Alemtuzumab is effective against severe chronic lymphocytic leukaemia-associated paraneoplastic pemphigus.

Alemtuzumab (ALZ) is a monoclonal antibody used in the treatment of a variety of lymphoproliferative diseases, primarily chronic lymphocytic leukaemia (CLL). Paraneoplastic pemphigus (PNP) is a severe mucocutaneous disease, which can occur in association with B-cell malignancies. A correct diagnosis of PNP relies on distinct clinical and histopathological features, and the demonstration, by direct immunofluorescence, of intercellular and basement membrane IgG deposits in the affected tissue. PNP is often refractory to immunosuppressive drugs and frequently has a fatal outcome. We report three cases where sustained remissions of both PNP and CLL were induced by ALZ. In one of these cases, ALZ was able to reinduce a sustained remission of PNP at the reappearance of the disorder years after the primary treatment. In all cases, the PNP diagnosis was confirmed by immunofluorescence. In conclusion, ALZ should be considered as a treatment option in severe CLL-associated PNP. Patients should be carefully selected and receive appropriate infectious prophylaxis before, during and after ALZ treatment, due to the risk of opportunistic infections secondary to combined disease- and drug-induced immunosuppression.

MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation.

Severe infections related to treatment are common in patients with multiple myeloma (MM). Genetic polymorphisms of the immune system may influence the risk of infections. Mannan-binding lectin (MBL) is part of the innate immune system, and individuals homozygous for wild-type MBL encoding gene (MBL2) have a well-functioning MBL pathway of complement activation, in contrast to individuals carrying one or two variant alleles. We evaluated 113 courses of high-dose melphalan and autologous stem cell transplantation (ASCT) in patients with MM. Patients homozygous for wild-type MBL2 had a significantly reduced risk of septicaemia during the ASCT procedure compared with patients carrying variant MBL2: Odds Ratio (OR) 0.19 (95% CI: 0.04-0.77), (P=0.02) in multivariate analysis. The risk of Common Toxicity Criteria grade 3-4 infections in general was not affected by wild-type MBL2: OR 1.20 (95% CI: 0.52-2.78), (P=0.67). The findings indicate that MBL to some extent protects against the most severe infections during ASCT.

Soluble CD163: a marker molecule for monocyte/macrophage activity in disease.

By immunoprecipitation we have identified a soluble plasma form of CD163 (sCD163), the IL-6 inducible macrophage-receptor for clearing haptoglobin-haemoglobin complexes. A sandwich ELISA for measuring sCD163 was established and used to determine the sCD163 levels in normal subjects and patients with inflammatory and myeloproliferative diseases. In normal subjects, the concentration of sCD163 was high (median 1.9 mg/l) with low intra-individual variation. Highly increased levels were seen in patients with sepsis, myeloid leukaemia and in patients with Gaucher disease characterized by accumulation of tissue macrophages. Although the physiological role of sCD163 remains unknown, our present data suggest that sCD163 might prove to be a valuable marker molecule in infectious and myeloproliferative diseases.

Association between deficiency of mannose-binding lectin and severe infections after chemotherapy.

The plasma protein mannose-binding lectin (MBL) activates the complement system by binding to carbohydrate structures presented by microorganisms and thus could be an important component of the innate immune defence system. We measured MBL in patients with leukaemia who were scheduled to undergo chemotherapy (ie, a population especially susceptible to infection) and related the results to severity of infection after chemotherapy. We showed a significant association between low concentrations of MBL and serious infections related to chemotherapy (p<0.0001). These results suggest that increasing concentrations of MBL in patients having chemotherapy could reduce susceptibility to infection.

[Invasive aspergillosis in hematological patients]. / Invasiv aspergillose hos haematologiske patienter.

