (French Group on Therapy for Adult Acute
Lymphoblastic Leukemia 1987), patients with greater than 5% blasts in their bone marrow on day 15 had a lower response rate (34% vs 91%), worse disease-free survival, and worse overall survival than patients with low blast counts on day 15.
Several other studies have shown that patients whose disease is in complete remission within 4 weeks of therapy have longer disease-free survival and overall survival than those whose disease enters remission after 4 weeks of treatment.
The use of consolidation chemotherapy is supported by several studies. In 1987, Fiere et al compared consolidation therapy with daunorubicin and cytosine arabinoside (Ara-C) versus no consolidation therapy in adults with ALL. The 3-year, leukemia-free survival rate was 38% for subjects receiving consolidation and maintenance therapy compared with 0% for those receiving maintenance therapy without consolidation (P<.05).
In a 1984 study reported by Hoelzer et al, subjects whose disease was in remission after induction received consolidation therapy consisting of dexamethasone, vincristine, and doxorubicin (Adriamycin), followed by cyclophosphamide, Ara-C, and 6-thioguanine beginning at week 20.
Subjects also received maintenance therapy with 6-mercaptopurine and methotrexate during weeks 10-20 and 28-130. The median remission of 20 months was among the longest reported at the time.
In the United Kingdom Acute Lymphoblastic Leukemia XA study, subjects were randomized to receive early intensification with Ara-C, etoposide, thioguanine, daunorubicin, vincristine, and prednisone at 5 weeks; late intensification with the same regimen at 20 weeks; both; or neither. The disease-free survival rates at 5 years were 34%, 25%, 37%, and 28%, respectively. These data suggest a benefit to early, rather than late, intensification.
One study by the Cancer and Leukemia Group B (CALGB) did not show a benefit to consolidation therapy. Subjects whose disease was in complete remission were randomized to receive maintenance therapy or intensification with 2 courses of Ara-C and daunorubicin followed by maintenance. Remission duration and overall survival were not affected by the randomization.
Because most studies showed a benefit to consolidation therapy, regimens using a standard 4- to 5-drug induction usually include consolidation therapy with Ara-C in combination with an anthracycline or epipodophyllotoxin.
The effectiveness of maintenance chemotherapy in adults with ALL has not been studied in a controlled clinical trial. However, several phase 2 studies without maintenance therapy have shown inferior results compared with historical controls.
A CALGB study of daunorubicin or mitoxantrone, vincristine, prednisone, and methotrexate induction followed by 4 intensifications and no maintenance was closed early because the median remission duration was shorter than in previous studies. A Dutch study using intensive postremission chemotherapy, 3 courses of high-dose Ara-C in combination with amsacrine (course 1), mitoxantrone (course 2), and etoposide (course 3), without maintenance, also yielded inferior results.
Although maintenance appears necessary, using a more intensive versus less intensive regimen does not appear to be beneficial.
Intensification of maintenance therapy from a 12-month course of a 4-drug regimen compared with a 14-month course of a 7-drug regimen (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto 0183) did not show a difference in disease-free survival between the 2 groups.
•Induction therapy: Various acceptable induction regimens are available.
•The most common approach is called ”3 and 7,” which consists of 3 days of a 15- to 30-minute infusion of an anthracycline (idarubicin or daunorubicin) or anthracenedione (mitoxantrone), combined with 100 mg/m2 of arabinosylcytosine (araC) as a 24-hour infusion daily for 7 days. Idarubicin is given at a dose of 12 mg/m2/d for 3 days, daunorubicin at 45-60 mg/m2/d for 3 days, or mitoxantrone at 12 mg/m2/d for 3 days.
•These regimens require adequate cardiac, hepatic, and renal function.
•Using these regimens, approximately 50% of patients achieve remission with one course. Another 10-15% enter remission following a second course of therapy
In contrast to patients with AML, patients with ALL frequently have meningeal leukemia at the time of relapse. A minority of patients have meningeal disease at the time of initial diagnosis. As a result, CNS prophylaxis with intrathecal chemotherapy is essential.