RESUMEN
OBJECTIVE: To investigate whether seemingly healthy first-degree relatives of patients with ankylosing spondylitis (AS) have clinical, laboratory, or imaging features of spondyloarthritis (SpA). METHODS: First-degree relatives (ages 18-40 years) of HLA-B27-positive AS patients were included in the pre-spondyloarthritis (Pre-SpA) cohort, a prospective inception cohort study. Clinical, biologic, and imaging features were recorded. First-degree relatives were classified according to several sets of SpA classification criteria. RESULTS: We report baseline features of 51 first-degree relatives included in this study. Twenty-nine (57%) had back pain, 2 (4%) had psoriasis, 1 (2%) had inflammatory bowel disease, and 1 (2%) had uveitis. Three (6%) had low-grade sacroiliitis, 1 (2%) had cervical syndesmophytes on radiography, and 10 (20%) had bone marrow edema on magnetic resonance imaging of the sacroiliiac joints. Seventeen of 51 first-degree relatives (33%) fulfilled SpA classification criteria: 7 (14%) fulfilled both Assessment of SpondyloArthritis international Society (ASAS) axial SpA and European Spondylarthropathy Study Group (ESSG) classification criteria, 6 (12%) fulfilled only ASAS axial SpA classification criteria, and 4 (8%) fulfilled only ESSG classification criteria; 3 (6%) also fulfilled the Amor criteria. None fulfilled other SpA classification criteria. First-degree relatives fulfilling the ASAS axial SpA and/or ESSG classification criteria had more frequent inflammatory back pain, had a higher level of disease activity, and had more psoriasis. No differences were found in parameters of inflammation, peripheral and extraarticular disease other than psoriasis, and HLA-B27 positivity between those who did and those who did not fulfill the ASAS axial SpA and/or ESSG classification criteria. Four first-degree relatives (12%) who did not fulfill the ASAS axial SpA and/or ESSG classification criteria had imaging abnormalities suggestive of SpA. CONCLUSION: A substantial proportion of seemingly healthy first-degree relatives of HLA-B27-positive AS patients have clinical and/or imaging abnormalities suggestive of SpA. Thirty-three percent could be classified as having SpA. Further follow-up will show which first-degree relatives will develop clinically manifest SpA.
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Dolor de Espalda/epidemiología , Familia , Enfermedades Inflamatorias del Intestino/epidemiología , Psoriasis/epidemiología , Sacroileítis/epidemiología , Espondiloartropatías/diagnóstico por imagen , Espondilitis Anquilosante , Uveítis/epidemiología , Adolescente , Adulto , Enfermedades de la Médula Ósea/diagnóstico por imagen , Enfermedades de la Médula Ósea/epidemiología , Estudios de Cohortes , Edema/diagnóstico por imagen , Edema/epidemiología , Femenino , Antígeno HLA-B27/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Osteofito/diagnóstico por imagen , Osteofito/epidemiología , Estudios Prospectivos , Radiografía , Sacroileítis/diagnóstico por imagen , Espondiloartropatías/fisiopatología , Espondilitis Anquilosante/genética , Adulto JovenAsunto(s)
Linfoma de Células B/diagnóstico , Dolor/etiología , Neoplasias del Recto/diagnóstico , Adulto , Biopsia , Femenino , Fisura Anal/diagnóstico , Seropositividad para VIH , Humanos , Inmunohistoquímica , Mucosa Intestinal/patología , Linfoma de Células B/complicaciones , Linfoma de Células B/diagnóstico por imagen , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Imagen por Resonancia Magnética , Neoplasias del Recto/complicaciones , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/patología , Recto/patología , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
BACKGROUND: Relapsed or refractory diffuse large B-cell and mantle-cell lymphoma have a poor prognosis. The EPOCH regimen and rituximab monotherapy have demonstrated activity as salvage therapies. Because of their non-overlapping toxicity, we evaluated their combination as salvage therapy in a phase II study. PATIENTS AND METHODS: Patients with relapsed or refractory CD20-positive large B-cell and mantle-cell lymphoma were offered treatment with rituximab 375 mg/m2 intravenously (i.v.) on day 1, doxorubicin 15 mg/m2 as a continuous i.v. infusion on days 2-4, etoposide 65 mg/m2 as a continuous i.v. infusion on days 2-4, vincristine 0.5 mg as a continuous i.v. infusion on days 2-4, cyclophosphamide 750 mg/m2 i.v. on day 5 and prednisone 60 mg/m2 orally on days 1-14. RESULTS: Fifty patients, with a median age of 56 years (range 23-72), entered the study. Twenty-five had primary diffuse large B-cell lymphoma, 18 transformed large B-cell lymphoma and seven mantle-cell lymphoma. The median number of prior chemotherapy regimens was 1.7 (range one to four). The median number of treatment cycles was four (range one to six). Possible treatment-related death occurred in two patients. Objective responses were obtained in 