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Biomedical subjects

G Schiller

Publications and source records attributed to G Schiller.

At least 19 recordsLinked to original sources
PubMed2006

[Need for psychosocial care in in-patients with tumour disease. Investigations conducted in a clinic specializing in tumour surgery].

BACKGROUND: Patients with tumour disease are in particularly stressful situation at all times. The aim of the present study was to find what proportion of patients on a surgical oncology ward would also benefit from psycho-oncological care. PATIENTS AND METHOD: Within a period of 6 months (IIIrd and IVth quarters of 2004) 406 of our tumour patients were questioned with the aid of a method (Po-Bado) developed specifically for use with such patients. RESULTS: According to this inquiry, it can be assumed that 41.4% of tumour patients are in need of professional psycho-oncological support. Patients who are in hospital for diagnostic procedures to confirm or exclude the suspicion of tumour disease have a greater need for such support (48.7%) than do patients who have been admitted for a scheduled operation (37.3%). Correlations were found between the need for this therapy and different disease situations. The prevalence of need was highest among patients with a second tumour, in whom it was 66.7%. The type of tumour disease also had an influence whether psycho-oncological care was indicated. The study revealed that patients with malignant soft-tissue tumours (49%) and patients with tumours of the upper digestive organs (48.7%) find the mental stress more difficult to cope with than patients who are in hospital for treatment of malignant skin tumours (31.8%) or malignant tumours of the mammary gland (38.7%). CONCLUSION: These results suggest that an adequate psycho-oncologic diagnostic at the start of a stationary stay are reasonable. This is a precondition for a well-directed psycho-oncologic intervention in order to enhance the disease accomplishment but at the same time the target-oriented supply of psycho-oncologic care in hospitals is a limited resource.

Adolescent↗
PubMed2006

Posaconazole as salvage therapy for zygomycosis.

Zygomycosis, an infection that is associated with significant morbidity and mortality, is becoming common in immunocompromised patients. Posaconazole is a new extended-spectrum azole antifungal that has demonstrated in vitro and in vivo activity against zygomycetes. This report provides the results from the first 24 patients with active zygomycosis who were enrolled in two open-label, nonrandomized, multicentered compassionate trials that evaluated oral posaconazole as salvage therapy for invasive fungal infections. Posaconazole was usually given as an oral suspension of 200 mg four times a day or 400 mg twice a day. Eleven (46%) of the infections were rhinocerebral. Duration of posaconazole therapy ranged from 8 to 1,004 days (mean, 292 days; median, 182 days). Rates of successful treatment (complete cure and partial response) were 79% in 19 subjects with zygomycosis refractory to standard therapy and 80% in 5 subjects with intolerance to standard therapy. Overall, 19 of 24 subjects (79%) survived infection. Survival was also associated with surgical resection of affected tissue and stabilization or improvement of the subjects' underlying illnesses. Failures either had worsening of underlying illnesses or requested all therapy withdrawn; none of the failures received more than 31 days of posaconazole. Posaconazole oral solution was well tolerated and was discontinued in only one subject due to a drug rash. Posaconazole appears promising as an oral therapy for zygomycosis in patients who receive required surgery and control their underlying illness.

Administration, Oral↗
PubMed2002

Interferon-alpha induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo.

The ability of interferon-alpha (IFN-alpha) to induce dendritic cell (DC) differentiation in chronic myeloid leukemia (CML) was evaluated. Peripheral blood mononuclear cells from CML patients cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology. Fluorescence in situ hybridization demonstrated that the DCs harbored the bcr/abl translocation. The DCs prepared with IFN-alpha/GM-CSF expressed significantly higher levels of class I and II HLA than those grown in interleukin-4 (IL-4) and GM-CSF. The DCs prepared from newly diagnosed CML patients using IFN-alpha/GM-CSF expressed immunoregulatory proteins at levels comparable to normal DCs. In contrast, DCs cultured from CML patients who did not achieve a cytogenetic response to IFN-alpha expressed significantly lower levels of class I HLA, CD40, CD54, CD80 and CD86 than normal DCs. The expression of CD86 by CML DCs was enhanced when they were cultured with IFN-alpha/IL-4/GM-CSF, or when IFN-alpha/GM-CSF-treated cells were induced to mature by CD40 ligand. The DCs from IFN-alpha failures were less stimulatory than normal DCs in the allogeneic mixed leukocyte reaction. CML patients who had a cytogenetic response to IFN-alpha initially had low numbers of bone marrow DCs that increased significantly with treatment, while nonresponders had more prevalent DCs at baseline that showed no consistent change with treatment. Therefore, IFN-alpha can induce DC differentiation from CML progenitor cells both in vitro and in vivo. The therapeutic activity of IFN-alpha in CML may be due to its ability to stimulate the generation of DCs that can present CML-specific antigens. Resistance to IFN-alpha may result when DC differentiation becomes impaired.

