26 results on '"Wijermans, P"'
Search Results
2. Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study.
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Holtzer-Goor, K., Schaafsma, M., Joosten, P., Posthuma, E., Wittebol, S., Huijgens, P., Mattijssen, E., Vreugdenhil, G., Visser, H., Peters, W., Erjavec, Z., Wijermans, P., Daenen, S., Hem, K., Oers, M., Uyl-de Groot, C., Holtzer-Goor, K M, Schaafsma, M R, Posthuma, E F M, and Huijgens, P C
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CHLORAMBUCIL ,CHRONIC lymphocytic leukemia ,PROBABILITY theory ,PSYCHOLOGICAL tests ,QUALITY of life ,QUESTIONNAIRES ,T-test (Statistics) ,KRUSKAL-Wallis Test ,THERAPEUTICS - Abstract
Purpose: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients.Methods: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment ("watch and wait"), chlorambucil treatment only, and patients with other treatment(s).Results: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy.Conclusions: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment. [ABSTRACT FROM AUTHOR]- Published
- 2015
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3. Factors that influence treatment decision-making in elderly DLBCL patients: a case vignette study.
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Poel, M., Mulder, W., Ossenkoppele, G., Maartense, E., Hoogendoorn, M., Wijermans, P., and Schouten, H.
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DIFFUSE large B-cell lymphomas ,OLDER patients ,DECISION making ,HEMATOLOGISTS ,CANCER chemotherapy ,SOCIAL support ,THERAPEUTICS - Abstract
Elderly patients with diffuse large B-cell lymphoma (DLBCL) are frequently not treated with standard immunochemotherapy, and this influences survival negatively. The purpose of this study was to gain more insight into treatment decision-making by hematologists. Case vignettes concerning patients with DLBCL were presented to hematologists in the Netherlands. Patient characteristics (age, comorbidity) differed per case. Respondents were asked in each case if they would treat the patient with curative intent by means of full-dose chemotherapy or chemotherapy with dose reduction or if they would not treat the patient with curative intent. The vast majority of respondents would treat an elderly patient diagnosed with DLBCL without a relevant medical history with full-dose chemotherapy irrespective of age. In the presence of comorbidity, lack of social support, cognitive disorders, and untreated depression dose reductions in advance are frequently applied or patients are not treated with curative intent. This is most pronounced for patients aged older than 80 years. Respondents working in a university hospital more frequently refrain form full-dose chemotherapy with curative intent compared to respondents working in tertiary medical teaching hospitals or general hospitals. Patients without a relevant medical history are generally treated with curative intent irrespective of age. Cognitive disorders, comorbidity, and depression reduce the change of being treated with curative intent. This is most prominent in the eldest patient category. [ABSTRACT FROM AUTHOR]
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- 2015
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4. Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years.
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Cornelissen, J J, Versluis, J, Passweg, J R, van Putten, W L J, Manz, M G, Maertens, J, Beverloo, H B, Valk, P J M, van Marwijk Kooy, M, Wijermans, P W, Schaafsma, M R, Biemond, B J, Vekemans, M-C, Breems, D A, Verdonck, L F, Fey, M F, Jongen-Lavrencic, M, Janssen, J J W M, Huls, G, and Kuball, J
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ACUTE myeloid leukemia ,DISEASE remission ,HEMATOPOIETIC stem cell transplantation ,CANCER chemotherapy ,PROGRESSION-free survival - Abstract
The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML. [ABSTRACT FROM AUTHOR]
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- 2015
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5. Presenting signs and symptoms in multiple myeloma: high percentages of stage III among patients without apparent myeloma-associated symptoms.
