RESUMO
High levels of circulating myeloid progenitor cells (CFU-GM) occur during the very early remission phase of acute nonlymphoblastic leukemia (ANLL). Autologous stem cell rescue using blood cells collected during this phase has shown that successful hemopoietic reconstitution can be achieved, but a higher CFU-GM dose appears to be required than when bone marrow cells are used. This suggests that during very early remission, the level of marrow repopulating pluripotent stem cells (PSC) in blood does not undergo the same amount of increase as does the CFU-GM. This study set out to determine whether the levels of the multilineage progenitor cell (CFU-Mix) would be better indicators of the PSC in these cells than the CFU-GM. Serial peripheral blood CFU-Mix and CFU-GM measurements were carried out in six ANLL patients during very early remission. The levels of peripheral blood CFU-Mix showed a mean 12-fold increase, as compared to a mean 20-fold increase in the CFU-GM. The timing of the increase in the CFU-Mix paralleled that of the CFU-GM. These findings suggest that the CFU-Mix is no better than the CFU-GM in predicting PSC levels during very early remission of ANLL, and is closer to the CFU-GM than to the PSC in ontogeny.
Assuntos
Células-Tronco Hematopoéticas/patologia , Leucemia/patologia , Doença Aguda , Contagem de Células Sanguíneas , Ensaio de Unidades Formadoras de Colônias , Granulócitos/patologia , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia/diagnóstico , Leucemia/terapia , Monócitos/patologia , PrognósticoRESUMO
Haemopoietic reconstitution was achieved in a patient with acute non-lymphoblastic leukaemia (ANLL) in relapse who was autografted with blood-derived stem cells collected during very early remission. The patient received a myeloid progenitor cell dose of 230 x 10(4) CFU-GM/kg body weight. Engraftment was evident in the bone marrow 7 days post-graft. Normal neutrophil and platelet counts were attained by day 14 and blood counts remained normal thereafter. An overshoot in peripheral blood haemopoietic progenitor levels occurred at the end of the second week, presumably the progeny of a family of early progenitor cells. The completeness of haemopoietic reconstitution is further illustrated by the satisfactory nucleated cell and myeloid progenitor cell yield when a bone marrow harvest was performed 4 1/2 months post-graft. Seven months post-graft, the patient remained in complete remission with normal blood counts and bone marrow cellularity, although haemopoietic progenitor levels were slightly reduced. The rapid recovery minimises aplasia-related risks and suggests that such autografting can be carried out safely in first remission. We propose that autografting using very early remission blood cells is a new therapeutic option for patients with acute ANLL.
Assuntos
Transplante de Medula Óssea , Leucemia Mieloide Aguda/terapia , Adolescente , Ensaio de Unidades Formadoras de Colônias , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucaférese , Transplante AutólogoRESUMO
Between November 1982 and November 1986 31 patients with acute myeloid leukaemia underwent peripheral blood stem cell apheresis during haemopoietic regeneration following induction chemotherapy. A retrospective analysis of the factors affecting the efficacy of stem cell harvest and of the clinical outcome of these patients was performed. The mean number of myeloid progenitor cells (CFU-GM) collected was significantly higher in the complete remission group (n = 22) than in the partial remission group (n = 9). Fifty x 10(4) CFU-GM/kg body weight or more, which produced rapid, complete and sustained haemopoietic reconstitution after autografting in our patients, were collected from six of nine patients who underwent three or four 7-litre aphereses over 5-7 days using a lymphocyte collection procedure on the Fenwal CS3000 [Protocol B] but only from two of 12 patients who underwent three or four 5-litre aphereses over 3-5 days using the Aminco Celltrifuge [Protocol A] (p less than 0.05). No adverse effects on the rates of neutrophil, platelet and lymphocyte recovery after induction chemotherapy or on long-term disease-free survival for patients who achieved a complete remission could be attributed to apheresis when compared with a historical control group of 39 patients who achieved complete remission following the same induction chemotherapy but did not undergo apheresis. We conclude that sufficient numbers of peripheral blood stem cells to produce safe and rapid haemopoietic reconstitution can be collected from most patients who achieve complete remission using apheresis Protocol B without impairment of haemopoietic recovery or adversely affecting the length of complete remission.
Assuntos
Remoção de Componentes Sanguíneos , Doenças da Medula Óssea/terapia , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Doenças da Medula Óssea/induzido quimicamente , Contagem de Células , Terapia Combinada , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Daunorrubicina/administração & dosagem , Daunorrubicina/efeitos adversos , Estudos de Avaliação como Assunto , Hematopoese , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/complicações , Estudos Retrospectivos , Tioguanina/administração & dosagem , Tioguanina/efeitos adversos , Transplante AutólogoRESUMO
The haematological recovery time, infection rate and supportive care requirements of patients receiving recovery phase autologous peripheral blood stem cell transplants (APBSCT) (n = 38), autologous bone marrow transplants (autoBMT) (n = 13) and allogeneic bone marrow transplants (alloBMT) (n = 14) were compared with respect to the time post-transplant to reach 0.1, 0.5 and 2.0 x 10(9) neutrophils/l and 50 and 150 x 10(9) platelets/l, the length of hospitalization, fever and antibiotic use, the incidence of documented infection and the number of red cell and platelet transfusions. The APBSCT group had a significantly more rapid recovery of neutrophils and platelets and their supportive care requirements were significantly less than the autoBMT and the alloBMT groups. There was no difference between the latter two groups. The most significant variables contributing to the differences in haematological recovery times were the granulocyte-macrophage progenitor (CFU-GM) dose infused and, to a lesser extent, patient age. The APBSCT group received a higher CFU-GM dose of 87 +/- 12 x 10(4)/kg BW compared with 12 +/- 5 and 17 +/- 3 x 10(4)/kg BW in the autoBMT and the alloBMT groups, respectively (p = 0.0001). Patient age showed a negative correlation with the rate of recovery because the APBSCT group, which recovered faster was also older (48 +/- 2 years, compared with 33 +/- 3 and 31 +/- 2, respectively, p = 0.0001). On multivariate analysis, CFU-GM dose was the only variable to show a significant correlation with all the haematological recovery endpoints studied in these 65 patients.(ABSTRACT TRUNCATED AT 250 WORDS)