Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Abnormal Karyotype , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Azacitidine/administration & dosage , Azacitidine/adverse effects , Bone Marrow Diseases/chemically induced , Disease Progression , Dose-Response Relationship, Drug , Drug Administration Schedule , Febrile Neutropenia/chemically induced , Female , France/epidemiology , Hospitalization/statistics & numerical data , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/mortality , Male , Multicenter Studies as Topic , Myelodysplastic Syndromes/mortality , Renal Insufficiency, Chronic/epidemiology , Retrospective Studies , Treatment OutcomeSubject(s)
Leukemia, Myeloid, Acute/etiology , Lymphoma , Myelodysplastic Syndromes/etiology , Neoplasms, Second Primary , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/mortality , Lymphoma/mortality , Lymphoma/therapy , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/mortality , Patient Outcome Assessment , Radiotherapy/adverse effects , Radiotherapy/methodsABSTRACT
Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.
Subject(s)
Bone Marrow Cells/metabolism , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/mortality , Myelodysplastic Syndromes/metabolism , Myelodysplastic Syndromes/mortality , Proto-Oncogene Proteins c-bcl-2/metabolism , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Biomarkers , Bone Marrow Cells/pathology , Female , Gene Expression , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/drug therapy , Neoplasm Staging , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , Treatment OutcomeABSTRACT
Chronic myelomonocytic leukemia (CMML) is a myelodysplastic syndrome/ myeloproliferative neoplasm whose diagnosis is currently based on the elevation of peripheral blood monocytes to >1 × 10(9)/L, measured for ≥3 months. Diagnosis can be ambiguous; for example, with prefibrotic myelofibrosis or reactive monocytosis. We set up a multiparameter flow cytometry assay to distinguish CD14(+)/CD16(-) classical from CD14(+)/CD16(+) intermediate and CD14(low)/CD16(+) nonclassical monocyte subsets in peripheral blood mononucleated cells and in total blood samples. Compared with healthy donors and patients with reactive monocytosis or another hematologic malignancy, CMML patients demonstrate a characteristic increase in the fraction of CD14(+)/CD16(-) cells (cutoff value, 94.0%). The associated specificity and sensitivity values were 95.1% and 90.6% in the learning cohort (175 samples) and 94.1% and 91.9% in the validation cohort (307 samples), respectively. The accumulation of classical monocytes, which demonstrate a distinct gene expression pattern, is independent of the mutational background. Importantly, this increase disappears in patients who respond to hypomethylating agents. We conclude that an increase in the fraction of classical monocytes to >94.0% of total monocytes is a highly sensitive and specific diagnostic marker that rapidly and accurately distinguishes CMML from confounding diagnoses.
