RESUMEN
OBJECTIVE: To describe activities in the field of autologous stem cell transplantation in haematological disorders in the Netherlands in the periods before and after 1993 (at that time blood was introduced as source of stem cells). DESIGN: Descriptive, retrospective cohort study. METHOD: Data were collected from the Netherlands Stem Cell Transplantation Registry TYPHON. Details of all transplant patients were reported to TYPHON by the individual transplantation centres. In this overview we describe the changes in transplantation-related mortality, relapse rates and survival in the periods 1 January 1980-31 December 1992 and 1 January 1980-31 December 2002. RESULTS: The number of autologous stem cell transplantations increased almost five-fold in the period 1993-2002. Since 1993 the main indications for transplantation were multiple myeloma (MM) and non-Hodgkin lymphoma (NHL), as well as acute myeloid leukaemia (AML), which was the main indication in the period before 1993. In the period before 1993 most relapses were observed in patients with acute lymphoblastic leukaemia (ALL) and MM, which resulted in low survival rates. After 1993 no great differences in relapse or survival rates were observed between the different disorders. The survival rates for patients with ALL improved during the last research period, especially among younger patients (< 45 years). CONCLUSION: The number of autologous stem cell transplantations has increased considerably since 1993, especially in patients with MM and NHL.
Asunto(s)
Enfermedades Hematológicas/mortalidad , Enfermedades Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia , Trasplante Autólogo , Adulto JovenAsunto(s)
Leucemia/terapia , Trasplante de Células Madre/métodos , Trasplante de Células Madre/estadística & datos numéricos , Donantes de Tejidos , Adolescente , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Donantes de Tejidos/estadística & datos numéricos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
Erythropoietin has been shown to shorten survival in cancer patients under certain circumstances. Possible mechanisms are an increase in thrombotic events, tumour progression, and induction of angiogenesis. The FDA advises its use in oncology only as a replacement for blood transfusions in patients receiving chemotherapy. In these patients, a rise in haemoglobin above 7.4 mmol/l should be avoided.
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Eritropoyetina/efectos adversos , Neoplasias/complicaciones , Neovascularización Patológica/inducido químicamente , Trombosis/inducido químicamente , Anemia/tratamiento farmacológico , Anemia/etiología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Eritropoyetina/uso terapéutico , Humanos , Neoplasias/tratamiento farmacológico , Neovascularización Patológica/prevención & control , Análisis de Supervivencia , Trombosis/prevención & control , Resultado del TratamientoRESUMEN
Fatigue is a highly prevalent and debilitating symptom in cancer survivors. The aim of this study was to assess the impact of fatigue and other cancer-related symptoms on the return to work of cancer survivors. A prospective inception cohort study with 12 months of follow-up was initiated. At 6 months following the first day of sick leave, levels of fatigue, depression, sleep problems, physical complaints, cognitive dysfunction and psychological distress were assessed, in addition to clinical, sociodemographic and work-related factors. Data were obtained from one academic hospital and two general hospitals in the Netherlands. 235 patients who had a primary diagnosis of cancer and underwent treatment with curative intent were included. The rate of return to work was measured at 6, 12 and 18 months. Hazard ratios (HRs) for the duration of sick leave up to 18 months following the first day of sick leave were calculated. The rate of return to work increased from 24% at 6 months to 64% at 18 months following the first day of sick leave. Fatigue, diagnosis, treatment type, age, gender, depression, physical complaints and workload were all related to the time taken to return to work. Fatigue scores were also strongly related to diagnosis, physical complaints, and depression scores. Fatigue at 6 months predicted a longer sick leave with a hazard ratio of 0.71 (95% Confidence Interval (C.I.) 0.59-0.85), adjusted for diagnosis, treatment type, age and gender. In a multivariate Cox regression analysis, diagnosis, treatment, age, physical complaints and workload remained the only significant predictors of duration of the sick leave. 64% of cancer survivors returned to work within 18 months. Fatigue levels predicted the return to work. This was independent of the diagnosis and treatment, but not of other cancer-related symptoms. Better management of cancer-related symptoms is therefore needed to facilitate the return to work of cancer patients.
