Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1-13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.
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PMID:Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide. 201 51

Twenty-five patients with recurrent or advanced-stage endometrial cancer were treated with cisplatin, doxorubicin, and cyclophosphamide (PAC) from May 1982 to November 1987. A retrospective chart analysis was performed to evaluate the effect of treatment on survival and progression-free interval. Toxicity was moderate. Neutropenia was the most common side effect. Age, performance status, and tumor cytoreduction were statistically significant predictors of survival time (P less than 0.03). In the 17 evaluable patients, the response rate was 47%. PAC is an active regimen in the treatment of endometrial cancer. Larger prospective studies are needed to evaluate whether tumor cytoreduction is important in the treatment of this disease.
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PMID:Treatment of advanced and recurrent endometrial cancer with cisplatin, doxorubicin, and cyclophosphamide. 205 Mar 2

Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors with middle- or outer-third myometrial invasion (16), grade 3 tumors with any degree of myometrial invasion (17), presence of extrauterine disease with no gross residual (17), or a high-risk histologic subtype including papillary serous (4), adenosquamous (5), or clear cell (1) tumors. Patients received PAC (50/50/500 mg/m2) at 4-week intervals for six cycles. Thirty patients (90%) completed therapy. Toxicity included severe neutropenia in 14 patients, neutropenic sepsis in 2 patients, and doxorubicin-related cardiomyopathy in 1 patient. There were no treatment deaths. Current median follow-up is 25 months. Nine patients (27%) have developed a recurrence, 7 of whom died, after a median interval of 14 months. Eight of the 9 with recurrence initially had extrauterine disease (P = 0.02). The resulting 2-year actuarial progression-free and overall survival rates were 79 and 83%, respectively. The median progression-free interval was 29 months for patients with extrauterine disease and 45+ months for those with no extrauterine disease (P = 0.02). These results suggest that a phase 3 randomized trial comparing adjuvant PAC with radiation therapy is warranted.
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PMID:Adjuvant chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC) for early-stage high-risk endometrial cancer: a preliminary analysis. 222 40

Long-term intermittent venous access was established in 26 children by means of a central venous catheter (CVC) with a subcutaneous injection port (Port-A-Cath) (PAC). As of December, 1985, PACs had been in place for 20-750 days (cumulative 10,890 days) with 647 entries into the system. The PACs were used for blood sampling and administration of chemotherapy, antibiotics, fluids, total parenteral nutrition (TPN), and blood products. One patient with sever neutropenia (absolute neutrophil granulocyte count [ANC] less than 0.1 x 10(9)/L) at the time of the PAC implant developed an infection around the port after 2 days, with subsequent septicemia (Bacillus cereus) necessitating removal of the PAC. Otherwise, no definite PAC-related infections occurred, including 258 days of neutropenia (ANC less than 0.5 x 10(9)/L). Two PACs were found occluded with greyish deposits of fat and organic material after long-term (45 and 61 days) continuous TPN and were removed. Malposition of catheter, extravasation, thrombosis, and other potential technical or psychological complications were not observed. The children continued normal activities, and the easy venous access decreased emotional stress during treatment. Local doctors were trained to use the PACs, with which they administered maintenance chemotherapy. We conclude that the use of PACs in children is safe, even in the first year of life, and has many advantages when compared with other CVCs currently in use. Strict indications, meticulous implantation technique, and adequate handling are, however, mandatory.
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PMID:Central venous catheter with subcutaneous injection port (Port-A-Cath): clinical experience with children. 315 37

This report describes in detail an unusual variant of a common variable immunodeficiency disease in a seven-year-old boy. The unique features were progressive neutropenia due to defective myelopoiesis, serum IgG and IgA deficiencies, defective immunoglobulin light-chain synthesis, absence of secretory IgA and IgM gammopathy. He had been born healthy, but following a thermal injury at the age of 1 1/2 years, he suffered recurrent attacks of sinopulmonary and urinary tract infections, enteritis due to enteropathogenic E. coli, Giardia lamblia and E. histolytica, developed pulmonary tuberculosis and died of deep mycotic infection of the oral cavity and obstruction of the bronchial tree. The cause of the defective myelopoiesis could not be determined, but it might have been due to prolonged sulphomamide therapy administered for controlling his persistent urinary tract infection due to paraphymosis.
Asian Pac J Allergy Immunol 1985 Dec
PMID:A rare case of variable immune deficiency with type II dysgammaglobulinaemia, light chain defect, gut associated IgA deficiency and progressive neutropenia. 393 29

