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- Angenendt, Linus, et al.
(författare)
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Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts
- 2019
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 37:29, s. 2632-2642
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.
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| 2. |
- Ferrari, Stefano, et al.
(författare)
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EURO-B.O.S.S. : A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma
- 2018
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Ingår i: Tumori. - : SAGE Publications. - 0300-8916 .- 2038-2529. ; 104:1, s. 30-36
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma.METHODS: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators' choice were also eligible for the study.RESULTS: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity.CONCLUSIONS: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.
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