68% of patients (28% complete responses, 40% partial responses). Nineteen patients received consolidating high-dose chemotherapy with autologous stem-cell transplantation. The median follow-up was 33 months. Three patients developed a secondary myelodysplastic syndrome. The median overall survival was 17.9 months; the projected overall survival at 1, 2 and 3 years was 66, 42 and 35%, respectively. The median event-free survival was 11.8 months; the projected event-free survival at 1, 2 and 3 years was 50, 30 and 26%, respectively. CONCLUSION: The rituximab-EPOCH regimen is effective and well tolerated, even in extensively pretreated patients with relapsed or refractory large B-cell lymphoma and mantle-cell lymphoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Terapia Recuperativa , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células del Manto/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Inducción de Remisión , Rituximab , Tasa de Supervivencia , Resultado del Tratamiento , Vincristina/administración & dosificaciónRESUMEN
Low-dose methotrexate (MTX) is used as disease-modifying therapy in severe rheumatoid arthritis and as maintenance treatment in patients with complete remission of acute lymphoblastic leukemia (ALL). It is generally well tolerated, but in 27% of patients acute pneumonitis leads to discontinuation of treatment. We describe a 56-year-old female patient with newly diagnosed pre-B-ALL. She was treated with induction chemotherapy in July 1999 which lead to complete remission. Maintenance treatment with low-dose MTX and 6-mercaptopurine (6-MP) was started in December 1999. In April 2000 she was hospitalized because of fever, cough, and rapidly progressive dyspnea. No pathogens could be cultured from blood or bronchoalveolar lavage fluid. Computed tomography of the lungs revealed interstitial infiltration and ground-glass opacities. Acute pneumonitis was diagnosed, and MTX was stopped. Prednisone therapy lead to rapid clinical amelioration of dyspnea and hypoxemia. Since for this patient there was no alternative leukemia therapy, MTX was successfully reintroduced in August 2000 without reappearance of any respiratory symptoms. We discuss risk profile, clinical and histological presentation, and therapy of MTX-induced pneumonitis. To our knowledge, this is the first patient with ALL in whom successful reintroduction of MTX after severe pneumonitis has been reported.
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Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Neumonía/inducido químicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Enfermedad Aguda , Femenino , Humanos , Mercaptopurina/administración & dosificación , Persona de Mediana Edad , Neumonía/diagnóstico , Neumonía/tratamiento farmacológico , Prednisona/uso terapéutico , Inducción de Remisión , Tomografía Computarizada por Rayos XAsunto(s)
Factor de Crecimiento Epidérmico/antagonistas & inhibidores , Eritema/inducido químicamente , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Quinazolinas/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Eritema/patología , Femenino , Gefitinib , Humanos , Neoplasias Pulmonares/complicaciones , Persona de Mediana EdadRESUMEN
The purpose of this study was to evaluate the efficacy of vinorelbine treatment in terms of prostate-specific antigen (PSA) response and clinical benefit (decrease of pain or analgesic score for the subgroup of patients with pain), as well as its toxicity in patients with progressive metastatic androgen-independent prostatic carcinoma. 44 patients with prostatic carcinoma progressing after orchiectomy or during treatment with hormonal agents were treated with vinorelbine at a dose of 30 mg/m(2) intravenously (i.v.) on days 1 and 8 of a 21-day cycle. Inclusion criteria were metastatic progressive prostatic carcinoma with prostate-specific antigen (PSA) serum levels >/=3 x upper limit of normal, World Health Organization (WHO) performance status /=2 was observed on the day of scheduled vinorelbine administration. 9 patients received less than three cycles, 6 due to rapid tumour progression. Treatment at day 1 had to be delayed in 13.7% of 183 cycles. Treatment at day 8 had to be omitted in 19.7% of all cycles. Grade >/=3 granulocytopenia occurred in 18% of patients. 4 patients had severe constipation. In 7 patients (15.9%, Confidence Interval (CI) 6.6-30.1%), a PSA response (>/=50% reduction of PSA levels) was observed. Among 8 patients with measurable disease, 3 had partial remission and 1 no change. Median time to PSA progression in 43 assessable patients was 11.9 weeks (range 3-52 weeks). Median duration of PSA response was 14 weeks (9-30 weeks). Clinical benefit was seen in 7 of 31 cases (23%) with baseline pain, there was no association with PSA response. Vinorelbine is a fairly well tolerated drug with a moderate single agent activity in patients with androgen-refractory prostate cancer.
