Abstract
Acute lymphoblastic leukemia (ALL) in patients over age 60 years is a poor prognosis disease with complete remission rate of 50–60% and median overall survival of less than a year. Between July 2004 and June 2007, we treated 17 elderly patients with newly diagnosed ALL with a modified pediatric protocol that included a remission induction phase, a CNS prophylaxis phase with intrathecal chemotherapy × 4, a 21-week intensification phase (7 cycles × 3 weeks each), and a 72-week maintenance phase. Induction chemotherapy consisted of vincristine 2 mg weekly × 3, doxorubicin 30mg/m2 × 2 doses, methotrexate 40mg/m2 × 1, asparaginase 12,000/m2 U × 1, and dexamethasone 40mg/day × 8 doses; BCR-ABL+ patients received imatinib mesylate 400 mg daily × 16 days instead of asparaginase. The intensification phase consisted of vincristine 2 mg × 7 doses, doxorubicin 30mg/m2 × 7 doses, asparaginase 6000 U/m2 weekly × 21 doses, 6-mercaptopurine 14/21 days, and dexamethasone 6 mg BID × 5/21 days. BCR-ABL+ patients received imatinib 400 mg daily × 14/21 days instead of asparaginase. Maintenance was the same as intensification except that no asparaginase was given. The median age was 66 years (range 60–78 years). Seven patients (41%) were BCR-ABL+ and four (24%) were pre-B with WBC > 30. Major side effects during the induction phase included infection (71%), hyperglycemia requiring insulin (24%), and cardiac toxicity (18%). The complete remission (CR) rate was 71% with an induction mortality of 29%. Of the five induction deaths, four were due to bacterial sepsis or pneumonia, and one was due to tumor lysis syndrome. CNS prophylaxis was well-tolerated except in one patient who required IV hydration for nausea/vomiting. Eleven patients proceeded to intensification. Major side effects during the intensification phase included infections (64%), peripheral neuropathy (64%), thrombosis (27%), and grade 3 nausea/vomiting (27%). Two patients required hospitalization during the intensification phase; there was one myocardial infarction and one acute pancreatitis. Eleven patients proceeded to the maintenance phase; major side effects during maintenance included infections (36%) and grade 3 peripheral neuropathy (18%). Two patients (17%) have relapsed, both during early maintenance phase; both had had a number of dose modifications and delays during intensification. The one year overall survival (OS) was 71% and the median OS has not been reached. After a median follow-up duration of 17 months (range 9–40 months), the median relapse-free survival (RFS) of the CR patients has not been reached; the one year RFS was 82%. These results show that administering a modified pediatric protocol to patients over age 60 years with ALL is feasible with an improved CR rate than generally reported. The OS and RFS also compare favorably to previously reported results, although further follow-up is required. However, induction mortality was high, and infectious complications persisted throughout the entire course of induction and intensification, though much diminished during the maintenance phase. Accrual to the protocol is continuing.
Pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first‐episode schizophrenia: Japanese Society of Clinical Neuropsychopharmacology treatment algorithms