Antigen Presentation↗
PubMed2002

Mapping the public health workforce I: a tool for classifying the public health workforce.

We aimed to develop a tool to identify members of the public health workforce and classify them using categories developed for the Chief Medical Officer's project to strengthen the public health function. The tool was developed to gain a picture of London's public health workforce, and needed to be reliable and easy to use in many settings inside and outside the health service. We needed to be able to classify posts from brief information without interrogation of postholders, so that the entire workforces of large organisations could be classified from information provided by only a few key informants. Key questions and decision rules were defined by presenting interviewees in public health with brief information on nine jobs and discussing with them the process by which they determined whether each post was in the public health workforce, and if so, in which category. The questions and decision rules were refined into a classification tool which was presented as a flow diagram and a questionnaire. Application of the tool revealed that it was understood by key informants and resulted in classifications which were accepted by the researchers. The tool has now been applied extensively in London and yielded useful results. Many other applications in public health workforce planning and development are anticipated.

Humans↗
PubMed2001

Purging of autologous peripheral-blood stem cells using CD34 selection does not improve overall or progression-free survival after high-dose chemotherapy for multiple myeloma: results of a multicenter randomized controlled trial.

PURPOSE: Although high-dose chemotherapy supported by autologous peripheral-blood progenitor-cell (PBPC) transplantation improves response rates and survival for patients with multiple myeloma, all patients eventually develop progressive disease after transplantation. It has been hypothesized that depletion of malignant plasma cells from autografts may improve outcome by reducing infused cells contributing to relapse. PATIENTS AND METHODS: A randomized phase III study using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34(+) autograft cells and passively purge malignant plasma cells was completed in 190 myeloma patients randomized to receive an autograft of CD34-selected or unselected PBPCs. RESULTS: After CD34 selection, tumor burden was reduced by 1.6 to 6.0 logs (median, 3.1), with 54% of CD34-enriched products having no detectable tumor. Median time to count recovery, number of transfusions, transplantation-related mortality, and days in hospital were equivalent between the two transplantation arms. With a median follow-up of 37 months, 33 patients (36%) in the selected and 34 patients (35%) in the unselected arm had died (P =.784). Median overall survival in the selected arm was reached at 50 months and is not reached at this time in the unselected arm (P =.78). Median disease-free survival was 100 versus 104 weeks (P =.82), with 67% of patients in the selected arm and 66% of patients in the unselected arm relapsing. CONCLUSION: This phase III trial demonstrates that although CD34 selection significantly reduces myeloma cell contamination in PBPC collections, no improvement in disease-free or overall survival was achieved.

Adult↗
PubMed2001

Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia.

PURPOSE: To determine the maximum-tolerated dose, pharmacokinetic interaction, and activity of PSC 833 compared with daunorubicin (DNR) and cytarabine in patients with poor-risk acute myeloid leukemia. PATIENTS AND METHODS: Patients received ara-C 3 g/m(2)/d on 5 consecutive days, followed by an IV loading dose of PSC 833 (1.5 mg/kg) and an 84-hour continuous infusion escalating from 6, 9, or 10 mg/kg/d. Daunorubicin was administered as a 72-hour continuous infusion at 34 or 45 mg/m2/d [corrected]. Responding patients received consolidation chemotherapy with DNR pharmacokinetics performed without PSC-833 on day 1, and with PSC-833 on day 4. Response was correlated with expression of P-glycoprotein and lung resistance protein (LRP), and in vitro sensitization of leukemia progenitors to DNR cytotoxicity by PSC 833. RESULTS: All 43 patients are assessable for toxicity and response. Grade 3 or greater hyperbilirubinemia (70%) was the only dose-dependent toxicity. Four patients (9%) succumbed to treatment-related complications. Twenty-one patients (49%) achieved a complete remission or restored chronic phase, including 10 of 20 patients treated at the maximum-tolerated dose of 10 mg/kg/d of PSC-833 and 45 mg/m(2) of DNR. The 95% confidence interval for complete response was 33.9% to 63.7%. Administration of PSC 833 did not alter the mean area under the curve for DNR, although clearance decreased approximately two-fold (P =.04). Daunorubicinol clearance decreased 3.3-fold (P =.016). Remission rates were not effected by mdr-1 expression, but LRP overexpression was associated with chemotherapy resistance. CONCLUSION: Combined treatment with infused PSC 833 and DNR is well tolerated and has activity in patients with poor risk acute myeloid leukemia. Administration of PSC 833 delays elimination of daunorubicinol, but yields variable changes in DNR systemic exposure.

