Successful treatment of hepatosplenic candidiasis with a liposomal amphotericin B preparation.

The case of a granulocytopenic patient with acute undifferentiated leukaemia and hepatosplenic candidiasis who was refractory to conventional deoxycholate amphotericin B (AmpB) and 5-flucytosine therapy is reported. He experienced severe AmpB-related side-effects, and was subsequently successfully treated with a pharmaceutical preparation of AmpB (5.7 g) entrapped in sonicated liposomes, composed of lecithin, cholesterol and stearylamine in a molar ratio of 4:3:1. Three months later, during maintenance chemotherapy, liposomal AmpB (5.1 g) was reinstituted due to the finding of biopsies positive for Candida albicans at bronchoscopy. After healing of the patient's fungal infection a left upper lobe resection was performed, which showed advanced fibrosis with signs of inflammation, but no evidence of fungal disease. Since no acute side-effects and only moderate hypokalaemia were observed, it appears that liposomal AmpB is superior to conventional AmpB treatment in granulocytopenic patients with hepatosplenic candidiasis and unbearable therapy-related side-effects.     

Acquired Trisomy 12 and Absent Y Chromosome in a Patient with Acute Undifferentiated Leukaemia

A 60-year-old man developed pancytopenia and then acute leukaemia. The neoplastic cells in marrow were undifferentiated by electron microscopy and by immunological and cyto-chemical markers. The only other cells present in marrow were lymphocytes, plasma cells, macrophages and non-haematopoietic elements. Prior to chemotherapy, cytogenetic analysis of marrow cells showed two karyotypically distinct cell populations, one with 45,X,-Y and the other with a 46,X,-Y, + 12 karyotype. All marrow cells stimulated by protein-A from staphylococcus aureus were 46,X,-Y, + 12. Phytohaemagglutinin-stimulated cells were normal, 46,XY. These findings suggest strongly that most of the undifferentiated leukaemic cells were missing the Y chromosome. A subpopulation of these leukaemic cells also had trisomy 12. These observations and previously published findings suggest that trisomy 12 occurs non-randomly in haematological disorders, and in particular, may be associated with B-lymphoid malignancy.     

C ASE R EPORT: Spontaneous peritonitis caused by Candida albicans

We report a 40-year-old man with decompensated alcoholic liver cirrhosis, who developed spontaneous peritonitis caused by Candida albicans after complete recovery from a recent episode of acute pancreatitis. The patient was successfully treated with amphotericin B. A search of the literature showed that this is the fourth reported case of spontaneous peritonitis caused by Candida albicans.     

The combination of oral amphotericin B with azoles prevents the emergence of resistant Candida species in neutropenic patients

The role of antifungal prophylaxis remains controversial and concerns exist that the use of azoles may potentiate the emergence of resistant Candida species. We used a strategy of combining the latest azole/triazole with oral amphotericin B to reduce this risk. We analysed data on Candida colonization and candidaemia in neutropenic patients from four prophylaxis periods (1985/6: ketoconazole and amphotericin B suspension; 1991/2 & 1997: fluconazole and amphotericin B suspension; 1998/9: itraconazole) to look for evidence of the emergence of potentially resistant species. Overall, the percentage of patients colonized with Candida fell significantly (69.3%, 57.5%, 43.2% and 46%, respectively, P < 0.001) due to a decrease in colonization with C. albicans (49%, 23.1%, 22.2% and 25.2%, respectively, P < 0.001). However, in 1998/9, increased colonization, particularly with C. glabrata in the lower gastrointestinal tract, was noted to coincide with the omission of oral amphotericin B. Despite an increasing population of 'high risk' patients, the incidence of candidaemia has not changed significantly (2%, 1.4%, 1.2% and 2% respectively). However, species causing candidaemia have changed, with resistant organisms now predominating. Our findings support the use of azole prophylaxis although, in view of the trends noted when itraconazole was used alone, we would recommend the additional use of oral amphotericin B.     

Development of Chronic Lymphocytic Leukaemia in a Patient with Polycythaemia Vera

A 73-year-old patient who had polycythaemia vera (PV), and who 6 years later developed chronic lymphocytic leukaemia (CCL) is described. 2 years after the appearance of CLL, the polycythaemic phase showed a remission following treatment with phlebotomy and busulfan. CLL did not make all the characteristics of PV disappear: leucocyte alkaline phosphatase and fibrosis of the bone marrow remained increased and the erythrocyte sedimentation rate remained low. The abnormal lymphocytes were B-cells and had the peculiarity that most of their nuclei showed a deep cleft, and some were bilobed. Chromosomal studies of the bone marrow showed the presence of a metacentric chromosome in the C-group, while the karyotype of the peripheral blood was normal. This case is described because of the rarity of the coexistence of these 2 diseases in the same patient.     

Acute Myeloid Leukaemia with the Philadelphia Chromosome

A case report of serial chromosome studies on a 26-year-old male with acute myeloid leukaemia (AML) is presented. The classic Philadelphia chromosome (Ph¹) transloca-tion, t (9; 22) was found in 77 % of the metaphases at diagnosis and in 100 % in relapse; during a 3-month remission period the cytogenetic picture was normal or the Ph1 was present in a minor cell population only. The clinical and morphologic features of this case indicated that it was really a case of AML and less likely chronic myeloid leukaemia (CML) presenting in blast crisis. It is suggested that the oncogen producing the 9; 22-translocation and CML may also induce AML in rare instances.     