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Ong, F., Hermans, J., Noordijk, E., Wijermans, P., Kluin-Nelemans, J., Noordijk, E M, Wijermans, P W, and Kluin-Nelemans, J C
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MULTIPLE myeloma diagnosis ,IMMUNOGLOBULIN analysis ,ALKALINE phosphatase ,COMPARATIVE studies ,DIFFERENTIAL diagnosis ,LACTATE dehydrogenase ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,MULTIPLE myeloma ,RESEARCH ,TUMOR classification ,EVALUATION research - Abstract
We studied the medical histories of 127 patients diagnosed with multiple myeloma included in a population-based registry of 945 patients with a para-protein or multiple myeloma in the region of the Comprehensive Cancer Center West (CCCW). We defined patients "not immediately diagnosed" or "delayed diagnosis" as those patients in whom myeloma was not included in the initial differential diagnosis. We found that 37% belonged to this category. These patients more often had symptoms not associated with multiple myeloma. Since a surprising 51% of patients with delayed diagnosis turned out to have stage-III myeloma, the physician should be alert to the presence of this disease, despite the fact that co-morbidity may mask its presence. [ABSTRACT FROM AUTHOR]
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- 1995
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6. Kaposi's sarcoma in an HIV-negative CLL patient as the cause of thrombocytopenia.
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Wijermans, P., Groningen, K., Royen, E., Bruijn, J., Wijermans, P W, van Groningen, K, van Royen, E A, and Bruijn, J A
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A patient is described with a rapidly progressive Kaposi's sarcoma following immunosuppressive therapy with fludarabine monophosphate (FAMP) for chronic lymphocytic leukemia. The development of this tumor was accompanied by progressive thrombocytopenia, due to trapping of the platelets in the Kaposi sarcoma, without signs of consumptive coagulopathy or microangiopathic hemolytic anemia. This sequestration process might be caused by the abnormal structure of the tumoral vessels, leading to exposure of subendothelial structures like collagen, von Willebrand's factor, and tenascin to the vessel lumen. A severe immunosuppression due to the lymphocytotoxic effect of FAMP on several T-cell subpopulations was seen. This case confirms the importance of immunosuppression as a co-factor in the development of Kaposi's sarcoma also in HIV-negative patients, and adds Kaposi's sarcoma to the differential diagnosis of thrombocytopenia in immunosuppressed patients. [ABSTRACT FROM AUTHOR]
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- 1994
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7. Intensive chemotherapy to improve outcome in patients with acute lymphoblastic leukemia over the age of 40: a phase II study for efficacy and feasibility by HOVON.
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Daenen, S, van der Holt, B, Dekker, A W, Willemze, R, Rijneveld, A W, Biemond, B J, Muus, P, van de Loosdrecht, A A, Schouten, H C, van Marwijk Kooy, M, Breems, D A, Demuynck, H, Maertens, J, Wijermans, P W, Wittebol, S, de Klerk, E W, and Cornelissen, J J
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LYMPHOBLASTIC leukemia treatment ,DRUG therapy ,THERAPEUTICS ,DRUG efficacy ,FEASIBILITY studies - Abstract
The article presents a study which examines the feasibility and effectiveness of intensive chemotherapy in acute lymphoblastic leukemia (ALL) patients over the age of 40. It notes that the study was participated by 60 patients with ALL who were treated with intensive chemotherapeutic regimen. It concludes that the regimen of intensive chemotherapy is feasible and demonstrated efficacy in patients with ALL up to 70 years of age.
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- 2012
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8. Effect of thalidomide with melphalan and prednisone on health-related quality of life (HRQoL) in elderly patients with newly diagnosed multiple myeloma: a prospective analysis in a randomized trial.
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Verelst, Silvia, Termorshuizen, F., Uyl-de Groot, C., Schaafsma, M., Ammerlaan, A., Wittebol, S., Sinnige, H., Zweegman, S., Marwijk Kooy, M., Griend, R., Lokhorst, H., Sonneveld, P., and Wijermans, P.
