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Biomedical subjects

H C Schouten

Publications and source records attributed to H C Schouten.

At least 19 recordsLinked to original sources
PubMed2006

High-vs low-dose cytarabine combined with interferon alfa in patients with first chronic phase chronic myeloid leukemia. A prospective randomized phase III study.

A prospective randomized phase III study was performed to evaluate whether intensified cytarabine would induce a higher response rate and longer event-free interval as compared to low-dose cytarabine in chronic myeloid leukemia (CML). One hundred and eighteen patients with CML in early chronic phase entered the study. Twenty-eight out of 32 patients assigned to group A received two cycles of a combination of intensified cytarabine and idarubicin followed by interferon alfa (IFN-alpha) maintenance, 28 patients in group B received standard treatment by a combination of low-dose cytarabine and IFN-alpha. Forty-nine patients with a human leukocyte antigen-identical sibling donor proceeded to allogeneic stem cell transplantation (allo-SCT) and nine patients were excluded from the analysis. Hematological response was observed in 97% of the patients in group A vs 86% of the patients in group B during the first year of treatment. In group A, 16 patients (50%) achieved a major cytogenetic response, which compared to seven patients (25%) with a major cytogenetic response in group B. With a median follow-up of 58 months (range 34-76), event-free survival was not significantly different between arms A and B. The estimated 5-year survival rate was 56% in the intensified arm and 77% in the low-dose arm (P = 0.05). Recipients of allo-SCT showed a 5-year estimated survival rate of 55%. Although intensified cytarabine induced a higher initial percentage of major and complete cytogenetic responses, responses were not sustained by IFN-alpha maintenance therapy.

Adolescent↗
PubMed2006

Graft-versus-tumor effects on murine mammary carcinoma in a model of nonmyeloablative haploidentical stem cell transplantation.

Despite a slight decrease in mortality over the last decade, breast cancer still remains a leading cause of cancer-related death in women. Although anti-tumor effects have been observed after allogeneic stem cell transplantation (SCT), this treatment is not standard care owing to graft-versus-host disease (GVHD) and scarcity of suitable donors. With the aim of reducing treatment-related mortality and increasing donor availability in clinical situations, we developed a preclinical mouse model that combines nonmyeloablative conditioning with the use of haploidentical donor-recipient pairs. To mimic active disease, CB6F1 mice were inoculated with 5 x 10(4) 4T1 mammary carcinoma cells 10 days before transplantation. Keratinocyte growth factor (KGF) was used as GVHD prophylaxis. Syngeneic (CB6F1) SCT did not cure any of the mice and KGF treatment did not influence tumor development. After transplantation with haploidentical (B6CBAF1) bone marrow and splenocytes, however, tumor outgrowth was reduced and long-term disease-free survival (>3 months) was observed in 9/18 (50%) (P=0.0011) of the animals. We conclude that in a model of murine breast cancer, a graft-versus-tumor effect can be induced by a nonmyeloablative haploidentical SCT procedure.