Asunto(s)
Fatiga/rehabilitación , Neoplasias/rehabilitación , Trabajo , Adulto , Estudios de Cohortes , Fatiga/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Estudios Prospectivos , Rehabilitación Vocacional , Ausencia por Enfermedad/estadística & datos numéricos , Análisis de Supervivencia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Stem cell doses necessary for engraftment after myelo-ablative therapy as defined for fresh transplants vary largely. Loss of CD34+ cell quality after cryopreservation might contribute to this variation. With a new early apoptosis assay including the vital stain Syto16, together with the permeability marker 7-AAD, CD34+ cell viability in leucapheresis samples of 49 lymphoma patients receiving a BEAM regimen was analysed. After freeze-thawing large numbers of non-viable, early apoptotic cells appeared, leading to only 42% viability compared to 72% using 7-AAD only. Based on this Syto16 staining in the frozen-thawed grafts, threshold numbers for adequate haematological recovery of 2.8-3.0 x 10(6) CD34+ cells/kg body weight determined for fresh grafts, now decreased to 1.2-1.3 x 10(6) CD34+ cells/kg. In whole blood transplantation of lymphoma patients (n = 45) receiving a BEAM-like regimen, low doses of CD34+ cells were sufficient for recovery (0.3-0.4 x 10(6)CD34+ cells/kg). In contrast to freeze-thawing of leucapheresis material, a high viability of CD34+ cells was preserved during storage for 3 days at 4 degrees C, leaving threshold doses for recovery unchanged. In conclusion, the Syto16 assay reveals the presence of many more non-functional stem cells in frozen-thawed transplants than presumed thus far. This led to a factor 2.3-fold adjustment downward of viable CD34+ threshold doses for haematological recovery.
Asunto(s)
Apoptosis , Criopreservación , Trasplante de Células Madre Hematopoyéticas/normas , Células Madre Hematopoyéticas/citología , Antígenos CD34/análisis , Recuento de Células , Supervivencia Celular , Hematopoyesis , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/inmunología , Humanos , Leucaféresis/métodos , Leucaféresis/normas , Linfoma no Hodgkin/terapia , Juego de Reactivos para Diagnóstico , Acondicionamiento Pretrasplante , Trasplante Autólogo/métodos , Trasplante Autólogo/normasRESUMEN
Thrombotic microangiopathy is an acute and severe syndrome characterised by a combination of thrombocytopenia, haemolytic anaemia with a negative direct antiglobulin test, and fragmentocytes in the blood smear. The condition can be idiopathic but can also be caused by various underlying diseases. The main causes are thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. By measuring the von Willebrand factor cleaving protease activity, it now appears possible to distinguish between the different causes of thrombotic microangiopathy, although the sensitivity and specificity of this measurement still need to be clarified. In patients with haemolytic uraemic syndrome without preceding diarrhoea, one should search for infectious foci outside the gastrointestinal tract, using a polymerase-chain reaction to detect the two different verotoxin genes where necessary. Plasmapheresis treatment has reduced the fatality rate amongst patients with thrombotic thrombocytopenic purpura from 90% to 10-25%. Since patients benefit most from rapid institution of treatment, yet the diagnostics currently take several days, the recommendation in case of doubt regarding the original diagnosis is to apply initial plasma exchange therapy to all patients with thrombotic microangiopathy.
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Síndrome Hemolítico-Urémico/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Trombosis/etiología , Proteínas ADAM , Proteína ADAMTS13 , Síndrome Hemolítico-Urémico/terapia , Humanos , Metaloendopeptidasas/sangre , Metaloendopeptidasas/metabolismo , Intercambio Plasmático , Recuento de Plaquetas , Púrpura Trombocitopénica Trombótica/terapia , Sensibilidad y Especificidad , Trombosis/terapia , Factor de von Willebrand/metabolismoRESUMEN
In two patients with multiple myeloma, men aged 72 and 54 years, diarrhoea developed upon chemotherapy with vincristin, doxorubicin and dexamethasone (VAD). In the second patient, diarrhoea developed after subsequent peripheral stem cell mobilisation. Pseudomembranous colitis was seen in the first patient during endoscopy but an enzyme immunoassay of the faeces was false negative for Clostridium difficile enterotoxin. The bacterium was later cultured from stool samples and toxins were detected in a repeated immunoassay. Stool samples of the second patient were positive for C. difficile enterotoxin. For both patients an antibiotic treatment resulted in a rapid recovery. In haemato-oncological patients, diarrhoea is often caused by oncolytic therapy. However, consideration should also be given to C. difficile infection as an alternative cause which is easily treatable.
