RESUMEN
A programme of repeated high dose chemotherapy for advanced breast cancer was developed using (1) cyclophosphamide 4 g/m2 followed by autologous peripheral blood stem cell (PBSC) collection; (2) three cycles of conventional dose chemotherapy; (3) high dose cyclophosphamide, cisplatin, and carmustine with PBSC rescue; and (4) high dose etoposide and melphalan with PBSC rescue. Fifteen eligible patients had advanced poor prognosis breast cancer either at initial diagnosis (one patient) or at relapse (14 patients). During the course of the protocol, there were three treatment related deaths, two patient withdrawals due to debilitating toxicity, five patient withdrawals due to disease progression, and one patient withdrawal due to inadequate collection of PBSC. The remaining four patients did not complete the planned protocol as the programme was terminated because of the unacceptable morbidity and mortality. They were treated with an alternative high dose chemotherapy protocol which was well tolerated. This study highlights the significant problems associated with a complex sequential high dose chemotherapy regimen. Cyclophosphamide mobilized PBSC infused following high dose chemotherapy enables rapid haematological recovery. However the non-haematological toxicity following high dose chemotherapy regimens is often severe and may limit the application of certain sequential high dose chemotherapy combinations in patients with breast cancer.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Médula Ósea , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/cirugía , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Transfusión Sanguínea , Terapia Combinada , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Persona de Mediana Edad , Trasplante AutólogoRESUMEN
Between April 1988 and March 1994 a total of 23 patients with haematological or non-haematological malignancies received serial peripheral blood stem cell (PBSC) mobilization to attain sufficient harvest for PBSC transplant at our institution. There was no improvement in yield with the second mobilization for group A patients (n = 12) who had the same dose of cyclophosphamide twice as mobilizing agent. For group B patients (n = 6). who had a higher dose of cyclophosphamide with the second mobilization, there was significant increase in CFU-GM yield. CD34+ cell yield was not measured. For group C patients, who received interleukin-3 plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with the first mobilization and chemotherapy plus GM-CSF with the second, there was significant increase in CFU-GM as well as CD34+ cell yield. Our results demonstrate that, at the doses studied, chemotherapy dose escalation and combining haemopoietic growth factor with chemotherapy improve progenitor cell yield in PBSC mobilization.
Asunto(s)
Neoplasias de la Mama/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/efectos de los fármacos , Linfoma no Hodgkin/terapia , Mieloma Múltiple/terapia , Neoplasias Ováricas/terapia , Adulto , Anciano , Eliminación de Componentes Sanguíneos/métodos , Neoplasias de la Mama/sangre , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Linfoma no Hodgkin/sangre , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Neoplasias Ováricas/sangre , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
We used cyclophosphamide at a dose of 7 g/m2 in patients with advanced cancer and compared the efficacy of this treatment to generate peripheral blood stem cells (PBSC) with the previously reported regimen of cyclophosphamide 4 g/m2 in a similar group of patients. None of these patients received haemopoietic growth factors. Twenty-two patients received 7 g/m2 and 37 received 4 g/m2. PBSC were collected by apheresis after the leukocyte count recovered to 1.0 x 10(9)/L. The yield of colony forming unit-granulocyte macrophage (CFU-GM) was higher for the 7 g/m2 group with a median of 35 x 10(4)/kg versus 15 x 10(4)/kg body weight (BW) (p < 0.05) and higher mononuclear cell yield with medians of 4.2 x 10(8)/kg compared with 3.1 x 10(8)/kg BW (p < 0.001). The percentage of patients achieving the minimum safe level of > 15 x 10(4) CFU-GM/kg BW was higher in the 7 g/m2 cyclophosphamide group (82%) than the 4 g/m2 cyclophosphamide group (51%). The duration of significant neutropaenia was a median of 11 compared with nine days (p < 0.004) and all patients receiving 7 g/m2 required admission to hospital and intravenous antibiotic therapy compared with 44% in the 4 g/m2 group. There was one death during the period of neutropaenia after cyclophosphamide in each group. Nineteen per cent of patients required platelet transfusions after cyclophosphamide 7 g/m2 compared with 18% after 4 g/m2. We conclude that the 7 g/m2 cyclophosphamide gives a higher yield of haemopoietic progenitor cells than the 4 g/m2 but at increased clinical toxicity.
Asunto(s)
Ciclofosfamida/administración & dosificación , Células Precursoras Eritroides/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Neutropenia/epidemiología , Academias e Institutos , Ciclofosfamida/efectos adversos , Ciclofosfamida/farmacología , Células Precursoras Eritroides/química , Fiebre/inducido químicamente , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/química , Mortalidad Hospitalaria , Humanos , Recuento de Leucocitos , Neutropenia/sangre , Neutropenia/inducido químicamente , Recuento de Plaquetas , Australia del Sur/epidemiología , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología , Trombocitopenia/terapia , Factores de TiempoRESUMEN
The collection efficiency (CE) of the Fenwal CS3000 in collecting peripheral blood stem cells during post-chemotherapy recovery phase ranges from 58% to 73%. Recently filgrastim (recombinant methionyl human granulocyte colony-stimulating factor [G-CSF]) has also been shown to be effective as a mobilization agent although mobilization occurs during elevated and not low normal leukocyte counts. We compared the mononuclear cell (MNC) CE and the myeloid progenitor cell (CFU-GM) CE among 11 patients with G-CSF mobilization (33 procedures) and 19 patients during recovery following myelosuppression chemotherapy (93 procedures). Pre-apheresis leukocyte, neutrophil, MNC, and PB CFU-GM counts were significantly higher in the G-CSF group, while the granulocyte percentage in the apheresis products was similar in both groups. Both MNC CE (81.8 +/- 4.5% vs. 64 +/- 2.4%) and CFU-GM CE (79.5 +/- 10.5% vs. 55.8 +/- 3.5%) were higher in the G-CSF group. Only the pre-apheresis MNC count showed an independently significant correlation for both CE (P < .001). The higher CE in the G-CSF group can only be partly explained by a rise in MNC count during apheresis. These data suggest that the blood cell separator works better with leukocytosis, and especially with a higher MNC count. The improvement in CE is another benefit of G-CSF mobilization over chemotherapy mobilization.