RESUMEN
BACKGROUND: Popular trend sports are characterized by intensive and high speed performance. Due to the high energy mechanism in falls, typical injury distributions and patterns result. OBJECTIVES: In a retrospective study the injury patterns and frequencies in mountain bike athletes were analyzed and pathophysiological, diagnostic and therapeutic options in the treatment of high energy injuries to the carpal bones are shown. MATERIAL AND METHODS: Based on a retrospective survey over 2 successive years, active mountain bike athletes (World Cup Series) were interviewed using a standardized questionnaire. Injury patterns and frequencies were analyzed. The pathophysiology, diagnostics and therapy of high energy carpal injuries are discussed. RESULTS: In this study 107 World Cup mountain bike athletes were enrolled. Injuries of the extremities were found in more than 75% of athletes with a higher prevalence in the upper extremities (40.7%) than the lower extremities (34.84%), followed by injuries of the head and face (13.3%, of which 10.6% were traumatic brain injuries) and the trunk (10.6%). Fractures and dislocations of the hand and wrist were found in approximately half of the athletes (50.9%). CONCLUSION: In popular trend sports injuries of the extremities are common, especially of the carpal bones and ligaments. It is important to distinguish stable from destabilizing injuries in order to provide adequate therapeutic options.
Asunto(s)
Traumatismos en Atletas/epidemiología , Ciclismo/lesiones , Ciclismo/estadística & datos numéricos , Huesos del Carpo/lesiones , Fracturas Óseas/epidemiología , Traumatismos en Atletas/terapia , Fracturas Óseas/terapia , Traumatismos de la Mano/epidemiología , Humanos , Internacionalidad , Montañismo/lesiones , Montañismo/estadística & datos numéricos , Traumatismo Múltiple/epidemiología , Traumatismo Múltiple/terapia , Prevalencia , Factores de Riesgo , Traumatismos de la Muñeca/epidemiologíaRESUMEN
BACKGROUND: Following treatment of distal radius fractures poor functional results can still be found despite satisfactory radiological findings. This may be due to concomitant carpal lesions occurring together with these fractures. The aim of this prospective study was to analyze the clinical outcome depending on the type of fracture and concomitant carpal lesions. PATIENTS AND METHODS: A total of 66 patients with distal radius fractures treated over a 1-year period could be assessed. The functional results were compared with the uninjured contralateral side. The follow-up examination included patient history, physical and radiographic examination as well as the DASH (Disability of the arm, shoulder and hand) questionnaire and the modified Mayo wrist score. RESULTS: The average follow-up time was 12.7 months and the mean age of the examined patients was 53 years. The fracture classification according to AO (AO Working party for osteosynthesis questions) showed 32% type A, 10% type B and 58% type C fractures. In 55% a concomitant carpal lesion was found and 44% of the patients required surgical treatment. All fractures united without complications. In all cases X-rays showed no loss of reduction postoperatively. Overall grip strength and wrist motion was reduced to 81% compared to the uninjured side. Patients regained good function represented in a mean DASH score of 24.8 points and a Mayo score of 70.6 points. The number of complete intraarticular fractures (type C) was significantly higher in patients who needed surgical treatment for carpal lesions compared to the groups where concomitant carpal lesions did not require invasive treatment or those where no carpal lesions were found. However, due to the operative treatment a comparable functional result could be obtained in all groups independent of the injury severity. CONCLUSIONS: The results demonstrate, if a correct restoration and surgical stabilization technique is used, clinical outcome following fractures of the distal radius also depends on an optimized management of concomitant carpal lesions.