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MULTIPLE myeloma ,THALIDOMIDE ,DISEASES in older people ,PREDNISONE ,QUALITY of life ,ANEMIA ,DIPHOSPHONATES - Abstract
Thalidomide with melphalan/prednisone (MPT) was defined as standard treatment in elderly patients with multiple myeloma (MM) based on five randomized trials. In one of these trials, HOVON49, a prospective health-related quality-of-life (HRQoL) study was initiated in order to assess the impact of thalidomide on QoL. Patients aged >65 years with newly diagnosed MM were randomized to receive melphalan plus prednisone (MP) or MPT, followed by thalidomide maintenance in the MPT arm. Two hundred eighty-four patients were included in this side study (MP, n = 149; MPT n = 135). HRQoL was assessed with the EORTC Core QoL Questionnaire (QLQ-C30) and the myeloma-specific module (QLQ-MY24) at baseline and at predetermined intervals during treatment. The QLQ-C30 subscales physical function ( P = 0.044) and constipation ( P < 0.001) showed an improvement during induction in favour of the MP arm. During thalidomide maintenance, the scores for the QLQ-MY24 paraesthesia became significantly higher in the MPT arm ( P<0.001). The QLQ-C30 subscales pain ( P = 0.12), insomnia ( P = 0.068), appetite loss ( P = 0.074) and the QLQ-MY24 item sick ( P = 0.086) scored marginally better during thalidomide maintenance. The overall QoL-scale QLQ-C30-HRQoL showed a significant time trend towards more favourable mean values during protocol treatment without differences between MP and MPT. For the QLQ-C30 subscales emotional function and future perspectives, difference in favour of the MPT arm from the start of treatment was observed ( P = 0.018 and P = 0.045, respectively) with no significant 'time × arm' interaction, indicating a persistent better patient perspective with MPT treatment. This study shows that the higher frequency of toxicity associated with MPT does not translate into a negative effect on HRQoL and that MPT holds a better patient perspective. [ABSTRACT FROM AUTHOR]
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- 2011
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9. Intensified chemotherapy inspired by a pediatric regimen combined with allogeneic transplantation in adult patients with acute lymphoblastic leukemia up to the age of 40.
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Rijneveld, A W, van der Holt, B, Daenen, S M G J, Biemond, B J, de Weerdt, O, Muus, P, Maertens, J, Mattijssen, V, Demuynck, H, Legdeur, M C J C, Wijermans, P W, Wittebol, S, Spoelstra, F M, Dekker, A W, Ossenkoppele, G J, Willemze, R, and Cornelissen, J J
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LYMPHOBLASTIC leukemia ,DRUG therapy ,CLINICAL trials ,ASPARAGINASE ,METHOTREXATE ,VINCRISTINE ,PATIENTS - Abstract
Event-free survival (EFS) at 5 years in pediatric acute lymphoblastic leukemia (ALL) is >80%. Outcome in adult ALL is still unsatisfactory, which is due to less cumulative dosing of chemotherapy and less strict adherence to timing of successive cycles. In the present phase II trial, we evaluated a pediatric regimen in adult patients with ALL under the age of 40. Treatment was according to the pediatric FRALLE approach for high-risk ALL patients and characterized by increased dosages of asparaginase, steroids, methotrexate and vincristin. However, allogeneic stem cell transplantation was offered to standard risk patients with a sibling donor and to all high-risk patients in contrast to the pediatric protocol. Feasibility was defined by achieving complete remission (CR) and completion of treatment within a strict timeframe in at least 60% of patients. In all, 54 patients were included with a median age of 26. CR was achieved in 49 patients (91%), of whom 33 completed treatment as scheduled (61%). Side effects primarily consisted of infections and occurred in 40% of patients. With a median follow-up of 32 months, EFS estimated 66% at 24 months and overall survival 72%. These data show that a dose-intensive pediatric regimen is feasible in adult ALL patients up to the age of 40. [ABSTRACT FROM AUTHOR]
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- 2011
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10. An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2′-deoxycytidine (decitabine) in 177 patients.
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Wijermans, P., Lübbert, M., Verhoef, G., Klimek, V., and Bosly, A.