Asunto(s)
Antibacterianos/administración & dosificación , Clostridioides difficile/aislamiento & purificación , Diarrea/microbiología , Enterocolitis Seudomembranosa/microbiología , Mieloma Múltiple/tratamiento farmacológico , Anciano , Antibacterianos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Clostridioides difficile/patogenicidad , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Enterocolitis Seudomembranosa/complicaciones , Enterocolitis Seudomembranosa/tratamiento farmacológico , Humanos , Masculino , Metronidazol/administración & dosificación , Persona de Mediana Edad , Resultado del Tratamiento , Vancomicina/administración & dosificación , Vincristina/uso terapéuticoRESUMEN
Examining peripheral blood smears provides valuable information in the diagnosis of anaemia despite large inter- and intraobserver variation. The classification of anaemia is usually based on the average erythrocyte size, referred to as the mean corpuscular volume (MCV). Microcytosis indicates a reduced haemoglobin synthesis caused by either an iron deficiency or haemoglobinopathy, a congenital disorder. Macrocytosis is the result of a disruption to the division and maturing of proerythroblasts in the bone marrow, due, for example, to vitamin B12 (folic acid) deficiency or excessive alcohol use. Furthermore, a high number of reticulocytes in the blood indicates an increased production of erythrocytes whereas a low total indicates an inadequate production level. In addition to the case history and the physical examination, the MCV and number of reticulocytes can provide guidance with respect to further diagnostic investigation.
Asunto(s)
Anemia/diagnóstico , Recuento de Eritrocitos/métodos , Algoritmos , Anemia/clasificación , Diagnóstico Diferencial , Índices de Eritrocitos , Humanos , Internet , Recuento de ReticulocitosRESUMEN
Patients with multiple myeloma (MM) refractory to alkylating agents frequently express P-glycoprotein (Pgp), which is associated with the multidrug resistance (MDR) phenotype. We have conducted a randomized phase II/III study of the MDR reversal agent cyclosporin A combined with VAD (vincristine, doxorubicin, dexamethasone) compared with standard VAD in patients with MM stage IIA/IIIA who were refractory to or progressive after treatment with alkylating agents. Out of 81 patients who were randomized, 75 were eligible and evaluable: 34 in the VAD + cyclosporin A arm versus 41 in the VAD arm. Toxicities of grade 2-3 were observed more often with VAD + cyclosporin A than with VAD only: nausea (30% versus 8%, P = 0.015), mucositis (18% versus 5%, P = 0.13), infection (45% versus 35%, P = 0.50). The treatment results were similar in the two arms: 53% versus 49% responded [95% CI (-18.5%, 26.9%)]. The median progression-free survival (PFS) was 8.6 months (VAD + cyclosporin A) versus 5.8 months (VAD): [log rank P = 0.16, hazard ratio = 0.71, 95% CI (0.44, 1.15)], and median overall survival was 13 months versus 14.6 months [log rank P = 0.89, hazard ratio = 0.96, 95% CI (0.62, 1.72)]. The cause of death was progressive disease (85%), toxicity (10%) or other (5%). Bone marrow analysis performed in 23 patients showed that the response rate was 67% in Pgp-positive versus 55% in Pgp-negative patients. Cyclosporin A combined with VAD is relatively well tolerated. There is no effect of cyclosporin A on the overall response rate, PFS and overall survival with VAD.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclosporina/administración & dosificación , Resistencia a Múltiples Medicamentos , Mieloma Múltiple/tratamiento farmacológico , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Anciano , Distribución de Chi-Cuadrado , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/metabolismo , Mieloma Múltiple/mortalidad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tasa de Supervivencia , Vincristina/administración & dosificaciónAsunto(s)
Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Aneuploidia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Actitud del Personal de Salud , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Manejo de Caso , Niño , Preescolar , Aberraciones Cromosómicas , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Resistencia a Antineoplásicos , Femenino , Humanos , Inmunofenotipificación , Lactante , Masculino , Proteínas de Fusión Oncogénica/análisis , Proteínas de Fusión Oncogénica/genética , Cromosoma Filadelfia , Médicos/psicología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Pronóstico , Pubertad , Factores de Riesgo , Translocación Genética , Resultado del TratamientoRESUMEN