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Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Vinblastina/análogos & derivados , Vinblastina/uso terapéutico , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Análisis de Supervivencia , Resultado del Tratamiento , VinorelbinaRESUMEN
The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as well as on the level of the tumor markers AFP, betaHCG and LDH. We report here on the results of a risk-adapted approach to the chemotherapy of germ cell tumors. Patients with low-risk tumors, defined as seminomatous disease and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and betaHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m(2) i.v. day 1, etoposide 120 mg/m(2) i.v. days 1-3 and bleomycin 30 IU i.v. days 1, 8 and 15 during the first 3 cycles (CEB(90)). Patients with high-risk disease were to receive 4 cycles of ifosfamide 1,500 mg/m(2) continuous infusion on days 1-4 together with mesna 1,200 mg/m(2) days 1-5, cisplatin 20 mg/m(2) i.v. days 1-5 and etoposide 100 mg/m(2) i.v. days 1-5 (VIP). Of the 60 patients treated with this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty-five of 51 patiens treated with CEB(90) achieved complete remission (CR), 4 achieved partial remission with marker negativity. Four patients with CR relapsed between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing CEB(90), 3 were treated successfully with surgery or further chemotherapy. With a median follow-up of 52 months, the estimated cause-specific 3-year survival is 93% (95% confidence interval, CI, 80-98%). Seven of 9 high-risk patients treated with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had successful salvage therapy. With a medium follow-up of 63 months all patients remain alive and free of disease. Forty-six patients receiving CEB(90) were retrospectively classified to be in the good prognosis group according to the international germ cell consensus classification. Their estimated 3-year survival was 95% (CI 81-99%). We thus confirm that CEB(90) is a well-tolerated outpatient regimen with good results in good prognosis germ cell tumors. Bleomycin at a cumulative dose of 270 U might contribute substantially to the inferior effect of carboplatin as compared to cisplatin. However, in view of the results of randomized studies favoring cisplatin over carboplatin, it is not recommended to use this regimen outside a clinical trial.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Germinoma/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/administración & dosificación , Bleomicina/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Estudios de Seguimiento , Germinoma/mortalidad , Germinoma/secundario , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Persona de Mediana Edad , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: In a phase II trial, 43 patients with hormone-refractory prostate cancer were treated with gemcitabine at a dose of 1,200 mg/m2 over 2 hours (later decreased to 1,000 mg/m2 due to hematological toxicity) on days 1, 8 and 15 of a 28 day cycle. PATIENTS AND METHODS: Inclusion criteria were proven tumor progression after hormonal treatment and increased PSA levels, a WHO PS < or = 2, adequate bone marrow reserve, liver and renal function and age < or =, 80 years. Response criteria were based on PSA levels (CR: normalization of PSA, PR: > 50% decrease). Quality of life (QL) was assessed with the EORTC QLQ-C30 on day 1 of each treatment cycle and on day 8 of the first cycle (range of scales 0-100). Physician-rated pain intensity and use of pain medication were assessed at the same timepoints. RESULTS: Hematological toxicity of gemcitabine led to a dose-reduction in 48% of all cycles. Three of forty-three patients (RR = 7%) showed a PSA response: one CR and three PR with time to treatment failure of 8.7, 6.6 and > or = 9.3 months. Seven patients (16%) had stable disease (NC) for a median duration of 7.1 months (range 6.1-11.7 months). There was one case with objective regression of lymph node metastases. Patients reported a considerably impaired health status/QL (n = 41, median = 50) and severe fatigue (n = 41, median = 55.6) at baseline, with no change under treatment. Pain (QLQ-C30) was also severe at baseline (N=41, median=50) but was improved at the end of cycles 1 (n = 33, median change = -16.7, P = 0.0002), 2 (n = 19, median change = -33.3, P = 0.0006), 3 (n = 14, median change = -16.7, P = 0.06) and 4 (n = 9, median change = -33.3, P = 0.04). Patient-rated pain and use of analgesics as combined endpoint yielded palliation for at least 8 weeks in 14 patients (32%). Nine of these patients showed at least stable disease (CR/PR or NC by PSA level), five indicated a benefit in spite of progressive disease. CONCLUSIONS: Gemcitabine in the dose and schedule indicated above has a significant beneficial impact on pain in patients with hormone-refractory prostatic carcinoma despite its limited activity in terms of PSA response and considerable, especially hematological, toxicity.