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MYELODYSPLASTIC syndromes treatment , *BONE marrow diseases , *DNA , *METHYLATION , *DISEASES in older people , *CLINICAL trials - Abstract
During the last 10 years, three European phase II studies were performed to investigate the treatment of elderly patients with myelodysplastic syndrome (MDS) with low-dose 5-aza-2′-deoxycytidine (decitabine, DAC). All these European trial data were reviewed on the basis of the International Prognostic Scoring System (IPSS) risk criteria and the response criteria as recently published by an international working group. To investigate the results in a larger cohort of patients and to determine risk factors, all data were pooled with some observations from the PCH 95-06 US phase II study. The response rate in the 177 patients evaluated (median age 70 years) was 49%. The median response duration was 36 weeks, and the median survival was 15 months. Analysis of the data according to sex, age, French–American–British classification, percentage of blasts in the bone marrow, IPSS risk group, lactate dehydrogenase and cytogenetics did not reveal any factor predictive of response. Overall, 69% of patients benefited, including those with stable disease during therapy. Response duration was significantly shorter with increasing risk (according to the IPSS classification). Haemoglobin level and neutrophil count showed an inverse correlation to the IPSS classification. Univariate analysis showed a significantly inferior survival for elderly patients (>75 years of age) and for those with high levels of serum lactate dehydrogenase (LDH) (more than two times the normal values). Patients with high-risk cytogenetic abnormalities according to the IPSS risk criteria showed better overall survival than those with intermediate-risk abnormalities. When analysed according to the IPSS risk classification, high-risk patients had worse survival prospects following decitabine therapy than those with intermediate risk; however, compared to the originally reported IPPS outcomes for high-risk patients, they probably showed better survival. During the treatment period, 18% of the patients progressed towards acute leukaemia. Decitabine showed a rather low toxicity profile in this elderly patient group. In conclusion, low-dose decitabine is an active drug for the treatment of MDS patients, even for those older than 75 years with bad prognostic characteristics. [ABSTRACT FROM AUTHOR]
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- 2005
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11. Quantification of outpatient management and hospitalization of patients with high-risk myelodysplastic syndrome treated with low-dose decitabine.
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Pitako, J., Haas, P., Bosch, J., Müller-Berndorff, H., Kündgen, A., Germing, U., Wijermans, P., and Lübbert, M.
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MYELODYSPLASTIC syndromes ,BONE marrow diseases ,HOSPITAL care ,OUTPATIENT medical care ,PATIENTS - Abstract
Intravenous low-dose 5-aza-2′-deoxycytidine (decitabine) in patients with advanced myelodysplastic syndrome (MDS) yields an approximately 50% overall response rate, including 20–25% complete remission. Decitabine-treated MDS patients can be managed as outpatients after completion of a 3-day infusion schedule. In-hospital nights (IHNs), overall survival (OS), and remaining life spent in hospital were evaluated and compared to a matched control group receiving different standard treatments. Between July 1992 and September 2001, 99 high-risk MDS patients, median age 70 years (range 49–86), were treated with low-dose decitabine. Durations of all hospitalizations were recorded. For matched-pair analysis, 44 decitabine-treated patients were matched to 44 MDS patients according to International Prognostic Scoring System classification, period of diagnosis, age, French–American–British classification, and gender. Median number of IHN across all patients was 56 and survival was 481 days, resulting in 84% of remaining life spent at home. In the matched-pair analysis, the median number of IHN was 57 in the decitabine group vs. 50 in the control group. Median survival was 400 vs. 371 days for the decitabine and control groups, respectively. Median number of remaining life spent at home was identical (83% for both groups). Matched patients who received only best supportive care ( n=12) had a shorter median survival than the decitabine patients (234 vs. 400 days), and the proportion of remaining life spent at home was slightly greater (82 vs. 77%). Interestingly, matched patients with induction therapy showed comparable IHN, OS, and remaining life spent at home. In conclusion, high-risk MDS patients treated with low-dose decitabine have better survival, and spend comparable time in hospital than patients treated with supportive treatment. [ABSTRACT FROM AUTHOR]
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- 2005
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12. Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.
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van Imhoff, G. W., van der Holt, B., MacKenzie, M. A., Ossenkoppele, G. J., Wijermans, P. W., Kramer, M. H. H., van't Veer, M. B., Schouten, H. C., van Marwijk Kooy, M., van Oers, M. H. J., Raemaekers, J. M. M., Sonneveld, P., Meulendijks, L. A. M. H., Kluin, P. M., Kluin-Nelemans, H. C., and Verdonck, L. F.
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STEM cell transplantation ,DRUG therapy ,THERAPEUTICS ,LYMPHOMAS ,MITOXANTRONE hydrochloride ,ANTINEOPLASTIC agents - Abstract
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.Leukemia (2005) 19, 945-952. doi:10.1038/sj.leu.2403733 Published online 31 March 2005 [ABSTRACT FROM AUTHOR]
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- 2005
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13. The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK...
