RESUMEN
Cytotoxic therapy is a cornerstone for patients with severe systemic lupus erythematosus (SLE). High-dose cyclophosphamide, 200 mg/kg, can induce a complete remission without the need for stem cell rescue in patients with autoimmune illnesses. Here we report on our first four patients treated for severe SLE with this treatment approach. Patients received cyclophosphamide, 200 mg/kg, divided over 4 days. Starting day 10, patients received filgrastim, 5 micrograms/kg/day, until their absolute neutrophil count (ANC) rose to 10.0 x 10(9)/l for two consecutive days. Disease activity as evaluated by scores from the Systemic Lupus Activity Measure-2, the SLE Disease Activity Index and the Responder Index for Lupus Erythematosus were completed before and after high-dose therapy. Before high-dose cyclophosphamide, SLE disease duration ranged from 8 to 21 (mean 12.5) years. Their average disease activity measured by SLAM-2 and SLEDAI was 15.5 (range 11-19) and 23.25 (range 20-26), respectively. At a median of 22 (range 12-39) months of follow-up, mean disease activity measured by SLAM-2 and SLEDAI decreased to 6.25 and 7.75, respectively. All patients experienced febrile neutropenia. No long-term morbidities or mortalities were observed. High dose cyclophosphamide is a therapy capable of decreasing disease severity in poor prognosis SLE patients. Future study is warranted for both refractory patients as well as primary therapy for patients with moderate to severe disease presentations.
Asunto(s)
Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Femenino , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Four patients with chronic inflammatory demyelinating polyneuropathy (CIDP) who were refractory to conventional treatment were treated with high-dose cyclophosphamide (200 mg/kg over 4 days). All improved in functional status and muscle strength. Nerve conduction studies improved in three of four. Other immunomodulatory medications have been discontinued. High-dose cyclophosphamide can be given safely to patients with CIDP and patients with disease persistence after standard therapy may have a response that lasts for over 3 years and results in long-term disease remission.
Asunto(s)
Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Trasplante de Células Madre , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/inmunología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Células Madre/inmunología , Resultado del TratamientoRESUMEN
PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.
Asunto(s)
Antineoplásicos/uso terapéutico , Trasplante de Médula Ósea , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Hematopoyesis , Interleucina-3/uso terapéutico , Linfoma no Hodgkin/terapia , Adolescente , Adulto , Anciano , Superficie Corporal , Terapia Combinada , Método Doble Ciego , Femenino , Humanos , Modelos Logísticos , Linfoma no Hodgkin/fisiopatología , Linfoma no Hodgkin/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recuento de Plaquetas , Proteínas Recombinantes de Fusión/uso terapéutico , Factores de Tiempo , Trasplante Autólogo , Resultado del TratamientoRESUMEN
While half of all patients receiving bone marrow transplantation (BMT) for malignancies and related diseases may achieve prolonged disease-free survival, 2-10% of patients undergoing allogeneic transplantation develop bronchiolitis obliterans (BrOb). We have hypothesized that total body irradiation (TBI) which has been used for pretreatment may influence the subsequent development of BrOb in patients undergoing allogeneic BMT. Since 1976, we have treated 104 patients undergoing allogeneic BMT with non-TBI preconditioning. Of 60 patients that survived and were evaluable for chronic graft versus host disease (GVHD) 26 developed chronic GVHD (43%). Four of 104 patients (3.9%) developed BrOb by clinical and/or pathologic findings. Four of 4 patients (100%) with BrOb had chronic GVHD. Two of these 4 patients (50%) were alive at the end of 2 years. These data demonstrate that chronic GVHD is a risk factor for BrOb in patients receiving non-TBI preconditioning regimens. The similar incidence of BrOb in this population compared to other studies using TBI suggest that the preconditioning regimen is not a factor in the development of BrOb. Further study is needed to confirm these findings. Allogeneic bone marrow transplantation (BMT) has revolutionized the therapeutic approach toward acute and chronic leukemias, aplastic anemia and rare immunodeficiency disorders. Half of all patients that undergo BMT achieve long-term disease-free survival but a similar number develop significant complications [1].(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Bronquiolitis Obliterante/etiología , Adulto , Bronquiolitis Obliterante/epidemiología , Bronquiolitis Obliterante/prevención & control , Busulfano/uso terapéutico , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Leucemia Mieloide Aguda/cirugía , Masculino , Persona de Mediana Edad , Factores de Riesgo , Irradiación Corporal TotalRESUMEN
We performed a retrospective analysis of 42 consecutive patients undergoing autologous BMT to determine the incidence of second and third degree heart block following the infusion of cryopreserved autologous bone marrow and to identify any predisposing characteristics. A decrease in heart rate > or = 10 beats/min was observed in 80.5% of patients, with a mean decrement of 27 +/- 7 beats/min. 48.8% of patients developed absolute bradycardia (< or = 60 beats/min). Four of 41 patients (9.7%) experienced high-grade heart block: 9.7% second degree and 4.8% third degree. Heart block patients did not differ from the non-heart block group with respect to age, interval from diagnosis or bone marrow harvest to transplant, cardiac risk factors, pretransplant electrocardiograms or radionuclide angiograms, transplant chemotherapy regimens or serum chemistry values. There was an increased incidence of heart block in patients with prior exposure to cyclophosphamide (p < 0.05) and vinca alkaloids (p < 0.05). There appears to be a high incidence of transient second and third degree heart block following autologous marrow infusion. This may be related to prior chemotherapy, but more likely is an effect of the infusate itself. Predisposing factors were not identified.
Asunto(s)
Trasplante de Médula Ósea/efectos adversos , Bloqueo Cardíaco/etiología , Enfermedad de Hodgkin/cirugía , Leucemia Mieloide Aguda/cirugía , Adolescente , Adulto , Ciclofosfamida/uso terapéutico , Femenino , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Alcaloides de la Vinca/uso terapéuticoRESUMEN
Neutrophilic eccrine hidradenitis (NEH) is a neutrophilic dermatosis primarily affecting the eccrine glands, and most commonly seen in patients undergoing chemotherapy for treatment of a malignancy. Rapid diagnosis may avert unnecessary changes in therapy to treat conditions which clinically mimic NEH. We describe a patient who developed NEH on three separate occasions provoked by two different chemotherapeutic agents--cytarabine and mitoxantrone. The lesions were morphologically distinct and differed in their anatomical distribution during each episode. The response to intravenous corticosteroids was dramatic, but lesions recurred after their withdrawal. This case illustrates the potential diversity of clinical lesions in a single patient with NEH, and its response to systemically administered corticosteroids.