RESUMEN
A retrospective survey of 210 consecutive patients aged ≥ 65 years (median age 69 years, range 65-88 years) with acute myeloid leukemia (AML) diagnosed at a single center over a 6-year period (January 2001 to December 2006) is presented. De novo AML was diagnosed in 179 (85.2 %) patients and 31 (14.7 %) patients had a secondary AML. Twenty-three patients had M0 (11 %), 36 M1 (17.15 %), 57 M2 (27.1 %), eight M3 (3.8 %), 45 M4 (21.4 %), 31 M5 (14.8 %), one M6 (0.5 %), one M7 (0.5 %), and eight patients had unclassified myeloid leukemia (3.8 %) according to French-American-British (FAB) Study Group Classification. Eight patients with M3 (acute promyelocytic leukemia) were excluded from the study. Cytogenetic analysis was performed in 172/202 (85 %) patients. The normal karyotype was found in 81/172 (47 %), high risk aberrations in 32/172 (18.6 %), and favorable karyotype in 13/172 (7.5 %) patients. Supportive and palliative therapies were applied in 115 (56.9 %) patients, a no induction chemotherapy (NIC) group, and 87 (43.1 %) patients received induction chemotherapy (IC group). Complete remission (CR) was achieved in 45/87 (51.7 %) in the IC group and in 5/115 (4.3 %) in the NIC group of patients. After a median follow up of 4 years, 194 (96 %) patients died. The variables significantly associated with a longer overall survival (OS) by univariate analysis were an age of <75 years, a better ECOG performance status (PS) (p = 0.000, CI 95.0 %, 1.358-2.049), a serum LDH activity <600 U/l (p = 0.000, CI 95.0 %, 1.465-2.946), lower white blood cell (WBC) count at diagnosis (p = 0.011, CI 95.0 %, 1.102-2.100), lower comorbidity HCT-CI index (p = 0.000, CI 95 % 2.209-3.458), absence of splenomegaly (p = 0.015, CI 95.0 %, 1.082-2.102) and hepatomegaly (p = 0.008, CI 95.0 %, 1.125-2.171), and no preceding nonhematological malignancy. Multivariate analysis showed that significant factors affecting OS in the IC group were achievement of CR (p = 0.000), the ECOG PS (p = 0.045) and the ECOG PS (p = 0.000), and HCT-CI (p = 0.000) in the NIC group of elderly patients. The present study suggests that a subgroup of elderly patients with both ECOG PS and HCT-CI ≤ 2 at presentation may be eligible for intensive induction chemotherapy.
Asunto(s)
Leucemia Mieloide/tratamiento farmacológico , Cuidados Paliativos , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Transfusión de Componentes Sanguíneos , Aberraciones Cromosómicas , Estudios de Cohortes , Comorbilidad , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Hidroxiurea/uso terapéutico , Inmunofenotipificación , Estimación de Kaplan-Meier , Cariotipificación , Leucemia Mieloide/sangre , Leucemia Mieloide/genética , Leucemia Mieloide/mortalidad , Leucemia Mieloide/patología , Masculino , Inducción de Remisión , Estudios Retrospectivos , Serbia/epidemiología , Resultado del TratamientoRESUMEN
Myeloid sarcoma (MS) is a rare disease that presents as an extramedullary tumor of myeloid cells. Most patients subsequently develop acute myelogenous leukemia (AML), and their prognosis is poor. Here, we report the case of a 28-year-old woman with a primary isolated myeloid sarcoma which originated in the gastrointestinal (GI) tract. Two months after initial presentation, bone marrow tests led to a diagnosis of AML. This case is noteworthy because GI tract infiltration with leukemic cells is very rare, and it is even more rare as an occurrence preceding the development of systemic leukemia.
Asunto(s)
Neoplasias Gastrointestinales/patología , Leucemia Mieloide Aguda/patología , Sarcoma Mieloide/patología , Adulto , Biopsia con Aguja , Progresión de la Enfermedad , Duodeno/patología , Endoscopía Gastrointestinal/métodos , Femenino , Estudios de Seguimiento , Neoplasias Gastrointestinales/diagnóstico , Humanos , Inmunohistoquímica , Intestino Delgado/patología , Leucemia Mieloide Aguda/diagnóstico , Sarcoma Mieloide/diagnóstico , Índice de Severidad de la Enfermedad , Negativa del Paciente al TratamientoRESUMEN
B-Chronic lymphocytic leukaemia (B-CLL) is a monoclonal malignancy characterized by an accumulation of terminally differentiated small and anergic B lymphocytes in the blood, bone marrow and other tissues. CD23 antigen, a trans-membrane glycoprotein, promotes the activation and proliferation of normal B lymphocytes and has an important role in the process of malignant transformation in B-CLL. This retrospective cohort study of 77 consecutive newly diagnosed B-CLL patients, 43 males, 34 females, median age of 62 years, examined CD23 expression and correlations with clinical parameters. CD23+ was negatively correlated with pro-lymphocyte infiltration of the bone marrow (P<0.01) and peripheral blood lymphocyte counts (P<0.001). Lower CD23 expression was correlated with lower serum immunoglobulin levels (P<0.05), especially IgG; while greater CD23 expression was positively correlated with higher CD5 levels. B-CLL patients with a percentage of CD23+ lymphocytes >40% had longer survival (92.8 months) than those expressing <40% (35.3 months) (P=0.001). CD23 is not uniformly expressed by lymphocytes in B-CLL patients, and the differences in expression are dependent on a number of clinical parameters, including the peripheral blood lymphocyte count and the degree of pro-lymphocyte infiltration of the bone marrow. CD23 expression is significantly decreased in patients with extremely high lymphocyte counts (PBL counts of >100 x 10(9)/l) and in the advanced stages of disease.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/inmunología , Receptores de IgE/metabolismo , Adulto , Anciano , Antígenos CD5/metabolismo , Estudios de Cohortes , Femenino , Humanos , Inmunoglobulinas/sangre , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/patología , Leucemia Linfocítica Crónica de Células B/fisiopatología , Linfocitos/inmunología , Linfocitos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
We report on characteristics of the first human cell line, PC-MDS, derived from a bone marrow of a patient with therapy-related myelodysplastic syndrome (t-MDS) who had no overt post-MDS leukemia. Classic cytology analyses, immunophenotyping, cytogenetic and molecular genetic procedures were used for characterization of the cell line. PC-MDS cells are positive for the expression of CD13, CD15, CD30, CD33, and CD45 antigen. Positive cytochemical staining and immunophenotype analyses indicated that PC-MDS cells have some characteristics of the early myeloid precursor cell. The karyotype analysis of PC-MDS cell line revealed various numerical and structural changes including those typically associated with t-MDS: del(5)(q13)[7], der(5)t(5;11)(p11;q11)[13], -7[6], del(7)(q31)[2], +20[3], -20[4]. Evaluation of methylation status in a promoter region of p15, p16 and MGMT genes showed biallelic hypermethylation pattern of 5' promoter region only in MGMT gene. PC-MDS is the first t-MDS derived cell line, and based on its immunological, cytogenetic and molecular characterization could be a new tool in evaluation of complex biology of MDS and a model for methylation studies.