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Huesos del Carpo/lesiones , Huesos del Carpo/cirugía , Fijación Interna de Fracturas/instrumentación , Traumatismo Múltiple/cirugía , Fracturas del Radio/cirugía , Traumatismos de la Muñeca/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Huesos del Carpo/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Traumatismo Múltiple/diagnóstico por imagen , Radiografía , Fracturas del Radio/diagnóstico por imagen , Resultado del Tratamiento , Traumatismos de la Muñeca/diagnóstico por imagen , Adulto JovenRESUMEN
This study investigated the incidence and frequency of injuries in mountainbike sports among competitive and recreational athletes. In a retrospective study design mountain-bike athletes were interviewed by means of a standardized questionnaire with regard to sports injuries and damages within the previous two years. The evaluation of time relative injury-rate was carried out under consideration of class and competition discipline. 75 % of the distributed questionnaires returned completed by 106 World-Cup (39 female symbol 67 male symbol, 23.1 y) and 134 recreational athletes (17 female symbol 117 male symbol, 27.4 y). Approximately 80 % of the World-Cup and about 50 % of the recreational athletes reported about at least one severe injury. World-Cup downhill athletes (1.08 injuries/ 1000 h) show a more than doubled time-related injury-rate in comparison with Cross-Country athletes (0.39 injuries/ 1000 h). Injuries of the lower (47 vs. 35 %) and upper extremity (40 vs. 41 %) show comparable prevalence for competitive and recreational cyclists. In the group of recreational athletes open wounds dominate, competitive athletes demonstrate a significant higher fracture-rate (p < 0.01). Within the World-Cup athletes head injuries stand out (n = 40). Although World-Cup participation does not result in essential injury-increase, the downhill discipline is characterized by a higher injury risk. Presumably in view of the performance orientation, there is a higher degree of risk readiness. Despite the riding performance and the obligatory safety equipment a remarkable number of bone and head injuries results.
Asunto(s)
Traumatismos en Atletas/etiología , Ciclismo/lesiones , Conducta Competitiva , Recreación , Adulto , Altitud , Traumatismos en Atletas/epidemiología , Causalidad , Estudios Transversales , Femenino , Alemania , Humanos , Masculino , Estudios Retrospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 x 10(9)/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Caracteres Sexuales , Adulto , Distribución por Edad , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Alquilantes/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Busulfano/administración & dosificación , Busulfano/efectos adversos , Causas de Muerte , Femenino , Humanos , Hidroxiurea/administración & dosificación , Hidroxiurea/efectos adversos , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Persona de Mediana Edad , Factores de Riesgo , Distribución por Sexo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
The objective of our study was to evaluate high-dose cytarabine in consolidation therapy in patients with newly diagnosed acute promyelocytic leukemia (APL). Patients (age 16-60 years) received induction therapy according to the AIDA protocol (all-trans retinoic acid, idarubicin) followed by one cycle of ICE (idarubicin, cytarabine, etoposide) and two cycles of HAM (cytarabine 3 g/m(2) q12h, days 1-3; mitoxantrone 10 mg/m(2), days 2 and 3). From 1995 to 2003, 82 patients were enrolled. In total, 72 patients (88%) achieved a complete remission, and 10 patients (12%) died from early/hypoplastic death (ED/HD). A total of 71 patients received at least one cycle of HAM. Relapse-free survival (RFS) and overall survival (OS) after 46 months were 83 and 82%, respectively. White blood cell count above 10.0 x 10(9)/l at diagnosis and additional chromosomal aberrations were unfavorable prognostic markers for OS, whereas no prognostic markers for RFS were identified including FLT3 mutations. In conclusion, high-dose cytarabine in consolidation therapy for patients with newly diagnosed APL is an effective treatment approach.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Citarabina/administración & dosificación , Idarrubicina/administración & dosificación , Leucemia Promielocítica Aguda/tratamiento farmacológico , Mitoxantrona/administración & dosificación , Tretinoina/administración & dosificación , Adolescente , Adulto , Femenino , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Proto-Oncogénicas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Inducción de Remisión , Tirosina Quinasa 3 Similar a fmsRESUMEN
Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Adulto , Transfusión Sanguínea , Terapia Combinada , Femenino , Granulocitos/fisiología , Hematopoyesis/efectos de los fármacos , Humanos , Macrófagos/fisiología , Masculino , Pelvis/efectos de la radiación , Factores de Tiempo , Trasplante AutólogoRESUMEN
