Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50 percent of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

Leucemia M3 variante: aspectos clínicos e diagnósticos / M3 variant leukemia: clinical and diagnosis features

A leucemia promielocítica (LMA M3) representa em média 5-10// dos casos de leucemias melóides agudas (LMA) registrados na literatura, acometendo preferencialmente adultos jovens e cursando com comportamento clínico-biológico distinto, quando comparada com as demais LMA. Caracteriza-se por morfolofia particular das células blásticas (M3 na classificaçäo FAB), translocaçäo dos cromossomos 15 e 17, e coagulaçäo intravascular disseminada ao diagnóstico ou após início da quimioterapia . Dentro deste subgrupo säo observados dois subtipos morfológicos conhecidos como LMA M3 hipergranular e LMA M3 hipogranular ou variante. Os autores analisaram 19 casos de LMA M3, diagnosticados dentre 217 casos de LMA, em seus aspectos clínicos e laboratoriais, e observaram que o reconhecimento da LMA M3 variante, apesar de se basear geralmente apenas em dados citomorfológicos, näo tem sido feito corretamente em nosso meio. Dos oito casos recebidos no serviço dos autores para estudo, apenas quatro foram encaminhados com o diagnóstico correto de seus serviços de origem, sendo os outros quatro casos diagnosticados como leucemia mielomonocítica (LMA M4). A imunofenotipagem, como técnica diagnóstica complementar à citomorfologia, permite esclarecer, definitivamente, casos duvidosos. A classificaçäo correta se faz cada vez mais necessária devido a aspectos terapêuticos e prognósticos particulares das LMA M3, que, ao contrário das outras formas de LMA, têm sido tratadas näo só com drogas citotóxicas, mas também com agentes indutores de diferenciaçäo celular, com excelentes resultados

The significance of phenotyping leukemias using monoclonal antibodies

1. Acute leukemias have been defined as major types as of lymphoblastic and myeloblastic leuckemias according to morphological and cytochemical criteria. 2. The thecnical improvements and standardization of immunofluorescence and immunocytology staining methods have provied new insights for classifying these disorders on the basis of monoclonal antibodies. 3. The scheme used to describe normal lymphoid and myeloid differentiation, when also used to describe their malignant counterparts, provides a well-established model for the immunological classification of acute leukemias. 4. In this review article, we suggest some guidelines for performing a series of cytochemical reactions using immunological markers to ensure a reliable diagnosis of acute leukemia