RISK FACTORS: Age over 60, Incidence appears increased following exposure to chemical agents such as benzene or to radiation (but acute myeloid leukemia [AML] is more common),
May follow aplastic anemia
GENERAL MEASURES Protective isolation from infection
SURGICAL MEASURES Surgical placement of a percutaneous silastic double-lumen central venous
catheter
ACTIVITY Ambulatory as tolerated
DIET
β’ Nutritional support including intravenous hyperalimentation, if necessary
β’ Avoid alcohol
DRUG(S) OF CHOICE
Optimal therapy is not yet known. All treatment regimens are still investigational, although clearly effective for some fraction of patients. CALGB protocol 9111 is an example of therapy (from Blood 1998; 92:1556-1564):
. Remission induction
. Cyclophosphamide 1200 mg/square meter on day 1 (800 mg/m2 if > 60 years old)
. Daunorubicin 45 mg/m2 on days 1, 2, and 3 (30 mg/m2 if > 60 years old)
. Vincristine 2 mg on days 1, 8, 15, and 22
. Asparaginase (L-asparaginase) 6000 units/m2 on days 5, 8, 11, 15, 18, and 22
. Prednisone 60 mg/m2 on days 1-21 (days 1-7 if > 60 years old)
. Filgrastim - G-CSF, 5 ΖΓg/kg/day SQ starting on day 4 has been shown to shorten the duration of
neutropenia and improve the CR rate, especially in older patients
. Imatinib mesylate 600-800 mg/day is effective alone and in combination with chemotherapy for Philadelphia
chromosome positive ALL
. Consolidation (repeat twice in 8 weeks
. Cyclophosphamide 1000 mg/m2 on day 1
. Intrathecal (IT) methotrexate 15 mg with hydrocortisone 50 mg on day 1
. Mercaptopurine (6-mercaptopurine) 60 mg/m2 on days 1-14
. Cytarabine 75 mg/m2 SC on days 1-4 and 8-11
. Vincristine 2 mg on days 15 and 22
. Asparaginase 6000 units/m2 on days 15, 18, 22, and 25
. CNS prophylaxis and interim maintenance - 2400 cGy cranial irradiation
. IT-methotrexate 15 mg with hydrocortisone 50 mg on days 1, 8, 15, 22, and 29
. Mercaptopurine (6-mercaptopurine) 60 mg/m2 on days 1-70
. Oral methotrexate 20 mg/m2 on days 36, 43, 50, 57, and 64
. Late intensification
. Doxorubicin 30 mg/m2 on days 1, 8, and 15
. Vincristine 2 mg on days 1, 8, and 15
. Dexamethasone 10 mg/m2 on days 1-14
. Cyclophosphamide 1000 mg/m2 on day 29
. Thioguanine (6-thioguanine) 60 mg/m2 on days 29-42
. Cytarabine 75 mg/m2 SC on days 29-32 and 36-39
. Prolonged maintenance
. Vincristine 2 mg/month for 16 months
. Prednisone 60 mg/m2 for 5 days with the vincristine
. Mercaptopurine (6-mercaptopurine) 60 mg/m2/day for 16 months
. Oral methotrexate 20 mg/m2/week for 16 months
. Philadelphia chromosome-positive ALL: imatinib mesylate (600-800 mg/day) is effective alone and in
combination with chemotherapy
Contraindications: Doses and schedule may need to be altered for older patients and for concurrent infection and organ toxicity
Precautions:
β’ Tumor lysis syndrome (elevated uric acid, potassium, and phosphate with decreased calcium leading to renal
failure, disseminated intravascular coagulation, and cardiac arrhythmias) may be prevented by administering
allopurinol 300 mg/day. Begin 2 days before chemotherapy begins. Reduce doses if used with mercaptopurine or azathioprine. Give increased fluids. IV urate oxidase (Rasburicase) can be used to treat
hyperuricemia rapidly
β’ Oral sulfamethoxazole-trimethoprim or aerosolized pentamidine is given for Pneumocystis carinii prophylaxis
β’ Profound immunosuppression. Take appropriate precautions when patient is neutropenic
β’ High dose cyclophosphamide causes severe nausea and vomiting. Use appropriate antiemetic regimen to
prevent.
β’ Neurotoxicity, ileus with vincristine
β’ Asparaginase may cause severe allergic reactions as well as impaired pancreatic and liver function. Monitor
serum glucose concentrations frequently and carefully. Pancreatitis or thrombosis may occur.
ALTERNATIVE DRUGS Other anthracyclines, investigational chemotherapy agents
PATIENT MONITORING Daily during induction chemotherapy for metabolic and infectious complications. Weekly during remission consolidation chemotherapy. Monthly during maintenance therapy. Every 3 months thereafter.
POSSIBLE COMPLICATIONS
β’ Infections (pneumocystis carinii pneumonia, bacterial pneumonia or sepsis, fungal pneumonia)
β’ Bleeding
β’ Need for transfusions
β’ Sterility from treatment
β’ Arachnoiditis and CNS effects from intrathecal chemotherapy and irradiation
β’ Pancreatitis and liver dysfunction from chemotherapy
β’ Relapse of ALL in marrow or extramedullary sites (CNS, testis)
EXPECTED COURSE/PROGNOSIS
β’ 80-95% of patients < 60 years old will achieve a complete remission, and 35-60% will remain free of disease
at 5 years
β’ Older patients (>60 years) do less well, but still 80% may achieve a complete remission
β’ Patients with unfavorable cytogenetic subtypes (especially t[9;22] and t[4:11]) should undergo allogeneic
bone marrow transplantation in fi rst remission if an HLA-identical donor were available