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Leukemia, acute lymphoblastic in adults (ALL)
OVERVIEW: A malignant proliferation and accumulation of immature lymphocytes
System(s) affected: Hemic/Lymphatic/Immunologic
Genetics: Increased incidence in children with Down syndrome or in rare familial diseases such as ataxia-telangiectasia, Bloom's syndrome, Fanconi's anemia, Klinefelter's syndrome, and neurofibromatosis. Can rarely occur in adult identical twins.
Incidence/Prevalence in USA: 1000 adult cases/year
Predominant age: Median age is 35-40 years but incidence increases with age
Predominant sex: Male > Female (slightly)
SIGNS AND SYMPTOMS: • Anemia - fatigue, shortness of breath, lightheadedness, angina, headache
• Thrombocytopenia - petechiae, ecchymoses, epistaxis, retinal hemorrhages
• Granulocytopenia - fever, infection
• Lymphocytosis - lymphadenopathy, hepato/splenomegaly, bone pain
• Immunosuppression
• Metabolic abnormalities - hyperuricemia, renal failure, increased lactic acid dehydrogenase (LDH)
• Central nervous system - cranial nerve palsies, confusion
CAUSES: Unknown. Epstein-Barr virus is implicated in Burkitt's leukemia/lymphoma.
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
DIAGNOSIS DIFFERENTIAL DIAGNOSIS: • Malignant disorders - other leukemias, especially AML; prolymphocytic leukemia; malignant lymphomas; multiple myeloma; bone marrow metastases from solid tumors (breast, prostate, lung, renal); myelodysplastic syndromes
• Nonmalignant disorders - aplastic anemia; myelofibrosis; autoimmune diseases (Felty's syndrome, lupus); infectious mononucleosis; autoimmune thrombocytopenic purpura; leukemoid reaction to infection
LABORATORY: • Anemia - normochromic, normocytic
• Thrombocytopenia
• Peripheral blood lymphoblasts
• Elevated LDH
• Elevated uric acid
Drugs that may alter lab results: N/A
Disorders that may alter lab results: N/A
PATHOLOGICAL FINDINGS: Diffuse replacement of marrow and lymph node architecture by sheets of malignant lymphoblasts
SPECIAL TESTS: • Immunophenotyping of marrow/blood lymphoblasts: B-lineage (CD19, CD20, CD24): T-lineage (CD2, CD5, CD7); CALLA ([common ALL antigen], CD10); human leukocyte antigen (HLA)-DR; terminal deoxynucleotidyl transferase (TdT); aberrant myeloid antigens (CD13); stem cell antigen (CD34)
• Cytochemical stains: Myeloperoxidase negative; Sudan black B usually negative; TdT positive; nonspecific esterase +/-; periodic acid Schiff (PAS) +/-
• Cytogenetics: Specific recurring chromosomal abnormalities have independent diagnostic and prognostic significance (hyperdiploidy > 50 chromosomes is favorable; the Philadelphia chromosome, t[9;22], the t[4;11], and the t[8;14] are unfavorable)
• Human leukocyte antigen (HLA) typing of patient and siblings for marrow transplantation
IMAGING: • Chest radiograph to evaluate for mediastinal mass or hilar adenopathy and for pulmonary infiltrates suggestive of infection
• Ultrasound exam to assess splenomegaly or renal enlargement suggestive of leukemic infiltration
DIAGNOSTIC PROCEDURES: • Bone marrow examination with aspiration, biopsy, immunophenotyping, cytochemistry, and cytogenetics
• Lymph node biopsy is rarely necessary but can be diagnostic
• Lumbar puncture should be done if neurological symptoms or signs are present. Repeat lumbar puncture after bone marrow remission is achieved to evaluate occult CNS involvement.
TREATMENT APPROPRIATE HEALTH CARE: • Inpatient care during remission induction chemotherapy
• Post-remission therapy is usually outpatient
• Access to the resources and expertise of a major oncology center is important for appropriate support
GENERAL MEASURES: Protective isolation from infection
SURGICAL MEASURES: Surgical placement of a percutaneous silastic double-lumen central venous catheter
ACTIVITY: Ambulatory as tolerated
DIET: • Nutritional support including intravenous hyperalimentation, if necessary
• Avoid alcohol
PATIENT EDUCATION: • Risks of infection, transfusion, chemotherapy
• Stop smoking
MEDICATIONS 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 µg/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
• 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
Contraindications: Doses and schedule may need to be altered for older patients and for concurrent infection and organ toxicity
Precautions:
• 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.
• Oral sulfamethoxazole-trimethoprim or aerosolized pentamidine is given for Pneumocystis carinii prophylaxis
• Profound immunosuppression. Take appropriate precautions when patient is neutropenic
• High dose cyclophosphamide causes severe nausea and vomiting. Use appropriate antiemetic regimen to prevent.
• Neurotoxicity, ileus with vincristine
• 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.
Significant possible interactions: N/A
ALTERNATIVE DRUGS: Other anthracyclines, investigational chemotherapy agents
FOLLOW UP PATIENT MONITORING: Daily during induction chemotherapy for metabolic and infectious complications. Weekly during remission consolidation chemotherapy. Monthly during maintenance therapy. Every 3 months thereafter.
PREVENTION/AVOIDANCE: N/A
POSSIBLE COMPLICATIONS: • Infections (pneumocystis carinii pneumonia, bacterial pneumonia or sepsis, fungal pneumonia)
• Bleeding
• Need for transfusions
• Sterility from treatment
• Arachnoiditis and CNS effects from intrathecal chemotherapy and irradiation
• Pancreatitis and liver dysfunction from chemotherapy
• Relapse of ALL in marrow or extramedullary sites (CNS, testis)
EXPECTED COURSE AND PROGNOSIS: • 80-95% of patients < 60 years old will achieve a complete remission, and 35-60% will remain free of disease at 5 years
• Older patients (>60 years) do less well, but still 80% may achieve a complete remission
• Patients with unfavorable cytogenetic subtypes (especially t[9;22] and t[4:11]) should undergo allogeneic bone marrow transplantation in first remission if an HLA-identical donor were available
MISCELLANEOUS ASSOCIATED CONDITIONS: N/A
AGE-RELATED FACTORS:
Pediatric: Bone growth and IQ development may be affected by treatment
Geriatric: N/A
Others: N/A
PREGNANCY: Many chemotherapy drugs are teratogenic
SYNONYMS: Acute lymphocytic leukemia
ICD-9-CM: 204.0 Lymphoid leukemia
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