RESUMO
We report a series of 43 consecutive therapy-related myelodysplastic syndromes (t-MDS) or acute myeloid leukemias (t-AML) observed for 6 years. This series consisted of 26 women and 17 men, ages ranging from 9 to 85 years. These cases were classified into three groups according to the primary diagnosis. Conventional cytogenetic and fluorescent in situ hybridization (FISH)/ multiplex FISH (M-FISH) methods were used to analyze cytogenetic characteristics of secondary MDS/AML. The features of chromosomal abnormalities were linked to the nature of the therapy and protocols used. A considerable proportion of recurrent balanced translocations characterized t-AML secondary to therapy. FISH techniques showed that conventional cytogenetics often underestimated associated translocations; some deletions were in fact derivative chromosomes associated with deletions. After treatment for lymphomas and chronic myeloproliferative diseases, there were more complex unbalanced abnormalities than the control group. Compared to other series, recurrent translocations appeared to be more numerous (25%), probably reflecting an evolution of therapeutic modalities.
Assuntos
Hibridização in Situ Fluorescente/métodos , Leucemia Mieloide Aguda/genética , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Amplificação de Genes , Deleção de Genes , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Translocação GenéticaRESUMO
Viral infection is an important cause of morbidity and mortality in the post-allograft period. Recently, a new therapeutic approach was developed in post-transplant lymphoproliferative disorder (PTLD) induced by Epstein-Barr virus (EBV): the anti-CD20 monoclonal antibody or rituximab. We performed a single-center study on the treatment effectiveness of rituximab in three EBV-induced PTLD and evaluated biologic data, such as T and B lymphocytes count, during PTLD development and treatment. Before PTLD treatment, blood cell profile showed a severe T lymphopenia with a progressive increase of CD8+ cells and B lymphopenia. Secondly, during treatment, there appeared a T response, as in primary EBV, and a regressive B lymphopenia.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfócitos B , Transplante de Medula Óssea , Infecções por Vírus Epstein-Barr/sangue , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/imunologia , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/imunologia , Linfócitos T , Anticorpos Monoclonais Murinos , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Criança , Feminino , Humanos , Lactente , Contagem de Linfócitos , Transtornos Linfoproliferativos/sangue , Transtornos Linfoproliferativos/virologia , Masculino , Rituximab , Transplante de Células-Tronco , Imunologia de TransplantesRESUMO
Based on our previous demonstration that quinine could be used clinically to reverse P-glycoprotein-mediated resistance, we designed a multicenter, randomized trial aiming to determine whether quinine would improve the survival of adult patients (15-60 years old) with de novo acute myelogenous leukemia (AML). These patients randomly received (n = 213) or did not receive (n = 212) a 30 mg/kg/day continuous intravenous infusion of quinine in combination with induction chemotherapy combining idarubicine and cytarabine and, depending on bone marrow examination at day 20, an additional course of cytarabine and mitoxantrone. The mean steady-state quinine concentration was 7.8 mg/L and the mean multidrug resistance reversing activity of serum was 1.96. Complete remission (CR) was obtained in 344 patients (80.9%) without significant influence of quinine. Of the patients in complete remission, 82 were assigned to receive HLA-matched bone marrow transplants, whereas 262 were assigned to 2 courses of intensive consolidation chemotherapy, with or without quinine, depending on initial randomization. The 4-year actuarial overall survival (OS) of the 425 eligible patients was 42.0% +/- 2.5%, without significant influence of quinine. Of 160 patients who could be studied, 54 demonstrated rhodamine 123 efflux. In these patients, quinine significantly improved the CR rate from 12 of 25 (48.0%) to 24 of 29 (82.8%) (P =.01). However, there was no significant difference in OS. Neither mdr1 gene nor P-glycoprotein expression influenced the outcome. We conclude that quinine does not improve the survival of adult patients with de novo AML, even though it improves CR rate in a small subgroup of patients defined by rhodamine 123 efflux.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Quinina/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adolescente , Adulto , Citarabina/administração & dosagem , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Leucemia Mieloide Aguda/metabolismo , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Estudos Prospectivos , Quinina/administração & dosagem , Rodamina 123/farmacocinéticaRESUMO
CD4(+)CD56(+) malignancies are rare hematologic neoplasms, which were recently shown to correspond to the so-called type 2 dendritic cell (DC2) or plasmacytoid dendritic cells. This study presents the biologic and clinical features of a series of 23 such cases, selected on the minimal immunophenotypic criteria defining the DC2 leukemic counterpart, that is, coexpression of CD4 and CD56 in the absence of B, T, and myeloid lineage markers. Clinical presentation typically corresponded to cutaneous nodules associated with lymphadenopathy or spleen enlargement or both. Cytopenia was frequent. Circulating malignant cells were often detected. Massive bone marrow infiltration was seen in 20 of 23 (87%) patients. Most tumor cells exhibited nuclei with a lacy chromatin, a blastic aspect, large cytoplasm-containing vacuoles or microvacuoles beside the plasma membrane, and cytoplasmic expansions resembling pseudopodia. Other immunophenotypic characteristics included both negative (CD16, CD57, CD116, and CD117) and positive (CD36, CD38, CD45 at low levels, CD45RA, CD68, CD123, and HLA DR) markers. The prognosis was rapidly fatal in the absence of chemotherapy. Complete remission was obtained in 18 of 23 (78%) patients after polychemotherapy. Most patients had a relapse in less than 2 years, mainly in the bone marrow, skin, or central nervous system. Considering these clinical and biologic features, the conclusion is made that CD4(+)CD56(+) malignancies constitute a genuine homogeneous entity. Furthermore, some therapeutic options were clearly identified. Finally, relationships between the pure cutaneous indolent form of the disease and acute leukemia as well as with the lymphoid/myeloid origin of the CD4(+)CD56(+) malignant cell are discussed.
Assuntos
Antígenos CD4/imunologia , Antígeno CD56/imunologia , Neoplasias Hematológicas/classificação , Neoplasias Hematológicas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígenos CD4/análise , Antígeno CD56/análise , Criança , Pré-Escolar , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/imunologia , Células Neoplásicas Circulantes/imunologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: The various epitopes of the CD34 molecule have been classified according to their different sensitivities to enzymatic cleavage by neuraminidase, chymopapain and a glycoprotease from Pasteurella haemolytica. Although monoclonal antibodies have been developed that specifically identify these epitopes, few studies have evaluated the distribution and quantitative expression of such epitopes on leukemic blasts. DESIGN AND METHODS: We report here a prospective multicenter study in which we examined and quantified the expression of the 3 classes of CD34 on fresh leukemic blast cells from 300 cases of acute myeloid leukemia (AML). The binding of monoclonal antibodies was studied by flow cytometry, allowing evaluation of blast cell positivity as well as their mean fluorescence intensity. These quantitative data were made comparable between centers by means of a calibration curve established with the same reagents in all laboratories. RESULTS: Quantitative expression of class I epitope was significantly higher than that of class II and class III epitopes (p<0.0001). The three classes were more frequently expressed in M0 and M1 and less in M3 and M5. The highest levels of CD34 expression were observed in M2, M0 and M1 and the lowest in M3, M5 and BAL for class II and III. CD34 expression was lower for all classes in cases with a normal karyotype, compared to in cases with structural or numerical abnormalities. INTERPRETATION AND CONCLUSIONS: In cases with a t(9;22) the expression of class I was significantly higher than that of class II and III and the opposite was observed in AML with t(15;17). Moreover, as a whole, a high intensity of class III CD34 appeared to be a marker of good prognosis.