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Antimetabolitos Antineoplásicos/administración & dosificación , Desoxicitidina/análogos & derivados , Cuidados Paliativos/métodos , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/mortalidad , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Neoplasias Óseas/secundario , Intervalos de Confianza , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Relación Dosis-Respuesta a Droga , Resistencia a Antineoplásicos , Estudios de Seguimiento , Hormonas/farmacología , Humanos , Infusiones Intravenosas , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Dimensión del Dolor , Antígeno Prostático Específico/análisis , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Tasa de Supervivencia , GemcitabinaRESUMEN
Several centres reported a favourable outcome after high-dose chemotherapy with autologous progenitor cell transplantation in selected patients with high-risk large cell non-Hodgkin's lymphoma in first remission. Based on these observations, we wanted to prospectively determine the outcome of a risk-adapted therapy for patients with large cell lymphoma. Patients aged 60 years or less received 12 weeks of VACOP-B chemotherapy. For high-risk patients in remission this was immediately followed by high-dose chemotherapy with cyclophosphamide, carmustine and etoposide and autologous progenitor cell transplantation. High-risk criteria were defined before the establishment of the International Index and included large cell lymphoma stage III or IV or mediastinal large lymphoma with sclerosis stage II or higher, and the presence of bulky tumours and/or an elevated LDH. 89 patients fulfilled the clinical selection criteria and were entered onto this multicentre study. 82 patients were evaluable after confirmation of large cell histology by pathology review. Of these, 51 were considered to be in the low-risk group and 31 in the high-risk group. The 3-year event-free survival for all patients was 68%. The 3-year event-free survival was 76% for the low-risk and 55% for the high-risk group (P = 0.061). Only 22/31 high-risk patients were able to receive the high-dose chemotherapy in first remission as intended. In conclusion, although our study demonstrated that a risk-adapted therapy for large cell lymphoma could be safely administered, the potential impact on outcome of the strategy chosen here is likely to be small.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células B Grandes Difuso/terapia , Adulto , Anciano , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Prospectivos , Factores de Riesgo , Vincristina/administración & dosificaciónRESUMEN
OBJECTIVE: To study the effect of cisplatin on plasma concentrations and urinary excretion of carnitine in ten patients with different malignancies treated with chemotherapy. METHODS: Carnitine concentrations were determined using a radioenzymatic assay and other metabolites by routine methods of clinical chemistry. Renal clearances were calculated by dividing urinary excretions by the respective plasma concentrations. RESULTS: Before treatment, all patients had a normal plasma carnitine concentration. During treatment with cisplatin, the plasma total carnitine concentration increased by approximately 30% and normalized 7 days after stopping therapy. Urinary excretion of total carnitine increased by a factor of 10 during cisplatin administration and also normalized 7 days after cessation of chemotherapy. This increase was due to excretion of both free carnitine and acylcarnitine and averaged approximately 1 mmol carnitine per day. Similarly, urinary clearance of total carnitine was increased during therapy with cisplatin by a factor of approximately 8 and returned to normal 7 days after chemotherapy. In comparison, patients with similar malignancies treated with radiotherapy showed no significant increase in renal carnitine excretion. Similar to urinary excretion of carnitine, excretion of glucose and phosphate, two metabolites also reabsorbed by the proximal tubule of the nephron, was increased during therapy with cisplatin. There was a strong linear correlation between urinary excretion of free carnitine and acylcarnitines. CONCLUSIONS: Treatment with cisplatin is associated with a tenfold increase in renal carnitine excretion, most likely due to inhibition of carnitine reabsorption by the proximal tubule of the nephron. Well-nourished patients support this loss of carnitine even after repeated cycles of chemotherapy without developing hypocarnitinaemia. However, cachectic patients with decreased dietary carnitine uptake may develop carnitine deficiency when treated repeatedly with chemotherapies including cisplatin.
