Fey, M.

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Annals of Oncology 18 (Supplement 2): ii47–ii48, 2007doi:10.1093/annonc/mdm033clinical recommendationsAcute myeloblastic leukemia in adult patients: ESMOClinical Recommendations for diagnosis, treatment andfollow-upincidenceThe crude incidence of acute myeloblastic leukemia (AML)in adults in Europe is 5–8 cases/100 000/year. The mortalityis 4–6 cases/100 000/year.diagnosisThe diagnosis of AML requires examination of peripheralblood and bone marrow samples. Work-up shouldcomprise morphological examination, cytochemistry,immunophenotyping, cytogenetic and selected molecularanalysis.risk assessmentRisk assessment in AML includes the patient’s age, the initialleukocyte count, the AML subtype, karyotype data and selectedmolecular markers. AML with the chromosomal translocationst(15;17) [acute promyelocytic leukemia (APL)], t(8;21) andt(16;16) (including acute myelomonocytic leukemia withpreponderance of eosinophil granulocytes) are considered asfavorable [II, A]. An antecedent or concomitant myelodysplasticsyndrome or complex aberrant karyotypes are adverseprognostic factors. Preexisting medical conditions such asdiabetes or coronary heart disease may affect the feasibility ofintensive chemotherapy. Elderly patients have an adverseprognosis and are more susceptible to treatment complications.If an infection is suspected, a thoracic computed tomography(CT) scan and an abdominal ultrasound or a CT scan may beperformed to assess lung, liver, spleen, lymph nodes and kidneysfor possible pathological alterations. Cardiac examinationincluding echocardiography is recommended for patients withcardiac risk factors or a history of heart disease [A].In addition to hematological and chemistry tests,a coagulation screening is to be performed before the insertionof central venous lines. Human leukocyte antigen (HLA)typing of patients and their family members identifies patientswho are candidates for an allogeneic bone marrow or stem-celltransplants [A].treatment planTreatment is divided into induction and consolidationchemotherapy. Whenever possible it should be planned witha curative intent. Candidates for allogeneic stem-celltransplantation should be identified early during induction.Patients with poor performance status and considerablecomorbidity, as well as elderly patients not eligible for curativetreatment, should receive supportive care. Whenever possibleAML treatment should be in clinical trials and in centersoffering a multidisciplinary approach. Such centers shouldprovide an adequate infrastructure including a fullhematology and medical oncology service, a close collaborationwith a bone marrow transplant unit, as well as an infectiousdisease service and an adequate transfusion service.induction chemotherapyChemotherapy should be postponed until all materialsatisfactory for diagnostic tests has been harvested. Patients withexcessive leukocytosis at presentation may require emergencyleukapheresis before induction chemotherapy. Especially inthese patients with high leukocyte counts, adequate measuresshould be taken to avoid tumor lysis syndrome during the firstdays of treatment (including a prephase if appropriate).Induction chemotherapy should include an anthracycline andcytarabine [II, A]. Patients failing to respond to one to twocycles of such treatment are considered refractory. APLinduction chemotherapy should be complemented withall-trans retinoic acid (ATRA) [II, A]. Hematopoietic growthfactors are an optional adjunct to intensive chemotherapy.consolidation therapyPatients entering clinical and hematological remission shouldreceive one to several cycles of postremission therapy [II, A].There is no consensus on a single ‘best’ postremission treatmentstrategy. Patients with good risk features as defined aboveshould receive chemotherapy only, preferably with high-dosecytarabine. All other patients with an HLA-identical siblingare candidates for allogeneic stem-cell transplantation in firstremission [III, A]. Patients with particular poor risk features andno donor in the family may qualify for an allogeneic transplantwith an unrelated matched donor [III, A]. The role of prolongedmonthly maintenance or high-dose consolidationCorrespondence to: ESMO Guidelines Working Group, ESMO Head Office,Via La Santa 7, CH-6962 Viganello-Lugano, SwitzerlandApproved by the ESMO Guidelines Working Group: August 2002, last update December2006. This publication supercedes the previously published version—Ann Oncol 2005;16 (Suppl 1): i48–i49.ª 2007 European Society for Medical Oncologychemotherapy with autologous peripheral stem-cell supportin AML is controversial. Maintenance chemotherapy andATRA are beneficial in APL [III, A].therapy of relapsed or refractorypatientsPatients in second or subsequent remission may qualify forallogeneic transplantation with an unrelated HLA-matcheddonor. In relapsed APL, arsenic trioxide can induce remissioneven if patients have become refractory to ATRA [III, B].response evaluationResponse to induction is monitored through clinicalexamination, serial peripheral blood counts and bone marrowaspirates. During induction-induced aplasia, a bone marrowaspirate should be obtained to monitor for early marrowresponse or leukemic blast persistence. The usual requirementsof AML remission are a normal cellularity of the bone marrow,blast levels <5% in bone marrow smears and morphologicallynormal hematopoiesis [B].follow-upPatients are followed clinically and with hematologicalexaminations to detect early relapse. Serial bone marrowexamination is of uncertain value in remission patients withoutany clinical or hematological evidence of relapse.noteLevels of evidence [I–V] and grades of recommendation[A–D] as used by the American Society of Clinical Oncologyare given in square brackets. Statements without grading wereconsidered justified standard clinical practice by the expertauthors and the ESMO faculty.literature1. Cheson BD, Cassileth PA, Head DR et al. Report on the National CancerInstitute-sponsored workshop on definitions of diagnosis and response inacute myeloid leukemia. J Clin Oncol 1990; 8: 813–819.2. Grimwade D, Walzer H, Oliver F et al. The importance of diagnosticcytogenetics on outcome in AML: analysis of 1612 patients entered into theMRC AML 10 trial. Blood 1998; 92: 2322–2333.3. Appelbaum FR, Baer MR, Carabasi MH et al. NCCN practice guidelines for acutemyelogenous leukemia. Oncology 2000; 14: 53–61.4. Zittoun RA, Manelli F, Willemze R et al. Autologous or allogeneic bone marrowtransplantation compared with intensive chemotherapy in acute myelogenousleukemia. New Engl J Med 1995; 332: 217–223.5. Stone RM, O’Donnell MR, Sekeres MA. Acute myeloid Leukemia. Hematology2004; 98–117.6. Smith M, Barnett M, Bassan R et al. Acute myeloid Leukemia. Crit Rev OncolHematol 2004; 50: 197–222.Coordinating author for the ESMO Guidelines Working Group:M. Fey11Invited author, Department of Medical Oncology, Inselspital andUniversity of Bern, Bern, Switzerlandclinical recommendations Annals of Oncologyii48 | ESMO Guidelines Working Group Volume 18 | Supplement 2 | April 2007

Acute myeloblastic leukemia in adult patients: ESMO Clinical Recommendations for diagnosis, treatment and follow-up

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