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Oosterveld, M, Suciu, S, Verhoef, G, Labar, B, Belhabri, A, Aul, C, Selleslag, D, Ferrant, A, Wijermans, P, Mandelli, F, Amadori, S, Jehn, U, Muus, P, Zittoun, R, Hess, U, Anak, O, Beeldens, F, Willemze, R, and de Witte, T
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MYELODYSPLASTIC syndromes ,ACUTE myeloid leukemia ,DRUG therapy ,STEM cell transplantation - Abstract
This report used the framework of a large European study to investigate the outcome of patients with and without an HLA-identical sibling donor on an intention-to-treat basis. After a common remission-induction and consolidation course, patients with an HLA-identical sibling donor were scheduled for allogeneic transplantation and patients lacking a donor for autologous transplantation. In all, 159 patients alive at 8 weeks from the start of treatment were included in the present analysis. In total, 52 patients had a donor, 65 patients did not have a donor and in 42 patients the availability of a donor was not assessed. Out of 52 patients, 36 (69%) with a donor underwent allogeneic transplantation (28 in CR1). Out of 65 patients, 33 (49%) received an autograft (27 in CR1). The actuarial survival rates at 4 years were 33.3% (s.e. = 6.7%) for patients with a donor and 39.0% (s.e. = 6.5%) for patients without a donor (P = 0.18). Event-free survival rates were 23.1% (s.e. = 6.2%) and 21.5% (s.e. = 5.3%), respectively (P = 0.66). Correction for alternative donor transplants did not substantially alter the survival of the group without a donor. Also, the survival in the various cytogenetic risk groups was not significantly different when comparing the donor vs the no-donor group. This analysis shows that patients with high-risk myelodysplastic syndrome and secondary acute myeloid leukemia may benefit from both allogeneic and autologous transplantation. We were unable to demonstrate a survival advantage for patients with a donor compared to patients without a donor. [ABSTRACT FROM AUTHOR]
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- 2003
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14. Chemotherapy only compared to chemotherapy followed by transplantation in high risk myelodysplastic syndrome and secondary acute myeloid leukemia; two parallel studies adjusted for various prognostic factors.
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Oosterveld, M., Muus, P., Suciu, S., Koller, C., Verhoef, G., Labar, B., Wijermans, P., Aul, C., Fiere, D., Selleslag, D., Willemze, R., Gratwohl, A., Ferrant, A., Mandelli, F., Cortes, J., de Witte, T., and Estey, E.
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LEUKEMIA treatment ,DRUG therapy ,STEM cells ,TRANSPLANTATION of organs, tissues, etc. - Abstract
Comparisons of the effectiveness of chemotherapy and transplantation in AML in first complete remission (CR) have focused almost exclusively on patients with de novo disease. Here we used Cox modelling to compare these strategies in patients with MDS and s-AML treated by the Leukemia Group of the EORTC or at the MD Anderson Cancer Center. All patients were aged 15-60. The 184 EORTC patients received conventional dose ara-C + idarubicin + etoposide for remission induction, and after one consolidation course, were scheduled to receive an allograft, or an autograft if a sibling donor was unavailable. The 215 MDA patients received various high-dose ara-C containing induction regimens, and in CR, continued to receive these regimens at reduced dose for 6-12 months. CR rates were 54% EORTC and 63% MDA (P = 0.09). Sixty-five of the 100 EORTC patients who entered CR received a transplant in first CR. Disease-free survival in patients achieving CR was superior in the EORTC cohort, the 4-years DFS rates were 28.9% (s.e. = 4.8%) EORTC vs 17.3% (s.e. = 3.7%) MDA (P = 0.017). Survival from CR was not significantly different in the EORTC and MDA groups, as was survival from start of treatment. After accounting for prognostic factors the conclusions were unchanged. Despite various problems with the analysis discussed below, the data suggest that neither transplantation nor chemotherapy, as currently practised, can be unequivocally recommended for these patients in first CR and that questions as to the superior modality may be less important than the need to improve results with both. [ABSTRACT FROM AUTHOR]
