A. Leukemias are curable with chemotherapy.

B. Approximately 30% of adults with acute leukemia can be cured of disease.

C. High-dose chemotherapy followed by allogeneic stem cell transplantation is a curative therapy for selected patients with leukemia; 40% to 50% chance of cure.

D. Four types of leukemia:

1. Acute lymphoblastic leukemia (ALL).

2. Acute myelogenous leukemia (AML).

3. Chronic lymphocytic leukemia (CLL).

4. Chronic myelogenous leukemia (CML).

A. Most cases are idiopathic; no lifestyle risk factors.

B. AML may arise as a result of prior chemotherapy or radiation therapy.

1. Therapy-related AML has a poor prognosis.

2. Associated with abnormalities of chromosome 5, 7, and 11.

C. AML may arise from a prior myelodysplastic or myeloproliferative syndrome.

A. ALL more common in children, but can occur in adults.

1. Can present with mediastinal mass.

2. Can present with central nervous system (CNS) and testicular involvement.

B. AML more common in adults.

1. Monocytic variants can have skin, gum, and CNS involvement.

C. Acute promyelocytic leukemia (APML).

1. Associated with bleeding and disseminated intravascular coagulation (DIC).

D. Chronic lymphocytic leukemia.

1. Often indolent disease of elderly.

E. Chronic myelogenous leukemia.

1. Can progress to acute leukemia.

a. Myeloid blast crisis (70% of cases).

b. Lymphoid blast crisis (30% of cases).

A. History.

1. Nonspecific symptoms of fatigue, shortness of breath, infection, bleeding.

B. Examination.

1. Pallor, petechiae, sometimes splenomegaly, or a flow murmur.

C. Laboratory studies.

1. Complete blood count.

a. Anemia, thrombocytopenia; white blood cell (WBC) count may be normal, high, or low.

D. Peripheral blood smear.

1. Increased immature cells.

E. Bone marrow aspirate and biopsy.

1. Flow cytometry, cytogenetics, molecular studies.

2. Acute leukemia defined as >20% blasts.

F. Molecular diagnostic studies.

1. BCR-ABL mutation diagnostic of CML.

2. PML-RAR-α diagnostic of APML.

3. FLT3 mutation is a negative prognostic feature for AML.

1. Induction chemotherapy with four to five chemotherapy drugs:

a. Asparaginase, prednisone, vincristine, doxorubicin.

b. CNS prophylaxis with intrathecal chemotherapy.

c. Intensification and maintenance chemotherapy over 18 to 24 months (outpatient).

d. Philadelphia chromosome-positive patients also receive tyrosine kinase inhibitor such as imatinib or dasatinib.

e. Allogeneic transplantation in first remission for high-risk or young patients.

f. Cure rate 90% for children, 50% for young adults, 15% over age 50.

1. Elderly patients have poor prognosis—consider supportive care with hydroxyurea, or outpatient treatment with 5-azacytidine or decitabine.

2. Induction chemotherapy with idarubicin and cytosine arabinoside (ARA-C).

3. Allogeneic stem cell transplantation for patients at high risk of relapse, often based on cytogenetics.

4. Cure rate 70% with favorable subtypes, 30% with higher risk, 10% over age 60.

1. Cure rate of >90%.

2. Over 5% of patients die of bleeding before diagnosis can be made.

3. Prompt diagnosis and treatment are essential.

4. All-trans-retinoic acid (ATRA) plus chemotherapy.

5. Consolidation with ATRA, daunorubicin, and arsenic.

1. Observation until disease progression, often many years.

2. Fludarabine- or bendamustine-based therapy.

3. Alemtuzumab or allogeneic stem cell transplantation for refractory patients.

4. Long natural history, but transplant only known curative therapy.

1. Oral tyrosine kinase inhibitor—imatinib, dasatinib, or nilotinib.

2. Long natural history with tyrosine kinase inhibitors, not clear if patients cured.

A. Leukostasis.