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31.
Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation 总被引:2,自引:0,他引:2
Phillips GL; Wolff SN; Herzig RH; Lazarus HM; Fay JW; Lin HS; Shina DC; Glasgow GP; Griffith RC; Lamb CW 《Blood》1989,73(8):2086-2092
Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results. 相似文献
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Wolff SN; Marion J; Stein RS; Flexner JM; Lazarus HM; Spitzer TR; Phillips GL; Herzig RH; Herzig GP 《Blood》1985,65(6):1407-1411
High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches. 相似文献
34.
Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia 总被引:2,自引:4,他引:2
Rabinowe SN; Soiffer RJ; Gribben JG; Daley H; Freedman AS; Daley J; Pesek K; Neuberg D; Pinkus G; Leavitt PR 《Blood》1993,82(4):1366-1376
Twenty patients with poor prognosis B-cell chronic lymphocytic leukemia (B-CLL) underwent uniform high-dose chemoradiotherapy followed by rescue with multiple monoclonal antibody-purged autologous bone marrow (BM) (12 patients) or T-cell-depleted allogeneic BM from HLA-identical siblings (8 patients) in a pilot study to assess the feasibility of BM transplantation (BMT) in this disease. All had poor prognosis disease by either staging, BM pattern, tumor doubling time criteria, or cytogenetics. All patients achieved remission criteria (defined as < or = 2 adenopathy, absence of splenomegaly, < or = 20% of the intertrabecular space involved on BM biopsy) before BMT. Despite the use of fludarabine, a median of three treatment regimens were required to achieve BMT eligibility. After BMT, all patients achieved complete hematologic engraftment. Toxicities were not significantly different between autologous versus allogeneic BMT. Two toxic deaths were observed. Of 19 evaluable patients, 17 clinical complete clinical remissions (89%) were observed, with 2 patients (1 allogeneic and 1 autologous) exhibiting persistent BM disease. Complete clinical remissions were documented at the phenotypic and molecular level for the majority of patients in whom dual fluorescence for CD5 and CD20 (15 of 15; 100%) and Ig gene rearrangements (11 of 14; 79%) were performed. Although long-term follow-up is needed to assess any potential impact on the disease-free and overall survival of these patients, this study shows the feasibility of using high-dose chemoradiotherapy and BMT in patients with poor prognosis B-CLL. 相似文献
35.
Stimulation of tyrosine phosphorylation after ligation of beta7 and beta1 integrins on human B cells 总被引:2,自引:0,他引:2
Manie SN; Astier A; Wang D; Phifer JS; Chen J; Lazarovits AI; Morimoto C; Freedman AS 《Blood》1996,87(5):1855-1861
B lymphocytes express several members of the integrin family of adhesion molecules that mediate cell-cell and cell-extracellular matrix interactions. In addition to beta1 integrins, predominantly alpha4 beta1, mature B cells also express alpha4 beta7, which is a receptor for vascular cell adhesion molecule-1 and fibronectin, and is also involved in the homing of B cells to mucosal sites through binding to a third ligand, mucosal address in cell adhesion molecule-1. Here we describe that crosslinking of alpha4 beta7 integrins on B cell lines and normal tonsillar B cells, induces tyrosine phosphorylation of multiple substrates of 105-130 kD, indicating that beta7 integrin plays a role as signaling molecule in B cells. This pattern of phosphorylated proteins was very similar to that induced following ligation of alpha4 beta1. Interestingly, ligation of alpha5 beta1 or alpha6 beta1 also stimulated the 105-125 kD group of phosphorylated proteins, whereas ligation of beta2 integrins did not. The focal adhesion tyrosine kinase p125FAK was identified as one of these substrates. Beta1 or beta7 mediated tyrosine phosphorylations were markedly decreased when the microfilament assembly was inhibited by cytochalasin B. These results suggest that intracellular signals initiated by different integrins in B cells may converge, to similar cytoskeleton-dependent tyrosine phosphorylated proteins. 相似文献
36.
BACKGROUND & AIMS: Microvascular endothelial cells mediate leukocyte homing, angiogenesis, and inflammation and healing and show tissue- specific adhesion molecules and functions. The activation of human intestinal mucosal microvascular endothelial cells (HIMECs) was studied in vitro to uncover possible abnormalities associated with inflammatory bowel disease. METHODS: HIMECs were isolated from normal and inflammatory bowel disease mucosa and assessed for phenotypic and morphological features, proliferative response, leukocyte binding capacity, and adhesion molecule expression. RESULTS: Basal proliferation by HIMECs was less than that of human umbilical vein endothelial cells (HUVECs) but increased proportionally more in response to vascular endothelial growth factor. Proinflammatory stimuli induced an activated, spindle-shaped morphology in HIMEC monolayers. Compared with HUVECs, unstimulated HIMECs showed less adhesiveness for U937 and MOLT4 cells and neutrophils, but cytokines and lipopolysaccharide substantially increased the binding capacity of HIMECs. HIMECs derived from inflammatory bowel disease mucosa showed a markedly greater leukocyte-binding capacity than normal mucosal HIMECs. Patterns of intercellular adhesion molecule 1, vascular cell adhesion molecule 1 and E-selectin messenger RNA expression were distinct in HIMECs, HUVECs, and mucosal mesenchymal cells. CONCLUSIONS: HIMECs represent differentiated endothelial cells with unique functional properties. Their dramatically enhanced capacity to bind leukocytes in inflammatory bowel disease suggests that HIMECs play an important role in initiating or maintaining inflammation. (Gastroenterology 1997 Jun;112(6):1895-907) 相似文献
37.
Extranodal malignant lymphoma: detection with FDG PET versus CT 总被引:19,自引:0,他引:19
Moog F; Bangerter M; Diederichs CG; Guhlmann A; Merkle E; Frickhofen N; Reske SN 《Radiology》1998,206(2):475
38.
39.
DA O'Sullivan VE Torres PA Gabow SN Thibodeau BF King EJ Bergstralh 《American journal of kidney diseases》1998,32(6):976-983
Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD. 相似文献
40.
Objective: To identify risk factors for development of dehydration in under five year olds with acute watery diarrhoea.Design: Hospital based unmatched case-control study.Setting: Diarrhoea Treatment Unit, Government Medical College Hospital, Nagpur, India.Participants: The study included 387 cases of diarrhoea having severe or moderate dehydration and 387 controls suffering from diarrhoea with mild or no dehydration.Risk factors: The study included infancy, female sex, religion, residing in urban slums or rural area, under nutrition, cessation of breast feeding during diarrhoeal episode, fluid intake decreased/stopped during diarrhoea, ORS not received, home available fluids (HAF) not received, both ORS and HAF not received, non-washing of hands by mother before preparation of food, after defaecation, after disposal of faeces, history of measles in the previous six months, frequency of stools >8/d, frequency of vomiting more than twice per day and temperature more than 99°F, as risk factors for development of dehydration.Statistical analysis: Univariate analysis included OR, 95% CI for OR and Chi-square test. Multivariate analysis was carried out by unconditional multiple logistic regression (MLR).Results: This study identified the significance of infancy, religion, severe undernutrition, non-washing of hands by mother before preparation of food, frequency of stool >8/d, frequency of vomiting >2/d, history of measles in previous six months, withdrawal of breast feeding during diarrhoea, withdrawal of fluids during diarrhoea and not giving ORS, HAF or both during diarrhoea, in the outcome of development of moderate or severe dehydration.Conclusions: Timely intervention in the preventable risk factors included in this study may prevent the development of moderate or severe dehydration in the children suffering form acute watery diarrhoea. 相似文献