Animals↗
PubMed2005

Course of mental fatigue and motivation in breast cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The purpose of this study is to determine the course of fatigue referring to cognitive symptoms (scale 'mental fatigue') as well as the motivation to start any activity (scale 'reduced motivation'), as a function of chemotherapy, in breast cancer patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective cohort study a sample of 157 patients with breast cancer was interviewed at the first, third and fifth cycle of adjuvant chemotherapy as well as 4 and 12 weeks after completion of adjuvant chemotherapy. Patients were treated with standard adjuvant chemotherapy, either a doxorubicin containing schedule or CMF (cyclophosphamide, methotrexate and fluorouracil). The psychological dimensions of fatigue were measured by the Multidimensional Fatigue Inventory. A linear multilevel model was used for analysing the courses. RESULTS: The course of mental fatigue and motivation were not affected by the type of chemotherapy. The course of mental fatigue and motivation varied, but seemed to be stable during the treatment of chemotherapy. After the completion of chemotherapy, a weak improvement was seen. Relatively many patients experienced depressive symptoms during the study. These symptoms were correlated with both dimensions of fatigue. At all measurements mental fatigue was influenced by type of operation where women with a mastectomy were significantly more mentally fatigued than women that had undergone a lumpectomy, but nevertheless they were significantly more motivated to start any activity. Age, marital status, number of treatments and the interval between the operation and the first treatment of chemotherapy also seemed to be important determinants. CONCLUSIONS: An unequivocal pattern of mental fatigue and reduced motivation during as well as after adjuvant chemotherapy was not found. Depressive symptoms were definitely related to these variables. Type of operation had a significant impact on mental fatigue and motivation to start any activity. Health care providers should be aware of the high rate of patients who experience depressive symptoms during and after the treatment of chemotherapy. Further research should include the trajectory preceding adjuvant chemotherapy and a longer study period afterwards. Moreover, the exact influence of the variables 'age', 'marital status', 'number of treatments' and 'the interval between the operation and the first treatment of chemotherapy' on fatigue is unclear and needs further study.

Adult↗
PubMed2005

Three-Layer Model for the design of a Protocol Support System.

OBJECTIVE: The aim of the PropeR project is to investigate the impact of Active Computerized Protocol Support (ACPS) on daily care processes in different settings (home care and hospital care). ACPS consists of an active Protocol Support System (PSS) that is linked to an Electronic Patient Record system. The aim of this paper is to describe how we have taken the organizational and social aspects into account in the hospital setting and the consequences of this approach for the design of the PSS. METHODS: Socio-technical approaches have been applied. Observations and interviews with various health care providers were performed at the hematology and oncology department of the University Hospital Maastricht. Ten extensive sessions with a specialist physician and research nurse took place to further elaborate a study protocol and to discuss how it is integrated in daily practice. The knowledge editor component of Gaston was used to build a computer interpretable version of the selected protocol. RESULTS AND CONCLUSIONS: To support the representation of a study protocol integrated in routine clinical care, a Three-Layer Model was developed. This model distinguishes the protocol description, local adaptations to the protocol and communication as three separate layers. These layers have been incorporated into the knowledge acquisition tool Gaston. The Three-Layer Model makes easy updating possible, and also supports transferability of computerized (study) protocols to other organizations.

Clinical Protocols↗
PubMed2005

Keratinocyte growth factor ameliorates acute graft-versus-host disease in a novel nonmyeloablative haploidentical transplantation model.

Allogeneic stem cell transplantations (SCT) are currently being used as a therapy for hematological malignancies, some solid tumors and nonmalignant bone marrow deficiencies. Nevertheless, clinical applicability is limited due to toxicity of conditioning regimens, graft-versus-host disease (GVHD) and the scarcity of HLA-identical family donors. New concepts are based on nonmyeloablative conditioning to reduce toxicity, prevention or amelioration of GVHD and the use of haploidentical donors to increase donor availability. To combine these requirements, we have developed a nonmyeloablative conditioning regimen, consisting of low-dose total body irradiation and cyclophosphamide-based chemotherapy. In a haploidentical F1 --> F1 mouse model, this nonmyeloablative transplantation protocol resulted in stable full donor chimerism, but also in the development of severe GVHD. Administration of keratinocyte growth factor (KGF) reduced GVHD, evident as reduced weight loss and a lesser degree of dermatitis, compared to saline-treated controls. KGF preserved plasma citrulline and tumor necrosis factor-alpha levels, both indicative for reduced injury to the gastrointestinal tract. This was confirmed by histological findings. At 6 months after transplantation, survival rates were significantly higher in KGF-treated animals as compared to phosphate buffered saline-treated controls. These results indicate that KGF preserves gut integrity and might therefore contribute substantially to reduction of lethal GVHD in (nonmyeloablative) haploidentical transplantation.

Acute Disease↗
PubMed2005

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

Adolescent↗
PubMed2005

Home care versus hospital care of patients with hematological malignancies and chemotherapy-induced cytopenia.

