Age and acute myeloid leukemia

Blood - Tập 107 - Trang 3481-3485 - 2006
Frederick R. Appelbaum, Holly Gundacker, David R. Head, Marilyn L. Slovak, Cheryl L. Willman, John E. Godwin, Jeanne E. Anderson, Stephen H. Petersdorf

Tóm tắt

We conducted a retrospective analysis of 968 adults with acute myeloid leukemia (AML) on 5 recent Southwest Oncology Group trials to understand how the nature of AML changes with age. Older study patients with AML presented with poorer performance status, lower white blood cell counts, and a lower percentage of marrow blasts. Multidrug resistance was found in 33% of AMLs in patients younger than age 56 compared with 57% in patients older than 75. The percentage of patients with favorable cytogenetics dropped from 17% in those younger than age 56 to 4% in those older than 75. In contrast, the proportion of patients with unfavorable cytogenetics increased from 35% in those younger than age 56 to 51% in patients older than 75. Particularly striking were the increases in abnormalities of chromosomes 5, 7, and 17 among the elderly. The increased incidence of unfavorable cytogenetics contributed to their poorer outcome, and, within each cytogenetic risk group, treatment outcome deteriorated markedly with age. Finally, the combination of a poor performance status and advanced age identified a group of patients with a very high likelihood of dying within 30 days of initiating induction therapy. The distinct biology and clinical responses seen argue for age-specific assessments when evaluating therapies for AML.

Tài liệu tham khảo

Leith CP, Chir B, Kopecky KJ, et al. Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group Study. Blood. 1997;89: 3323-3329. Leith CP, Kopecky KJ, Chen I-M, et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia. a Southwest Oncology Group study. Blood. 1999;94: 1086-1099. Cassileth PA, Harrington DP, Appelbaum FR, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998;339: 1649-1656. Slovak ML, Kopecky KJ, Cassileth PA, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood. 2000;96: 4075-4083. 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. 1998;91: 3607-3615. Anderson JE, Kopecky KJ, Willman CL, et al. Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study. Blood. 2002;100: 3869-3876. Petersdorf S, Rankin C, Terebolo H, Head D, Appelbaum F. A phase II study of standard dose daunomycin and cytosine arabinoside (ARA-C) with high dose ARA-C induction therapy followed by sequential high dose ARA-C consolidation for adults with previously untreated acute myelogenous leukemia: a Southwest Oncology Group study (SWOG 9500) [abstract no. 55]. Proc Am Soc Clin Oncol. 1998;17: 15a. Young IT. Proof without prejudice: use of the Kolmogorov-Smirnov test for the analysis of histograms from flow systems and other sources. J Histochem Cytochem. 1977;25: 935-941. Mengis C, Aebi S, Tobler A, Dahler W, Fey MF. Assessment of differences in patient populations selected for excluded from participation in clinical phase III acute myelogenous leukemia trials. J Clin Oncol. 2003;21: 3933-3939. SEER Cancer Statistics Review, 1975-2001. Bethesda, MD: National Cancer Institute; 2004. Hann IM, Stevens RF, Goldstone AH, et al. Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council. Blood. 1997;89: 2311-2318. Goldstone AH, Burnett AK, Wheatley K, et al. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98: 1302-1311. Grimwade D, Walker H, Harrison G, et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML); analysis of 10 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98: 1312-1320. Moorman AV, Roman E, Willett EV, Dovey GJ, Cartwright RA, Morgan GJ. Karyotype and age in acute myeloid leukemia. Are they linked? Cancer Genet Cytogenet. 2001;126: 155-161. Schoch C, Kern W, Krawitz P, et al. Dependence of age-specific incidence of acute myeloid leukemia on karyotype [letter]. Blood. 2001;98: 3500. Horrigan SK, Westbrook CA, Kim AH, Banerjee M, Stock W, Larson RA. Polymerase chain reaction-based diagnosis of del (5q) in acute myeloid leukemia and myelodysplastic syndrome identifies a minimal deletion interval. Blood. 1996;88: 2665-2670. Fairman J, Wang RY, Liang H, et al. Translocations and deletions of 5q13.1 in myelodysplasia and acute myelogenous leukemia: evidence for a novel critical locus. Blood. 1996;88: 2259-2266. Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol. 2001;19: 1405-1413. Luna-Fineman S, Shannon KM, Lange BJ. Childhood monosomy 7: epidemiology, biology, and mechanistic implications (review). Blood. 1995;85: 1985-1999. Rossi G, Pelizzari AM, Bellotti D, Tonelli M, Barlati S. Cytogenetic analogy between myelodysplastic syndrome and acute myeloid leukemia of elderly patients. Leukemia. 2000;14: 636-641. Buchner T, Berdel WE, Schoch C, et al. Therapeutic outcome in prognostic subgroups of de-novo acute myeloid leukemia (AML) and the role of the age factor: a study in 1834 patients of 16 to 84 years [abstract no. 6552]. J Clin Oncol. 2005;23(Part 1): 573s. Schoch C, Kern W, Schnittger S, Buchner T, Hiddemann W, Haferlach T. The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica. 2004;89: 1082-1090. Appelbaum FR, Kopecky KJ, Slovak ML, et al. The clinical spectrum of adult acute myeloid leukemia (AML) associated with core binding factor (CBF) translocations [abstract no. 6513]. J Clin Oncol. 2005;23: 563s. McMurray MA, Gottschling DE. An age-induced switch to a hyper-recombinational state. Science. 2003;301: 1908-1911. Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL. The aging of hematopoietic stem cells. Nat Med. 1996;2: 1011-1016. Rufer N, Dragowska W, Thornbury G, Roosnek E, Lansdorp PM. Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol. 1998;16: 743-747. Issa JP. Age-related epigenetic changes and the immune system (review). Clin Immunol. 2003;109: 103-108.