A soluble form of CD8 antigen (sCD8) has been shown to be released by activated CD8 + lymphocytes. Measurements of sCD8 may serve as an index of suppressor/cytotoxic cell activity. To assess the clinical significance of this observation in response to malignancy, we have investigated the sCD8 concentrations in 38 patients with hairy cell leukemia (HCL) not yet treated with any systemic therapy. The median plasma sCD8 level of the 20 nonsplenectomized patients was 1,025 U/ml and was significantly higher than that in the 18 patients who had previous splenectomy (median = 200 U/ml, p less than 0.0001), or in 14 normal controls (median = 350 U/ml, p less than 0.0001). Compared to controls, splenectomized patients had also significantly lower levels of sCD8 (p less than 0.01). The median concentration of soluble interleukin-2 receptor (sIL2R) in nonsplenectomized patients was 14,500 U/ml and was in the same range as in splenectomized patients (15,000 U/ml). There was no overlap in sIL2-R levels between controls (median = 300 U/ml) and patients. Investigation of serial plasma samples in 7 patients who received deoxycoformycin (DCF) and 11 patients treated with interferon alpha (IFN-alpha) showed a normalization of sCD8 levels and a decrease of sIL2R concentrations in those patients who showed hematological improvement. Normalization of sIL2R was, however, only observed in patients with complete remission. Our observation indicates that splenectomy might cause a reduction of the activation of suppressor/cytotoxic cells in patients with HCL. Treatment with either DCF or IFN-alpha also modulates the sCD8 levels to normal range. Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy.
Asunto(s)
Antígenos de Diferenciación de Linfocitos T/análisis , Leucemia de Células Pilosas/inmunología , Receptores de Interleucina-2/análisis , Esplenectomía , Antígenos/análisis , Antígenos CD8 , Coformicina/análogos & derivados , Coformicina/uso terapéutico , Humanos , Interferón Tipo I/uso terapéutico , Leucemia de Células Pilosas/terapia , PentostatinaRESUMEN
Our multicenter study on the treatment of hairy cell leukemia (HCL) started in December 1984 and the present data cover the time up to June 30, 1986. Ninety-seven patients were enrolled. For induction of response daily doses (6 micrograms) of low dose human recombinant alpha 2c-interferon (arg) was chosen. Further dose reduction (3 micrograms) was possible for patients who improved within the first 3-4 weeks. Patients with known risk factors started at lower doses (0.6 microgram daily). As infections are known to be the main cause of death in HCL, splenectomy was not mandatory before treatment. Thirty-nine patients received treatment with interferon. Nevertheless, infections remained the major cause of death in the study. The protocol did not prevent fatal infections in nine of the 34 splenectomized patients. The regimen proved safe for all but one of the nonsplenectomized patients. According to this experience, new criteria are needed for the choice of primary treatment in HCL. In our opinion splenectomy should become restricted to selected cases.
Asunto(s)
Interferón Tipo I/uso terapéutico , Leucemia de Células Pilosas/terapia , Antineoplásicos/uso terapéutico , Trastornos de la Coagulación Sanguínea/complicaciones , Terapia Combinada , Humanos , Infecciones Oportunistas/complicaciones , Estudios Prospectivos , Proteínas Recombinantes/uso terapéutico , Esplenectomía/efectos adversos , Factores de TiempoRESUMEN
Four randomized prospective studies on interferon alpha (IFN) in CML report varying degrees of prolongation of the chronic phase of CML and of survival as compared to conventional therapies. There is agreement that IFN prolongs survival as compared to standard busulfan. There is disagreement, however, as to which degree IFN is superior to hydroxyurea. Whereas the randomized studies of the Italian cooperative group and of the British MRC find a statistically significant survival advantage of IFN over hydroxyurea of about 20 months, this difference is only 10 months in the German randomized study and not significant. One reason for this difference might be the more intensive treatment schedule for the hydroxyurea control group in the German study. Other reasons might be differences in risk profiles between the patient groups studied and in strategies of IFN therapy. About 1% of the human genome consists of retroviral or retroviral-like sequences. By analogy to animal models, endogenous retroviruses might also have pathogenic potential in human disease. The transposon-like structure of retroviruses that enables them to integrate at almost any position in the host genome and the capability of retroviruses to serve as efficient vehicles of cellular genes are in support of a pathogenic potential. Furthermore, particles resembling retroviruses have been observed long ago in human embryonic and malignant tissues and cell lines. Sequence information and the transcriptional activity of the endogenous sequences argue against the possibility that these sequences are only fossil relics of early evolutionary periods. Most of the sequences appear to be inactivated by stop codons or frameshifts, making the genomic localization of open reading frames with biological activity difficult. Up to now, mutagenesis by insertion of retroviral-like sequences in sporadic cases of human disease appears to be the only example of pathogenic relevance of retroviruses in man.
