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Results for “multiagent systems”

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PubMed1985

Conversion to resectability by intra-arterial infusion chemotherapy after failure of systemic chemotherapy.

A 17 cm hepatoblastoma was unresectable at initial exploration. Multiagent chemotherapy (ADR, CTX, VCR, 5FU, BLEO) incurred minimal response at 5 months. Infuse-A-Ports were placed in each hepatic artery and FUDR infused intermittently but there was no response at 6 weeks. Adriamycin and vincristine were then begun via the Infuse-A-Port, with prompt regression of the tumor mass. The intra-arterial course was continued 3 months. Repeat arteriography showed vascular distortion but exploration revealed no gross tumor. A persistent alpha-feto-protein elevation prompted repeat arteriography 4 months afterward. A 3 cm calcific tumor was removed via an extended left lobectomy. Selective hepatic arterial infusion appeared to potentiate chemotherapy after systemic chemotherapy had failed to produce sufficient cytoreduction to allow safe surgical excision. The intra-arterial chemotherapy for unresectable hepatoblastoma warrants further investigation.

Antineoplastic Agents↗

PubMed1986

Growth and development following marrow transplantation for leukemia.

One hundred forty-two patients between the ages of 1 and 17 years who survived disease-free more than 1 year after marrow transplantation for hematologic malignancy had growth and development evaluations from one to 14 years posttransplant (median 4 years). Prior to transplant all children received multiagent chemotherapy and 55 also received central nervous system irradiation, but none had growth and development evaluations. Marrow transplant preparation included high-dose chemotherapy and total body irradiation (TBI) given as a single dose of 9.2 to 10.0 Gy (79 patients) or as fractionated doses of 2.0 to 2.25 Gy/d for six to seven days (63 patients). After transplant abnormal thyroid function was present in 39%. Stimulated 11-desoxycortisol levels were subnormal in 24% of patients evaluated. Growth hormone (GH) deficiency was present in 17 of 25 children who received previous cranial irradiation. Partial GH deficiency was present in 4 of 25 who received previous cranial irradiation and in 6 of 18 who had not received cranial irradiation. Height velocity was decreased in all patients. After transplant, height was significantly influenced by chronic graft-v-host disease and single-dose TBI. Sixty-eight percent had delayed development of secondary sexual characteristics. Gonadal failure occurred in nearly all who were postpubertal at transplant. While it is not possible to determine how many of these endocrine abnormalities occurred as a result of treatment administered prior to transplantation, these data do demonstrate that children who become long-term survivors after marrow transplantation for hematologic malignancy have endocrine abnormalities that adversely affect growth and development.

Adrenal Cortex↗

PubMed2002

Coordinated response to reports of possible anthrax contamination, Idaho, 2001.

In 2001, the intentional release of anthrax spores in the eastern United States increased concern about exposure to anthrax nationwide, and residents of Idaho sought assistance. Response from state and local agencies was required, increasing the strain on epidemiologists, laboratorians, and communications personnel. In late 2001, Idaho's public health communications system handled 133 calls about suspicious powders. For each call, a multiagency bridge call was established, and participants (public health officials, epidemiologists, police, Federal Bureau of Investigation personnel, hazardous materials officials, and others) determined which samples would be tested by the state public health laboratory. A triage system for calls helped relieve the burden on public safety and health systems.

Anthrax↗

PubMed1983

Successful treatment of primary central nervous system lymphomas with chemotherapy after osmotic blood-brain barrier opening.

Three patients with primary central nervous system (CNS) lymphoma have had major tumor regression with multiagent chemotherapy given in association with reversible blood-brain barrier opening used to enhance drug delivery to the tumor. In addition, in one patient barrier modification was carried out in the posterior fossa by mannitol infusion into the vertebral artery without untoward effects, an approach not heretofore accomplished. Computed tomographic (CT) studies documented that discontinuation of steroids rapidly effected an increase in the delivery of contrast agent to the tumor. CT monitoring of the degree of barrier modification showed tumor nodules and tumor size not apparent on the control scans, thereby providing additional evidence of the existence of a blood-brain barrier in CNS tumors. These studies further show that drug (contrast) delivery to the tumor, as well as to the surrounding barrier, is enhanced after reversible blood-brain barrier modification. Finally, chemotherapy administered by this approach resulted in defined, objective tumor responses in these three patients.

Adult↗

PubMedDate not supplied

Improved hematopoiesis using amifostine in secondary myelodysplasia.