Asunto(s)
Médula Ósea/patología , Síndromes Mielodisplásicos/patología , Células Progenitoras Mieloides/patología , Adulto , Antineoplásicos/uso terapéutico , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/metabolismo , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Genes Codificadores de los Receptores de Linfocitos T/genética , Genes p16 , Humanos , Región Variable de Inmunoglobulina/genética , Inmunofenotipificación , Hibridación Fluorescente in Situ , Cariotipificación , Masculino , Reacción en Cadena de la Polimerasa , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor/genéticaAsunto(s)
Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Poliendocrinopatías Autoinmunes/complicaciones , Aplasia Pura de Células Rojas/tratamiento farmacológico , Adulto , Femenino , Reordenamiento Génico de Linfocito T/genética , Humanos , Mutación , Ácido Micofenólico/uso terapéutico , Poliendocrinopatías Autoinmunes/genética , Reacción en Cadena de la Polimerasa/métodos , Aplasia Pura de Células Rojas/complicaciones , Aplasia Pura de Células Rojas/genética , Factores de Transcripción/genética , Proteína AIRERESUMEN
It has been recognized that some patients with myelodysplastic syndromes (MDS) develop immunologic abnormalities, but little is known of its correlations to MDS-specific disease features. In a retrospective study of 284 MDS patients, we identified 32 patients (11.3%) with clinical or serologic immunological abnormalities (group A) and compared them to the remaining 252 cases (group B). Group A consisted of 20 patients with clinical signs of autoimmune disease and 12 asymptomatic patients with serologic immunological abnormalities only. Apart from significant female predominance in group A (M/F = 2.5 vs M/F = 0.7, p = 0.001), the other clinical and biological features such as median age, distribution of MDS subtypes, incidence of karyotyopic abnormalities, "abnormal" in vitro growth of GM-progenitors and survival times were similar in the two groups. Autoimmune manifestations partially responded to immunosuppressive therapy, with moderate improvement of peripheral cytopenia. In addition, CD3(+), CD4(+), CD8(+), CD19(+), and CD56(+) cells were quantified in peripheral blood of 38 patients. Matched with similarly aged healthy control group, most MDS patients showed significant lymphocytopenia, mainly due to the reduction of T-helper series (in both absolute numbers and percentage). B-cells were reduced in absolute numbers, but their percentage still overlapped with the control. No major abnormalities of natural killer cells (CD56(+)) were seen. We conclude that autoimmune diseases and asymptomatic immunologic abnormalities are common in patients with MDS, but except for female predominance, no correlation between these abnormalities and MDS-specific disease features were found.
Asunto(s)
Autoinmunidad/inmunología , Subgrupos Linfocitarios/citología , Síndromes Mielodisplásicos/inmunología , Factores de Edad , Anciano , Técnicas de Cultivo de Célula/métodos , Citogenética , Citocinas/metabolismo , Femenino , Células Progenitoras de Granulocitos y Macrófagos/metabolismo , Humanos , Inmunofenotipificación , Células Asesinas Naturales/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Acquired amegakaryocytic thrombocytopenia (AATP) in adults is a rare disorder characterized by severe thrombocytopenia and decreased or absent megakaryocytes in an otherwise normal bone marrow. We present a 44-yr-old man in whom the diagnosis of AATP was established in January 2001. Immunophenotyping of the peripheral blood lymphocytes showed a relative increase in the subpopulation of gamma/delta T-cell receptor (TCR) positive (gamma/delta TCR(+)) and (CD4, CD8) negative T lymphocytes, and PCR suggested a monoclonal pattern of TCR gamma chain gene rearrangement. Cytogenetic examination of his bone marrow cells showed a normal male karyotype but RT-PCR analysis revealed a BCR-ABL (p210) fusion transcript. The inhibition of CFU-Mk growth mediated by the patient's T lymphocytes indicated that the pathogenic mechanism for AATP could be an immunological attack on megakaryocyte progenitors where the gamma/delta TCR-positive T lymphocytes are directly involved. The case emphasizes the complex association of T-lymphocyte monoclonal proliferation and AATP.