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Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Antineoplásicos/uso terapéutico , Busulfano/uso terapéutico , Línea Celular , Genoma Humano , Alemania , Humanos , Hidroxiurea/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/virología , Retroviridae/aislamiento & purificación , Medición de Riesgo , Tasa de SupervivenciaRESUMEN
Chronic myeloid leukemia (CML) in older patients has not been studied well. To assess the long-term outcome of older patients with Philadelphia- and/or BCR-ABL-positive CML, 199 patients aged >/=60 years representing 23% of 856 patients enrolled in the German randomized CML-studies I (interferon alpha (IFN) vs hydroxyurea (HU) vs busulfan (BU) and II (IFN+HU vs HU alone) were analyzed after a median observation time of 7 years. In all, 45 patients were treated with Bu, 63 with HU, and 91 with IFN. The 5-year survival was 38% in patients >/=60 years and 47% in patients <60 years (P<0.001). Whereas 5-year survival in chemotherapy-treated older patients was inferior to that in younger patients (33 vs 46%, P=0.006 for HU and 29 vs 38%, P=0.042 for Bu), no significant survival difference could be verified in IFN-treated patients (46 vs 53%, P=0.077). Calculation of age-adjusted, relative survival confirmed these results. Adverse effects of IFN were similar in both age groups, but IFN dosage to achieve treatment goals was lower in older patients. We conclude that the course of CML is not different in the elderly. They require lower IFN doses, achieve the same hematologic and cytogenetic response rates and the same survival advantage at comparable toxicity.
Asunto(s)
Antineoplásicos/uso terapéutico , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Proteínas Tirosina Quinasas/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Busulfano/uso terapéutico , Niño , Femenino , Estudios de Seguimiento , Proteínas de Fusión bcr-abl , Humanos , Hidroxiurea/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide/terapia , Enfermedad Aguda , Adolescente , Adulto , Algoritmos , Citarabina/uso terapéutico , Análisis Citogenético , Femenino , Humanos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Mitoxantrona/uso terapéutico , Inducción de Remisión/métodos , Medición de Riesgo , Trasplante de Células Madre/métodos , Trasplante de Células Madre/mortalidad , Análisis de SupervivenciaRESUMEN
The purpose of our study was (i) to evaluate the impact of all-trans retinoic acid (ATRA) given as adjunct to chemotherapy and (ii) to compare second consolidation vs maintenance therapy in elderly patients with acute myeloid leukemia (AML). A total of 242 patients aged >or=61 years (median, 66.6 years) with AML were randomly assigned to ATRA beginning on day +3 after the initiation of chemotherapy (ATRA-arm, n=122) or no ATRA (standard-arm, n=120) in combination with induction and first consolidation therapy. A total of 61 patients in complete remission (CR) were randomly assigned to second intense consolidation (n=31) or 1-year oral maintenance therapy (n=30). After induction therapy the intention-to-treat analysis revealed a significant difference in CR rates between the ATRA- and the standard-arm (52 vs 39%; P=0.05). Event-free (EFS) and overall survival (OS) were significantly better in the ATRA-compared to the standard-arm (P=0.03 and 0.01, respectively). OS after second randomization was significantly better for patients assigned to intensive consolidation therapy (P<0.001). The multivariate model for survival revealed lactate dehydrogenase, cytogenetic risk group, age, and first and second randomization as prognostic variables. In conclusion, the addition of ATRA to induction and consolidation therapy may improve CR rate, EFS and OS in elderly patients with AML.