BACKGROUND: The purpose of this review study is to examine the accumulating evidence of safety of home care, with regard to infection-related morbidity and mortality, for patients with chemotherapy-induced cytopenia, in light of previous studies on the necessity of protective isolation (PI). PATIENTS AND METHODS: The existing literature on PI, and home care of cytopenic patients after chemotherapy, published in the English language, based on a Medline search, is reviewed. RESULTS: The studies published so far on home care versus hospital care are all non-randomized studies and confirm that home care of cytopenic patients is safe, in terms of morbidity and mortality due to infections. On the other hand, the majority of studies on the comparison of PI with standard hospital care conclude that an infection-preventive effect of PI exists. The pooled statistics performed confirmed that such an effect of PI exists regarding the occurrence of severe infections, although no benefit to mortality has been shown. CONCLUSIONS: Regarding home care, only the results of a prospective, randomized study of sufficient power will enable definitive conclusions to be drawn as to whether home care is equally safe as hospital-based care with PI.

Antibiotic Prophylaxis↗
PubMed2005

Acute lymphoblastic leukaemia in pregnancy.

Two cases of pregnant patients with acute lymphoblastic leukaemia (ALL) are presented. ALL is rare in pregnancy. The basic principle of ALL treatment is combination chemotherapy with sequential administration of induction, consolidation and maintenance therapy, and this also holds for ALL in pregnancy. The prognosis of ALL in pregnancy is poor and termination of the pregnancy needs to be considered.

Abortion, Induced↗
PubMed2004

Prevalence and course of fatigue in breast cancer patients receiving adjuvant chemotherapy.

BACKGROUND: The purpose of this study was to determine the prevalence of fatigue and the course of fatigue as a function of chemotherapy in breast cancer patients undergoing adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective cohort study, a sample of 157 patients with breast cancer were interviewed, using the Rotterdam Symptom Checklist and the Multidimensional Fatigue Inventory, at the first, third and fifth cycle of adjuvant chemotherapy, as well as 4 and 12 weeks after the last cycle of adjuvant chemotherapy. Patients were treated with either a doxorubicin-containing schedule, or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). RESULTS: The courses of general and physical fatigue are to a large extent similar. After the last cycle of chemotherapy, the CMF group reported a significant increase in fatigue, which was followed by a significant reduction. In the doxorubicin group a significant increase in fatigue was only seen during the first cycles of chemotherapy. The fatigue experienced at the first and the last measurements do not differ significantly. CONCLUSIONS: The prevalence of fatigue increased significantly after the start of chemotherapy. After chemotherapy treatment the prevalence rate seemed to decline. A different impact of chemotherapy on the course of fatigue was found. In the doxorubicin group a direct increase in fatigue was found. In the CMF group a moderate direct increase occurred, followed by a delayed strong increase. An increase in fatigue was associated with a decrease in daily functioning. At all measurement occasions fatigue was affected by type of operation, such that women with a mastectomy were more fatigued than women that underwent a lumpectomy. Receiving radiotherapy also led to an increase in fatigue. With this knowledge breast cancer patients can be better informed about what they can expect. Further research should include interventions addressing how to reduce or cope with fatigue during as well as after receiving adjuvant chemotherapy.

Adult↗
PubMed2003

The PropeR way to support medical doctors in daily practice. Developing the protocol based DSS.

