Treatment Option Overview
Note: Some citations in the text of this section are followed by a level of
evidence. The PDQ editorial boards use a formal ranking system to help the
reader judge the strength of evidence linked to the reported results of a
therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more
information.)
Successful treatment of acute myeloid leukemia (AML) requires the control of
bone marrow and systemic disease and specific treatment of central nervous
system (CNS) disease, if present. The cornerstone of this strategy includes
systemically administered combination chemotherapy. Because only 5% of
patients with AML develop CNS disease, prophylactic treatment is not
indicated.[1-3]
Treatment is divided into two phases: remission induction (to attain remission) and
postremission (to maintain remission). Maintenance therapy for AML was
previously administered for several years but is not included in most current
treatment clinical trials in the United States, other than for acute promyelocytic leukemia. (Refer to the Adult Acute Myeloid Leukemia in Remission
section of this summary.) Other studies have used more intensive
postremission therapy administered for a shorter duration of time after which
treatment is discontinued.[4] postremission therapy appears to be effective
when given immediately after remission is achieved. [4]
Since myelosuppression is an anticipated consequence of both the leukemia and
its treatment with chemotherapy, patients must be closely monitored during
therapy. Facilities must be available for hematologic support with multiple
blood fractions including platelet transfusions, as well as for the treatment
of related infectious complications.[5] Randomized trials have shown similar
outcomes for patients who received prophylactic platelet transfusions at a
level of 10,000/mm3 rather than 20,000/mm3.[6] The incidence of platelet alloimmunization was similar among
groups randomly assigned to receive pooled platelet concentrates from random
donors; filtered, pooled platelet concentrates from random donors; ultraviolet
B-irradiated, pooled platelet concentrates from random donors; or filtered
platelets obtained by apheresis from single random donors.[7]
Colony-stimulating factors, e.g., granulocyte colony–stimulating factor (G-CSF)
and granulocyte-macrophage colony–stimulating factor (GM-CSF), have been
studied in an effort to shorten the period of granulocytopenia associated with
leukemia treatment.[8] If used, these agents are administered after completion
of induction therapy. GM-CSF was shown to improve survival in a randomized
trial of AML in patients aged 55 to 70 years (median survival was 10.6 months
vs. 4.8 months). In this Eastern Cooperative Oncology Group (ECOG) (E-1490) trial, patients were randomized to receive GM-CSF
or placebo following demonstration of leukemic clearance of the bone marrow;[9]
however, GM-CSF did not show benefit in a separate similar randomized trial in
patients aged 60 years and older.[10] In the latter study, clearance of the marrow
was not required before initiating cytokine therapy. In a Southwest Oncology Group (SWOG-9031) randomized trial of
G-CSF given following induction therapy to patients older than 65 years, complete
response was higher in patients who received G-CSF, due to a decreased
incidence of primary leukemic resistance. Growth factor administration did not
impact on mortality or on survival.[11,12] Because the majority of randomized clinical trials have not shown an impact of growth factors on survival, their use is not routinely recommended in the remission induction setting.
The administration of GM-CSF or other myeloid growth factors before and during
induction therapy, to augment the effects of cytotoxic therapy through the
recruitment of leukemic blasts into cell cycle (growth factor priming), has
been an area of active clinical research. Evidence from randomized studies of
GM-CSF priming have come to opposite conclusions. A randomized study of GM-CSF
priming during conventional induction and postremission therapy showed no
difference in outcomes between patients who received GM-CSF and those who did
not receive growth factor priming.[13,14][Level of evidence: 1iiA] In
contrast, a similar randomized placebo-controlled study of GM-CSF priming in
patients with AML aged 55 to 75 years showed improved disease-free survival
in the group receiving GM-CSF (median disease-free survival for patients who
achieved complete remission was 23 months vs. 11 months; 2-year disease-free
survival was 48% vs. 21%), with a trend towards improvement in overall
survival (2-year survival was 39% vs. 27%, P = .082) for patients aged 55 to 64
years.[15][Level of evidence: 1iiDii]
References
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Sheinberg DA, Maslak PG, Weiss MA: Acute leukemias. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 2088-116.
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Wiernik PH: Diagnosis and treatment of acute nonlymphocytic leukemia. In: Wiernik PH, Canellos GP, Dutcher JP, et al., eds.: Neoplastic Diseases of the Blood. 3rd ed. New York, NY: Churchill Livingstone, 1996, pp 283-302.
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Morrison FS, Kopecky KJ, Head DR, et al.: Late intensification with POMP chemotherapy prolongs survival in acute myelogenous leukemia--results of a Southwest Oncology Group study of rubidazone versus adriamycin for remission induction, prophylactic intrathecal therapy, late intensification, and levamisole maintenance. Leukemia 6 (7): 708-14, 1992.
[PUBMED Abstract]
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Cassileth PA, Lynch E, Hines JD, et al.: Varying intensity of postremission therapy in acute myeloid leukemia. Blood 79 (8): 1924-30, 1992.
[PUBMED Abstract]
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Supportive Care. In: Wiernik PH, Canellos GP, Dutcher JP, et al., eds.: Neoplastic Diseases of the Blood. 3rd ed. New York, NY: Churchill Livingstone, 1996, pp 779-967.
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Rebulla P, Finazzi G, Marangoni F, et al.: The threshold for prophylactic platelet transfusions in adults with acute myeloid leukemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. N Engl J Med 337 (26): 1870-5, 1997.
[PUBMED Abstract]
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Leukocyte reduction and ultraviolet B irradiation of platelets to prevent alloimmunization and refractoriness to platelet transfusions. The Trial to Reduce Alloimmunization to Platelets Study Group. N Engl J Med 337 (26): 1861-9, 1997.
[PUBMED Abstract]
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Geller RB: Use of cytokines in the treatment of acute myelocytic leukemia: a critical review. J Clin Oncol 14 (4): 1371-82, 1996.
[PUBMED Abstract]
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Rowe JM, Andersen JW, Mazza JJ, et al.: A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490). Blood 86 (2): 457-62, 1995.
[PUBMED Abstract]
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Stone RM, Berg DT, George SL, et al.: Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia. Cancer and Leukemia Group B. N Engl J Med 332 (25): 1671-7, 1995.
[PUBMED Abstract]
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Dombret H, Chastang C, Fenaux P, et al.: A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group. N Engl J Med 332 (25): 1678-83, 1995.
[PUBMED Abstract]
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Godwin JE, Kopecky KJ, Head DR, et al.: A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: a Southwest oncology group study (9031). Blood 91 (10): 3607-15, 1998.
[PUBMED Abstract]
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Buchner T, Hiddemann W, Wormann B, et al.: GM-CSF multiple course priming and long-term administration in newly diagnosed AML: hematologic and therapeutic effects. [Abstract] Blood 84 (10 Suppl 1): A-95, 27a, 1994.
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Löwenberg B, Boogaerts MA, Daenen SM, et al.: Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia. J Clin Oncol 15 (12): 3496-506, 1997.
[PUBMED Abstract]
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Witz F, Sadoun A, Perrin MC, et al.: A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients. Groupe Ouest Est Leucémies Aiguës Myéloblastiques (GOELAM). Blood 91 (8): 2722-30, 1998.
[PUBMED Abstract]
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