Asunto(s)
Anemia Refractaria con Exceso de Blastos/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide/terapia , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Terapia Combinada , Citarabina/administración & dosificación , Etopósido/administración & dosificación , Humanos , Idarrubicina/administración & dosificación , Persona de Mediana Edad , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Trasplante Homólogo , Tretinoina/administración & dosificaciónRESUMEN
The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hidroxiurea/administración & dosificación , Interferón-alfa/administración & dosificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Causas de Muerte , Niño , Análisis Citogenético , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Hidroxiurea/toxicidad , Masculino , Persona de Mediana Edad , Inducción de Remisión/métodos , Medición de Riesgo , Análisis de Supervivencia , Trasplante HomólogoRESUMEN
The production of protease by malignant cells has been held responsible for invasion. The effect of aprotinin, a broad-spectrum protease inhibitor, on malignant invasion was examined histologically in organotypical cocultures of precultured embryonic chick heart fragments with two human melanoma cell lines and one virus-transformed fetal mouse carcass cell line. In the presence of 400 KIU/ml aprotinin, invasion was still permissive, while in the comparison with 0.1 microgram/ml vincristine, a microtubule and directional motility inhibitor and a well-documented anti-invasive agent, invasion was completely stopped. Aprotinin remained stable in the culture medium so that the presence of invasion cannot be explained by low drug concentration. It is concluded that aprotinin-sensitive proteases are not implicated in invasion in vitro in the cell types investigated, and that this in vitro technique deserves further interest for the study of protease inhibitors in the mechanism of invasion.
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Aprotinina/farmacología , Invasividad Neoplásica , Inhibidores de Proteasas/farmacología , Animales , Adhesión Celular/efectos de los fármacos , Transformación Celular Viral , Embrión de Pollo , Medios de Cultivo , Humanos , Melanoma/patología , Miocardio/patología , Inhibidores de Tripsina/metabolismo , Células Tumorales Cultivadas , Vincristina/farmacologíaRESUMEN
Quantitative analysis of surface molecule expression on viable alveolar macrophages (AM) by use of flow cytometry is hampered by non-specific antibody binding to various AM FcIgG receptors as well as extensive and heterogeneous autofluorescence of this cell type. The following approaches were undertaken to circumvent these obstacles. FcIgG receptors were blocked by excess human immunoglobulin. The use of a long wave-emitting dye (phycoerythrin/cyanine-5 tandem conjugate) permitted avoidance of the peak (green) AM autofluorescence range. Moreover, a cell-by-cell compensation for the remaining red autofluorescence background was employed. This was based on two facts: (i) strict correlation between green (F488/530) and red autofluorescence (F488/660) for all AM populations investigated; and (ii) neglectable overlap of the antibody-associated red fluorescence into the 530 nm autofluorescence detection wavelength. A fraction of the green autofluorescence (F488/530; channel 1) was then subtracted from the red fluorescence (F488/660; channel 2) on a cell-by-cell basis using standard two colour fluorescence compensation circuits. The validity of this FACS technique was confirmed by comparison with immunocytochemical staining and a reverse rosetting method. On AM lavaged from carcinoma-bearing but otherwise disease-free human lungs, the pattern of surface antigen expression was assessed with a panel of monoclonal antibodies. When applying to complex mixtures of bronchoalveolar lavage cells, the autofluorescence was employed to separate AM from granulocytes and lymphocytes. In conclusion, the presently described FACS technique allows quantitative immunostaining of surface molecules on AM, even when present in low copy numbers on highly autofluorescent cells originating from smokers.
