Monolateral renal infarction and erythromelalgia in a case of chronic myelogenous leukemia.
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Aged, 80 and over↗
Biomedical subjects
Manfred Mitterer
Publications and source records attributed to Manfred Mitterer.
Paraneoplastic stiff-person syndrome, heterotopic soft tissue ossification and gonarthritis in a HLA B27-positive woman preceding the diagnosis of Hodgkin's lymphoma.
Paraneoplastic neurologic syndromes associated with Hodgkin's lymphoma include the stiff-person syndrome. A case of stiff-person syndrome is reported who first presented with muscular hyperactivity and acute respiratory failure followed by heterotopic soft tissue ossification and acute seronegative gonarthitis. Initial improvement of a tetanus-like clinical picture was achieved with benzodiazepam given by continuous infusion for analgo-sedation to mechanically ventilate the patient followed by baclofen after successful weaning. The patient was HLA B27 positive and on conventional testing no autoantibodies were detected including anti-glutamic acid decarboxylase antibodies (anti-GAD). Months later in the absence of signs of stiff-person syndrome, mediastinal lymphadenopathy and pleural effusions developed which were diagnosed as classical Hodgkin's lymphoma that was successfully treated with polychemotherapy. No relapse of paraneoplastic neurologic syndromes was seen after two years of lymphoma remission. The case illustrates that stiff-person syndrome may precede the clinical appearance of symptomatic Hodgkin's lymphoma.
Female↗
Functional T-cell anergy in a case of persistent polyclonal B-cell lymphocytosis.
The T-cell population of a patient with persistent polyclonal B-cell lymphocytosis (PPBL) presenting with an intermittent Epstein-Barr virus (EBV)-associated disease was studied. Unstimulated T-cells did not express CD40 ligand (CD40L), whereas activation with IL-2 led to expression of this costimulatory molecule. CD40L expression was inhibited upon incubation with the supernatant of an EBV-positive B-cell line (SM) which had been grown spontaneously from the patient's peripheral blood cells. The supernatant of SM cells effectively inhibited cytotoxic T-cells. Elevated levels of IL-10, TNF-alpha and soluble CD40 were found in the supernatant of SM cells. Additionally, enhanced levels of LMP-1 protein were detected.
Adult↗
Hyperfractionated cyclophosphamide in combination with pulsed dexamethasone and thalidomide (HyperCDT) in primary refractory or relapsed multiple myeloma.
Sixty patients with advanced multiple myeloma received 2-6 monthly treatment courses combining hyperfractionated cyclophosphamide (300 mg/m2 i.v. over 3 h q 12 h x 6, d 1-3) with pulsed dexamethasone (20 mg/m2/d p.o., d 1-4, 9-12, 17-20) and once daily thalidomide at individually escalating doses (100-400 mg/d) depending on tolerability (HyperCDT). Responding patients were maintained on daily thalidomide and monthly dexamethasone pulses. Complete, partial and minor response rates were 4%, 68% and 12% respectively; overall response rate was 84% (efficacy analysis). Median event-free and overall survival was 11 and 19 months respectively. During at least one treatment cycle, 67% of patients experienced grade 4 neutropenia resulting in 17% grade 3 and 9% grade 4 infections. Side-effects, presumably related to thalidomide, included neuropathy (40% grade 2, 16% grade 3), constipation (17%), oedema (5%), bradycardia (5%), skin reactions (3%), cerebrovascular events (5%) and deep vein thromboses (8%). Thromboses were not related to known thrombophilic risk factors. Four patients with prior myeloma therapy > 50 months developed myelodysplastic syndrome or secondary acute myeloid leukaemia 2-4 months after study entry. HyperCDT is a highly active and reasonably well-tolerated salvage regimen in advanced or refractory multiple myeloma.
Acute Disease↗
T-cell receptor excision circles: a novel prognostic parameter for the outcome of transplantation in multiple myeloma patients.