An 11-year-old boy with multiply relapsed lymphoblastic disease became transfusion dependent with myelodysplasia and chromosomal abnormalities after 5 years of aggressive therapy. At 5 years of age, he presented with transient idiopathic hypoplastic anemia and neutropenia that spontaneously resolved within a month. Three months later, he experienced lymphoblastic lymphoma in the left parotid region and subsequently experienced disease relapse in his testicles, bone marrow, and central nervous system during a 3-year period. He has received multiagent chemotherapy, autologous peripheral blood stem-cell transplantation, and testicular and whole neuraxis irradiation therapy. After craniospinal irradiation, he did not recover normal bone marrow function. His bone marrow was hypocellular, and he required platelet and erythrocyte transfusions and granulocyte colony-stimulating factor. Marrow cytogenetic studies revealed new multiple translocations. Within a month of the initiation of intravenous amifostine at 200 mg/m2/dose three times a week, his leukocyte count, neutrophil count, and hemoglobin level normalized. His platelet count also improved sufficiently to achieve transfusion independence. He has returned to school and engages in other normal activities for his age. Amifostine may improve hematopoiesis in secondary myelodysplastic syndromes in children.

Amifostine↗

PubMed2005

GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia.

The probability of event-free survival of childhood acute lymphoblastic leukemia (ALL) approaches 80% or more with the use of modern multiagent chemotherapeutic regimens. One major contribution to this success has been reduction of the rate of central nervous system (CNS) relapses to less than 5%. However, heterogeneity is observed with regard to the incidence of CNS relapse in homogenously treated patient populations. One potential explanation for this heterogeneity is variation in the genetic background of these populations. Glutathione S-transferase P1 and P-glycoprotein are implicated in resistance to a variety of chemotherapeutic agents and have been localized to the blood-brain barrier. In a matched case-control study, we investigated the associations between CNS relapse in childhood ALL and the presence of phenotypically relevant single nucleotide polymorphisms within the GSTP1 (codon 105 and 114) and MDR1 genes (ABCB1; coding for Pgp; exon 26, C3435T). Significant reductions in risk of CNS relapse were observed for patients homozygous for the GSTP1 Val105 allele as well as for patients with the MDR1 3435T/T or C/T genotype. For both genotypes, the effect was restricted to patients at intermediate or high risk of treatment failure. These results suggested a modulating role for host genetic variation in the development of CNS relapse in childhood ALL treated according to Berlin-Frankfurt-Münster protocols.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

Primary CD30+ve cutaneous T-cell lymphoma associated with chronic burn injury in a patient with longstanding psoriasis.

An increased incidence of lymphoma has been reported in psoriatic patients, but most cases are nodal B-cell lymphoma. We report a unique case of CD30-expressing cutaneous T-cell lymphoma arising from underlying psoriatic plaque after intractable caustic burns and cellulitis in the palm of a patient with generalized chronic plaque psoriasis. Molecular studies confirmed a localized clonal T-cell expansion, and the lesion responded dramatically to multiagent chemotherapy. The case highlighted the possible role of chronic systemic and local T-cell activation in the pathogenesis of primary CD30+ve cutaneous T-cell lymphoma, and the importance of histologic assessment in chronic nonhealing skin lesions.

Burns↗

PubMed2000

Primary and secondary cutaneous CD30(+) lymphoproliferative disorders: a report from the Dutch Cutaneous Lymphoma Group on the long-term follow-up data of 219 patients and guidelines for diagnosis and treatment.

To evaluate our diagnostic and therapeutic guidelines, clinical and long-term follow-up data of 219 patients with primary or secondary cutaneous CD30(+) lymphoproliferative disorders were evaluated. The study group included 118 patients with lymphomatoid papulosis (LyP; group 1), 79 patients with primary cutaneous CD30(+) large T-cell lymphoma (LTCL; group 2), 11 patients with CD30(+) LTCL and skin and regional lymph node involvement (group 3), and 11 patients with secondary cutaneous CD30(+) LTCL (group 4). Patients with LyP often did not receive any specific treatment, whereas most patients with primary cutaneous CD30(+) LTCL were treated with radiotherapy or excision. All patients with skin-limited disease from groups 1 and 2 who were treated with multiagent chemotherapy had 1 or more skin relapses. The calculated risk for systemic disease within 10 years of diagnosis was 4% for group 1, 16% for group 2, and 20% for group 3 (after initial therapy). Disease-related 5-year-survival rates were 100% (group 1), 96% (group 2), 91% (group 3), and 24% (group 4), respectively. The results confirm the favorable prognoses of these primary cutaneous CD30(+) lymphoproliferative disorders and underscore that LyP and primary cutaneous CD30(+) lymphomas are closely related conditions. They also indicate that CD30(+) LTCL on the skin and in 1 draining lymph node station has a good prognosis similar to that for primary cutaneous CD30(+) LTCL without concurrent lymph node involvement. Multiagent chemotherapy is only indicated for patients with full-blown or developing extracutaneous disease; it is never or rarely indicated for patients with skin-limited CD30(+) lymphomas. (Blood. 2000;95:3653-3661)

Adolescent↗

PubMed1996

Carboplatin pharmacokinetics in young children with brain tumors.