Asunto(s)
Líquido del Lavado Bronquioalveolar/citología , Citometría de Flujo/métodos , Macrófagos Alveolares/inmunología , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes , Humanos , Inmunofenotipificación , Formación de Roseta/métodosRESUMEN
In a cooperative study at 13 centres in the Federal Republic of Germany, 213 adult patients with AML were treated for remission induction by a 9-day regimen consisting of cytosine arabinoside, daunorubicin and thioguanine (TAD) according to previously described sequencing. Complete remission was achieved in 70% of all patients. Complete remission rate was 57% in the 49 patients 60 years of age and older and 74% in the 164 patients under 60 years. Sixty-eight per cent of all complete remissions and 75% of those in the higher age group were induced by one induction course. Median survival was 10 months for all patients treated and 16 months for responders. Median remission duration was 13 months with 72 patients still in continuous remission for 1-31 months. Remission duration was not significantly different for patients treated either by monthly maintenance therapy or induction type consolidation without further therapy. However, patients completing two consolidation courses had a significantly longer remission duration of 22 months. Compared to similar multicentre studies on AML therapy the intensified induction regimen applied in this study shows an improvement even in older patients.
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Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Adulto , Anciano , Citarabina/uso terapéutico , Daunorrubicina/uso terapéutico , Evaluación de Medicamentos , Humanos , Persona de Mediana Edad , Factores de TiempoRESUMEN
The activity of the BCR/ABL hybrid gene is associated with a growth advantage of the chronic myelogenous leukemia (CML) stem cell. Suppression of BCR/ABL hybrid gene expression can be a valuable tool for leukemic cell purging. Antisense oligonucleotides (ODNs) have the capacity to specifically downregulate gene expression. Data reported on the effect they have on BCR/ABL hybrid gene expression are controversial. We present data illustrating that prolongation of ODN half-life by means of chemical or sequence modification has only limited specific growth suppressive effect on BCR/ABL-positive clonogenic cells in vitro. Compared to unmodified phosphodiester ODNs (PO-ODNs) spanning the BCR/ABL junctions, modified ODNs with either a 3'-GC-clamp (GC-ODNs) or ODNs with one 3'-inverted nucleotide (3'-3' ODNs) to prevent 3'-exonuclease degradation, showed significantly prolonged extra- and intracellular half lives and different subcellular distributions in CML cell lines. In clonogenic assays from patients with CML, the modified ODNs were to some extent able to reduce colonies expressing BCR/ABL (GC-ODNs >3'-3'-ODNs >PO-ODNs). This difference did not become significant statistically. We demonstrate a substantially diminished hybridization efficacy of the modified antisense ODNs used, which may serve as a possible explanation for the failure to augment the leukemic cell purging efficacy.
RESUMEN
It is the long-term goal of the German CML Study Group and of the Süddeutsche Hämoblastosegruppe (SHG) to improve survival of patients with chronic myelogenous leukemia (CML). In a first randomized study (CML Study I) monotherapies with hydroxyurea or interferon alpha (IFN-alpha) were compared with a standard busulfan regimen with regard to duration of the chronic phase and survival. The main results of this study were published, 1-3 and a long-term follow up is planned. In a second randomized study the effect of the combination of IFN-alpha and hydroxyurea versus hydroxyurea monotherapy on survival is being investigated. This paper provides a first preliminary report on the study concept, patient recruitment, state of documentation and initial patients' characteristics 9 months after closure of the study.
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Antineoplásicos/administración & dosificación , Hidroxiurea/administración & dosificación , Interferón-alfa/administración & dosificación , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/terapia , Adulto , Protocolos Clínicos , Terapia Combinada , Femenino , Alemania , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Chromosome analysis of bone marrow (BM) aspirate from a 36-year-old man with chronic myeloid leukemia (CML) in blastic phase (BP) showed a four-break rearrangement t(11;9)(9;22)(q23; p22q34;q11), which can be considered a t(9;22)(q34;q11) and a secondary t(9;11)(p22;q23). It is not surprising that additional chromosome abnormalities occur in patients with Ph-positive CML in BP, but it is of interest that t(9;11)(p22;q23), characteristic of acute myeloid leukemia French-American-British (FAB) type M5 (ANLL-M5) was observed. The possible meaning of this additional change in BP of CML is discussed.
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Crisis Blástica/genética , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 22 , Cromosomas Humanos Par 9 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Translocación Genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Bandeo Cromosómico , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Humanos , Cariotipificación , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Vincristina/administración & dosificaciónRESUMEN
From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.