The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS). Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic repopulation and enhance the efficacy of chemotherapy. In a prospective randomized multicentre phase II trial, a total of 64 patients with poor risk primary MDS were randomized to receive either granulocyte colony-stimulating factor (G-CSF, filgrastim, AMGEN, Breda, The Netherlands) 5 microg/kg/day subcutaneously or no G-CSF in addition to daunomycin (30 mg/m2/days 1, 2 and 3 intravenous bolus) and cytarabine (200 mg/m2 days 1-7, continuous infusion). The overall complete response rate was 63%: 73% for patients receiving filgrastim as compared to 52% in the standard arm (P = 0.08). Overall survival at 2 years was estimated at 29% for patients assigned to the filgrastim arm and 16% for control patients (P = 0.22). The median time for recovery of granulocytes towards 1.0 x 10(9)/l post-chemotherapy was 23 days in the filgrastim-treated patients vs 35 days in the standard arm (P = 0.015). There were no differences in time of platelet recovery, length of hospital stay, duration of antibiotic use or infectious complications between the two treatment groups. However the earlier recovery of neutrophils in the filgrastim group was associated with a reduced interval of 9 days between the induction and consolidation cycle. In patients with poor risk MDS the use of filgrastim during and after induction therapy results in a significantly reduced neutrophil recovery time. Further study may be warranted to see if the apparent trend of the improved response to chemotherapy in combination with filgrastim can be confirmed in greater number of patients and to assess the effect of the addition of filgrastim on survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Hematopoyesis/efectos de los fármacos , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/patología , Síndromes Mielodisplásicos/fisiopatología , Pronóstico , Proteínas Recombinantes , Inducción de RemisiónRESUMEN
The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34+ cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 microg/m2) during an average of 20 days. Higher dose regimens of G-CSF (450 microg/m2 and 600 microg/m2) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34+ cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery.
Asunto(s)
Trasplante de Médula Ósea , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide/terapia , Enfermedad Aguda , Adolescente , Adulto , Anciano , Antígenos CD34 , Antineoplásicos Alquilantes/uso terapéutico , Busulfano/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Movilización de Célula Madre Hematopoyética , Humanos , Masculino , Persona de Mediana Edad , Acondicionamiento Pretrasplante , Trasplante AutólogoRESUMEN
Interleukin 6 plays a key role in the pathogenesis of multiple myeloma (MM). Therefore we conducted a phase I dose-escalating study with chimaeric monoclonal anti-IL6 antibodies (cMab) in MM patients resistant to second-line chemotherapy. The cMab (CLB IL6/8; Kd 6.25 x 10(-12)M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28, repectively, with a daily dose of 5 mg in patients 1-3, 10 mg in patients 4-6, 20 mg in patients 7-9 and 40mg in patients 10-12 (total dose 140 mg, 280mg, 560 mg and 1120 mg of anti-IL6, respectively). 11/12 patients had elevated pretreatment IL6 levels. Except for transient thrombocytopenia in two patients there was no toxicity. There were no changes in haemoglobin levels, granulocyte count, liver enzymes or renal function. No human anti-chimaeric antibodies were induced. This was also reflected in a long half-life time of the cMab (median 17.8 d), resulting in accumulation of the anti-IL6 cMab and high levels of circulating IL6. However, this was in the form of biologically inactive IL6/cMab complexes and did not result in acceleration of the disease. Although C-reactive protein (CRP) levels were decreased to below detection level in 11/12 patients, indicating effective IL6 blocking, none of the patients achieved a response according to the standard criteria. We conclude that this chimaeric anti-IL6 Mab has a low toxicity, low immunogenicity and a long T1/2. A dose of 40 mg/d for 14 d can safely be used in future phase II studies.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Interleucina-6/administración & dosificación , Mieloma Múltiple/terapia , Proteínas Musculares , Anciano , Agranulocitosis/etiología , Anticuerpos Monoclonales/análisis , Anticuerpos Monoclonales/farmacocinética , Proteína C-Reactiva/análisis , Conectina , Relación Dosis-Respuesta Inmunológica , Femenino , Semivida , Humanos , Interleucina-6/inmunología , Interleucina-6/farmacocinética , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Proteínas de Mieloma/análisis , Proteínas Recombinantes de Fusión , Análisis de Supervivencia , Trombocitopenia/etiología , Resultado del Tratamiento , Microglobulina beta-2/análisisRESUMEN
