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Biomedical subjects

P W Wijermans

Publications and source records attributed to P W Wijermans.

At least 19 recordsLinked to original sources
PubMed2005

[Modern treatment methods for multiple myeloma: guidelines from the Dutch Haemato-Oncology Association (HOVON)].

The treatment for multiple myeloma has undergone many changes over the past decade. Intensive therapy with autologous stem-cell support has improved the clinical outcome significantly in younger patients. Reduced intensity conditioning regimens have lowered the high treatment-related mortality of myeloablative allogeneic transplantation. New effective anti-myeloma drugs such as bortezomib and thalidomide analogues have become available. These new developments have made it necessary to formulate recommendations to facilitate decisions concerning the management of myeloma patients. The Myeloma Working Party of the Dutch Haemato-Oncology Association (Stichting Haemato-Oncologie voor Volwassenen Nederland) has developed therapy guidelines based on phase-II and phase-III studies as well as the expertise of the working party. These include upfront induction therapy followed by autologous transplantation for patients aged up to 65 years and oral melphalanprednisone treatment for patients with severe co-morbidities and patients over the age of 65 years. Patients under the age of 66 with an HLA-identical (family) donor are candidates for non-myeloablative stem-cell transplantation following autologous stem-cell transplantation. For second-line treatment, thalidomide, combined with dexamethasone is recommended. Younger patients responding to second-line treatment are candidates for a second autologous transplant. Bortezomib is indicated for those patients refractory to the previous two lines of treatment. All patients should receive long-term bisphosphonates. Erythropoietin may be considered in symptomatic anaemia as well as antibiotic prophylaxis during induction therapy which includes dexamethasone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Interferon-alpha as maintenance therapy in patients with multiple myeloma.

BACKGROUND: The effect of interferon-alpha 2b (IFN-alpha-2b) on progression-free and overall survival as well as quality of life (QoL) was studied in mainly elderly patients with multiple myeloma (MM), who reached a plateau phase after melphalan/prednisone induction. PATIENTS AND METHODS: In an open phase III trial, 262 patients, median age 69 years (range 34-91), received at least 10 monthly courses of melphalan/prednisone followed by response evaluation. Plateau phase was reached by 128 patients. Next, 90 patients were randomized between IFN-alpha-2b and no maintenance therapy. Reasons for non-randomization were: refusal (18), concomitant disease (nine), protocol violation (six), WHO performance status >2 (four) and allogeneic transplantation (one) RESULTS: At a median follow-up from diagnosis of 97 months (0-140) for those patients alive, IFN-alpha-2b therapy was associated with improved progression-free survival (median 13.5 versus 8.4 months from randomization), although this did not translate in a better overall survival (41 versus 38.4 months). One-third of patients discontinued IFN-alpha due to toxicity. No differences were observed between patient groups in QoL. CONCLUSIONS: IFN maintenance therapy in MM prolongs progression-free survival and, provided that the burden of toxicity is not too high, does not adversely affect QoL.

Adult↗
PubMed2005

Quantification of outpatient management and hospitalization of patients with high-risk myelodysplastic syndrome treated with low-dose decitabine.

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.

Aged↗
PubMed2005

An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients.

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.

Adult↗
PubMed2005

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer.

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.

Cohort Studies↗
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↗
PubMed2004

The effects of 5-aza-2'-deoxycytidine (Decitabine) on the platelet count in patients with intermediate and high-risk myelodysplastic syndromes.

