| 1. |
- Juliusson, Gunnar, et al.
(author)
-
Epidemiology and Etiology of AML
- 2021
-
In: Acute Myeloid Leukemia. - Cham : Springer International Publishing. - 2197-9774 .- 2197-9766. - 9783030726768 - 9783030726782 ; , s. 1-22
-
Book chapter (peer-reviewed)abstract
- Acute myeloid leukemia (AML) is a grave disease with an incidence of 4 per 100,000 a year. It can present in all ages, but the median age is 70 years. One-third of such patients have secondary AML, that is, AML following chemoradiotherapy or a transformation from previous myelodysplastic syndrome (MDS) or myeloproliferative neoplasia. A combination of genetic, epigenetic, and environmental factors may be responsible for the development of most cases of AML. The pathogenesis of AML is characterized by the serial acquisition of somatic mutations and several genes are recurrently mutated in AML. Exposures to benzene, cigarette smoking, pesticides, embalming fluids, accidental or professional ionization radiation, therapeutic radiotherapy, and radioactive I-131 therapy can cause AML with or without a preceding MDS phase. Alkylating agents (e.g., melphalan, cyclophosphamide), topoisomerase-II inhibitors (e.g., etoposide, doxorubicin), and other drugs (e.g., azathioprine) are described to be associated with the development of therapy-related AML (t-AML). Furthermore, about 5–15% of adults and 4–13% of pediatric patients with MDS or AML carry germline pathogenic variants in cancer susceptibility genes. Individuals with clonal hematopoiesis (CHIP) progress to AML at a rate of about 1% per year. Higher age of onset, obesity, previous autoimmune disease, and antecedent MDS or MPN are associated with a risk for developing AML.
|
|
| 2. |
- Löwenberg, Bob, et al.
(author)
-
Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML : the HOVON-SAKK-132 trial
- 2021
-
In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 5:4, s. 1110-1121
-
Journal article (peer-reviewed)abstract
- Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% +/- 2% standard error and overall survival, 54% = 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.
|
|
