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Older patients (>60 to 65 years of age) remain a therapeutic challenge. These patients are offered so-called reduced-intensity or nonmyeloablative BMT.
Adding growth factors (granulocyte-colony stimulating factor [G-CSF]) may reduce toxicity in older patients (but is not broadly accepted).
Hypomethylating agent, such as 5-azacitidine, significantly prolongs survival in older adults with low marrow blast count (<30%).
Pediatric Considerations
Tolerate intense treatments better
Pregnancy Considerations
Chemotherapy is a viable option in the 2nd and 3rd trimesters.
MEDICATION
First Line
- APL (APL, AML with t[15;17])
- All-trans retinoic acid (ATRA) and arsenic trioxide both promote maturation to granulocytes.
- Idarubicin is often added to induction therapy.
- Treatment of AML in younger adults: AML (other than APL)
- Induction (daunorubicin or idarubicin [anthracycline and cytarabine]): The generally accepted combination is 3 + 7 (anthracycline is given for 3 days and cytarabine for 7 days) or more intensive regimens with high dose of cytarabine (HiDAC) or high dose of anthracycline.
- Remission is typically consolidated in younger patients by the following:
- In good-risk AML, 3 to 4 cycles of HiDAC and BMT is reserved for time of recurrence.
- In poor-risk patients, 1 to 2 cycles of HiDAC (until donor is identified) are followed by allogeneic BMT.
- Intermediate-risk AML should be treated based on individual patient 's features, donor availability, and access to clinical trials. A meta-analysis showed that even intermediate-risk patients benefit from allogeneic BMT (4)[A].
- Treatment of AML in older adults (>65 years of age) remains a challenge. These patients have poor performance status, more likely secondary AML, higher incidence of unfavorable cytogenetics, comorbidities, shorter remissions, and shorter overall survival.
- Intensive chemotherapy may be feasible for patients with good performance status; alternative regimens with mitoxantrone, fludarabine, and clofarabine. New drugs (hypomethylating agents as above, FLT3 inhibitors, monoclonal antibodies, etc.) are being studied in clinical trials (5)[A].
- Contraindications: comorbidities; therapy has to be individualized.
- Precautions
- If organ failure, some drugs may be avoided or dose reduced (e.g., no anthracyclines in patients with preexisting cardiac problems).
- Patients will be immunosuppressed during treatment. Avoid live vaccines. Administer varicella-zoster or measles immunoglobulin as soon as exposure of patient occurs.
- Significant possible interactions: Allopurinol accentuates the toxicity of 6-mercaptopurine.
Second Line
Healthy, younger patients usually are offered reinduction chemotherapy and allogeneic BMT.
ISSUES FOR REFERRAL
- AML should be managed by specialized team led by a hematologist/oncologist.
- Refer patient to a transplant center early because a search for a donor may be necessary.
SURGERY/OTHER PROCEDURES
- BMT: Decision between myeloablative and nonmyeloablative approach should be based on patient 's performance status, comorbidities, and AML risk factors.
- Allogeneic BMT is acceptable in first remission in intermediate- or high-risk AML or in second remission in all other AML patients. Matched related donor used to be preferred over matched unrelated donor (lower risk of graft-versus-host disease); recent data suggest equal outcomes, as allogeneic transplant regimens and posttransplant care have improved significantly.
- Haploidentical transplants and cord blood may be used as alternative sources of hematopoietic stem cells for adults.
- Autologous BMT may be acceptable in specific situations (e.g., no donor is available).
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Induction treatment for AML requires inpatient care, usually on a specialized ward. Episodes of febrile neutropenia typically require admission and IV antibiotics.
IV Fluids
Appropriate hydration to prevent TLS
Nursing
IV may lead to chemical burns in the event of extravasation.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Ambulatory, as tolerated; no intense or contact sports; no aspirin due to risk of bleeding.
Patient Monitoring
- Repeat bone marrow studies to document remission and also if a relapse is suspected.
- Follow CBC with differential, coagulation studies, uric acid level, and other chemistries related to TLS (creatinine, potassium, phosphate, calcium); monitor urinary function at least daily during induction phase and less frequently later.
- Physical evaluation, including weight and BP, should be done frequently during treatment.
DIET
Ensure adequately balanced calorie/vitamin intake. Total parenteral nutrition (TPN) in case of severe mucositis
PATIENT EDUCATION
- Leukemia Society of America, 600 Third Avenue, New York, NY 10016, 212-573-8484
- National Cancer Institute, Bethesda, MD, has pamphlets and telephone education.
- Baker LS. You and Leukemia: A Day At a Time. Philadelphia, PA: Saunders; 1978.
PROGNOSIS
AML remission rate is 60 " 80%, with only 20 " 40% long-term survival. The wide variable prognosis is due to prognostic group (age, cytogenetics, and genetics).
COMPLICATIONS
- Acute side effects of chemotherapy, including febrile neutropenia
- TLS
- DIC
- Late-onset cardiomyopathy in patients treated with anthracyclines
- Chronic side effects of chemotherapy (secondary malignancies)
- Graft-versus-host disease in patients who have received allogeneic BMT
REFERENCES
11 D Άhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010;115(3):453 " 474.22 Patel JP, G Άnen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079 " 1089.33 Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223 " 232.44 Koreth J, Schlenk R, Kopecky KJ, et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA. 2009;301(22):2349 " 2361.55 Fenaux P, Mufti GJ, Hellstr Άm-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J Clin Oncol. 2010;28(4):562 " 569.
ADDITIONAL READING
O 'Donnell MR, Appelbaum FR, Coutre SE, et al. Acute myeloid leukemia. J Natl Compr Canc Netw. 2008;6(10):962 " 993.
SEE ALSO
Disseminated Intravascular Coagulation; Leukemia, Acute Lymphoblastic in Adults (ALL); Leukemia, Chronic Myelogenous; Myelodysplastic Syndromes; Myeloproliferative Neoplasms
CODES
ICD10
- C92.00 Acute myeloblastic leukemia, not having achieved remission
- C92.01 Acute myeloblastic leukemia, in remission
- C92.02 Acute myeloblastic leukemia, in relapse
ICD9
- 205.00 Acute myeloid leukemia, without mention of having achieved remission
- 205.01 Acute myeloid leukemia, in remission
- 205.02 Acute myeloid leukemia, in relapse
SNOMED
- 91861009 Acute myeloid leukemia, disease (disorder)
- 91860005 Acute myeloid leukemia in remission (disorder)
CLINICAL PEARLS
- Prognosis of leukemia depends on the cytogenetic and molecular profile of the disease.
- Allogeneic transplant remains the only therapy with curative potential for patients with intermediate- and high-risk AML.