5-Aza-2'-deoxycytidine, a DNA-hypomethylating agent, can induce clinical remissions in patients with high-risk myelodysplastic syndromes (MDS). During treatment an increase in platelet count is frequently the first positive event to be seen. In this study, we analyzed the platelet response of patients with high-risk MDS on low-dose 5-aza-2'-deoxycytidine therapy. We evaluated 162 from the 170 patients entered in three consecutive Phase II studies. One hundred twenty-six of them were thrombocytopenic at start of the therapy. All patients had an IPSS risk score of Intermediate I or higher. A rise in platelet count preceded a good trilineage response. In 58% of the thrombocytopenic patients a platelet response was already seen after one cycle of therapy. During therapy 69% of the patients with a low platelet count showed a response. Due to disease progression the final response rate was 63% in thrombocytopenic patients. No correlation was found between the platelet response and either the presence or absence of an adequate number of megakaryocytes or serum thrombopoietin levels. However, platelet response strongly predicted for overall survival (P < 0.0001). 5-Aza-2'-deoxycytidine has a clinically significant, often long lasting, effect on the platelet count in a substantial number of high-risk MDS patients.

Adult↗
PubMed2004

Early response to therapy and survival in multiple myeloma.

Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

Adult↗
PubMed2004

Testing families with HFE-related hereditary haemochromatosis.

HFE-related hereditary haemochromatosis is the most common autosomal recessive disorder in the Caucasian population. In 1996 the responsible gene (called HFE) was identified. Two mutations (C282Y and H63D) are considered most important and occur frequently in the Caucasian population. We describe a family of an affected proband in which first- and second-degree relatives were tested phenotypically and genotypically. In second-degree relatives both C282Y homozygosity as well as compound heterozygosity were found. Family testing can be useful to detect persons who will possibly develop iron overload. We must be aware that testing first-degree relatives only carries a 2.5% chance that persons at risk of developing iron loading will not be detected. Cascade screening of second-degree relatives might be cost-effective.

Amino Acid Substitution↗
PubMed2002

[Thalidomide in the treatment of refractory multiple myeloma: a Dutch study of 72 patients: an antitumor effect in 45%].

OBJECTIVE: To determine the efficacy and side effects of thalidomide in the treatment of refractory multiple myeloma. DESIGN: Retrospective, descriptive. METHOD: Data were obtained by means of case research on patients with refractory multiple myeloma who were treated with thalidomide at four regional hematological centres in the period from 1 May 1999 to 31 May 2001. The patients had previously been treated with one, two or three schedules of chemotherapy. The starting dose of thalidomide was 200 mg per day and the dose was increased gradually to a maximum of 800 mg per day depending on the tolerance. RESULTS: The 72 patients included 43 men and 29 women with an average age of 62 years (range: 38-82 years). The median follow-up was 13 months (range: 2-25). Thalidomide as a single agent was prescribed for 64 patients, of whom 29 (45%) responded; a complete response was achieved in 3 patients, a partial response in 18, and a minor response in 8. In 4 of 11 patients with an extramedullary plasmacytoma a decrease in size was observed. The median duration of the response was 9 months (range: from 2 till > 24). The median overall survival from the start of thalidomide treatment was 9 months. Thalidomide plus dexamethasone was given to 9 patients who did not respond to thalidomide alone, and in 6 of them a reduction of M-protein was then observed. The most frequent adverse effects were constipation, drowsiness, somnolence, dizziness, venous thrombosis and polyneuropathy. Doses of up to 400 mg per day were generally well tolerated. CONCLUSION: Thalidomide has antitumour activity in refractory multiple myeloma.

Adult↗
PubMed2002

[The CBO professional guideline 'monoclonal gammopathy' (paraproteinemia) (revision)].

The revised guideline 'Monoclonal gammopathy (paraproteinaemia)' of the Dutch Institute for Health Care Improvement (CBO) describes the most recent clinically relevant developments in the field of monoclonal proteins (M-proteins). Criteria with both prognostic and therapeutic significance are established for 'monoclonal gammopathy of undetermined significance' (MGUS) and (smouldering) multiple myeloma. If an M-protein is found incidentally, the therapeutic consequences will be determined mainly by the probability that the M-protein fits in with the diagnosis or the clinical findings in the patient in question, as well as with the type and extent of the monoclonal gammopathy. A myeloma risk score enables the treating physician to judge whether a bone marrow examination and determination of the skeletal status are required. The revised guideline contains specific clinical questions and indications that can be used on the laboratory order forms and which facilitate the interpretation of the test results. The investigation of skeletal abnormalities must fulfill established criteria in order to be able to discriminate between MGUS and multiple myeloma, and for the staging of multiple myeloma. There is no indication for routine MRI, but MRI must be performed urgently in patients with radicular symptoms or a (threatened) transverse lesion. Both cytology and histology of the bone marrow are an essential part of the initial diagnosis and classification of multiple myeloma. Cytogenetic studies of the bone marrow are recommended as well. In the case of unexplained polyneuropathy, an M-protein should be looked for.