- Published
- 2002
15. A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group. Dutch-Belgian Hemato-Oncology Cooperative Group.
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Ossenkoppele, G J, van der Holt, B, Verhoef, G E G, Daenen, S M G J, Verdonck, L F, Sonneveld, P, Wijermans, P W, van der Lelie, J, van Putten, W L J, Löwenberg, B, Verhoef, G E, Daenen, S M, and van Putten, W L
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GRANULOCYTE-macrophage colony-stimulating factor ,MYELODYSPLASTIC syndromes ,DRUG therapy - Abstract
The purpose of this study was to determine the safety and efficacy of filgrastim as an adjunct to induction and consolidation chemotherapy in poor risk patients with myelodysplastic syndrome (MDS). Filgrastim was given both during and after chemotherapy with the objective to accelerate hematopoietic repopulation and enhance the efficacy of chemotherapy. In a prospective randomized multicentre phase II trial, a total of 64 patients with poor risk primary MDS were randomized to receive either granulocyte colony-stimulating factor (G-CSF, filgrastim, AMGEN, Breda, The Netherlands) 5 microg/kg/day subcutaneously or no G-CSF in addition to daunomycin (30 mg/m2/days 1, 2 and 3 intravenous bolus) and cytarabine (200 mg/m2 days 1-7, continuous infusion). The overall complete response rate was 63%: 73% for patients receiving filgrastim as compared to 52% in the standard arm (P = 0.08). Overall survival at 2 years was estimated at 29% for patients assigned to the filgrastim arm and 16% for control patients (P = 0.22). The median time for recovery of granulocytes towards 1.0 x 10(9)/l post-chemotherapy was 23 days in the filgrastim-treated patients vs 35 days in the standard arm (P = 0.015). There were no differences in time of platelet recovery, length of hospital stay, duration of antibiotic use or infectious complications between the two treatment groups. However the earlier recovery of neutrophils in the filgrastim group was associated with a reduced interval of 9 days between the induction and consolidation cycle. In patients with poor risk MDS the use of filgrastim during and after induction therapy results in a significantly reduced neutrophil recovery time. Further study may be warranted to see if the apparent trend of the improved response to chemotherapy in combination with filgrastim can be confirmed in greater number of patients and to assess the effect of the addition of filgrastim on survival. [ABSTRACT FROM AUTHOR]
- Published
- 1999
16. Peripheral blood stem cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia?
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Vellenga, E, van Putten, W L J, Boogaerts, M A, Daenen, S M G J, Verhoef, G E G, Hagenbeek, A, Jonkhoff, A R, Huijgens, P C, Verdonck, L F, van der Lelie, J, Schouten, H C, Gmür, J, Wijermans, P, Gratwohl, A, Hess, U, Fey, M F, and Löwenberg, B
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AUTOTRANSPLANTATION ,BONE marrow transplantation ,LEUKEMIA treatment ,MYELOID leukemia - Abstract
The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 × 10
6 CD34+ cells/kg (range 0.1–72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 μg/m2 ) during an average of 20 days. Higher dose regimens of G-CSF (450 μg/m2 and 600 μg/m2 ) given during an average of 11 days resulted in 28 patients in a yield of 3.6 × 106 CD34+ cells/kg (range 0–60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 × 106 CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 × 109 /l, 17 vs 37 days) and platelets (>20 × 109 /l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery. [ABSTRACT FROM AUTHOR]- Published
- 1999
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17. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma.
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Lokhorst, H M, Sonneveld, P, Cornelissen, J J, Joosten, P, van Marwijk Kooy, M, Meinema, J, Nieuwenhuis, H K, van Oers, M H J, Richel, D J, Segeren, C N, Veth, G, Verdonck, L F, and Wijermans, P W
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COMPLICATIONS from organ transplantation ,STEM cells ,MULTIPLE myeloma - Abstract
We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m
2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including α-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM. [ABSTRACT FROM AUTHOR]- Published
- 1999
- Full Text
- View/download PDF
18. Continuous infusion of low-dose 5-Aza-2'-deoxycytidine in elderly patients with high- risk myelodysplastic syndrome.
- Author
-
Wijermans, P. W., Krulder, J. W. M., Huijgens, P. C., and Neve, P.