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Antineoplásicos/farmacología , Carnitina/orina , Cisplatino/farmacología , Neoplasias/metabolismo , Adulto , Anciano , Antineoplásicos/uso terapéutico , Glucemia/efectos de los fármacos , Carnitina/sangre , Cisplatino/uso terapéutico , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Fosfatos/sangreAsunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Citarabina/efectos adversos , Erupciones por Medicamentos/diagnóstico , Leucemia Mieloide Aguda/tratamiento farmacológico , Púrpura/inducido químicamente , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Diagnóstico Diferencial , Femenino , HumanosRESUMEN
We describe the phenomenon of waning of focal hepatic and/or splenic lesions on abdominal computed tomographic (CT) scan during neutropenia in patients with chronic disseminated candidiasis. After observation of the phenomenon in one patient, a total of five cases were prospectively monitored with serial CT scans. After the diagnosis of disseminated candidiasis, hepatic lesions decreased in size and conspicuousness in three patients, while in two others they disappeared completely during a subsequent chemotherapy-induced neutropenia. After recovery of the neutrophils, the lesions reappeared or increased in conspicuousness in all five patients. Of three patients treated with a second cycle of myeloablative chemotherapy, lesions again decreased in two patients during neutropenia and increased again in one patient after neutrophil recovery. In all five patients, candidiasis eventually resolved after prolonged antifungal treatment. In chronic disseminated candidiasis, hepatic or splenic lesions may transiently disappear during neutropenia. Thus, antifungal therapy should not be discontinued on the basis of radiologic findings alone.
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Candidiasis/patología , Hígado/patología , Neutropenia/complicaciones , Neutropenia/patología , Adolescente , Adulto , Candidiasis/diagnóstico por imagen , Candidiasis/etiología , Enfermedad Crónica , Femenino , Humanos , Hígado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neutropenia/diagnóstico por imagen , Radiografía , Tomógrafos Computarizados por Rayos XRESUMEN
BACKGROUND: Intensification of post-remission therapy improves the cure rate of acute myeloid leukemia (AML) but is often accompanied by unacceptable toxicity. From 1985 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III trial to evaluate the effectiveness of one single postremission course of high-dose cytarabine (HDAC) in terms of leukaemia-free and overall survival in adults with de novo AML. PATIENTS AND METHODS: Adult (15-65 years) AML patients in remission after two induction courses were randomly assigned to one consolidation course either with standard (SDAC: 100 mg/sqm 24 hours infusion over seven days) or with high-dose cytarabine (HDAC: 3000 mg/sqm every 12 hours as one-hour-infusion for six days). In addition, both arms included daunorubicin (45 mg/sqm daily on days 1 to 3). Thereafter, patients were observed without maintenance until relapse. RESULTS: After two induction courses 208/276 eligible patients achieved remission (CR: 169, 61%, PR: 39, 14%), 41 were resistant (15%) and 20 died early (7%). Seventy-one patients in remission were not randomized. One hundred thirty-seven were randomized in CR/PR (67 SDAC, 70 HDAC). 4/70 patients randomized to HDAC did not receive it. Treatment-related mortality in HDAC was 1.4% (1/66). WHO grade 3-4 toxicities occurred in 14/67 SDAC and in 38/66 HDAC patients (P < 0.0001). The median event free survival was 10.8 (SDAC) vs. 12.2 months (HDAC; P = 0.18). The median overall survival was 24.6 (SDAC) vs. 32.6 months (HDAC; P = 0.07). Although statistically uncertain, HDAC reduced the hazard of progression (hazard ratio: 0.69, P = 0.08) and of death (hazard ratio: 0.70, P = 0.13). For 112 patients stratified as CR the estimated four-year disease-free survival was 25% (+/-6%) with SDAC and 37% (+/-6%) with HDAC (P = 0.09). The overall survival rates at four years were 38% (+7%) and 48% (+7%), respectively (P = 0.10). In multivariate analysis HDAC significantly reduced the hazard of relapse by 39% compared to SDAC (hazard ratio = 0.61, 95% CI: 0.37-0.99; P = 0.049). CONCLUSIONS: We conclude that early consolidation of adult AML in CR with a single course of HDAC is superior in terms of outcome to one cycle of SDAC. The results of our intensive, single course HDAC group compare favourably with less intensive, repetitive HDAC cycles, suggesting that Ara-C dose intensity may be more important than total dosage. In addition, our treatment strategy is much less toxic and less expensive.
