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Adult Acute Erythroleukemia: an Analysis of 91 Patients Treated at a Single Institution

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Adult Acute Erythroleukemia: an Analysis of 91 Patients Treated at a Single Institution Leukemia (2009) 23, 2275–2280 & 2009 Macmillan Publishers Limited All rights reserved 0887-6924/09 $32.00 www.nature.com/leu ORIGINAL ARTICLE Adult acute erythroleukemia: an analysis of 91 patients treated at a single institution FPS Santos1, S Faderl1, G Garcia-Manero1, C Koller1, M Beran1, S O’Brien1, S Pierce1, EJ Freireich1, X Huang2, G Borthakur1, C Bueso-Ramos3, M de Lima4, M Keating1, J Cortes1, H Kantarjian1 and F Ravandi1 1Department of Leukemia, University of Texas - M. D. Anderson Cancer Center, Houston, TX, USA; 2Department of Biostatistics, University of Texas - M. D. Anderson Cancer Center, Houston, TX, USA; 3Department of Hematopathology, University of Texas - M. D. Anderson Cancer Center, Houston, TX, USA and 4Department of Stem Cell Transplantation, University of Texas - M. D. Anderson Cancer Center, Houston, TX, USA Acute erythroleukemia (AML-M6) is an uncommon subtype of erythroid (AML-M6a), but with the lower blast threshold of 20%) acute myeloid leukemia (AML); it is considered to have a poor plus the entity known as pure erythroleukemia (AML-M6b), prognosis. From 1 January 1980 to 21 May 2008, 91 patients with newly diagnosed AML-M6 were seen at the University of when more than 80% of BM cells are immature cells (with an Texas–M.D. Anderson Cancer Center (UT–MDACC). Forty-five undifferentiated or pro-normoblastic appearance) committed 8 patients (50%) had a history of myelodysplatic syndrome exclusively to the erythroid lineage. (MDS), compared with 41% in our control group (patients with AML-M6 has been considered to be a subtype of AML with other AML subtypes) (P ¼ 0.08). Poor-risk cytogenetics were a worse prognosis.9–13 It is very uncommon in children,14,15 and more common in patients with AML-M6 (61% versus 38%, it corresponds to 3–5% of adult AML cases.12 Familial and P ¼ 0.001). Complete remission rates were 62% for patients with congenital forms have been described.16,17 It is often associated AML-M6, comparing with 58% for the control group (P ¼ 0.35). Median disease free survival (DFS) for patients with AML-M6 with an antecedent diagnosis of myelodysplastic syndrome was 32 weeks, versus 49 weeks for the control group (P ¼ 0.05). (MDS) and the presence of poor-risk chromosome abnormal- Median overall survival (OS) of patients with AML-M6 was 36 ities.9,18–20 Owing to its rarity, the clinical experience with weeks, compared with 43 weeks for the control group (P ¼ 0.60). AML-M6 is limited. It is also not clear if the pathological On multivariate analysis for DFS and OS, AML-M6 was not an diagnosis of AML-M6 is associated with a worse prognosis or if independent risk factor. AML-M6 is commonly associated with a previous diagnosis of MDS and poor-risk karyotype. The the worse prognosis reported with this leukemia is because of its diagnosis of AML-M6 does not impart by itself a worse frequent association with poor-risk karyotype and other poor- prognosis, and treatment decisions on this disease should be risk features. guided by well known AML prognostic factors. The objective of this study is to describe the clinical Leukemia (2009) 23, 2275–2280; doi:10.1038/leu.2009.181; and biological features of patients with AML-M6 treated at published online 10 September 2009 the University of Texas–M.D. Anderson Cancer Center Keywords: acute erythroleukemia; clinical features; prognosis (UT–MDACC) and to compare them with patients with non- M6 AML. We also evaluated the impact of a diagnosis of AML-M6 in response rate and survival independent of other Introduction risk factors. Acute erythroleukemia (AML-M6) was first described in 1912 1 2 by Copelli, but it was Di Guglielmo who coined the term Patients and methods ‘eritroleucemia’, describing an abnormal proliferation of ery- 3 throid cells, myeloblasts and megakaryocytes. In 1923 Di Patients Guglielmo4 described a case of pure erythroleukemia char- Adult patients with newly diagnosed AML-M6 seen at acterized by pure proliferation of erythroid immature elements, UT–MDACC between 1 January 1980 and 21 May 2008 were akin to acute leukemia. In 1953 Dameshek proposed the term compared with patients with other AML subtypes, excluding ‘Di Guglielmo’s Syndrome’, which described three phases of those with acute promyelocytic leukemia. Charts were manually alterations in the bone marrow (BM): an erythremic phase, an reviewed. Patients were treated on studies conducted at erythromyeloblastic phase and a myeloblastic phase, similar to UT–MDACC. Studies were approved by the Institutional Review acute myeloid leukemia (AML).5 Board and conducted in accordance with the Declaration of The French–American–British classification of AML in 1976 Helsinki. All patients provided written informed consent before established the first set of criteria for the diagnosis of AML-M6.6 study entry. A diagnosis of