|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 22, No 12 (June 15), 2004: pp. 2510-2511 © 2004 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.99.301
Prognosis in Therapy-Related Acute Myeloid Leukemia and Impact of KaryotypeLaboratory for Leukemia Diagnostics, Ludwig-Maximilians-University, University Hospital Grosshadern, Department of Internal Medicine III, Munich, Germany To the Editor: The treatment of patients with therapy-related acute myeloid leukemia (t-AML) has been a matter of debate because of the unfavorable prognosis in these cases. This has led to the suggestion to treat patients by intensive standard therapies only in case of an available allogeneic stem cell donor. In fact, several large series indicated an overall dismal outcome in patients with t-AML,1-4 backing up the general reluctance to intensively treat these patients. The results reported in a recent contribution by Josting et al5 are in line with these data, with a 2-year event-free survival of 2% and an overall survival of 8% at 2 years. Probably contributing to this dismal outcome, 24 of the 46 reported patients received no treatment or supportive care only after the diagnosis of acute myeloid leukemia (AML). An additional reason may have been the high frequency of unfavorable karyotypes in this series. Similar results have been reported by Smith et al6 in 306 patients with t-AML with a 5-year overall survival of 10%. An impact of the karyotype has been observed with a better outcome in cases with balanced aberrations and a worse outcome in patients with abnormalities in chromosomes 5 and 7. Treament in this cohort was also variable and ranged from supportive care only to bone marrow transplantation. These data point to two highly important questions in patients with t-AML: (1) What is the role of standard AML therapy? (2) What is the prognostic impact of karyotype aberrations in these cases? We have reported a series of 93 patients with t-AML, most of whom were treated uniformly within the German AML Cooperative Group trials.7 As compared to 1,091 patients with de novo AML, unfavorable cytogenetics were present more frequently in t-AML cases (46.2% v 20.4%) and median overall survival was worse (10 v 15 months; P = .0007). However, there was a large impact of karyotype aberrations in patients with t-AML, which is confirmed in an updated analysis including 121 t-AML cases and 1,511 de novo AML cases (Fig 1). The median survival of t-AML patients ranges from 26.7 months (favorable karyotype) to 5.6 months (unfavorable karyotype). These data clearly demonstrate that the presence of t-AML, per se, does not indicate a poor prognosis, at least in the context of a clinical trial applying standard intensive chemotherapy. It rather indicates a relatively worse prognosis, which is strongly influenced by the karyotype. Accordingly, both parameters have been shown in a multivariate analysis to carry independent impact (P = .001 for t-AML; P < .0001 for karyotype).
In line with these data, an analysis of the Medical Research Council trials composed of intensive chemotherapies, similar to the German AML Cooperative Group trials, revealed comparable results in 155 patients with t-AML.8 As compared with de novo AML, unfavorable karyotypes were more frequent (27% v 11%), and overall survival at 2 years was shorter in t-AML (30% v 44%). Outcome was significantly influenced by the karyotype, and the presence of t-AML resulted in an inferior outcome within all cytogenetic risk groups. These results indicate that the presence of t-AML does not give sufficient information to estimate the prognosis of a patient. At least in the context of standardized intensive chemotherapies, the karyotype of the disease reveals highly important prognostic information, allowing the identification of patients whose prognosis does not differ from patients with de novo AML and intermediate karyotypes. Thus, these patients clearly benefit from the application of standard therapies instead of supportive care only. As a consequence, in patients with t-AML, like in those with de novo AML, cytogenetics should be performed on a regular basis at diagnosis, and these patients should be included into clinical trials in order to assure optimum treatment and to further improve the results. These data strongly speak against a diagnostic and therapeutic nihilism in patients with t-AML. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Mauritzson N, Albin M, Rylander L, et al.: Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976–1993 and on 5098 unselected cases reported in the literature 1974–2001. Leukemia 16:2366–2378, 2002[CrossRef][Medline]
2. Ng AK, Bernardo MV, Weller E, et al.: Second malignancy after Hodgkin disease treated with radiation therapy with or without chemotherapy: Long-term risks and risk factors. Blood 100:1989–1996, 2002 3. Andersen MK, Larson RA, Mauritzson N, et al.: Balanced chromosome abnormalities inv(16) and t(15;17) in therapy-related myelodysplastic syndromes and acute leukemia: Report from an international workshop. Genes Chromosomes Cancer 33:395–400, 2002[CrossRef][Medline] 4. Slovak ML, Bedell V, Popplewell L, et al.: 21q22 balanced chromosome aberrations in therapy-related hematopoietic disorders: Report from an international workshop. Genes Chromosomes Cancer 33:379–394, 2002[CrossRef][Medline]
5. Josting A, Wiedenmann S, Franklin J, et al.: Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: A report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol 21:3440–3446, 2003
6. Smith SM, Le Beau MM, Huo D, et al.: Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: The University of Chicago series. Blood 102:43–52, 2003 7. Schoch C, Kern W, Schnittger S, et al.: Karyotype is an independent prognostic parameter in therapy-related acute myeloid leukemia (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia 18:120–125, 2004[CrossRef][Medline] 8. Goldstone AH, Burnett AK, Avivi I, et al.: Secondary acute myeloid leukemia has a worse outcome than de novo AML, even taking into account cytogenetics and age. AML 10, 11, 12 MRC Trials. Blood 100:88a, 2002 (abstr 322)
Related Correspondence
Related Article
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2004 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