Because extrapelvic failure is common in women with high-risk endometrial carcinoma, the curative impact of adjuvant irradiation is limited. To address the issue of systemic failure, we prospectively treated 62 at-risk patients with postoperative chemotherapy between October 1985 and April 1992. Patients were considered eligible if they had grade 2 disease with mid- or outer one-third myometrial invasion, grade 3 tumor with any myometrial invasion, completely resected extrauterine disease, or variant histology (clear cell, papillary serous). Adjuvant therapy consisted of intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) given every 4 weeks for six courses. Toxicity was moderate: 31 patients (50%) had grade 3/4 neutropenia; dose reductions were mandated in 39 cases. However, there were only four hospital admissions for toxicity during 366 treatment cycles. All but three patients completed planned treatment. Recurrences have been noted in 14 of 29 patients with extrauterine disease and in 8 of 33 without. Eighteen of the 22 recurrences (82%) were outside the pelvis. At this writing, 17 patients with recurrence were dead, and 4 are alive with disease. Median time to recurrence was 13 months. Observed progression-free intervals for those with and without extrauterine disease are 26 and 36+ months, respectively, over a median follow-up period of 37 months. Actuarial 3-year survivals for those with and without extrauterine spread were 46 and 82%, respectively. Although adjuvant PAC did not prevent distant failure in women with extrauterine disease, the survival rate was greater than that anticipated for patients with disease confined to the uterus. A randomized trial comparing adjuvant irradiation to PAC is warranted in this subset.
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PMID:Postoperative adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy in women with high-risk endometrial carcinoma. 795 65

We have conducted an open, controlled study on the febrile neutropenia effects by Lenograstim (Granocyte) therapy following cytotoxic chemotherapy of cisplatinum and cyclophosphamide in patients with primary advanced epithelial ovarian cancer. Eligible patients (n = 17) were divided into 2 groups receiving a combined chemotherapy of intravenous cisplatinum (70 mg/m2) and cyclophosphamide (700 mg/m2) with or without the addition of Lenograstim. Subcutaneous administration of Lenograstim (100 micrograms/day) for 7 consecutive days was given from day 8 to day 14 of the 3rd to the 5th cycle of chemotherapy in Lenograstim treated patients. After 3 cycles of treatment, Lenograstim treated patients (group 1, n = 10) showed a significant improvement in white blood cell (WBC) count as compared with group 2 (control) of 7 patients (p = 0.00002). Group 1 patients also showed an increased C-reactive protein, though of no significance. There were no significant differences among the 2 groups regarding ESR, hematocrit, platelet counts and blood chemistry profiles. This preliminary data encourages more study of the benefits of Lenograstim in the treatment of ovarian cancer.
Asian Pac J Allergy Immunol 1998 Mar
PMID:The use of lenograstim (Granocyte) in chemotherapy for ovarian cancer. 968 Nov 28