- Subjects
- *
BONE marrow diseases , *LEUKEMIA treatment , *MYELOID leukemia , *MYELODYSPLASTIC syndromes , *HEMATOPOIETIC growth factors , *ANTINEOPLASTIC agents , *AGING parents - Abstract
There is no standard therapy for elderly patients with high-risk myelodysplastic syndrome (MDS). The treatment options of low-dose Ara-C and haematopoietic growth factors are disappointing in regard to response rate or response duration. We tested the treatment with a 72-h continuous infusion of low-dose 5-Aza-2′'-deoxycytidine (DAC) in a group of 29 elderly patients with high-risk MDS. In 15 patients (54%) we observed a response. Eight complete responses were reached, even among patients with bad prognostic cytogenetic findings. The actuarial median survival from the start of the therapy was 46 weeks. The only (and major) toxicity was myelosuppression, leading to a prolonged cytopenic period and thus leading to five toxic deaths (17%) in this high-risk patient group. We conclude that DAC is an effective drug in the treatment of MDS patients and that it probably works via its cytotoxic activity. Myelotoxicity is its major adverse effect. [ABSTRACT FROM AUTHOR]
- Published
- 1997
19. A randomized phase II study on the effects of 5-Aza-2'-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893).
- Author
-
Willemze, R., Suciu, S., Archimbaud, E., Muus, P., Stryckmans, P., Louwagie, E. A., Berneman, Z., Tjean, M., Wijermans, P., Dohner, H., Jehn, U., Labar, B., Jaksic, B., Dardenne, M., and Zittoun, R.
- Subjects
ANTINEOPLASTIC agents ,ACUTE myeloid leukemia ,LYMPHOCYTIC leukemia ,MYELOID leukemia ,LEUKEMIA treatment ,CANCER chemotherapy ,LEUKEMIA ,HUMAN cytogenetics ,PATIENTS - Abstract
5-Aza-2′-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2′-deoxycytidine 125 mg/m² as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m² as a 1 h infusion on days 6 and 7 (n = 30) or idarubicin 12 mg/m² as a 15 mm infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR); eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2′-deoxycytidine is a good antileukernic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia. [ABSTRACT FROM AUTHOR]
- Published
- 1997
20. Intraocular non-Hodgkin's lymphoma treated with systemic and intrathecal chemotherapy and radiotherapy.
- Author
-
Rouwen, A., Wijermans, P., Boen-Tan, T., and Stilma, J.
- Abstract
A case of therapy-resistant bilateral intermediate uveitis is presented. Vitreous biopsy and lumbar puncture resulted in the diagnosis of high-grade malignant non-Hodgkin's lymphoma (NHL). Because chemotherapy and radiotherapy continue to yield better results in the treatment of NHL and a cure can be reached in a large group of patients with high-grade malignant NHL, early diagnosis is very important. We therefore recommend early vitreous biopsy in persistent, bilateral, granulomatous intermediate uveitis, especially in older patients. Our patient achieved a complete remission (follow-up period at the time of writing, 18 months after the beginning of polychemotherapy and radiotherapy). The chemotherapy modalities are briefly discussed. [ABSTRACT FROM AUTHOR]
- Published
- 1989
- Full Text
- View/download PDF
21. Acute lymphoblastic leukaemia in adults: immunological subtypes and clinical features at presentation.
- Author
-
van't Veer, M B, van Putten, W L, Verdonck, L F, Ossenkoppele, G J, Löwenberg, B, Kluin-Nelemans, J C, Wijermans, P W, Schouten, H C, Sizoo, W, and Dekker, A W
- Subjects
ANTIGEN analysis ,ANTIGENS ,B cell lymphoma ,CENTRAL nervous system ,COMPARATIVE studies ,HEMOGLOBINS ,IMMUNOPHENOTYPING ,LACTATE dehydrogenase ,LONGITUDINAL method ,LYMPH nodes ,LYMPHOBLASTIC leukemia ,RESEARCH methodology ,MEDICAL cooperation ,RESEARCH ,SPLEEN diseases ,EVALUATION research ,T-cell lymphoma ,HEPATOMEGALY ,LEUKOCYTE count ,PLATELET count - Abstract
In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SI-HON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed. [ABSTRACT FROM AUTHOR]
- Published
- 1993
- Full Text
- View/download PDF
22. Acute lymphoblastic leukaemia in adults: Immunological subtypes and clinical features at presentation.
- Author
-
Veer, M., Putten, W., Verdonck, L., Ossenkoppele, G., Löwenberg, B., Kluin-Nelemans, J., Wijermans, P., Schouten, H., Sizoo, W., and Dekker, A.