PURPOSE: The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children given in combination with cyclophosphamide and etoposide. PATIENTS AND METHODS: Carboplatin was administered as part of a multiagent chemotherapy regimen to 21 pediatric patients less than 5 years of age with newly diagnosed, malignant central nervous system tumors. Patients, received cyclophosphamide, 1.2 g/m2, on day 1 and carboplatin on day 2 followed by etoposide, 100 mg/m2, each day. Carboplatin doses were calculated to achieve a targeted area under the serum concentration versus time curve (TAUC) of 5, 6.5 or 8 mg/ml.min based on each patient's measured glomerular filtration rate (GFR). Carboplatin pharmacokinetic parameters were determined after course 1 and then after every third course of therapy. RESULTS: The median carboplatin clearance and GFR after course 1 were 118 and 98 ml/min per m2, respectively. Targeted doses based on measured GFR reliably achieved the TAUC for carboplatin. The median (range) carboplatin clearance for four children less than 1 year of age was 76 (66-84) ml/min per m2, significantly lower (P = 0.05) than the value of 131 (80-158) ml/min per m2 for children from 1 to 4 years of age. The mean carboplatin clearance declined by 23% in 12 patients studied from course 1 to course 4 of therapy. The decrease was greater than 20% (range 20-53%) in 7 of the 12 patients studied. CONCLUSION: Carboplatin clearance for children aged between 1 and 4 years at diagnosis is approximately 45% higher than previously reported for pediatric patients, but declines after four courses of therapy. For children less than 1 year of age, carboplatin clearance per square meter is approximately 40% lower than patients 1 to 4 years of age. There are corresponding differences in GFR that provide a plausible explanation for the age and therapy-related changes in carboplatin clearance. Toxicity was acceptable for patients treated at a TAUC of 6.5 mg/ml.min for carboplatin given with etoposide and cyclophosphamide. The average carboplatin dose required for this AUC was 767 mg/m2.

Adolescent↗

PubMed2002

[Prognostic factors of childhood acute lymphoblastic leukemia].

The cure rate for children with acute lymphoblastic leukemia in big treatment centers in Western countries is now about 80%. This accomplishment is owe to patients successful treatment based on combination of multiagent chemotherapy, risk-based intensification of therapy and central nerve system prophylaxis. Stratification of patients is according to prognostic factors that predict risk of relapse. It is necessary to consider the interrelationship of prognostic factors. In host-related factors, which are generally known as age, gender, race, and pharmacogenetics. Disease-related factors include white blood cell count, immunopheno typing, cytogenetic or molecular genetics features, etc. Treatment-related factors are what can be modified. Early response to treatment is often the strongest prognostic factor. Large, controlled and usually randomized clinical trials greatly improve the prognosis of childhood acute lymphoblastic leukemia.

Child↗

PubMed1998

The classification of gestational trophoblastic disease: a critical review.

Gestational trophoblastic disease defines a group of conditions which arises from the fetal chorion. Two of the most important advances in the management of gestational trophoblastic disease have been the standardisation of terminology, and the concept of risk assignment based on classification or staging systems which allows rationalisation of treatment. Gestational trophoblastic disease is unique as the prognosis is dependent not only on the anatomic extent but also the presence of prognostic factors. A staging system similar to that used for other cancers does not apply to this disease because in most cases diagnosis is bases not on histology but on clinical or biochemical parameters. Metastatic spread to distant organs can occur early, even in the absence of disease in the uterus or pelvis. Staging in gestational trophoblastic disease must include prognostic factors in addition to anatomic extent of disease. Broadly there are two categories of classification in current use. The first is based on the usual staging system as in other cancers, with four stages of disease, but at the same time prognostic factors are incorporated. This has the important advantages of simplicity and uniformity with other staging systems. However the main pitfall is that no recommendations are made for treatment. The other broad category consists of risk tables, based on anatomic spread as well as prognostic factors. Here patients are assigned varying risk scores, with guidelines for multiagent chemotherapy at the outset in high-risk patients to minimise drug resistant disease. The ideal system would be one which has four stages of disease, so that comparison is easier, with recommendations for combination chemotherapy beyond a certain stage of disease.