To determine the morbidity associated with long-term use of a totally implantable central venous access device (Port-A-Cath [PAC]) in patients with AIDS, we studied 68 consecutive patients with AIDS requiring 79 such devices for long-term use, inserted over a period of 5 years. The total number of PAC-days was 20,159. At least one PAC-related complication occurred with 40 of 79 PACs (50.6% [95% confidence interval (CI): 39.6%-61.6%]), and 16 devices (20.2% [95% CI, 11.4%-29.0%]) had to be removed because of complications. Device-related infection occurred with 33 of 79 PACs (41.7% [95 CI, 30.8%-52.6%]). The predominant infection occurring with PACs was chamber infection, with an incidence of 0.16 per 100 PAC-days. The predominant organisms isolated from patients with chamber infections but also from those with device-related bacteremia were gram-positive cocci (79.4%). The presence of neutropenia (odds ratio [OR] = 9.72; 95% CI, 3.0-31.3; P < .001) and a CD4 cell count lower than 0.025 x 10(9)/L (OR = 6.14; 95% CI, 1.9-19.2; P = .002) were independent predictors of infection. The antibiotic lock technique was associated with decreased device loss when compared with isolated systemic antibiotic therapy (OR = 0.05; 95% CI, 0.0-0.59; P = .008). This technique may be useful to treat PAC infection in patients with AIDS, for whom the risk of PAC-related complications is very high.
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PMID:Morbidity associated with long-term use of totally implantable ports in patients with AIDS. 1047 40

In hematopoiesis, cytokine levels modulate blood cell replacement, self-renewal of stem cells, and responses to disease. Feedback pathways regulating cytokine levels and targets for therapeutic intervention remain to be determined. Amino boronic dipeptides are orally bioavailable inhibitors of dipeptidyl peptidases. Here we show that the high-affinity inhibitor Val-boro-Pro (PT-100) can stimulate the growth of hematopoietic progenitor cells in vivo and can accelerate neutrophil and erythrocyte regeneration in mouse models of neutropenia and acute anemia. Hematopoietic stimulation by PT-100 correlated with increased cytokine levels in vivo. In vitro, PT-100 promoted the growth of primitive hematopoietic progenitor cells by increasing granulocyte-colony-stimulating factor (G-CSF), interleukin-6 (IL-6), and IL-11 production by bone marrow stromal cells. Two molecular targets of PT-100 are expressed by stromal cells- CD26/DPP-IV and the closely related fibroblast activation protein (FAP). Because PT-100 was active in the absence of CD26, FAP appears to be the hematopoietic target for PT-100. Interaction of PT-100 with the catalytic site seems to be required because amino-terminal acetylation of PT-100 abrogated enzyme inhibition and hematopoietic stimulation. PT-100 is a therapeutic candidate for the treatment of neutropenia and anemia. The data support increasing evidence that dipeptidyl peptidases can regulate complex biologic systems by the proteolysis of signaling peptides.
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PMID:Hematopoietic stimulation by a dipeptidyl peptidase inhibitor reveals a novel regulatory mechanism and therapeutic treatment for blood cell deficiencies. 1273 65

X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder caused by mutations of the gene encoding the CD40 ligand (CD40L). It is characterized by recurrent infections with markedly decreased serum IgG, IgA and IgE levels but normal or elevated IgM levels. We report the clinical manifestations and complete immune studies in the first family with molecularly proven XHIM in Taiwan. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgA, and IgE were noted in his plasma specimen: IgM, 128 mg/dl; IgG, 18 mg/dl; IgA, 4 mg/dl); IgE, 1 IU/ml. Whole blood flow cytometry when he was 21 months old showed that only a small percentage (0.48%) of his in vitro-activated CD4+ T cells expressed CD40L. When he was 3 years old, repeated flow cytometry showed essentially the same result (0.4%), compared with his father's CD40L expression of over 85%. The patient's mother had moderately decreased CD40L expression (74.4%). Hyper-IgM syndrome was confirmed by CD40L mutation analysis in the boy, which revealed a Lys 96 stop (nucleotide A307T) in exon 2 of CD40L, with a truncated protein resulting in the loss of the entire TNF domain. His mother was a carrier and apparently the individual in whom the mutation originated. Eleven other family members, including the patient's father, sister, and grandmother, and the mother's sisters and their children, all had normal results on CD40L mutation analysis. The patient has remained without significant bacterial infection on a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, although he has had recurrent oral ulcers and neutropenia. Bone marrow transplantation is planned.
Asian Pac J Allergy Immunol 2005 Mar
PMID:De novo mutation causing X-linked hyper-IgM syndrome: a family study in Taiwan. 1599 75


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