An increasing incidence of invasive aspergillosis over the last decades is well documented in patients with haematological malignancies and is the most significant fungal infection in patients undergoing bone marrow transplantation and in aplastic anaemia. The diagnosis is difficult as clinical signs and symptoms usually are non-specific, but can be supported by frequent radiological examinations of the chest and sinuses and successive demonstrations of Aspergillus antigen in serum. The prognosis depends on the course of the underlying disease. A regeneration of the neutrophil granulocyte number is a condition for successful treatment. Early antifungal therapy is often necessary in neutropenic patients with fever and a lung infiltrate that does not remit following broad spectrum antibacterial treatment. Because of the risk of relapse after successful treatment these patients should receive prophylactic antifungal treatment during subsequent neutropenic episodes.

[Invasive aspergillosis in two hematological patients]. / Invasiv aspergillose hos to haematologiske patienter.

We present two cases of invasive aspergillosis in patients with acute myeloid leukemia. In neutropenic patients with antibiotic resistent fever, without specific symptoms or signs, invasive aspergillosis should be considered. Diagnostic approaches such as X-ray/CT-scan of the thorax and sinuses, relevant cultures and antigen detection should be performed. Due to diagnostic difficulties and the rapid progression of the infection empirical antifungal therapy should be given. During subsequent neutropenic episodes prophylactic antifungal therapy can possibly preempt recurrence.

[Castleman's disease--difficult diagnosis]. / Morbus Castleman--en vanskelig diagnose.

A case of Mb. Castleman of the localized plasma cell type is reported. This disease expresses several symptoms from different organ systems and therefore an extensive investigation program is often performed. Diagnosis is possible through consideration of all clinical components at the same time: Refractory anaemia, high and refractory SR, weight loss, B-symptoms, but at the same time a relatively good health. CT-scan-demonstration of a localized tumour is an important clue. Histopathologically, the tumour shows vascular hyperproliferation and plasmacytosis of varying maturation. Immunophenotyping of the plasma cells and immunoblasts usually reveals a polyclonal population. Needle biopsies from several regions may be necessary to detect the polyclonality, because monoclonality is often widespread locally in the tumour. HHV8 is correlated to the multicentric PC-type of Mb. Castleman. However, no HHV8 was found in this case.

[Atypical mycobacteria. Disseminated infection in patients with hematologic diseases]. / Atypiske mykobakterier. Dissemineret infektion hos hoematologiske patienter.

During the last decade interest in atypical mycobacteria (AM), especially Mycobacterium avium complex (MAC) has been intense, as a large number of AIDS patients develop disseminated infection with MAC. Disseminated infection has also been reported in other immunocompromised patients, but in much fewer cases. Among haematological diseases hairy cell leukemia (HCL) and chronic myelogenous leukemia (CML) seem to predispose to disseminated AM infection. We review 53 cases of disseminated AM infection in haematological patients reported in the literature, 39 with HCL, ten CML, and four other haematological diseases, and a review of possible treatment is given. The prognosis seems to depend on the course of the underlying haematological disease, and we conclude that early diagnosis and treatment of the infection is of great importance. Blood and bone marrow should therefore be cultivated for mycobacteria in such patients with persistent fever of unknown cause, and in cases with negative cultures and elevated serum values of alkaline phosphatase liver biopsy should be considered.

[Disseminated Mycobacterium avium infection in three patients with hematologic diseases]. / Dissemineret Mycobacterium avium-infektion hos tre haematologiske patienter.

We report three cases of disseminated Mycobacterium avium complex infection in immunocompromised haematological patients. We conclude that in haematological patients with longlasting fever of unknown cause Mycobacterium avium complex infection should be considered and the relevant cultures from blood and bone marrow should be done.

[Preventive strategies against infections in autologous bone marrow transplantation]. / Infektionsstrategi ved autolog knoglemarvstransplantation.