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Antimetabolitos Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Leucemia Mieloide/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Citarabina/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Leucemia Mieloide/mortalidad , Masculino , Persona de Mediana Edad , Inducción de Remisión , Tasa de SupervivenciaRESUMEN
Induction therapy of promyelocytic leukemia with all-trans retinoic acid is a standard therapy despite significant side-effects. The most important, the "retinoic acid syndrome", consists of a hyperinflammatory reaction with capillary leakage (edema, pleural, and pericardial effusion), infiltration of myeloid cells into internal organs and systemic signs of inflammation. We describe here two cases of another hyperinflammatory reaction during all-trans retinoic acid therapy, the Sweet's syndrome, consisting of infiltrates of the skin and internal organs by neutrophilic granulocytes. Fever, painful erythematous cutaneous plaques, prominent musculoskeletal involvement (myositis, fasciitis), a sterile pulmonary infiltration and intercurrent proteinuria characterized the clinical course of all-trans retinoic acid-associated Sweet's syndrome. Treatment with glucocorticoids led to resolution of the syndrome within 48 h. Three other cases of all-trans retinoic acid-associated Sweet's syndrome without involvement of internal organs, prominent on our cases, were published previously. Recognition of ATRA-associated Sweet's syndrome is of practical importance.
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Leucemia Promielocítica Aguda/tratamiento farmacológico , Síndrome de Sweet/inducido químicamente , Tretinoina/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Fiebre , Humanos , Persona de Mediana Edad , Inducción de Remisión , Síndrome de Sweet/patología , Tretinoina/uso terapéuticoRESUMEN
BACKGROUND: Type and duration of treatment for highly aggressive non-Hodgkin's lymphoma has been a matter of debate over the past decade. To determine the therapeutic efficacy of an abbreviated treatment regimen, 26 patients with newly-diagnosed highly aggressive lymphomas, 17 of them belonging to the International Working Formulation (IWF) group I and 9 with Burkitt's lymphoma (IWF J), were entered in a study using short-term weekly chemotherapy followed by high-dose therapy and autologous bone marrow transplantation. PATIENTS AND METHODS: Besides histology, requirements for entry into to the study were age between 16 and 60 years, stage 1 bulky disease and elevated LDH or stage II to IV disease with or without bulk or elevated LDH, and an absence of HIV infection or CNS involvement at diagnosis. The treatment plan was 12 weeks of MACOP-B or VACOP-B chemotherapy followed by high dose therapy and autologous bone marrow transplantation in first complete remission. RESULTS: Twenty patients (76%), 16 (62%) of those on MACOP-B or VACOP-B, 1 who had received 2 cycles of ProMACE-CytaBOM prior to MACOP-B and 3 after a first salvage regimen, achieved complete remissions. Seventeen patients (65%) were transplanted in first remission, and 15 (58%) after induction treatment with only MACOP-B or VACOP-B. Reasons for not being given high dose therapy and autologous bone marrow transplantation (ABMT) were failure to achieve complete remission in 6 patients, early relapse in 2 and severe pulmonary toxicity associated with chemotherapy in 1. The median time of follow-up was 45 months. At 3 years, the estimated event-free survival was 31% (CI 14%-50%) and the overall survival 48% (CI 25%-67%). There were no deaths from toxic effects of treatment. Pretreatment factors associated with relapse were stage III or IV disease, age over 30 years and bone marrow involvement. Logrank analysis showed that age was the only factor significantly associated with poor event-free survival. CONCLUSION: Short-term weekly chemotherapy followed by high-dose therapy with the CBV regimen in first remission is not a higly effective treatment for advanced lymphoblastic and Burkitt's lymphomas. The 30% rate of failure to achieve partial remission after 6 weeks and/or complete response after 12 weeks of MACOP-B or VACOP-B treatment, as well as the 42% failure rate to undergo ABMT in first remission, suggest that more aggressive chemotherapy should be used in the beginning.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Linfoma de Burkitt/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Bleomicina/administración & dosificación , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/mortalidad , Carmustina/administración & dosificación , Ciclofosfamida/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Leucovorina/administración & dosificación , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Prednisona/administración & dosificación , Inducción de Remisión , Tasa de Supervivencia , Trasplante Autólogo , Vincristina/administración & dosificaciónRESUMEN