Acute Disease↗
PubMed2001

Transplantation of IL-2-mobilized autologous peripheral blood progenitor cells for adults with acute myelogenous leukemia in first remission.

In order to improve leukemia-free survival we evaluated the feasibility and efficacy of autologous transplantation of interleukin-2 (IL-2)-mobilized peripheral blood progenitor cells for adult patients with acute myelogenous leukemia in first remission. Forty-nine consecutive patients (median age 49, range 21-70) with acute myelogenous leukemia in first remission were enrolled on a study of high-dose cytarabine/mitoxantrone consolidation chemotherapy with post-recovery IL-2 used as a method of in vivo purging for the purpose of autologous peripheral blood progenitor cell transplantation. A median of 2.08 x 10(6) CD34+ peripheral blood progenitor cells/kg were infused 1 day after preparative conditioning with 11.25 Gy total body irradiation and cyclophosphamide (120 mg/kg). Forty-one patients received myeloablative chemoradiotherapy followed by the infusion of IL-2-mobilized autologous peripheral blood progenitor cells. The median times to both neutrophil and platelet recovery were 16 days (range, 2-43) and 23 days (8-318+ days), respectively. Twenty-seven patients remain alive with 24 in continued first complete remission. Median remission duration for all eligible patients is 8 months, and actuarial leukemia-free survival is 49+/-15%. The actuarial risk of relapse is 43+/-16%. Toxicity of autologous peripheral blood progenitor cell transplant included treatment-related death in three patients and serious organ toxicity in 12. Advanced age was a negative prognostic factor for leukemia-free survival. Results were compared to an age-matched historical control treated with autologous transplantation of chemotherapy-mobilized progenitor cells; no significant difference in favor of IL-2 mobilization could be demonstrated. Our results demonstrate that autologous transplantation of IL-2-mobilized peripheral blood progenitor cells is feasible in an unselected population of adult patients with acute myelogenous leukemia in first remission with minimal toxicity but no clear evidence of benefit in leukemia-free survival.

Adult↗
PubMed2001

Continuous quality improvement: educating towards a culture of clinical governance.

The National Health Service in England and Wales has recently adopted a policy aimed at embedding continuous quality improvement (CQI) at all levels and across all services. The key goal is to achieve changes in practice which improve patient outcomes. This paper describes the use of a training course for multiprofessional groups of participants tailored to offer them relevant knowledge, management and team working skills, and approaches to personal and career development. These were intended to assist them in changing their practice for the benefit of patients. The participants rated the course highly in fulfilling its objectives. One cohort followed up for 6 months named changes in practice which related specifically to learning from the course. This paper shows the important contribution of multiprofessional learning to CQI and presents a useful method of evaluating links between learning and performance.

Education, Continuing↗
PubMed2001

Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis.

The newly discovered member of the tumor necrosis factor superfamily, Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), has been identified as an apoptosis-inducing agent in sensitive tumor cells but not in the majority of normal cells, and hence it is of potential therapeutic application. However, many tumor cells are resistant to Apo2L/TRAIL-mediated apoptosis. Various chemotherapeutic drugs have been shown to sensitize tumor cells to members of the tumor necrosis factor family. However, it is not clear whether sensitization by drugs and sensitivity to drugs are related or distinct events. This study examined whether an Adriamycin-resistant multiple myeloma (MM) cell line (8226/Dox40) can be sensitized by Adriamycin (ADR) to Apo2L/TRAIL-mediated apoptosis. Treatment with the combination of Apo2L/TRAIL and subtoxic concentrations of ADR resulted in synergistic cytotoxicity and apoptosis for both the parental 8226/S and the 8226/Dox40 tumor cells. Adriamycin treatment modestly up-regulated Apo2L/TRAIL-R2 (DR5) and had no effect on the expression of Fas-associated death domain, c-FLIP, Bcl-2, Bcl(xL), Bax, and IAP family members (cIAP-1, cIAP-2, XIAP, and survivin). The protein levels of pro-caspase-8 and pro-caspase-3 were not affected by ADR, whereas pro-caspase-9 and Apaf-1 were up-regulated. Combination treatment with Apo2L/TRAIL and ADR resulted in significant mitochondrial membrane depolarization and activation of caspase-9 and caspase-3 and apoptosis. Because ADR is shown to sensitize ADR-resistant tumor cells to Apo2L/TRAIL, these findings reveal that ADR can still signal ADR-resistant tumor cells, resulting in the modification of the Apo2L/TRAIL-mediated signaling pathway and apoptosis. These in vitro findings suggest the potential application of combination therapy of Apo2L/TRAIL and subtoxic concentrations of sensitizing chemotherapeutic drugs in the clinical treatment of drug-resistant/Apo2L/TRAIL-resistant multiple myeloma.