The routine microbial surveillance, the prophylatic antibiotic regime and the management of infections were retrospectively evaluated in 26 autologous bone marrow transplantation episodes. The surveillance specimens indicated that ciprofloxacin prophylaxis was effective in minimising gram-negative functions. The comparison between specimens taken before and during the granulocytopenic period showed a shift towards more yeast, otherwise there were no big differences. The surveillance specimen could not identify the causative organisms in case of fever. The proven infections comprised four cases of bacteriaemia and one case of gastro-enteritis. Two patients died from disseminated Aspergillus infection not diagnosed prior to death. In 11 episodes the cause of fever remained unknown. Both fungal infections were related to nearby building construction work. None of the patients with bacterial infections were in a serious clinical condition. In the future the number of routine microbial surveillance specimens will be reduced. The aim of surveillance will be to monitor the potential occurrence of fluoroquinolone resistance, and more attention will be paid to possible fungal infections. The antibacterial policy will be continued.

The influence of antimicrobial prophylaxis on the microbial and clinical findings in patients after autologous bone marrow transplantation.

The influence of a prophylactic regimen consisting of ciprofloxacin 250 mg bid, was examined by surveillance cultures from nose, throat, axilla, gingiva, exit site of central venous catheters, blood, rectum and urine of 60 patients undergoing autologous bone marrow transplantation during a 6-year period. None of the 60 patients developed any infectious with Gram-negative rods belonging to the Enterobacteriaceae, or deep fungal infections, during hospitalization. All patients were neutropenic. Febrile episodes were seen in all patients but 3. From 13 patients, microorganisms in the blood, mostly nonhaemolytic streptococci (9/13), were cultured. Surveillance cultures did not predict later infections, but revealed the marked influence of the prophylactic antibiotics on the normal flora. Thus, mainly streptococci, coagulase-negative staphylococci and yeasts were cultured from the sites examined. It is concluded that the future objective of the microbiological surveillance should be restricted to monitoring the possible selection of drug-resistant microorganisms, and that routine cultures of blood and urine are unnecessary.

[Acute porphyria and multiple organ failure during treatment with lamotrigine]. / Akut porfyri og multiorgansvigt under behandling med lamotrigin.

A 38-year-old female suffered from an acute porphyric attack, multi-organ failure and disseminated intravascular coagulation (DIC) within two weeks of starting lamotrigine, a new antiepileptic drug. The porphyric attack was characterized by excess urinary excretion of aminolevulinic acid (ALA), porphobilinogen (PBG) and coproporphyrin III, a pattern similar to that seen in hereditary coproporphyria, however the diagnostic criteria for this specific porphyria were not fulfilled. We suggest that the observed clinical picture represents a rare adverse reaction to lamotrigine.

Parvovirus B19 infection infrequently involved in children and adults with myelodysplastic syndrome.

Parvovirus B19 infection has occasionally been reported to mimic myelodysplastic syndrome (MDS) or to cause worsening of anemia in MDS. We examined the presence of parvovirus DNA in a series of children (n=19) and adults (n=39) with a diagnosis of MDS. The series of adults included only refractory anemia (RA) and RA with ring sideroblasts (RARS). Investigation for parvovirus B19 DNA in bone marrow cells was performed employing the nested form of the polymerase chain reaction (PCR). Only a 51-year-old male with RA tested positive for parvovirus DNA. Serial examinations demonstrated the disappearance of parvovirus DNA from the bone marrow. We conclude that parvovirus infection may only rarely mimic MDS or be a superimposed infection in childhood MDS or in RA and RARS in adults.

Parvovirus B19 infection associated with encephalitis in a patient suffering from malignant lymphoma.

A parvovirus B19 infection was established in a 58-year-old woman undergoing treatment for malignant lymphoma. Clinically, the patient displayed a variety of neurologic symptoms that could not readily be explained by the mere presence of lymphoblastic cells within the central nervous system. This is the first time parvovirus B19 DNA has been detected in the cerebrospinal fluid of a patient suffering from encephalitis.

Capnocytophaga (Capnocytophaga ochracea group) bacteremia in hematological patients with profound granulocytopenia.