Female↗

PubMed2002

Supratentorial embryonal tumors in children under 5 years of age: an SFOP study of treatment with postoperative chemotherapy alone.

BACKGROUND: To determine the effectiveness of multiagent chemotherapy as sole post-operative treatment of supratentorial central nervous system (CNS) embryonal tumors in young children. PROCEDURE: The data of 25 children under 5 years of age diagnosed with supratentorial embryonal tumors (17 primitive neuroectodermal tumors, four pinealoblastomas, and four medulloepitheliomas) treated exclusively by postoperative chemotherapy (CT) between 1990 and 1997 were reviewed. RESULTS: Fifteen tumors were hemispheric and 10 were deeply seated. Four children presented with disseminated leptomeningeal disease. Total resection was performed in nine patients, subtotal in 9, partial in 3, and a diagnostic biopsy only in 2. Two children did not undergo surgery. Twenty-four children relapsed with a median time of 5.5 months. The median overall survival was 12 months, and the 2-, and 5- year survivals were 30 and 14%, respectively. The 2- year disease-free survival was 4%. There was a significantly worse prognosis in patients undergoing incomplete resection and in the group with deeply situated tumors. Four relapses were treated by second surgery followed by high-dose chemotherapy and radiotherapy. Two of them remain in CR2, and all these children are free of late sequelae. CONCLUSIONS: CT alone failed to maintain disease-free survival in most of the children, although, disease progression was delayed to some extent. Children under 5 years with supratentorial embryonal tumors should undergo total surgical resection if possible.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Osteosarcoma of the trunk treated by multimodal therapy: experience of the Cooperative Osteosarcoma study group (COSS).

The case histories of all patients with osteosarcoma of the trunk entered into the consecutive studies COSS 80 through COSS 86 of the Cooperative German/Austrian Osteosarcoma Study Group (COSS) were analyzed in order to evaluate their clinical characteristics and the impact of modern neoadjuvant therapy on prognosis. They were compared to those of all patients with extremity osteosarcoma treated according to the same protocols. While tumors of the trunk comprised only 32 (4.8%) of 665 primary classical osteosarcomas, secondary osteosarcomas were much more likely to be located in bones of the axial skeleton (6 of 18, 33%). Patients with primary osteosarcoma of the axial skeleton were older (mean: 20.8 vs. 15.2 years, P < 0.01) and were more likely to present with metastases at diagnosis (34% vs 12%, P < 0.001) than those with primary extremity osteosarcoma. In contrast to extremity tumors, local surgical treatment failure was very common in osteosarcomas of the trunk. Complete tumor removal was achieved in less than half of all evaluable cases. The prognosis of eight patients with localized primary axial osteosarcoma and effective surgical local control was not inferior to that of 483 equally evaluable patients with extremity tumors. In conclusion, while secondary systemic spread of axial osteosarcoma may be avoided in patients treated with multiagent chemotherapy, successful treatment is often barred by primary metastatic disease and inability to control the local tumor site.

Adolescent↗

PubMed2001

[Anti-CD20 antibodies in primary cutaneous B-cell lymphoma. Initial results in dermatologic patients].

BACKGROUND AND OBJECTIVE: Primary cutaneous B cell lymphomas (pCBCL) are rare extra-cutaneous non-Hodgkin lymphomas which occur on the trunk as follicle center cell lymphoma or on the leg as large B cell lymphoma. The currently accepted therapy of pCBCL (excision and/or radiotherapy, systemic interleukin 2 and interferon alpha 2a, local injection of cisplatin or multiagent chemotherapy, i.e. CHOP) is insufficient for treatment of multifocal pCBCL and secondary extracutaneous involvement. For this reason, the new synthetic chimeric, monoclonal anti-CD20 antibody Rituximab is an alternative treatment for patients with pCBCL. PATIENTS/METHODS: Four patients with pCBCL localized to the trunk or head were treated with Rituximab (375 mg/kg weekly for 4-8 weeks, then maintenance therapy every 4 weeks for 6 months). RESULTS: All 4 patients showed a response (2/4 partial; 2/4 complete). Side effects were minimal. CONCLUSIONS: Rituximab is an alternative immunotherapeutic drug for the treatment of pCBCL. Our initial experience with this new modality are presented and discussed.

Aged↗

PubMed2001

On the relative importance of haplodiploidy, assortative mating and social synergy on the evolutionary emergence of social behavior.

