Paul Aridgides MSIV, Upstate Medical University and Neha Vapiwala, MD The Abramson Cancer Center of the University of Pennsylvania Last Modified: October 31, 2007
Leukemia is defined as a malignant, marrow-based neoplasm of hematopoietic or lymphoid cells. The key feature of leukemia is the presence of tumor cells circulating in the blood. Acute leukemia involves aberrant differentiation and proliferation of malignantly transformed progenitor cells, and can be rapidly fatal if untreated. The two main types of acute leukemia are named for the stem cell of origin: acute lymphoblastic leukemia (ALL)if it involves lymphocytes, and acute myeloid leukemia (AML) if it involves myelocytes. Of note, both lymphocytes and myelocytes are subtypes of white blood cells. While ALL and AML are clinically similar in that they both typically present with symptoms secondary to cytopenias (lowered cell counts), there are significant laboratory features and prognostic factors that can be used to distinguish ALL from AML and to dictate therapy, as discussed below.
Note: The characteristic presentation of T cell ALL is an older age boy with mediastinal mass and leukocytosis.
Staging is not clearly defined for ALL, and patients with confirmed diagnoses are grouped as:
untreated (not in remission) - defined as an abnormal white blood cell count and differential, abnormal hematocrit/hemoglobin and platelet counts, abnormal bone marrow with more than 5% blasts, and signs and symptoms of the disease.
in remission - where a patient has received remission-induction treatment and now has normocellular bone marrow with less than 5% blasts, no signs or symptoms of the disease, no signs or symptoms of central nervous system leukemia or other extramedullary infiltration, and all normal hematologic laboratory values.
recurrence – defined as any failure since starting treatment, further characterized according to time since diagnosis and relapse site (bone marrow, extramedullary)
Prognosis – grouped into low-, standard-, and high-risk; grouping schemes (particularly genetic analysis) are an area of active research  Worse prognoses if:
age is <2 y or >9 y
high WBC counts
presence of (4;11) or (9;22) chromosomal translocations .
presence of CNS disease
poor early response to treatment
Risk assessment is critical to achieving cure with an acceptable degree of toxicity. Generally, patients with higher-risk disease receive more aggressive therapy.
High-dose chemotherapy regimens with at least two rounds of induction (prednisone or dexamethasone, vincristine, L-asparaginase, +/- an anthracycline), consolidation and maintenance.
Long-term, disease-free survival is seen in 30-40% of patients 
Delayed intensification was a major advance in 1983, followed by advances in bone marrow transplantation (high dose chemo +/- total body irradiation followed by marrow infusion) . Allogenic transplantation is of particular benefit in high-risk disease (chromosomal translocations) and after poor response to initial therapy.
Central nervous system coverage to prevent or treat disease (intrathecal chemotherapy or irradiation) is critical for long term control
WHO Classification (preferred for prognostic significance )
AML with recurrent genetic abnormalities
t(8;21) FAB M2, inv(16)/t(16;16), t(15;17) FAB M3, 11q23
AML with multilineage dysplasia (MPD)
following MDS/MPD, dysplasia in 2 or more cell lines
AML and myleodysplastic syndromes (MDS), therapy related
alkylating agents/radiation-related, topoisomerase II inhibitor-related
AML, not otherwise categorized
with subtypes identical to FAB classification
Epidemiology, Etiology and Pathogenesis
Incidence of AML is 13,000 cases per year in the US . AML accounts for 80-90% of adult acute leukemias, 10% of childhood leukemias and virtually all neonatal acute leukemias.
Etiologic factors are thought to include exposure to carcinogens and mutagens, such as benzene, alkylating agents and ionizing radiation; inherited genetic conditions such as Fanconi's anemia and Down's syndrome; and viruses.
Pathogenesis involves clonal evolution through multiple steps. AML etiology and pathogenesis is considered similar to myelodysplasia, (also known as MDS, refractory anemia, preleukemia or smoldering leukemia), which is a clonal abnormality of pluripotential stem cells with defective maturation and ineffective hematopoiesis
History: Present with cytopenia-related symptoms, as with ALL
Physical Exam: Pallor, petechiae, fever, organ involvement
Labs: Cytopenias common; consider a medical emergency if WBC count is >100,000 or there are DIC-type indices
Staging is similar to ALL in that there is no clear-cut system; patients are classified as
untreated - newly diagnosed leukemia with no prior treatment, abnormal bone marrow with more than 20% blasts, signs and symptoms of the disease, and typically abnormal hematologic cell counts
in remission - a normal peripheral blood cell count and normocellular marrow with less than 5% blasts in the marrow, no signs or symptoms of the disease, and no signs or symptoms of central nervous system leukemia or other extramedullary infiltration.
relapsed or refractory- evidence of disease as described above after achieving remission or unsuccessful treatment
Prognosis - three most important factors are age, WBC count, and cytogenetics 
Unfavorable prognoses [6,12,13] for patients with:
age >60 y
WBC > 30,000
disease secondary to MDS, chemo or XRT
Complex karyotypic abnormalities
Favorable prognosis with :
t (8;21), inv(16)/t(16;16), t(15;17)
AML chemotherapy is administered in two basic phases, induction and post-remission.
Induction with daunorubicin + anthracycline with 70-80% complete remission rate, but also 100% relapse rate if no further therapy is given .
For APL t(15;17), whose unique fusion product PML-RARα contains retinoic acid receptor, regimens containing all-trans-retinoic acid (ATRA) as a differentiation agent results in remission rates around 90% and a 70% cure rate 
A retrospective analysis of long-term AML survivors showed a 13% incidence of malignancies secondary to treatment 
1. Catovsky D, Matukis E, Buccheri V, et al: A classification of acute leukemia for the 1990's. Ann Hematol 62:16-21, 1991
2. Matutes E, Morilla R, Farahat N, et al: Definition of acute biphenotypic leukemia. Haematologia 82:64-66, 1997
3. Harris NL, Jaffe ES, Diebold J, et al: The World Health Organization classification of neoplastic diseases of the hematopoeitic and lymphoid tissues. Ann Oncol 10:1419-1432, 1999
4. Gurney JG, Severson RK, Davis S et al: Incidence of cancer in children in the United States. Sex -, race-, and 1-year age-specific rates by histologic type. Cancer75:2186-2195, 1995
5. Smith MA, Ries LA, Gurney JG, et al.: Leukemia. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program Leukemia, 1999.
6. Preston DI, Kusumi S, Tomonaga M, et al: Cancer incidence in atomic bomb survivors: part III. Radiat Res 137:S68-S97, 1994 (suppl)
7. Pui C and Evans WE: Treatment of Acute Lymphoblastic Leukemia. NEJM 354:166-178, 2006
8. Faderl S, Kantarjian HM, Talpaz M, et al: Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia. Blood 91:3995-4019, 1998
10. Vardiman JW, Harris NL, Brunning RD: The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100:2292-2302, 2002
11. Jemal A, Siegel R, Ward E et al: Cancer Statistics, 2007. CA Cancer J Clin57:43-66, 2007
12. Byrd JC, Mrozek K, Dodge RK et al: Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100:4325-4336, 2002
14. Bishop JF: The treatment of adult acute myeloid leukemia. Semin Oncol 24:57-69, 1997
15. Zittoun RA, Mandelli F, Willemze R, et al: Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med 332:217-223, 1995
16. Ohno R, Asou N, and Ohnishi K: treatment of acute promyelocytic leukemia: strategy toward further increase of cure. Leukemia 17:1454-1463, 2003
17. Micallef IN, Rohatiner AZ, Carter M et al: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haem 113:443-445, 2001
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