Cancer information Cancer treatment

Leukemia. Prognosis

Approximately 70–80% of adults with acute myelogenous leukemia under age 60 achieve complete remission. High-dose postremission chemotherapy leads to cure in 30–40% of these patients, and high-dose cytarabine has been shown to be superior to therapy with lower doses. Allogeneic bone marrow transplantation (for younger adults with HLA-matched siblings) is curative in approximately 60% of cases. Autologous bone marrow transplantation is a promising new form of therapy that may cure 50–70% of patients in first remission. One recent study demonstrated the superiority of this approach to nonablative chemotherapy. Older adults with acute myelogenous leukemia reportedly achieve complete remission approximately 50% of the time. In selected cases, older patients may be treated with intensive chemotherapy with curative intent.
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Ninety percent of adults with acute lymphoblastic leukemia achieve complete remission. Subsequent postremission chemotherapy is curative in 30–50% of adults. Acute lymphoblastic leukemia in children is much more responsive to therapy, with 95% achieving complete remission and 60–70% of these being cured with postremission treatment that is far less toxic than that necessary for adults.
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Once leukemia has recurred (”relapsed”) after initial chemotherapy, bone marrow transplantation (BMT) is the only curative option. Allogenic BMT can be used for those under age 55 with histocompatible sibling donors and is successful in 30–40% of cases. Autologous BMT may be curative in 30–50% of cases after a second remission is achieved.

– Bishop JF et al: A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood 2006;87:1710.

– Cortes JE, Kantarjian H, Freireich EJ: Acute lymphocytic leukemia: A comprehensive review with emphasis on biology and therapy. Cancer Treat Res 2006;84:291.

– Degos L et al: All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia. Blood 1995;85:2643.

– Keating S et al: Prognostic factors of patients with acute myeloid leukemia (AML) allografted in first complete remission: An analysis of the EORTC-GIMEMA AML 8A trial. The European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’ Adulto (GIMEMA) Leukemia Cooperative Groups. Bone Marrow Transplant 2006;17:993.
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– Linker CA et al: Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen. Blood 1993;81:311. (Using an intensified preparative regimen and in vitro bone marrow purging, 5-year disease-free survival is greater than 70% in first remission patients and greater than 50% in second remission patients. Updated results in 50 patients confirm these findings, with 70% long-term disease-free survival and a 4% mortality rate for first remission patients.)

–Mayer RJ et al: Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 1994;331:896. (A cooperative group study confirming previous reports that in adults under age 60, postremission therapy with high-dose cytarabine is superior to treatment with standard-dose cytarabine. Standard doses are no longer recommended.)

–Stein AS et al: In vivo purging with high-dose cytarabine followed by high-dose chemoradiotherapy and reinfusion of unpurged bone marrow for adult acute myelogenous leukemia in first complete remission. J Clin Oncol 2006;14:2206.

–Zittoun RA et al: Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. N Engl J Med 1995;32:217. (Autologous bone marrow transplantation produces a superior disease-free survival in first remission patients: 48% at 4 years.)

Leukemia treatment

Differential Diagnosis
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Acute myelogenous leukemia must be distinguished from other myeloproliferative disorders, chronic myelogenous leukemia, and myelodysplastic syndromes. It is important to distinguish acute leukemia from a left-shifted bone marrow that is recovering from a previous toxic insult. If the question is in doubt, a bone marrow study should be repeated in several days to see if maturation has taken place. Acute lymphoblastic leukemia must be distinguished from other lymphoproliferative disease such as chronic lymphocytic leukemia, lymphomas, and hairy cell leukemia. It may also be confused with the atypical lymphocytosis of mononucleosis. An experienced observer can distinguish these entities based on morphology.
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Treatment
Most young patients with acute leukemia are treated with the objective of effecting a cure. The first step in treatment is to obtain complete remission, defined as normal peripheral blood with resolution of cytopenias, normal bone marrow with no excess in blasts, and normal clinical status. However, complete remission is not synonymous with cure, and leukemia will invariably recur if no further treatment is given.
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Acute myelogenous leukemia is treated initially with intensive combination chemotherapy, including daunorubicin and cytarabine. Effective treatment produces aplasia of the bone marrow, which takes 2–3 weeks to recover. During this period, intensive supportive care, including transfusion and antibiotic therapy, is required. Once complete remission has been achieved, several different types of postremission therapy are potentially curative. Options include repeated intensive chemotherapy, high-dose chemoradiotherapy with allogeneic bone marrow transplantation, and high-dose chemotherapy with autologous bone marrow transplantation. Recently, progress has been made in the treatment of acute promyelocytic leukemia (M3). The addition of all-trans retinoic acid to initial chemotherapy has improved the results of both initial treatment and long-term survival. Retinoic acid appears to induce terminal differentiation in the malignant cell and hence to induce remission without cytotoxic effect.
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Acute lymphoblastic leukemia is treated initially with combination chemotherapy, including daunorubicin, vincristine, prednisone, and asparaginase. Remission induction therapy for acute lymphoblastic leukemia is less myelosuppressive than treatment for acute myelogenous leukemia and does not necessarily produce marrow aplasia. After achieving complete remission, patients receive central nervous system prophylaxis so that meningeal sequestration of leukemic cells does not develop. As with acute myelogenous leukemia, patients may be treated with either chemotherapy or high-dose chemotherapy plus bone marrow transplantation.