Bone Marrow Examination↗
PubMed2002

Disappearance of a mucosa-associated lymphoid tissue (MALT) lymphoma of the urinary bladder after treatment for Helicobacter pylori.

A59-yr old man presented with macroscopic hematuria. A non-Hodgkin's lymphoma of the MALT type of the urinary bladder, stage I A-E, was diagnosed. Radiotherapy was advised, but the patient refused this kind of treatment. Because of the known relationship of a gastric MALT lymphoma and Helicobacter pylori, the patient was treated with HP eradication therapy. Afterwards the lymphoma disappeared. The patient is 3 yr later in a persistent complete remission. This is the first known case of the disappearance of a MALT lymphoma of the urinary bladder after treatment with HP eradication therapy.

Biopsy↗
PubMed2002

Age-related differences among patients with follicular lymphoma and the importance of prognostic scoring systems: analysis from a population-based non-Hodgkin's lymphoma registry.

BACKGROUND: The influence of age on the outcome of follicular non-Hodgkin's lymphoma (FL) was studied in a population-based non-Hodgkin's lymphoma registry. PATIENTS AND METHODS: This study comprised 214 follicular lymphoma patients. Grade I/II was considered separately from grade III FL. The data were analyzed with respect to three age groups: <60, 60-69 and >or=70 years. RESULTS: The overall survival rate decreased in the older age groups. Grade III patients showed a statistically significant decrease in overall survival in comparison with grade I/II patients (P = 0.03). Cause-specific survival analysis showed that in the older age groups, there was an increasing influence of concomitant disease on the death rate, especially among grade III FL patients >70 years of age. The survival curve in grade III FL patients was shown to reach a plateau. The prognostic scoring system, according to the Italian Lymphoma Intergroup, fitted better to grade I/II patients, while the International Prognostic Index showed better discrimination amongst grade III patients. CONCLUSIONS: Separate grading for follicular lymphoma is useful. An age >70 years has a negative impact on outcome, but the contribution of concomitant disease herein is important. Different prognostic scoring systems should be applied to the different grades of FL.

Age Factors↗
PubMed2000

Report of an international working group to standardize response criteria for myelodysplastic syndromes.

Standardized criteria for assessing response are essential to ensure comparability among clinical trials for patients with myelodysplastic syndromes (MDS). An international working group of experienced clinicians involved in the management of patients with MDS reviewed currently used response definitions and developed a uniform set of guidelines for future clinical trials in MDS. The MDS differ from many other hematologic malignancies in their chronicity and the morbidity and mortality caused by chronic cytopenias, often without disease progression to acute myeloid leukemia. Whereas response rates may be an important endpoint for phase 2 studies of new agents and may assist regulatory agencies in their evaluation and approval processes, an important goal of clinical trials in MDS should be to prolong patient survival. Therefore, these response criteria reflected 2 sets of goals in MDS: altering the natural history of the disease and alleviating disease-related complications with improved quality of life. It is anticipated that the recommendations presented will require modification as more is learned about the molecular biology and genetics of these disorders. Until then, it is hoped these guidelines will serve to improve communication among investigators and to ensure comparability among clinical trials. (Blood. 2000;96:3671-3674)

Disease Progression↗
PubMed1999

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.

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/m2 (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 alpha-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.

Adult↗
PubMed1999

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.

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.

Adult↗