PURPOSE: The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT. RESULTS: For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients. CONCLUSION: Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Linfoma/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carmustina/administración & dosificación , Carmustina/efectos adversos , Terapia Combinada , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Filgrastim , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Recuento de Leucocitos , Linfoma/mortalidad , Masculino , Persona de Mediana Edad , Neutropenia/sangre , Neutropenia/inducido químicamente , Neutropenia/terapia , Neutrófilos , Estudios Prospectivos , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
Maintenance chemotherapy for up to 3 years is traditionally given to patients with acute lymphoblastic leukaemia (ALL) achieving complete remission. We questioned the value of such maintenance therapy in adult patients treated with intensive induction/consolidation. In a phase II study (SAKK 33/86) 63 patients between 17 and 72 years of age (median 27 years) with newly diagnosed ALL were treated with three intensive cycles of marrow-ablative chemotherapy. All subtypes were included. No maintenance phase was added. 53 patients (84%) entered a complete remission (CR) and 21 (33%) continue to be in unmaintained remission for 11-69 months (median 21 months). The disease-free survival of patients achieving CR and completing all three cycles is 40% at 3 years, with a 95% confidence interval of +/- 19%. These findings are comparable to the results of conventional studies. We conclude that maintenance therapy might not be needed in all adult ALL patients. Its value should be tested in a randomized trial. For patients failing, novel approaches are needed to improve outcome in adult ALL.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Anciano , Trasplante de Médula Ósea , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Probabilidad , Recurrencia , Inducción de Remisión/métodosRESUMEN
Clinical results of the treatment of malignant lymphomas with a high risk of relapse by dose intensification and autologous bone marrow transplantation are reported. Since 1988, 68 patients with a median age of 34 years (range 16 to 56 years) received dose intensification, including 25 non-Hodgkin's lymphomas in first remission (12 lymphoblastic or Burkitt's lymphomas and 13 large cell lymphomas with risk factors), 20 aggressive non-Hodgkin's lymphomas in chemosensitive relapse, and 23 Hodgkin's lymphomas in chemosensitive relapse. The calculated 3-year overall survival and relapse-free survival was 72% (CI: 57-82%) and 61% (CI: 47-73%) respectively. Treatment related deaths were seen in 4.4%. The median duration of hospitalization was 30 days (range 19-51 days). The relapse-free 3-year survival for the separate treatment groups was 80% for lymphoblastic and Burkitt's lymphomas in first remission, 77% for large cell lymphomas with clinical risk factors in first remission, 39% for aggressive non-Hodgkin's lymphomas in chemosensitive relapse, and 59% for Hodgkin's lymphomas in chemosensitive relapse. These excellent results were obtained with acceptable toxicity and justify the use of dose intensification for a group of young patients with high risk lymphomas.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trasplante de Médula Ósea , Linfoma de Burkitt/terapia , Linfoma de Células B Grandes Difuso/terapia , Adolescente , Adulto , Linfoma de Burkitt/mortalidad , Terapia Combinada , Relación Dosis-Respuesta a Droga , Trasplante de Células Madre Hematopoyéticas , Humanos , Linfoma de Células B Grandes Difuso/mortalidad , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Although hyperviscosity syndrome may lead to cerebral hypoxia and produce some degree of dementia, this condition is rarely recognized. We report a patient in whom moderate dementia was the only manifestation of a hyperviscosity syndrome due to an IgG-κ myeloma. Dementia dramatically improved following plasmapheresis.