This paper describes the first phase of the development of a Protocol based Decision Support System (PDSS) that will be linked to an Electronic Patient Record system (EPR system). The protocol system will be pro-active: the physician will be automatically prompted from the EPR of a particular patient if the protocol that applies for that patient defines it necessary. The PropeR project studies the impact of a PDSS that is linked to an EPR on daily care processes. There are two areas of research: hospital and home care. This paper describes the application in the hospital. The protocol that is being computerized is a treatment protocol for Acute Myelogenous Leukaemia (AML) that also studies treatment alternatives (conventional versus experimental treatment). This paper based AML protocol has been translated into a formal representation. The KA-tool Gaston is used to make this representation. Twenty-eight subprotocols have been organized in a hierarchical structure with three levels. One of the aims of the project is to make a representation of the AML protocol that can be used in other organizations as well. The main problem we encountered is that the representation not only contains the content of the protocol, but also aspects of application of that protocol in daily care of the hospital and aspects of support. The solution to this problem is the creation of two layers of representation: the first layer is an exact copy of the protocol and thus sharable and the second layer focuses on the support of the protocol in the daily working processes and is mainly domain specific: for the University Hospital Maastricht. At the moment, this division into two layers is being discussed.

Acute Disease↗
PubMed2002

Advantages and limitations of (non-)myeloablative allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (allo-SCT) is the treatment of choice for a variety of malignant diseases, not only as a method to regain haematopoiesis after myeloablative therapy, but also for its apparent antitumour effect. However, treatment-related morbidity and mortality are considerable. A potential way to overcome this problem is by decreasing the intensity of chemotherapy and/or radiotherapy given prior to transplantation. This reduced-intensity conditioning regimen is the basis of non-myeloablative allo-SCT (also referred to as mini SCT), a new treatment modality that relies more heavily on the antitumour effect exerted by the donor cells than on the antitumour effect of the conditioning therapy. The aim of this article is to place the concept of non-myeloablative SCT in a historical context and to discuss the advantages and disadvantages of regular myeloablative SCT compared with non-myeloablative SCT. Furthermore, human trials regarding non-myeloablative SCT are reviewed, and several experimental techniques are discussed that aim to augment the antitumour effect of an allogeneic graft.

Animals↗
PubMed2002

Non-myeloablative allogeneic stem cell transplantation in patients with solid tumours and patients with a haematological malignancy.

Allogeneic stem cell transplantation (allo-SCT) is a treatment option for several haematological tumours, not only to regain haematopoiesis after myeloablative chemotherapy and/or radiotherapy, but also for its apparent antitumour effect. This so-called graft-versus-tumour effect might not only be effective against haematological tumours, where it has best been proven, but also against solid tumours. To reduce morbidity and treatment-related mortality of allo-SCT, efforts are being made to establish engraftment of allogeneic stem cells after a non-myeloablative conditioning regimen and create a 'mini transplantation'. Such a therapy relies more heavily on the graft-versus-malignancy effect than on the antitumour effect exerted by the chemotherapy/radiotherapy. Here, we report the outcomes of 15 patients with haematological disease or solid tumours who underwent an SCT in the University Hospital Maastricht after a non-myeloablative fludarabine/cyclophosphamide conditioning regimen. Although results are promising, adjustments will be needed to ensure long-term stable engraftment and optimise the antitumour effect.

Adult↗
PubMed2001

Treatment of elderly patients with intermediate- and high-grade non-Hodgkin's lymphoma: a retrospective population-based study.

PURPOSE AND METHODS: Nowadays more people are becoming older. The median age of a patient with non-Hodgkin's lymphoma (NHL) at diagnosis is over 60 years. The incidence of NHL in elderly has increased in the last decades. Therefore, in the future, NHL will be diagnosed more often in the elderly. Data of all patients in the south-east of the Netherlands with newly diagnosed NHL between January 1991 and January 1995 were analysed in a retrospective multicentre population-based study to investigate if and how elderly patients (> 60 years) with advanced NHL (Ann Arbor Staging > or = IIB) of intermediate- and high-grade malignancy were treated. Treatment modalities applied, outcome, and causes of death were evaluated. Treatment was considered inadequate if it deviated from the standard anthracycline-containing chemotherapy (CNOP/CHOP) for a minimum of six cycles. RESULTS: The entry criteria were met by 68 patients. Of these patients, 57 (83.8%) were treated and 11 (16.2%) were not treated. The treatment consisted of CHOP (36 patients), CNOP (6 patients), chlorambucil (13 patients), or COP (2 patients). Forty-two of 68 patients had adequate treatment, but 14 of 42 (33.3%) patients had a suboptimal numbers of cycles (< 6). Of 28 patients with adequate chemotherapy, only 16 had the optimal number of cycles and dose; the result is that the treatment of 76.5% (52/68) of patients differed from that of their younger counterparts. The most important reason for treatment not being optimal was high age (23%) or poor performance (35%). In the appropriately treated patients, 62.5% (10/16) had a complete response. Survival in the CHOP/CNOP-treated group was better than in other groups. The main cause of death in the total study group was NHL. The results cannot be explained by the different international prognostic index. CONCLUSION: A significant subset (76.5%) of elderly people with intermediate/high-grade NHL received suboptimal therapy, mainly because of a suboptimal performance status. However, a significant part of the patients (23%) were not treated optimally because of high age, despite a good performance. For improving the overall survival in the elderly, it is not only the schedule that is important, but also the intention to treat the elderly patient.