PURPOSE AND METHODS: Optimization of remission-induction and postremission therapy in elderly individuals with acute myeloid leukemia (AML) was the subject of a randomized study in patients older than 60 years. Remission-induction chemotherapy was compared between daunomycin (DNR) 30 mg/m2 on days 1, 2, and 3 versus mitoxantrone (MTZ) 8 mg/m2 on days 1, 2, and 3, both plus cytarabine (Ara-C) 100 mg/m2 on days 1 to 7. Following complete remission (CR), patients received one additional cycle of DNR or MTZ chemotherapy and were then eligible for a second randomization between eight cycles of low-dose (LD)-Ara-C 10 mg/m2 subcutaneously every 12 hours for 1 2 days every 6 weeks or no further treatment. RESULTS: A total of 242 patients was randomized to DNR and 247 to MTZ. Median age of both study groups was 68 years. Secondary AML was documented in 26% and 25% of patients in either arm. The probability of attaining CR was greater (P = .069) with MTZ (47%) than with DNR (38%). Median duration of neutropenia was 19 (DNR) and 22 days (MTZ). The greater response rate to MTZ therapy correlated with reduced occurrence of chemotherapy resistance (32% v 47%, P = .001). With a median follow-up of 6 years, 5-year disease-free survival (DFS) is 8% in each arm. Overall survival estimates are not different between the groups (6% v 9% at 5 yrs). Poor performance status at diagnosis, high WBC count, older age, secondary AML, and presence of cytogenetic abnormalities all had an adverse impact on survival. Secondary AML and abnormal cytogenetics predicted for shorter duration of CR. Among complete responders, 74 assessable patients were assigned to Ara-C and 73 to no further therapy. Actuarial DFS was significantly longer (P = .006) for Ara-C-treated (13% [SE = 4.0%] at 5 years) versus nontreated patients (7% [SE = 3%]), but overall survival was similar (P = .29): 18% (SE = 4.6%) versus 15% (SE = 4.3%). Meta-analysis on the value of Ara-C postremission therapy confirms these results. CONCLUSION: In previously untreated elderly patients with AML, MTZ induction therapy produces a slightly better CR rate than does a DNR-containing regimen, but it has no significant effect on remission duration and survival. Ara-C in maintenance may prolong DFS, but it did not improve survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Daunorrubicina/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Mitoxantrona/administración & dosificación , Enfermedad Aguda , Anciano , Citarabina/administración & dosificación , Daunorrubicina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mitoxantrona/efectos adversos , Pronóstico , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
PURPOSE: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. MATERIALS AND METHODS: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). RESULTS: The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. CONCLUSION: Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.
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Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Recuento de Células Sanguíneas , Supervivencia sin Enfermedad , Estudios de Evaluación como Asunto , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Factores de Tiempo , Resultado del TratamientoRESUMEN
The case is described of a 42-year-old patient with acute myeloid leukemia who received two courses of chemotherapy complicated by prolonged bone marrow depression. He was admitted to hospital with fever, hepatosplenomegaly and bilateral nodular pulmonary infiltrates. After admission diffuse cutaneous skin nodules, and hypodense lesions in the hemispheres and cerebellum developed. Cultures of cerebrospinal fluid, bronchoalveolar lavage fluid, skin biopsy specimens and blood revealed Scedosporium prolificans, indicative of disseminated mycosis. Treatment with amphotericin B and fluconazole was unsuccessful and the patient died within five days after admission. Features that may enhance early recognition of Scedosporium prolificans infection by both clinicians and microbiologists, as well as options in the treatment of infection with this fungal agent are discussed.
