RESUMEN
We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. In univariate analysis, significant risk factors for survival included anemia, thrombocytopenia, increased levels of white blood cells, absolute neutrophils, absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone marrow blasts, and presence of circulating immature myeloid cells (IMCs). Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. On multivariable analysis, increased AMC (>10 × 10(9)/l, relative risk (RR) 2.5, 95% confidence interval (CI) 1.7-3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4-2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2-2.2) and decreased platelet count (<100 × 10(9)/l, RR 1.4, 99% CI 1.0-1.9) remained significant. Using these four risk factors, a new prognostic model for overall (high risk, RR 4.4, 95% CI 2.9-6.7; intermediate risk, RR 2.0, 95% CI 1.4-2.9) and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9-12.8; intermediate risk, RR 2.6, 95% CI 1.1-5.9) performed better than other conventional risk models and was validated in an independent cohort of 268 CMML patients.
Asunto(s)
Leucemia Mielomonocítica Crónica/genética , Leucemia Mielomonocítica Crónica/mortalidad , Proteínas Represoras/genética , Empalmosomas/genética , Adulto , Anciano , Anciano de 80 o más Años , Anemia/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Proteínas Nucleares/genética , Fosfoproteínas/genética , Pronóstico , Factores de Empalme de ARN , Ribonucleoproteína Nuclear Pequeña U2/genética , Ribonucleoproteínas/genética , Factores de Riesgo , Factores de Empalme Serina-Arginina , Factor de Empalme U2AF , Análisis de Supervivencia , Trombocitopenia/mortalidad , Organización Mundial de la Salud , Adulto JovenRESUMEN
Unlike the case with acute myeloid leukemia, there is limited information on the prognostic impact of isocitrate dehydrogenase (IDH) mutations in myelodysplastic syndromes (MDS). In the current study of 277 patients with MDS, IDH mutations were detected in 34 (12%) cases: 26 IDH2 (all R140Q) and 8 IDH1 (6 R132S and 2 R132C). Mutational frequency was 4% (2 of 56) in refractory anemia with ring sideroblasts, 12% (16 of 130) in refractory cytopenia with multilineage dysplasia, 14% (2 of 14) in MDS-unclassifiable, 14% (6 of 42) in refractory anemia with excess blasts (RAEB)-1 and 23% (8 of 35) in RAEB-2. Normal karyotype was noted in all but one IDH1-mutated cases and 13 IDH2-mutated cases. Multivariable analysis identified presence of mutant IDH1 (P=0.0004; hazard ration 4.0, 95% confidence interval 1.9-8.8), revised International Prognostic Scoring System risk category (P<0.0001), and red cell transfusion need (P=0.002) as independent predictors of inferior survival. In a similar multivariable analysis, mutant IDH1 was the only variable associated with shortened leukemia-free survival (P=0.001; hazard ration 7.0, 95% confidence interval 2.3-20.8). The presence of IDH2R140Q did not affect the overall (P=0.54) or leukemia-free (P=0.81) survival. The current study suggests a powerful adverse prognostic effect for mutant IDH1 in MDS.
Asunto(s)
Isocitrato Deshidrogenasa/genética , Mutación , Síndromes Mielodisplásicos/patología , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Síndromes Mielodisplásicos/enzimología , Síndromes Mielodisplásicos/genética , Pronóstico , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Monosomal karyotype (MK) refers to the presence of two or more distinct autosomal monosomies or a single monosomy associated with a structural abnormality. In acute myeloid leukemia, MK has been shown to be prognostically worse than an otherwise complex karyotype. The current study examines whether the same holds true for myelodysplastic syndromes (MDS). A total of 127 MDS patients (median age 70 years) with a complex karyotype were considered; 106 (83%) met the above-stipulated criteria for MK and 21 (17%) had a complex karyotype without monosomies. Survival was significantly inferior in patients with MK compared with those with a complex karyotype without monosomies (P=0.01; HR 1.9, 95% confidence interval (95% CI), 1.1-3.3). Multivariable analysis identified MK (P=0.002), advanced age (P=0.0004) and bone marrow blast percentage (0.04) as independent risk factors for survival. There was no difference in survival among MK patients further substratified by the presence or absence of monosomy 7 and/or monosomy 5. Although not statistically significant, leukemia-free survival was also worse with MK compared with complex karyotype without monosomies (P=0.09; HR 2.7, 95% CI 0.8-9.0). MK in MDS identifies a prognostically worse subgroup of patients with a complex karyotype, regardless of whether monosomy 7 or 5 is part of the MK component.
Asunto(s)
Monosomía , Síndromes Mielodisplásicos/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Deleción Cromosómica , Cromosomas Humanos Par 5 , Cromosomas Humanos Par 7 , Bases de Datos Factuales , Femenino , Humanos , Cariotipificación , Masculino , Síndromes Mielodisplásicos/mortalidad , Pronóstico , Análisis de Supervivencia , Adulto JovenRESUMEN
This study evaluated the contributing roles of flow cytometric immunophenotyping of blood and bone marrow and immunohistochemical paraffin section staining of bone marrow biopsies in the staging of B-cell malignant lymphoma. Flow immunophenotyping was performed on a marrow specimen in 175 cases; a corresponding blood specimen was also immunophenotyped in 135 of these cases. Morphologic marrow involvement by lymphoma was found in 59 cases; flow immunophenotyping identified 54 cases with a monoclonal B-cell process: morphology-positive/flow-positive (n = 49), morphology-positive/flow-negative (n = 10), morphology-negative/flow-positive (n = 5), and morphology-negative/flow-negative (n = 111). The 10 morphology-positive/flow-negative cases included 5 follicular and 5 large-cell lymphomas with minimal marrow involvement. All 5 morphology-negative/flow-positive cases were from patients with large-cell lymphomas and bulky clinical disease. Because the blood contained the same B-cell clone in 2 of 2 morphology-negative/flow-positive cases studied, blood contamination of marrow may account for these findings. Blood flow cytometric immunophenotyping studies were positive in 32 cases; 30 had marrow involvement by morphology and were from patients with follicular, mantle cell, lymphoplasmacytic, small lymphocytic, or marginal zone lymphomas. From our results, we conclude that (1) bone marrow flow cytometric immunophenotyping is not a cost-effective replacement for good morphologic evaluation in lymphoma staging and that (2) a positive peripheral blood flow cytometric immunophenotyping study when performed in low-grade lymphomas correlates with marrow involvement.