Advances in multiagent simulation techniques make it possible to study more realistic dynamics of complex systems and allow evolutionary theories to be tested. Here I use simulations to assess the relative importance of reproductive systems (haplodiploidy vs. diploidy), mate selection (assortative mating vs. random mating) and social economics (pay-off matrices of evolutionary games) in the evolutionary dynamics leading to the emergence of social cooperation in the provision of parental care. The simulations confirm that haplo-diploid organisms and organisms mating assortatively have a higher probability for fixing alleles and require less favorable conditions for their fixation, than diploids or organisms mating randomly. The simulations showed that social behavior was most likely to emerge a) when the cost for parental investment was much lower than the benefits to the offspring, b) when cooperation improved synergistically the fitness of offspring compared to the corresponding egoistic behavior and c) when alleles coding for altruistic or social behavior could be rapidly fixed in the population, thanks to mechanisms such as haplo-diploidy and/or assortative mating. Cooperative social behavior always appeared if sociality conferred much higher fitness gains compared to non cooperative alternatives suggesting that the most important factors for the emergence and maintenance of social behavior are those based on energetic or efficiency considerations. The simulations, in congruence with the scant experimental evidence available, suggest that economic considerations rather than genetic ones are critical in explaining the emergence and maintenance of sociality.

Animals↗

PubMed2004

Successful treatment of congenital systemic juvenile xanthogranuloma with Langerhans cell histiocytosis-based chemotherapy.

Juvenile xanthogranuloma (JXG), one of the most common forms of non-Langerhans cell histiocytosis (LCH), usually presents in young children as spontaneously regressing cutaneous lesions. However, the systemic type of JXG is difficult to treat in newborn infants, and fatal cases have been reported. In the patient described here, solid masses were discovered by fetal sonography during the 38th gestational week. At birth she had multiple tumors on the back, cheek, and hip as well as marked hepatosplenomegaly accompanied by respiratory failure. Laboratory results indicated pancytopenia, obstructive liver dysfunction, and coagulopathy. Brain magnetic resonance imaging revealed a tumor at the left pontine angle, and dysmorphic histiocytes were present in her spinal fluid. She was diagnosed with systemic JXG by histopathologic findings of the hip mass. The LCH-based multiagent chemotherapy including cytarabine, vincristine, methotrexate, and prednisolone ameliorated the symptoms rapidly. She was treated for 12 months and is currently doing well as a normally developing 2-year-old.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Perspectives in melanoma treatment with signal transduction.

Data from all parts of the world show a rising incidence of cutaneous malignant melanoma. The latter is one of the most difficult malignancies to treat. Early stage melanoma is curable but once metastatic it is almost uniformly fatal. Systemic therapy for advanced melanoma includes chemotherapy, either with dacarbazine alone or a multiagent combination chemotherapy, and biological therapy with recombinant interferon-alpha and/or interleukine-2. However none of these treatments options has produced long-term control of the disease except on rare occasion. In the present review, new strategies in the treatment of malignant melanoma that are now under investigations are discussed. Such new strategies might could be open new perspectives avoiding the toxicity of the conventional treatments too. In particular, possible agents acting on signal transduction pathways, such as Protein Kinase C modulators, and on the cell cycle are reviewed. Melanoma is the most immunogenic tumor among all tumor neoplasia. The feature has led to test several immunological strategies for manipulating immune responses in order to induce tumor growth control in vivo. Thus, the most interesting and recent strategies in this field and in particular the possibility to use specific vaccines are also considered.

Animals↗

PubMed1988

[Cis-platinum, vincristine and peplomycin (CVP) therapy for carcinoma of the uterine cervix].

Surgery and radiation therapy are major treatments for carcinoma of the uterine cervix. However, there has been little improvement in survival recently. Since 1982, we have introduced multiagent chemotherapy consisting of cis-platinum, vincristine and peplomycin (CVP) to control systemic disease and to do cytoreduction prior to operation and/or radiation therapy. Our results are as follows. Thirty-one patients have been treated with CVP. Among eleven patients initially treated with CVP, 7 patients responded well to this regimen alone, including three patients who entered complete clinical remission. This indicates that this regimen is effective against carcinoma of the uterine cervix. Two patients who were thought to be candidates for radical hysterectomy became able to have less extensive surgery following CVP treatment. It is difficult for this CVP combination to control bulky tumors within previously radiated fields, probably because of poor vascularity due to pelvic fibrosis caused by radiation. Metastatic disease were also able to be controlled by this combination especially in two patients with pulmonary metastases. Nausea, vomiting and mild myelosuppression were frequently encountered, but they were tolerated well by the patients. However, great care must be taken in using peplomycin when the cumulative dose becomes large.

Adult↗