Apoptosis↗
PubMed2000

Effect of short-term interferon therapy on the outcome of subsequent HLA-identical sibling bone marrow transplantation for chronic myelogenous leukemia: an analysis from the international bone marrow transplant registry.

Allogeneic bone marrow transplantation (BMT) is the only curative therapy for chronic myelogenous leukemia (CML), though several studies indicate that prolonged survival can result from interferon-alpha (IFN-alpha) treatment. IFN-alpha is now often used as initial therapy for CML, before donor availability is known. Because identifying potential donors can take several weeks to months, it is important to know whether IFN-alpha adversely affects outcome of a subsequent BMT. If it does, initiation of IFN-alpha therapy might be delayed until donor availability is determined and avoided in patients for whom BMT is planned. We studied 873 patients who received HLA-identical sibling BMT for chronic-phase CML in 153 centers participating in the International Bone Marrow Transplant Registry. The object was to compare outcome in the 664 who received only hydroxyurea before BMT with outcome in the 209 who received IFN-alpha with or without hydroxyurea. The median duration of IFN-alpha therapy was 2 months (range, 1 to 39 months). Cox proportional hazards analysis was used to compare engraftment, graft-versus-host disease (GVHD), nonrelapse mortality, relapse, survival, and leukemia-free survival after adjustment for other prognostic variables. We found a higher risk of nonengraftment among patients given IFN-alpha than among those given hydroxyurea alone (2% versus 0.2%; P = 0.01). Patients who received IFN-alpha had a lower risk of relapse (relative risk, 0.17; 95% confidence interval, 0.04-0.70). Probabilities of GVHD, nonrelapse mortality, survival, and leukemia-free survival were similar in the two treatment groups. These results suggest that a short course of IFN-alpha does not adversely affect survival after a subsequent HLA-identical sibling BMT for chronic-phase CML. (Blood. 2000;95:410-415)

Actuarial Analysis↗
PubMed2000

Comparison of preparative regimens in transplants for children with acute lymphoblastic leukemia.

PURPOSE: Preparative regimens involving total-body irradiation (TBI) produce significant late toxicities in some children who receive bone marrow transplants, including impaired growth and intellectual development. Busulfan is often used as an alternative to TBI, but there are few data regarding its relative efficacy. PATIENTS AND METHODS: We compared outcomes of HLA-identical sibling transplants for acute lymphoblastic leukemia (ALL) in children (< 20 years of age) who received cyclophosphamide plus TBI (CY/TBI) (n = 451) versus those who received busulfan plus cyclophosphamide (Bu/CY) (n = 176) for pretransplant conditioning. Patients received transplants between 1988 and 1995 and their results were reported to the International Bone Marrow Transplant Registry by 144 participating institutions. The CY/TBI and Bu/CY groups did not differ in gender, immune phenotype, leukocyte count at the time of diagnosis, chromosome abnormalities, remission status, or length of initial remission. T-cell depletion was used more frequently in the CY/TBI group; the Bu/CY group included a higher proportion of children who were less than 5 years of age. The median follow-up period was 37 months. RESULTS: The 3-year probabilities of survival were 55% (95% confidence interval [CI], 50% to 60%) with TBI/CY and 40% (95% CI, 32% to 48%) with Bu/CY (univariate P =.003). The 3-year probabilities of leukemia-free survival were 50% (95% CI, 45% to 55%) and 35% (95% CI, 28% to 43%), respectively (univariate P =.005). In a multivariate analysis, the risks of relapse were similar in the two groups (relative risk [RR], 1.30 for Bu/CY v CY/TBI; P =.1). Treatment-related mortality was higher in the Bu/CY group (RR, 1.68; P =.012). Death and treatment failure (relapse or death, inverse of leukemia-free survival) were more frequent in the Bu/CY group (RR, 1. 39; P =.017 for death; RR, 1.42; P =.006 for treatment failure). CONCLUSION: These data indicate superior survival with CY/TBI conditioning, compared with Bu/CY conditioning, for HLA-identical sibling bone marrow transplants in children with ALL.

