Acute lymphocytic leukemia, 204.0
Acute myelogenous leukemia, 205.0
Chronic lymphocytic leukemia, 204.1
Chronic myelogenous leukemia, 205.1
I. Definition
A. Malignancy that causes hematopoietic progenitor cells to lose their ability to mature normally and differentiate
B. Cells proliferate in uncontrolled fashion and ultimately replace normal bone marrow, leading to decreased production of normal RBCs, WBCs, and platelets.
II. Incidence/predisposing factors
A. No clear cause; suggested greater incidence in benzene and petroleum product exposure
B. Slightly higher incidence in populations of European descent
C. Constitutes 80% of all childhood leukemias, with peak onset at ages 3 to 7, and 20% of adult leukemias; incidence of second peak at age 60
D. ALL is the most common cancer and the leading cause of death in children younger than 15 years of age.
E. Survivors of ALL are at risk for late sequelae of secondary brain tumors.
F. Childhood ALL survivors are at greater risk for reduced growth (secondary to cranial irradiation and resultant decreased bone mass), learning disabilities, and osteoporotic fractures in later life.
III. Subjective findings
A. Usually sudden onset of acute illness for days or weeks
B. Fever
C. Anorexia
D. Fatigue
E. Bone and joint pain
F. Dyspnea
G. Gum hypertrophy and gingival bleeding
H. Epistaxis
I. Angina
IV. Physical examination findings
A. Pale, with purpura and petechiae
B. Generalized lymphadenopathy
C. Gingival hypertrophy
D. Stomatitis
E. Hepatosplenomegaly
F. Bone tenderness, particularly in the sternum and tibia
V. Laboratory/diagnostic findings
A. Pancytopenia with circulating blasts is the hallmark of the disease.
B. Blasts present in the peripheral smear in 90% of cases.
C. Bone marrow is usually hypercellular; diagnosis requires that more than 30% of cells are blasts. (The World Health Organization has proposed changing the threshold between myelodysplastic syndrome [MDS] and acute myelogenous leukemia [AML] to 20% marrow blasts and deleting the category of RAEB-t [refractory anemia with excess blasts in transformation].)
D. Anemia occurs in most patients; decreases in RBCs and in hemoglobin (Hgb) and hematocrit (Hct) levels range from mild to severe.
E. Platelets are usually decreased but may be in the normal range.
F. Bone marrow biopsy is often essential for establishing the diagnosis owing to the variability of preceding factors.
G. Hyperuricemia and azotemia are present.
H. Terminal deoxynucleotidyl transferase (TdT) is present in 95% of cases.
I. Consider ordering the following:
1. Immunophenotyping by fluorescent activated cell sorter (FACS) with monoclonal antibodies directed at leukemia-specific antigens at the time of diagnosis. Monoclonal antibodies may be used to define other phenotypes of ALL.
a. Primitive B-lymphocyte antigens include CD19 and sometimes CD10.
b. T-cell ALL is diagnosed by the finding of CD2, CD5, and CD7.
2. Cytogenetic studies (prognostic value)
a. Hyperdiploid states: more favorable prognosis
b. Unfavorable prognosis found with Philadelphia chromosomes t(9;22) and t(4:11).
3. Bone marrow stains
a. Periodic acid–Schiff (PAS)—positive
b. Sudan black—negative
c. Myeloperoxidase—negative
d. Terminal TdT—positive
4. Chromosome analysis
6. Electron microscopy (rarely used except in poorly differentiated leukemia)
7. Molecular genetic studies
8. Screening lumbar puncture (if CNS involvement)
VI. Management
A. Hematology/Oncology referral for suspected cases
B. Treatment is usually supportive or is designed to eradicate leukemic cell mass.
1. Cures are infrequent except in children.
2. In adults, expect at least a 25% disease-free 5-year survival, and with aggressive regimens, a 35% to 40% 5-year survival.
C. Supportive care may include the following, when indicated:
1. Transfusion of RBCs or platelets
2. Hydration
3. Aggressive antibiotic therapy for infection
4. Allopurinol, 100-200 mg PO 3 times a day, to prevent hyperuricemia and renal damage, should be initiated before marrow-ablative chemotherapy is initiated.
5. Acetazolamide, 500 mg/day, to promote alkalinization of urine
D. If patient remains uremic, consider dialysis before initiation of chemotherapy.
E. Chemotherapy
1. Given according to protocols
2. Divided into three phases:
a. Remission induction
b. Postremission therapy
c. CNS prophylaxis
3. Remission induction
a. Initial treatment is combination chemotherapy.
b. A number of combinations are used.
i. Usual drugs include vincristine and prednisone.
ii. L-Asparaginase or daunorubicin is frequently added.
iii. Intrathecal methotrexate with L-asparaginase is another standard combination.
c. Maintenance therapy usually includes 6-mercaptopurine and methotrexate.
4. Postremission therapy
a. Short courses of further chemotherapy are given.
b. Usually chemotherapy agents not used to initiate therapy are given, such as
i. High-dose methotrexate
ii. Cyclophosphamide
iii. Cytarabine
5. CNS prophylaxis: intrathecal methotrexate alone or in combination with radiation therapy
a. CNS relapse is much higher in ALL than in AML.
F. Bone marrow transplantation should be considered at the time of first relapse or second remission.
G. M.D. Anderson Cancer Center has reported a regimen for relapsed ALL that alternates four cycles of fractionated high-dose cyclophosphamide, vincristine, doxorubicin, and dexamethasone with four cycles of high-dose cytosine-arabinoside/daunorubicin (HDAC) and high-dose methotrexate.
ACUTE MYELOGENOUS LEUKEMIA (AML)
I. Definition
A. Malignancy of hematopoietic progenitor cell
B. An acute leukemia very similar to ALL, distinguished by morphologic examination and cytochemistry that differentiates myeloblasts from lymphoblasts
II. Incidence/predisposing factors
A. No clear cause
B. Chromosomal abnormalities are found in most patients with acute leukemias.
C. Increased incidence in patients with Down syndrome
D. Predominant type of acute leukemia in adults: 80% of acute leukemias in individuals over age 20
E. Incidence increases with age: Median age is 50 years.
F. Increased incidence of associated disseminated intravascular coagulation (DIC), especially with acute promyelocytic leukemia (M3 variant)
III. Subjective findings
A. Bleeding
B. Fever
C. Anorexia
D. Fatigue
E. Headache
F. Bone and joint pain
G. Bone tenderness—particularly in the sternum and tibia
IV. Physical examination findings
A. Occasional lymphadenopathy
B. Hepatosplenomegaly
C. Stomatitis and gingival hypertrophy
D. Purpura, petechiae, overt bleeding
E. Signs of infection
