RESUMO
Eighty-nine patients were transplanted with allogeneic bone marrow after a standard conditioning regimen consisting of cyclophosphamide and fractionated total body irradiation (2 x 4.5 Gy) with average dose rates of 4.1 and 12.3 cGy/min, respectively. The average rectum and lung dose was 9.2 +/- 0.45 and 7.5 +/- 0.78 Gy. In vivo dosimetry was performed in 71 patients irradiated with 18 MV X-rays from left and right lateral. Forty-three patients (48%) died. After increasing the dose rate the incidence of interstitial pneumonitis increased, but the number of relapses decreased.
Assuntos
Anemia/radioterapia , Transplante de Medula Óssea , Leucemia/radioterapia , Síndromes Mielodisplásicas/radioterapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Irradiação Corporal Total/métodos , Adolescente , Adulto , Anemia/tratamento farmacológico , Anemia/cirurgia , Transplante de Medula Óssea/efeitos adversos , Terapia Combinada , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Leucemia/tratamento farmacológico , Leucemia/cirurgia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/cirurgia , Países Baixos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Prognóstico , Dosagem Radioterapêutica , Irradiação Corporal Total/efeitos adversosAssuntos
Interferon Tipo I/uso terapêutico , Leucemia de Células Pilosas/terapia , Adulto , Idoso , Contagem de Células Sanguíneas , Medula Óssea , Avaliação de Medicamentos , Feminino , Humanos , Interferon Tipo I/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêuticoRESUMO
Bone marrow cells of five patients with acute myeloid leukemia were fractionated by means of counterflow centrifugation (elutriation). The different fractions were enriched with cells belonging to subsequent stages of the cell cycle. Cytokinetic evaluation of these cell fractions was performed by [3H]thymidine autoradiography, [3H]thymidine incorporation and DNA/RNA-flow cytometry. Phosphorylation of cytosine arabinoside (ara-C, 1-beta-D-arabinofuranosylcytosine) in the different fractions was measured by incubation of the cells for 30 min with 1.07 microM [3H]ara-C. Phosphorylation of ara-C in the whole bone marrow samples ranged from 5.9 to 33.2 pmol/10(6) cells. In the fractions containing only G1-phase cells, phosphorylation ranged from 1.2 to 19.5 pmol/10(6) cells. The phosphorylation seems to increase before DNA synthesis starts. Maximal activities were found in the fractions enriched with cells in late G1- or S-phase of the cell cycle. In these fractions the ara-C phosphorylating activity was 1.5-8 times higher compared to the fractions with the lowest activity. One may therefore assume that not only S-phase cells are killed by ara-C, but that G1-phase cells which can phosphorylate ara-C, may also be doomed when they enter S-phase, since the elimination of the intracellular cytosine arabinoside tri-phosphate (ara-CTP) is a relatively slow process. The fraction of G1-phase cells phosphorylating ara-C, may be an important determinant in the extent of the cell-killing effect of ara-C treatment in the different leukemias.