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Dermatomicosis/microbiología , Leucemia Mieloide/complicaciones , Hongos Mitospóricos/aislamiento & purificación , Infecciones Oportunistas/microbiología , Enfermedad Aguda , Adulto , Dermatomicosis/diagnóstico , Dermatomicosis/patología , Resultado Fatal , Humanos , Huésped Inmunocomprometido , Masculino , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/patologíaRESUMEN
Since 1990, Pneumocystis carinii pneumonia (PCP) was diagnosed in 15 adult HIV-negative haematologic patients in our hospital. None of them had received PCP prophylaxis. All except one had been treated with prednisone. Symptoms usually started after stopping or tapering. In six patients the diagnosis of PCP was delayed because of confounding bacterial isolates from blood, sputum or urine leading to unsuccessful antibiotic treatment. PCP was diagnosed by demonstrating pneumocysts in bronchoalveolar lavage fluid. In four patients additional fungal or viral pathogens were identified. The infections were not clustered. The patients were treated with co-trimoxazole and, in case of a pO2 < 60 mmHg, with prednisone. Three patients died (20%); they all had a coinfection with cytomegalovirus and/or aspergillus. The others recovered completely. There were no relapses. Primary PCP prophylaxis should be considered in patients with lympho-proliferative disease and exposure to prednisone.
Asunto(s)
Seronegatividad para VIH , Enfermedades Hematológicas/complicaciones , Neumonía por Pneumocystis/diagnóstico , Adulto , Anciano , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Antiinflamatorios/uso terapéutico , Infecciones Bacterianas/sangre , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/orina , Líquido del Lavado Bronquioalveolar/microbiología , Diagnóstico Diferencial , Femenino , Enfermedades Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Micosis/complicaciones , Neumonía por Pneumocystis/complicaciones , Neumonía por Pneumocystis/tratamiento farmacológico , Prednisona/uso terapéutico , Recurrencia , Esputo/microbiología , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Virosis/complicacionesRESUMEN
PURPOSE: To investigate the value of intensive consolidation chemotherapy not followed by maintenance therapy in adult acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A multicenter phase II trial was conducted in 130 adult patients with ALL between 16 and 60 years of age. After standard induction therapy, postinduction chemotherapy was given: three courses of high-dose cytarabine (2,000 mg/m2 every 12 hours for four doses) in combination with amsacrine (course one), mitoxantrone (course two), and etoposide (course three). CNS prophylaxis consisted of 10 injections of intrathecal methotrexate (IT MTX). Patients younger than 50 years with an HLA-identical sibling were eligible to receive allogeneic bone marrow transplantation (BMT). RESULTS: Ninety-five patients (73%) achieved complete remission (CR); 82% were younger than 50 years and 41% were older than 50 years. Seventeen patients (13%) were resistant to chemotherapy, and 18 (14%) died during induction treatment. Only age and performance status were significantly associated with response (P<.001 and .03, respectively). Death during consolidation occurred in four patients. The estimated 5-year overall survival (OS) was 22% for the entire group and 26% for patients younger than 35 years. Disease-free survival (DFS) at 5 years was 28% +/- 6 for patients younger than 35 years, 25% +/- 9 for patients between 35 and 50 years, and 0% for patients older than 50 years. Increasing age (P<.01) and expression of CD34 (P<.01) were adverse factors. Only three patients (3%) developed an isolated CNS relapse. CONCLUSION: Intensive consolidation including high-dose cytarabine not followed by maintenance therapy provides an outcome for adult patients with ALL that may be worse or even inferior compared with studies using long-term maintenance therapy. High-dose cytarabine in combination with IT MTX was effective for CNS prophylaxis.