AML-M6a (mixed erythroid/myeloid) A revision of the French–American–British classification defined was considered if more than 50% of the total nucleate BM cells AML-M6 as the presence of more than 50% erythroid cells with were of erythroid lineage and more than 20% of non-erythroid more than 30% blasts among non-erythroid BM nucleated 8 cells were blasts. AML-M6b (pure erythroleukemia) was cells.7 The World Health Organization (WHO) classification diagnosed in patients who presented with more than 80% of recognizes the French–American–British entity (mixed myeloid/ 8 BM nucleate cells consisting of immature erythroid precursors. On the basis of previous reports of similar cases we also Correspondence: Dr F Ravandi, Department of Leukemia, University considered a diagnosis of AML-M6b in patients who presented of Texas - M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, with acute undifferentiated leukemia with blasts that were Unit 428, Houston, TX 77030, USA. E-mail: [email protected] positive by immunophenotyping for glycophorin A, even though 21–24 Received 8 April 2009; revised 14 July 2009; accepted 21 July 2009; these cases did not fit the current WHO criteria. Also of published online 10 September 2009 importance, no patient had received erythropoietin at the time Adult acute erythroleukemia FPS Santos et al 2276 of BM aspiration for the diagnosis to be confirmed. Pathology remaining 30 patients, 5 patients had diagnostic criteria for reports of BM biopsies were reviewed for information about AML-M6b (more than 80% of BM cells consisted of immature dysplasia in one or more hematopoietic lineages. Cytogenetic erythroid precursors) and 8 patients did not fulfill the criteria for data was stratified into three subgroups (modified from previous AML-M6b but presented with undifferentiated leukemia with reports25–27): Poor-risk (À5, À7, þ 8 and 11q involvement and blasts positive for glycophorin A. The remaining 17 patients complex karyotype), good-risk (t(8;21) or Inv(16) t(16;16)) and were diagnosed as having AML-M6 in our institution, on the intermediate-risk (neither good nor poor ). Patients received basis of morphology and/or positivity for periodic acid Schiff different treatment regimens according to the period of diagnosis (PAS) stain, but as they did not fulfill the current criteria for and prevailing studies. The treatment regimens were divided this disease, they were excluded from this analysis. All these 17 into: Group 1, regimens with cytarabine (ara-C) and anthra- patients were diagnosed before the current WHO criteria were cyclines. Group 2, regimens with ara-C and fludarabine without defined. Thus, 91 patients remained for our analysis, corre- anthracyclines. Group 3, regimens with ara-C plus topotecan. sponding to 3.0% of all patients with AML. There was a higher Group 4, other ara-C containing regimens. Group 5, miscella- proportion of patients with AML-M6 diagnosed in the decades neous non-ara-C containing intensive chemotherapy regimens. of 1990 and 2000, probably a reflection of the advances in immunophenotyping and establishment of diagnostic criteria for this entity: there were 6 (1%) of 612 patients during 1980–1989, Criteria for response and survival, and statistical analysis 34 (3.1%) of 1087 patients during 1990–1999 and 51 (3.9%) of Complete remission (CR) was defined by the presence of o5% 1276 patients from 2000–2008 (P ¼ 0.002). This can also be an blasts in the BM with more than 1 Â 109/l neutrophils and more artifact because we excluded 17 patients who were diagnosed in than 100 Â 109/l platelets in the peripheral blood.28,29 A relapse the time period from 1980 until 1999, when the WHO criteria was defined by more than 5% blasts in a BM aspirate unrelated for AML-M6b were not established. The clinical features of to recovery or by the presence of extramedullary disease. patients with AML-M6 are summarized in Table 1. They were Disease-free survival (DFS) was calculated from the time of CR different from patients with other AML subtypes in a number of until relapse or death in CR. Event free survival (EFS) was characteristics. There was a male predominance (68% versus calculated from the beginning of treatment until an event. An 55%, P ¼ 0.02), a slightly higher prevalence of antecedent event was defined as relapse, resistant disease and death. hematological disorder (AHD)/MDS (50% versus 41%, P ¼ 0.08) Induction death was defined as death occurring before and more frequent finding of dysplastic changes in BM cells achievement of CR or confirming resistant disease. Overall (80% vs 50%, Po0.001). They also had, at presentation, lower survival (OS) was calculated from the time of diagnosis until hemoglobin levels (Po0.001), lower WBC count (Po0.001), death. All patients alive at last follow-up were censored. lower platelet count (Po0.001) and a higher prevalence of Categorical and continuous variables were compared by the poor-risk cytogenetic abnormalities (61% versus 38%, w2/Fischer’s exact test and Mann–Whitney U test, respectively.30 Po0.001).
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