The clinical and microbiological features of 7 cases of bacteremia due to Capnocytophaga (Capnocytophaga ochracea group) are reported. They were diagnosed during 1991-93 at three hospital clinics. Five patients were < 10 years old and all had hematological disorders, 4 acute lymphoblastic leukemia and 1 each had aplastic anemia, non-Hodgkin lymphoma, and myelodysplastic syndrome. All were profoundly granulocytopenic with an absolute granulocyte count < 0.13 x 10(9)/l, and all but 1 had oral lesions as a possible portal of entry. A favourable response to antibiotic therapy was recorded in all patients but one who, being profoundly granulocytopenic, rapidly succumbed to Pseudomonas aeruginosa septicemia. None of the isolates were beta-lactamase producers. In addition to penicillin the isolates were susceptible to broad-spectrum cephalosporins and ciprofloxacin, but resistant to aminoglycosides.

[Kasabach-Merritt syndrome]. / Kasabach Merritt-syndrom.

Kasabach Merritt syndrome, first recognized in 1940, is characterized by haemangiomatosis, thrombocytopenia and intravascular coagulation. It is most often seen in children, rarely in adults. The mortality rate is 20-30%. Treatment is by removing the haemangiomatosis and correcting the consumptive coagulopathy. The purpose of this paper is to present a patient with Kasabach Merritt syndrome with haemangiomatosis in the spleen and the liver. A review of the relevant literature is given.

The effect of iron overload and iron reductive treatment on the serum concentration of carbohydrate-deficient transferrin.

The concentration of carbohydrate-deficient transferrin in serum (CDT) has been used as a reliable indicator of recent alcohol consumption. We have investigated the utility of this laboratory test in 20 patients with hereditary haemochromatosis (HH) by simultaneous evaluation of serum concentrations of liver transaminases, gamma-glutamyl transpeptidase, iron, transferrin and assessment of the liver iron concentration by magnetic resonance imaging. 11 patients were re-examined during iron depletion with phlebotomies. In all 11 patients intensive but not maintenance iron removal was associated with an increase in serum CDT, in three patients even to levels above the reference range. The mean serum CDT increased from 8.5 (SD 2.2) U/l to 16.6 (SD 7.2) U/l (P < 0.001). Iron mobilization from the liver was found particularly responsible for the increase in serum CDT. Independent of this finding we found a significant semi-logarithmic correlation (r = -0.77, P = 0.009) between the MRI determined liver iron concentration and serum CDT in the patients not on iron depletion. Our findings indicate that the utility of serum CDT as a measure of alcohol consumption in patients with HH may be compromised, especially during intensive iron depletion.

Changing etiology of bacteremia in patients with hematological malignancies in Denmark.

To ascertain whether the microbiological etiology of bacteremia among patients with hematological malignancies has changed in Denmark, the species distribution of clinically relevant blood culture isolates from the Hematological Department at Rigshospitalet, Copenhagen in 1990 was compared with 2 previous studies (1970-72; 1981-85). In addition, time trends of the etiology of bacteremia among hematological patients in Copenhagen (eastern Denmark) and in Arhus (western Denmark) were compared. In contrast to many other studies, a significant increase in the proportion of Gram-negative aerobes was observed in Copenhagen (from 43% in 1981-85 to 55% in 1990; p < 0.05), whereas in Arhus the proportion of Gram-positive aerobes increased steadily during the 1980s (from 34% to 51%; p < 0.05). In Copenhagen, non-hemolytic streptococci and Xanthomonas maltophilia increased significantly and accounted for 10% (p < 0.01) and 5% (p < 0.05) respectively, of all isolates in 1990, whereas Staphylococcus aureus during the 2 decades studied decreased from 25% to 8% (p < 0.001). In both regions, a decrease was observed in the proportion of Pseudomonas aeruginosa which accounted for only about 5% of all isolates in 1990. No changes were observed in the rates of anaerobes and yeasts. Several factors may contribute to the reported differences in the etiology of bacteremia among hematological patients, e.g. criteria used to assign the clinical significance of the isolate, blood culture system used, practice of using indwelling intravenous catheters, different policies with respect to antimicrobial treatment, and the degree of immunosuppression. A local surveillance of blood culture isolates is mandatory if changes in etiology and resistance development are to be detected.