Adolescent↗
PubMed1999

Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma.

High-dose chemotherapy followed by autologous transplantation has been shown to improve response rates and survival in multiple myeloma and other malignancies. However, autografts frequently contain detectable tumor cells. Enrichment for stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor contamination in phase I/II studies. To more definitively assess the safety and efficacy of CD34 selection, a phase III study was completed in 131 multiple myeloma patients randomized to receive an autologous transplant with either CD34-selected or unselected peripheral blood progenitor cells after myeloablative therapy. Tumor contamination in the autografts was assessed by a quantitative polymerase chain reaction detection assay using patient-specific, complementarity-determining region (CDR) Ig gene primers before and after CD34 selection. A median 3.1 log reduction in contaminating tumor cells was achieved in the CD34 selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA). Successful neutrophil engraftment was achieved in all patients by day 15 and no significant between-arm difference for time to platelet engraftment occurred in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. In conclusion, this phase III trial demonstrates that CD34-selection of peripheral blood progenitor cells significantly reduces tumor cell contamination yet provides safe and rapid hematologic recovery for patients receiving myeloablative therapy.

Adolescent↗
PubMed1999

Collection of peripheral blood progenitor cells (PBPC) based on a rising WBC and platelet count significantly increases the number of CD34+ cells.

The kinetics of mobilization and optimal timing of peripheral blood progenitor cell (PBPC) collection were evaluated in 190 patients with multiple myeloma undergoing stem cell harvest after mobilization with cyclophosphamide, prednisone and G-CSF. There was a strong correlation between the WBC count and the number of CD34+ cells circulating in peripheral blood (r = 0.875). Initiating leukapheresis based on rising WBC and platelet counts rather than on a fixed day increased the mean number of CD34+ cells 115% (9.7 to 20.9 x 10(6) CD34+ cells/kg; P = 0.010) for the total of all leukaphereses and 59% for the total of all CD34-selected products (5.1 to 8.1 x 10(6) CD34+ cells/kg; P = 0.011). Although the yield and purity of the CD34-selected product were not significantly affected (P > or = 0.071), the percentage of patients with concentrations of CD34+ cells in the initial leukapheresis of > 1% increased from 47% to 70% (P = 0.004). The mean purity of the selected product was related to the starting percentage: 48.9% if < 1% and 81.5% if > or = 1% (P < 0.001). Collection of stem cells based on rising WBC and platelet counts significantly increased the number of CD34+ cells in leukaphereses and CD34-selected products in comparison with collection on a fixed day.

Adult↗
PubMed1999

Transplantation of autologous peripheral blood progenitor cells procured after high-dose cytarabine-based consolidation chemotherapy for adults with secondary acute myelogenous leukemia in first remission.

Patients with acute myelogenous leukemia secondary to an antecedent hematologic disturbance or cytotoxic chemotherapy are considered to have a very low likelihood of leukemia-free survival regardless of the form of post-remission therapy. The purpose of this study is to evaluate, on the basis of intention to treat, the feasibility and efficacy of high-dose cytarabine/anthracycline consolidation chemotherapy followed by autologous transplantation of chemotherapy/rHuG-CSF-mobilized peripheral blood progenitor cells for seventeen adult patients (median age 63, range 27 to 68) with secondary acute myelogenous leukemia in first remission. Ten eligible patients underwent autologous transplantation of peripheral blood progenitor cells procured following high-dose cytarabine/mitoxantrone consolidation chemotherapy used as a method of in vivo purging. A median of 5 collections (range 2 to 13) were required to procure a median of 9.27 x 10(8) total mononuclear cells/kg (range 2.35 to 21.44 x 10(8) per kg). The median number of CD34-positive progenitor cells was 1.18 x 10(6) kg (range 0.34 to 30.9 x 10(6) kg). After preparative conditioning with 11.25 Gy total body radiation and cyclophosphamide (120 mg/kg) and autologous transplantation, the median time to neutrophil and platelet recovery were 18 days (range 12 to 29 days) and 25 days (range 8 to 158+ days), respectively. After a median follow-up for surviving patients of 33.4 months (range 7.5 to 54 months), 9 of 17 patients (53%) remain alive with 7 in continued first remission. The median remission duration is 13 months (3 to 53 months) and actuarial leukemia-free survival at 3 years is 51+/-25%. Toxicity of autologous peripheral blood progenitor cell transplant included serious liver and pulmonary toxicity in 2 and 1 patient, respectively. Our results demonstrate that a postremission program of high-dose cytarabine-based consolidation chemotherapy followed by autologous transplantation of chemotherapy-mobilized peripheral blood progenitor cells is feasible for patients with secondary acute myelogenous leukemia producing prolonged leukemia-free survival with minimal toxicity.