- Abstract
In 91 of 106 adult patients with acute lymphoblastic leukemia (ALL) enrolled in the treatment protocol ALL HOVON-5 between May 1988 and October 1991, the immunophenotype of the leukemia was determined and correlated with clinical characteristics at presentation. The immunological marker analysis was performed in ten laboratories, all members of the Dutch Study Group on Immunophenotyping of Leukemias and Lymphomas (SIHON). Undifferentiated blasts were found in four patients, 67 had B-lineage ALL, 18 had T-lineage ALL, and two had biphenotypic ALL. The age of T-lineage ALL patients was lower (mean 29.3) than that of B-lineage ALL patients (mean 35.5). Tumor mass, as expressed by leukocyte count, organomegaly, and LDH, was more pronounced in T-lineage ALL. Hemoglobin and platelet count was similar in all (sub)types. CD34 was expressed in 58% of the leukemias, but most frequently in the common B-ALL (70%). Thirteen percent of the leukemias expressed one or more markers not associated with their lineage. In this prospective study immunological data were not evaluable for 15 patients. On four of them data were not available because of dry tap, for six patients the typing was technically insufficient, and for four patients the results were unclassifiable; with one patient the marker analysis was not performed. [ABSTRACT FROM AUTHOR]
- Published
- 1993
- Full Text
- View/download PDF
23. Analysis of efficacy and toxicity of thalidomide in 122 patients with multiple myeloma: response of soft-tissue plasmacytomas.
- Author
-
Wu, K L, Helgason, H H, van der Holt, B, Wijermans, P W, Lokhorst, H M, Smit, W M, and Sonneveld, P
- Subjects
LETTERS to the editor ,MULTIPLE myeloma ,THALIDOMIDE - Abstract
Presents a letter to the editor about the analysis of the efficacy and toxicity of thalidomide in 122 patients with multiple myeloma.
- Published
- 2005
- Full Text
- View/download PDF
24. Longterm meningeal involvement as the only clinical manifestation of low grade malignant non-Hodgkin's lymphoma.
- Author
-
Heimans, J., Wijermans, P., Polman, C., Huijgens, P., Ossenkoppele, G., and Kamp, G.
- Abstract
We present the case of a 56-year old man who developed -at the age of 46-paraesthesia and numbness in the perianal region, the feet and lower legs accompanied by the presence of B-lymphocytes in the cerebrospinal fluid (CSF). Despite intensive work-up an explanation was not found until he developed hepato-splenomegaly ten years after the initial symptoms. Haematologic evaluation at that time disclosed a low-grade malignant B-cell lymphoma. Repeated CSF examination revealed 31 leukocytes/mm, of which were mainly lymphocytes. These proved to be B-lymphocytes of monoclonal origin. These findings suggest that a leptomeningeal localisation of a low-grade malignant lymphoma had been present for ten years before systemic manifestation of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 1990
- Full Text
- View/download PDF
25. Epigenetic therapy in MDS and acute AML: focus on decitabine.
- Author
-
Lübbert, M. and Wijermans, P.
- Subjects
- *
PREFACES & forewords , *HEMATOLOGY - Abstract
The article presents a preface for the December 15, 2005 issue of the "Annals of Hematology."
- Published
- 2005
- Full Text
- View/download PDF
26. Epigenetic therapy in MDS and AML: focus on decitabine.
- Author
-
Lübbert, M. and Wijermans, P.
- Subjects
- *
GENE therapy - Abstract
A correction to the article "Epigenetic therapy in MDS and acute AML: focus on decitabine" that was published online in the July 14, 2006 issue is presented.
- Published
- 2006
- Full Text
- View/download PDF
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