Aged↗
PubMed2001

The effect of optimal treatment on elderly patients with aggressive non-Hodgkin's lymphoma: more patients treated with unaffected response rates.

A substantial part of elderly patients (with good performance) with intermediate or high-grade non-Hodgkin's lymphoma (NHL) are not treated with the standard chemotherapy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). If NHL patients are not treated with CHOP, the outcome is inferior. By adding granulocyte colony-stimulating factor (G-CSF) to CHOP chemotherapy, we aimed at treating more patients with less toxicity. We performed a multicenter population-based study (in the southeast of the Netherlands) in which elderly patients (> or = 60 years) with intermediate or high-grade stage > or = IIB NHL were treated with CHOP chemotherapy and growth factor G-CSF to increase the number of patients treated according to standard protocols. We also evaluated elderly NHL patients who were not treated with CHOP chemotherapy. Adequate therapy was defined as > or = six cycles or a total of five cycles when complete remission was achieved after three cycles. Seventy-nine NHL patients fulfilled the selection criteria. The patients were treated with CHOP plus G-CSF (n=46), CHOP (n=19), cyclophosphamide, vincristine, and prednisone (COP) (n=2), chlorambucil and prednisone (n=2), or prednisone (n=1). Nine patients were not treated with chemotherapy. The median age was 72 years (60-87). Of the 79 NHL patients, 65 were treated with CHOP chemotherapy (82%); 38 of 65 patients (59%) were adequately treated. The complete remission rate in the NHL group treated with CHOP was 65% (42 of 65 patients). The overall 3-year survival was 50%. Most of the patients died from progressive NHL (53% in the CHOP and 77% in the group not treated with CHOP). The treatment-related mortality was 15% in the CHOP group. The most important reason for not treating patients with CHOP (with or without G-CSF) was poor performance (WHO > or = 2). A significant subset of patients can be treated with CHOP chemotherapy with acceptable toxicity. The combination of CHOP plus G-CSF increased the absolute number of treatable elderly patients, resulting in more (absolute) patients with complete remission and overall survival compared to our previous study.

Aged↗
PubMed2001

The use of thalidomide in chronic refractory graft versus host disease.

BACKGROUND: Chronic graft versus host disease (GvHD) is a serious complication of allogenic bone marrow transplantation. As prednisone and ciclosporine A are not always effective in its treatment, we investigated the value of thalidomide. METHODS: We describe the results of thalidomide in 12 patients with chronic prednison/ciclosporin A refractory GvHD seen in our clinic since 1991. A case history is given as illustration. RESULTS: Four patients had a complete remission of chronic GvHD on thalidomide; five patients showed a partial response. Of these five patients, three died eventually of respectively ongoing GvHD, pneumonia and recurrent leukemia. There were no serious side effects, except for one patient who had to stop thalidomide because of polyneuropathy. CONCLUSIONS: It is worthwhile to give thalidomide in prednison/ciclosporin A refractory chronic GvHD. Probably thalidomide should be given earlier in the course of GvHD, this needs further study.

Adult↗