This study investigated whether T-cell receptor excision circles (TRECs) are a prognostic marker for the outcome of myeloma patients undergoing a tandem autologous peripheral blood stem cell transplantation (PBSCT). Twenty-five patients were enrolled. Samples were obtained at study enrollment, after conventional therapy, between first and second transplantation and 3, 6, 12 and 24 months after the second PBSCT. TRECs were quantified using real-time polymerase chain reaction. A high variation in TREC levels was found at diagnosis (median TREC level 136/10(5) peripheral blood mononuclear cells (PBMCs); range 1-1729), suggesting individual differences in thymic output of naive T cells. Patients with more than 136 TRECs/10(5) P BMCs at diagnosis had a statistically significant better overall survival (P=0.05) and event-free survival (P=0.045), whereas low TREC levels correlated with a higher incidence of infectious complications. Median TREC values were lowest after the first PBSCT (52/10(5) PBMCs) and reached the baseline 12 months after the second transplantation. Patients with high TREC levels after the second PBSCT had a significantly higher probability of being in complete or partial remission 30 months after the second PBSCT. TREC levels were not correlated with beta2-microglobulin and C-reactive protein levels at diagnosis. These data suggest that TRECs could be a relevant prognostic factor for patients who receive high-dose chemotherapy and autologous PBSCT.
Adult↗
Functional analysis of the mutated Epstein-Barr virus oncoprotein LMP1(69del): implications for a new role of naturally occurring LMP1 variants.
BACKGROUND AND OBJECTIVES: The role of carboxyterminal deletions of the latent membrane protein-1 (LMP1) in Epstein-Barr virus (EBV) infection and oncogenesis is unclear. Here we describe functional properties of a rare 69-bp LMP1 deletion mutant (LMP1(69del)) isolated from a patient with polyclonal B-cell lymphocytosis. DESIGN AND METHODS: Colony focus assay was used to evaluate the transforming capacity of LMP1(69del) in comparison to that of wild-type LMP1 from EBV strain B95/8. Transient transfectants of B-, T-, epithelial and 3T3 cells, and stable transfectants with ecdysone-inducible LMP1 expression were produced. The signaling capacity of both LMP1s on nuclear transcription factors NFkappaB and AP-1 were studied. Secretion of matrix metalloproteinase MMP-9, apoptosis, and EBV lytic and latent gene expression were also investigated. RESULTS: LMP(69del) showed transforming properties comparable to those of the wild-type oncoprotein. Induction of NFkappaB but a markedly reduced influence on AP-1 were observed. Both oncoproteins induced secretion of MMP-9, and enhanced pre-apoptotic effects in Jurkat-T cells leading to increased Fas/Apo-1 and doxorubicin-mediated apoptosis. Furthermore, LMP1(69del) showed a more effective down-regulation of the EBV lytic cycle master gene BZLF1(Zebra) than did wild-type LMP1. INTERPRETATION AND CONCLUSIONS: (i) LMP1(69del) possesses oncogenic properties, (ii) the observed impaired activity on AP-1 does not interfere with MMP-9 induction, (iii) the enhanced inhibition of BZLF1 could compensate for previously described mutations of our isolate leading to a more lytic phenotype and may be responsible for counteracting permanent virus replication in the chronic active EBV syndrome observed in this patient.
Animals↗
The CD19+ B-cell counts at peripheral blood stem cell mobilization determine different levels of tumour contamination and autograft purgability in low-grade lymphoma.
The tumour load of peripheral blood stem cell (PBSC) harvests and the outcome of ex vivo immunomagnetic B-cell purging was investigated in 19 patients with low-grade lymphoma. To quantify the tumour load, we combined fluorescence-activated cell sorting measurement of CD19+ B-cells and determination of the B-cell light chain ratio (LCR) with consensus complementarity-determining region III-polymerase chain reaction (CDRIII-PCR) and gene scan analysis. The number of tumour cells was calculated using B-cell extracts from the PBSCs. Two different patterns were distinguished. In eight patients (42%) with CD19+ B cells >1% in the apheresis product, a high tumour load was found, characterized by a monoclonal LCR, positive PCR in seven out of eight cases, >5 x 10(7) extracted lymphoma cells in six out of seven PCR-assessable cases, and the presence of residual lymphoma after purging in six of seven cases. In 11 patients (58%) with <1% CD19+ B-cells in the product, a low tumour load was indicated by a polyclonal LCR, positive PCR in only 4 out of 11 cases, >5 x 10(7) extracted lymphoma cells in zero out of four PCR-assessable cases, and the presence of residual lymphoma after purging in zero out of four of these cases. The level of residual lymphoma following purging largely depended on the level of tumour contamination. CD19+ B-cells >50/microl in the peripheral blood at mobilization predicted a high tumour load in the apheresis product.
Adult↗