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H C van Zaanen

Publications and source records attributed to H C van Zaanen.

11 recordsLinked to original sources
PubMed2000

[Renal insufficiency due to light chain multiple myeloma].

In 3 female patients, aged 65, 83 and 76 years, with severe renal failure, light chain multiple myeloma was diagnosed, following a substantial delay on the part of the doctors concerned. Either the diagnosis had not suspected or the serum proteins had been misinterpreted. After a while, the first two patients declined further treatment with chemotherapy and haemodialysis, and subsequently died. The third patient attained a creatinine clearance of 20 ml/min and was subsequently treated for the multiple myeloma in the outpatients department. The absence of a paraprotein peak in the serum does not exclude the possibility of a multiple myeloma. In the case of light chain disease, the gammaglobulin region is, in fact, often empty. Treatment of multiple myeloma consists of a rapid rehydration and forced diuresis; the usefulness of plasmapheresis has not been demonstrated.

Acute Kidney Injury↗
PubMed1999

[Pleural amyloidosis as a cause of excessive pleural effusions].

A 83-year-old woman known with a stable disease multiple myeloma was hospitalized frequently with dyspnoea caused by copious bilateral pleural effusions. Thoracentesis was performed repeatedly but pleural effusions returned. Extensive laboratory and radiological examinations failed to reveal the cause of the pleural effusions. Finally, after pleural biopsy the diagnosis of amyloidosis of the pleura could be made. The patient died in hospital from a stroke. Pleural amyloidosis is rarely reported and is accompanied by large uni- or bilateral pleural effusions even without amyloidosis of the heart.

Aged↗
PubMed1998

Chimaeric anti-interleukin 6 monoclonal antibodies in the treatment of advanced multiple myeloma: a phase I dose-escalating study.

Interleukin 6 plays a key role in the pathogenesis of multiple myeloma (MM). Therefore we conducted a phase I dose-escalating study with chimaeric monoclonal anti-IL6 antibodies (cMab) in MM patients resistant to second-line chemotherapy. The cMab (CLB IL6/8; Kd 6.25 x 10(-12)M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28, repectively, with a daily dose of 5 mg in patients 1-3, 10 mg in patients 4-6, 20 mg in patients 7-9 and 40mg in patients 10-12 (total dose 140 mg, 280mg, 560 mg and 1120 mg of anti-IL6, respectively). 11/12 patients had elevated pretreatment IL6 levels. Except for transient thrombocytopenia in two patients there was no toxicity. There were no changes in haemoglobin levels, granulocyte count, liver enzymes or renal function. No human anti-chimaeric antibodies were induced. This was also reflected in a long half-life time of the cMab (median 17.8 d), resulting in accumulation of the anti-IL6 cMab and high levels of circulating IL6. However, this was in the form of biologically inactive IL6/cMab complexes and did not result in acceleration of the disease. Although C-reactive protein (CRP) levels were decreased to below detection level in 11/12 patients, indicating effective IL6 blocking, none of the patients achieved a response according to the standard criteria. We conclude that this chimaeric anti-IL6 Mab has a low toxicity, low immunogenicity and a long T1/2. A dose of 40 mg/d for 14 d can safely be used in future phase II studies.

Aged↗
PubMed1997

Modulation of chronic excessive interleukin-6 production in multiple myeloma does not affect thyroid hormone concentrations.

Interleukin-6 (IL6) is believed to be involved in alterations of thyroid hormone metabolism in acute nonthyroidal illness. To evaluate the effects of IL6 on thyroid hormone metabolism in a chronic IL6-mediated disease, we measured thyroid hormone concentrations in multiple myeloma patients treated with intravenous anti-IL6 chimeric monoclonal antibodies ([cMabs] Kd = 6.25 x 10(-12) mol/L). Twelve patients were studied, receiving at least one complete treatment cycle of 14 days (daily dose: 5 mg, n = 3; 10 mg, n = 3; 20 mg, n = 3; and 40 mg, n = 3). Eight of them also completed a second treatment cycle of 14 days. Thyroid hormone concentrations were measured before, during, and after treatment with the anti-IL6 cMab. Even in the group with the lowest dosage, IL6 activity measured by the B9 bioassay was blocked completely. Compared with the reference ranges, 10 of 12 patients had one or more abnormal pretreatment values for thyroid hormone concentrations. Thyroid autoantibodies were negative in all patients. There was no correlation between thyroid hormone concentrations and IL6 levels, although plasma IL6 levels were increased in all but one subject. Moreover, neutralization of free IL6 by the anti-IL6 cMab did not affect thyroid hormone concentrations, although IL6-dependent C-reactive protein (CRP) levels decreased to undetectable levels in 11 of 12 patients. Two patients developed infectious complications resulting in increased free IL6 and CRP levels and in profound alterations of thyroid hormone levels consistent with an acute euthyroid sick syndrome. We conclude that IL6 is not a major determinant of thyroid hormone abnormalities in a chronic disease like multiple myeloma, but IL6 may be involved in thyroid hormone metabolism in acute diseases (probably in combination with other factors).

Aged↗
PubMed1996

Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop.

