RESUMEN
High-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) enables dose escalation in the treatment of childhood malignancies. Here we report our experience of using peripheral blood progenitor cells (PBPC) to restore haematopoiesis in five children using a simple cell mobilising regime and non-cryopreservation of the harvests. Cells were mobilised using cyclophosphamide and granulocyte colony stimulating factor. Each patient underwent only two leukaphereses, the product being stored before use at 4 degrees C. Successful autologous PBPC transplantation was achieved with melphalan conditioning chemotherapy and re-infusion of the total progenitor cell product. No colony stimulating factors were administered after transplantation. The median numbers of mononuclear cells collected per patient was 10.0 x 10(8)/kg (range 8.13-19.44) and CFU-GM 57.6 x 10(4)/kg (range 10.4-178.85). All patients subsequently engrafted with the median number of days to a neutrophil count > 0.5 x 10(9)/l being 11 (range 10-16), and to a platelet count > 50 x 10(9)/l being 14 (range 12-31). The median number of in-patient days was only 20 (range 19-30). The median demand for blood was 2 units (range 1-2), and platelets 4 units (range 2-28). Usage of systemic antimicrobials and intravenous feeding was also low. Using this simple strategy, collection and transplantation of autologous progenitor cells can be a straightforward procedure in children. It is possible that this could enable dose escalation in some poor prognosis paediatric tumours.
Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Melfalán/uso terapéutico , Neoplasias/terapia , Adolescente , Transfusión de Sangre Autóloga , Niño , Preescolar , Ciclofosfamida/uso terapéutico , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Leucaféresis , Masculino , Neoplasias/tratamiento farmacológico , Infecciones Oportunistas/tratamiento farmacológico , Resultado del TratamientoRESUMEN
We analysed 57 patients with non-myeloid malignancies who received a non-purged autologous PBSCT. All had similar mobilisation and conditioning regimens. A high prior chemotherapy score and the number of chemotherapy lines used (P = 0.015 and P = 0.01, respectively) were adverse predictors of CD34 cell yields. Lower CD34 values (P = 0.002) were seen in patients treated with potent stem cell toxins (BCNU, melphalan, CCNU and mustine), designated toxicity factor 4 agents (TF4). All patients infused with grafts containing CD34 cell doses between 1.0 and 2.0 x 10(6)/kg (range 1.25-1.90) engrafted by day 51. The only variable associated with slow platelet recovery was exposure to TF4 (P = 0.007). The majority of patients with CD34 >1.0 x 10(6)/kg achieved rapid and sustained engraftment and the only predictive factor of delayed recovery is prior exposure to stem cell toxins. Potential PBSCT candidates should if possible avoid first line and salvage chemotherapy containing TF4 drugs. We therefore advocate a minimum CD34 threshold of >1.0 x 10(6)/kg in patients without extensive prior chemoradiotherapy, and > or = 2.0 x 10(6)/kg in all other patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Hematológicas/terapia , Movilización de Célula Madre Hematopoyética , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/patología , Adolescente , Adulto , Antígenos CD34 , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Recuento de Células Sanguíneas , Carmustina/farmacología , Carmustina/uso terapéutico , Terapia Combinada , Femenino , Neoplasias Hematológicas/sangre , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Lomustina/farmacología , Lomustina/uso terapéutico , Masculino , Mecloretamina/farmacología , Mecloretamina/uso terapéutico , Melfalán/farmacología , Melfalán/uso terapéutico , Persona de Mediana Edad , Trasplante AutólogoRESUMEN
The results from 40 patients who have undergone autologous bone marrow transplantation (ABMT) for relapsed or refractory Hodgkin's disease between March 1988 and September 1992 have been analysed. In contrast to our results in patients with relapsed HD, our results in patients with refractory HD are comparatively poor. Conventional salvage chemotherapy also seems inappropriate in these patients and we therefore believe they should be offered high-dose chemotherapy before their disease becomes refractory to conventionally scheduled regimens. Peripheral blood stem cell (PBSC) transplant now offers an attractive alternative to ABMT and may replace both intensive salvage chemotherapy and ABMT as the optimum treatment for patients who fail to respond to conventional chemotherapy regimens.
Asunto(s)
Trasplante de Médula Ósea/estadística & datos numéricos , Enfermedad de Hodgkin/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea/mortalidad , Terapia Combinada , Resistencia a Medicamentos , Femenino , Enfermedad de Hodgkin/mortalidad , Humanos , Tablas de Vida , Masculino , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Terapia Recuperativa , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Fetal erythroblasts circulating in maternal blood are important candidate cells for non-invasive prenatal diagnosis. We have cultured erythroblasts from 16 maternal blood samples, both with and without prior enrichment by magnetic activated cell sorting (MACS), in a semi-solid medium containing growth factors. Individual colonies were examined by PCR with sex chromosome-specific primers and microsatellite marker primers. No conclusive Y-chromosome specific amplification could be demonstrated in any of the 16 cases, even when the mother was confirmed to be carrying a male fetus. All colonies tested by microsatellite marker PCR were of maternal origin. Our results suggest that the probability of obtaining fetal colonies from fetal erythroblasts circulating in maternal blood is very low and that approaches for culturing fetal erythroblasts in vitro cannot yet be used reliably for prenatal diagnosis using current methods for fetal cell enrichment.