Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials
by
, , ,
Safaa M. Ramadan
1,2,3, 
Stefan Suciu
1,
Marian J. P. L. Stevens-Kroef
4
,
Roelof Willemze
5,
Sergio Amadori
6,
Theo de Witte
7,
Bob Löwenberg
8,
Petra Muus
7,9,
Boris Labar
10,
Liv Meert
1,
Gaetan de Schaetzen
1,
Giovanna Meloni
11,
Giuseppe Leone
12,
Marco Vignetti
13,
Jean-Pierre Marie
14,
Michael Lübbert
15 and
Frédéric Baron
16,17,* 1
EORTC Headquarter, 1200 Brussels, Belgium
2
Currently in the Hemato-oncology Division, European Institute of Oncology, 20141 Milan, Italy
3
Currently in the Department of Medical Oncology, NCI-Cairo University, 11796 Cairo, Egypt
4
Department of Human Genetics, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
5
Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
6
Hematology, University Tor Vergata, 00133 Rome, Italy
7
Department of Hematology, Radboud University Medical Centre, 6525 GA Nijmegen, The Netherlands
8
Hematology, Erasmus University Medical Center Rotterdam, 3000CA Rotterdam, The Netherlands
9
Department of Hematology, Kings College Hospital, London SE5 9RS, UK
10
Department of Hematology, University Hospital Center Rebro, 10000 Zagreb, Croatia
11
Department of Cellular Biotechnologies and Hematology, Sapienza University, 00161 Rome, Italy
12
Istituto di Ematologia, Università Cattolica S. Cuore, 00168 Rome, Italy
13
Data Center and Health Outcomes Research Unit, Italian Group for Adult Hematologic Diseases (GIMEMA), 00182 Rome, Italy
14
Department Hematology and Tumor Bank, Saint-Antoine Hospital, AP-HP & University Pierre & Marie Curie, 75571 Paris, France
15
Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Faculty of Medicine, 79106 Freiburg, Germany
16
GIGA-I3, Hematology, University of Liège, 4000 Liège, Belgium
17
Hematology, CHU of Liège, 4000 Liège, Belgium
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(11), 3334; https://doi.org/10.3390/cancers12113334
Submission received: 11 October 2020
/
Revised: 5 November 2020
/
Accepted: 8 November 2020
/
Published: 11 November 2020
(This article belongs to the Special Issue Updates in Acute Myeloid Leukemia)
Simple Summary
Secondary acute myeloid leukemia (s-AML) refers to the development of AML following myelodysplatic syndrome or other hematological malignancies, or after a solid tumors, or nonmalignant diseases or following exposure to environmental or occupational carcinogens. Here, we report data from 960 s-AML patients who were treated in 13 EORTC collaborative trials conducted between May 1986 and January 2008. The main aims of our study were (1) to assess whether overall survival of s-AML patients improved over time, (2) to identify initial disease features associated with overall survival. We observed that overall survival of younger patients improved over the years, in parallel with introduction of high-dose cytarabine in induction remission chemotherapy. This suggests that this strategy should be further investigated in younger patients with s-AML. Furthermore, this study confirmed that the sAML patients having adverse cytogenetic risk features and those with high white blood cells at diagnosis had a dismal survival, regardless of their age group.
Abstract
We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p < 0.001): 7.7% (95% CI: 1.3–21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1–30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7–44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39; p = 0.01), WBC ≥ 25 × 109/L (HR = 2.00; p < 0.0001), age 46-60 years (HR = 1.65; p < 0.001) and poor-risk cytogenetics (HR = 2.17; p < 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43; p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >60 years of age (n = 502), the OS was dismal, and there was no improvement over time.