Serum Beta2-Microglobulin in Acute and Chronic Leukaemia

The serum concentration of beta₂-microglobulin (beta₂-m) was measured in 69 patients with acute or chronic lympho- and myeloproliferative disorders. Serum beta₂-m was found significantly increased in 12 out of 14 patients with chronic lymphatic leukaemia. The serum concentration was proportional to the estimated lymphatic infiltration of tissues but inversely related to the number of circulating lymphocytes. Cytostatic treatment was followed by a decrease in serum beta₂-m, but normalization of the serum concentration was not observed. 11 patients with chronic granulocytic leukaemia all had significantly elevated serum concentrations of beta₂-m and increased serum concentrations were also found in patients with acute leukaemias. Thus, 12 out of 25 patients with acute myeloid leukaemia and all of 5 patients with acute myelomonocytic leukaemia as well as 4 out of 5 patients with acute lymphatic leukaemia had increased serum beta₂-m levels. In acute leukaemia no correlation could be demonstrated between the blood lymphocyte concentration and serum beta₂-m. Also no significant changes in serum beta₂-m were found in either remission or relapse of the acute leukaemia. It is concluded that serum beta₂-m in patients with chronic leukaemia may reflect the total amount or turn-over of leukaemic cells in the body and that repeated determinations of serum beta₂-m in these patients might be useful as an estimate of the residual leukaemic cell mass after therapy. Apart from this the determination of serum beta₂-m seems to be of little, if any, clinical use in leukaemia.     

Treatment of Candida albicans pericarditis in a heart transplant patient

Pericarditis due to Candida species is a rare clinical entity, associated with thoracic surgery and immunosuppression. We report here the second case of pericarditis due to Candida albicans in a heart transplant patient, which presented as tamponade approximately 3 weeks post transplant, in the absence of evidence of sternal osteomyelitis. The patient was treated with pericardiocentesis and a combination of caspofungin and fluconazole, but the patient ultimately required the explantation of retained epicardial leads and the creation of a pericardial window. This case illustrates that Candida species must be considered in the differential diagnosis in post-transplant pericarditis, and that foreign body removal is, as always, key in helping to resolve such infections. This case also demonstrates the first use of caspofungin with fluconazole to treat Candida pericarditis. We discuss the conflicting data regarding the use of caspofungin, alone or in combination therapy, in treating infections involving biofilms, such as the infected pericardium.     

Subcutaneous Cerebrospinal Fluid Reservoirs in Patients with Acute Leukaemia

Subcutaneous cerebrospinal fluid (Ommaya) reservoirs were inserted in 23 patients with acute leukaemia and 2 patients with malignant lymphoma. In 9 leukaemia patients reservoirs were used for the prophylaxis of central nervous system leukaemia: only 1 patient developed meningeal leukaemia but less invasive therapy has now been shown to achieve effective prophylaxis and prophylactic use of Ommaya reservoirs has been discontinued. In 16 patients, reservoirs were inserted as aids to the treatment of meningeal leukaemia or lymphoma. Intracranial disease was successfully controlled and recurrences were prevented but patients eventually died from relapse of their systemic disease. The principal complications of the subcutaneous reservoirs were obstruction, misplacement, and one case of infection. Leucoencephalo-pathy in several patients was attributable to irradiation and cytotoxic drugs and not to the reservoirs. Problems due to misplacement of the reservoir occurred in 3 out of 13 reservoirs inserted by the occipital route and in only 1 of 12 reservoirs inserted by a frontal approach. With adequate supervision, the reservoirs are valuable aids to intrathecal therapy in patients with established meningeal leukaemia or lymphoma.     

Autopsy Findings in Leukaemia

Out of 38 leukaemic cases only 16 had extensive leukaemic infiltration at death. 15 patients had slight or moderate and 7 no infiltration at all. 12 of the 15, and 5 of the 7 died with septicaemia. The latter patients must have died of complications rather than of the leukaemia itself. Although it has been possible to reduce the incidence of septicaemia during life, terminal septicaemia does not yet seem to be preventable. Septicaemia was revealed at autopsy in 27 of 38 patients; 25 of these also had clinical signs of septicaemia before death. Necrotizing gastrointestinal lesions may cause endogenous infection. In the present material, almost every second patient had fungal septicaemia. Out of 7 patients having oral candidiasis in vivo 5 had systemic candidiasis at autopsy, but only half of the patients with systemic candidiasis had visible oral growth. Modern treatment of leukaemia seems to be able to prevent intracranial haemorrhage in 90% of the cases. On the other hand, vacuolization of muscle and liver tissue was a frequent finding in leukaemia. It is suggested as being caused by fatty degeneration. Vacuolization of myocardial cells was found in 7 out of 13 cases. Among these 7, 4 had had intermittent hypokalaemia.     