Adult↗
PubMed1999

Selectivity of TRAIL-mediated apoptosis of cancer cells and synergy with drugs: the trail to non-toxic cancer therapeutics (review).

There have been many advances in the therapy of cancer following the introduction of cytotoxic chemotherapeutic drugs. Notable responses were observed in primary tumors and often in malignant metastatic tumors. However, one of the consequences of chemotherapy is the development/acquisition of drug-resistant phenotypes and the development of multiple drug resistance. The development of drug resistance remains a major obstacle in the treatment of such tumors and therefore, there is an obvious need for alternative approaches such as immune/gene therapy. The cloning of biologically active cytotoxic molecules has been considered as potential new therapeutics in the destruction of drug-resistant tumor cells. For instance, some members of the TNF-superfamily are characterized by their ability to inflict cell death upon binding to their cognate receptors. TNF-alpha was the first molecule to be tested for its anti-tumor activity, followed by Fas-ligand. These two molecules are efficient in killing a variety of tumor cells, however, they cause significant damage to normal tissues that result in life-threatening toxicities. Therefore, the search for a cytotoxic molecule that is selective for tumor cells has continued until the recently discovered new member of the TNF superfamily, namely TRAIL/APO-2L. TRAIL has been shown to be selectively cytotoxic in inducing apoptosis against tumor cells and has minimal or no toxicity against normal tissues, as examined both in vitro and in vivo in mice. Therefore, TRAIL is a new agent that has great potential for its in vivo anti-cancer effect, whether used alone or in combination with drugs. Studies from our laboratory have recently demonstrated that tumor cells that are resistant to TRAIL can be sensitized by subtoxic concentrations of drugs/cytokines and the sensitized tumor cells are significantly killed by TRAIL. This review describes the current status of research studies performed with TRAIL by other investigators as well as by our laboratory.

Animals↗
PubMed1999

Community crisis intervention: the Coldenham tragedy revisited.

Crisis intervention is commonly thought of as acute psychological first-aid applied within close temporal proximity to the precipitating event. This paper reports the positive effects of a comprehensive crisis intervention applied over three years after the precipitating event and on a "community-wide" basis.

Child↗
PubMed1998

Cladribine in the treatment of advanced relapsed or refractory low and intermediate grade non-Hodgkin's lymphoma.

BACKGROUND: Cladribine (2-chlorodeoxyadenosine) is a purine nucleoside analog with cytotoxic activity against both resting and proliferating cells. Clinical studies with cladribine have reported antitumor activity against various hematologic malignancies. METHODS: The authors studied responses to cladribine among patients with low and intermediate grade non-Hodgkin's lymphoma that had been refractory to or relapsed after prior chemotherapy. Cladribine was given intravenously over 2 hours at a dose of 0.14 mg/kg daily for 5 consecutive days, repeated every 4 weeks. RESULTS: Twenty-eight patients (16 males, 12 females) with a median age of 58 years (range, 41-75 years) were accrued. Twenty-three patients had low grade and 5 had intermediate grade lymphoma. Stage IV disease was present in 22 (79%), and 17 (61%) had systemic B-symptoms. The majority (57%) had received 2 or more prior chemotherapy regimens (median, 2; range, 1-5); 6 had had prior fludarabine therapy. Major responses were documented in 32% (9 of 28 patients), with 4 complete remissions (CR) and 5 partial remissions (PR) after a median of 4 cycles (range, 1-9). One CR occurred in one patient with intermediate grade diffuse large cell lymphoma, and three of six patients who had had prior fludarabine therapy experienced CR or PR with cladribine. Severe hematologic toxicities included reversible neutropenia, protracted thrombocytopenia, and lymphopenia. Other reported adverse effects included mild-to-moderate fatigue, nausea, and diarrhea. CONCLUSIONS: Cladribine is an active single agent in the treatment of patients with refractory or relapsed advanced stage indolent lymphoma, with major responses in one third of patients.

Adult↗