In vitro as well as in vivo observations have shown that IL6 plays a key role in the pathogenesis of multiple myeloma. Therefore we started a phase I/II dose escalating study with chimeric monoclonal anti-IL6 antibodies (cMab) in multiple myeloma (MM) patients resistant to second-line chemotherapy. Here we describe the pharmacological data as well as a new method for calculating the endogenous IL6 production. The cMab (CLB IL6/8; Kd: 6.25 x 10(-12) M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28. Daily dose: 5 mg in patients 1-3, 10 mg in patients 4-6, and 20 mg in patients 7-9 (total dose 140, 280, and 560 mg of anti-IL6, respectively). Using the pharmacokinetic data of free IL6 and the binding characteristics of the cMab, the endogenous IL6 production could be calculated from day to day using a one-compartment open model. The median half-life time of this antibody was 17.6 d. No human antichimeric antibodies were induced. Pre-treatment median endogenous IL6 production in the MM patients was 60 micrograms/d (range 13.8-230; normal controls < 7 micrograms/d). During treatment with anti-IL6 cMabs, the endogenous IL6 production immediately decreased in all patients to below 3 micrograms/d and never reached the pre-treatment value during the treatment period, except in two patients who developed an active infection, resulting in an IL6 production of 128 and 1,208 micrograms/d, respectively. We concluded that in MM patients endogenous IL6 production is 2-30 times higher than in healthy individuals. The anti-IL6 cMab strongly suppress this endogenous IL6 production, probably by blocking a positive feed-back loop, but this cMab does not prevent infection-induced IL6 production. The chimeric anti-IL6 Mabs have a long half-life time, a low immunogenicity, and are able to block IL6-dependent processes in vivo.

Aged↗
PubMed1995

A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flowcytometry.

In this paper we describe a new, rapid and sensitive method to determine plasma cell isotype and clonality in bone marrow using flowcytometry. With the use of a new fixation and permeabilization reagent (Permeafix), which preserves cell structure and morphology, and a monoclonal antibody (Mab) specific for plasma cells (B-B4), it has become possible to specifically select plasma cells and to determine the cytoplasmatic immunoglobulins by flowcytometry. Thirty successive bone marrow aspirates from multiple myeloma patients and patients with MGUS were studied as well as 10 bone marrow samples from patients with reactive plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin smears and FACS analysis. There were no discrepancies between plasma cell isotype as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow detection of very low numbers of plasma cells and to determine whether these plasma cells are mono- or polyclonal. Possible applications are discussed.

Antibodies↗
PubMed1995

Corynebacterium CDC group JK (Corynebacterium jeikeium) sepsis in haematological patients: a report of three cases and a systematic literature review.

We describe 3 patients with Corynebacterium jeikeium sepsis in neutropenic phase during treatment for acute myeloid leukaemia. Fever was the first symptom. All had a central venous catheter which was removed. Two patients developed subcutaneous nodules containing pus when the neutrophil count recovered; 1 had intracutaneous and pulmonary lesions. They were treated with vancomycin and recovered when the neutrophil count started to rise. A review of 80 neutropenic patients with C. jeikeium sepsis reported in the literature, together with our 3 cases indicates that risk factors for infection are the presence of a central venous catheter, being an adult male or postmenopausal female, profound and prolonged neutropenia and exposure to multiple antibiotics. Skin lesions are reported in 48% and pulmonary lesions in 36% of the patients. The overall mortality is 34% but in patients with recovery of the bone marrow only 5%. Therefore haematopoietic growth factors should be considered in neutropenic patients with C. jeikeium infection.

Adult↗
PubMed1994

Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity.

BACKGROUND: Glutamine-supplemented total parenteral nutrition (TPN) improved the nitrogen balance in catabolic situations. In animal studies, parenteral glutamine supplementation appeared to maintain gut integrity. This study was performed to evaluate the possible positive effects of glutamine supplementation in catabolic hematologic patients. METHODS: This was a prospective double-blind placebo-controlled pilot study, in which 20 treatment cycles in unselected hematologic patients with intensive chemotherapy were studied. Glutamine was given as a dipeptide. Patients were randomized per treatment cycle to receive isonitrogenous TPN (0.272 g nitrogen/kg of body weight) and isoenergetic TPN (2200 kcal NPE/day) without or with 40 g L-alanyl-L-glutamine (26 g glutamine) until the neutrophil count was greater than 0.5 x 10(9)/L. The daily oral food intake was recorded and analyzed carefully. Toxicity grades for performance status, mucositis, and diarrhea were scored according to the World Health Organization classification. RESULTS: No differences in neutropenic period, fever, extra antibiotics, and toxicity scores were observed, except for a gain in body weight per treatment cycle in favor of the glutamine-supplemented TPN. No side effects or allergic reactions were noted after the dipeptide administration. CONCLUSION: Supplementation of glutamine dipeptide was safe but had no significant positive clinical effect.

Adult↗
PubMed1993

Interleukin-6, a new target for therapy in multiple myeloma?

During the past few years much insight has been gained into the immunobiology of multiple myeloma. It has become evident that the growth of myeloma cells is regulated by cytokines, notably interleukin-6. In this paper a brief review is given of the evidence derived from in vitro as well as in vivo observations that interleukin-6 is involved in the pathogenesis of multiple myeloma, and the implications of these findings for the development of new therapeutic strategies are discussed.

Animals↗
PubMed1992

Thiamine deficiency in hematologic malignant tumors.

The case is reported of a patient with acute myeloid leukemia with severe right-sided congestive heart failure that responded to treatment with thiamine. Leukocytes cells contain relatively high concentrations of thiamine-dependent enzymes compared with erythrocytes. Because no other cause could be found, it was postulated that consumption of thiamine by blast cells was responsible for the deficiency. After studying this patient, the thiamine pyrophosphate (TPP) effect was measured in five other consecutive patients with fast-growing hematologic malignant tumors. In two patients, the TPP effect was elevated slightly, but another patient had a definite thiamine deficiency with severe cardiac failure. It is suggested that the clinician be alert for this underdiagnosed potentially fatal but easily treatable deficiency in nonalcoholic patients with fast-growing hematologic cancers.

Adult↗