Familial Monocytic Leukaemia A Report of Two Families

2 families with a total of 5 cases of acute monocytic leukaemia are described. Possible implications for the pathogenesis of acute leukaemia are discussed.     

A Study of the Reproducibility of the Diagnostic Criteria for Acute Leukaemia

The Leukaemia Group of Middle Sweden recently started a new multicentre study of treatment of adult patients with acute leukaemia from 6 centres. The criteria for the diagnosis, subclassification, degree of leukaemic bone marrow infiltration, remission and relapse are to be used by the morphologists of 6 different pathology departments. The reproducibility of the criteria has been studied by 3 of the morphologists concerned, in a retrospective review of a strictly consecutive series of 79 adult patients treated at Södersjukhuset, Stockholm, Sweden, in the years 1978 to 1981. The results show that the reproducibility of the criteria and the concordance of the morphologists when using them increased when the criteria were made more detailed and precise.     

Acute Myeloid Leukaemia Complicating a Breast Cancer after Mastectomy and Radiotherapy

The author reports a patient treated three years ago for a breast carcinoma. High doses of X-ray had been delivered after radical mastectomy. The possible relationship between this exposure and a rapidly fatal acute myeloid leukaemia is emphasized.     

Chronic Myelocytic Leukaemia Presenting in Blastic Transformation: Two Cases Primarily Diagnosed as Acute Myelocytic Leukaemia

The interval from diagnosis of chronic myelocytic leukaemia (CML) to onset of blastic transformation (BT) can vary from days to several years. This blastic phase of CML is indistinguishable from acute myelocytic leukaemia (AML), both clinically and morphologically. The Ph¹ chromosome has occasionally been demonstrated in acute leukaemia and it has been suggested that these cases may represent CML presenting in BT. 2 such patients are reported, in 1 of whom the characteristics after treatment further confirmed the diagnosis of CML. Differentiation between CML presenting in BT and AML has both prognostic and therapeutic value. For this reason it is recommended that cytogenetic screening for the Ph¹ chromosome should be included in the initial examination of patients with acute leukaemia.     

Massive Pericardial Effusion in a Case of Acute Pericarditis with Slight ST-Segment Elevation of Short Duration

We present the case of a 77-year-old woman who suffered from chest pain. Her white blood cell count was 10,200/μL and C-reactive protein level was 5.5 mg/dL. There was no electrocardiogram abnormality up to 5 hours after admission. At 15 hours, slight ST-segment elevation occurred, but this disappeared on day 4. Imaging revealed slight pericardial effusion. Nonsteroidal anti-inflammatory drugs and antibiotics were administered. However, the pericardial effusion, inflammatory response, and bilateral heart failure worsened. Pericardiotomy on day 6 released 350 mL of fluid, and symptoms improved. Viral pericarditis was assumed. Massive pericardial effusion is rare in cases of acute viral pericarditis, as is slight, short-duration ST-segment elevation.     

心电图PR段改变对急性心包炎的临床诊断价值

目的探讨体表心电图PR段改变对急性心包炎的临床诊断价值。方法对60例急性心包炎病人不同时间记录的首次心电图进行分析,测量各导联PR段的方向和幅度。以60例心肌梗死和60例早期复极综合征为对照。结果60例急性心包炎病人中,44例(73.3%)在I、Ⅱ、Ⅲ、aVF、V3~V6导联普遍出现PR段下移,aVR导联出现PR段抬高。普遍导联PR段改变的检出率在发病第l天,第2天记录的心电图中最高,达88.6%,随后记录的心电图中逐渐降低。在心肌梗死中有1.7%记录到普遍PR段下移,在早期复极综合征中普遍PR段下移的检出率也为1.7%。结论普遍导联PR段下移是急性心包炎早期心电图的特征性改变。     

Trisomy 8 in Acute Myeloid Leukaemia

Two cases of acute myeloid leukaemia with trisomy 8 in all examined bone marrow cells are reported. The occurrence and the prognostic significance of trisomy C in myeloproliferative disorders are discussed. The published reports of myeloproliferative disorders with chromosomal abnormalities identified by the banding technique are reviewed. It is to be noted that among group C anomalies in the acute myeloid leukaemias, only involvement of chromosome no. 7, 8 and 9 have been reported so far.     

Acute Myelogenous Leukaemia Occurring at the Same Time in Husband and Wife

Acute myelogenous leukaemia was diagnosed within a 1 week's interval in a married couple without consanguinity. The husband had acute myelomonocytic leukaemia whereas the wife had acute myelogenous leukaemia of the classical type. Neither the histories nor findings contributed to an understanding of leukaemogenesis. The calculated risk that a husband and wife should develop acute myelogenous leukaemia within the same year is approximately 1:400 millions.     

Myelomatosis Terminating in Acute Myelogenic Leukaemia

A case of acute myelogenic leukaemia developing after 7 months treatment with alkylating agents for multiple myeloma is reported. The patient was also given irradiation for an expansive process in the thoracic column. By immunofluorescence staining of the bone marrow cells there was no evidence for production of pathological globulins in the blast cells, while the plasma cells contained IgA, kappa.