Michael E. J. Beard

Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia

Bone marrow clones with abnormal chromosomes were observed in 56% of 66 patients with forms of acute myeloid leukemia [French-American-British (FAB) M1-M6]. Acute myeloblastic leukemia (AML, M1 and M2) was the most common form, and 65% of these patients showed chromosomal abnormalities compared with 41% of patients with acute myelomonocytic leukemia (AMMoL, M4). The recognized nonrandom chromosomal abnormalities found were trisomy 8, monosomy 5 or 7, trisomy 1q, t(6;9), t(8;21), t(15;17), and abnormalities in 17q. There was also a strong involvement of chromosome No. 11: Abnormalities were found in eight patients when their leukemia was diagnosed and in a further three patients during the course of karyotypic evolution. Six of these patients had AMMoL or AMoL. Complex or multiple clones were found in 37% of AML patients at diagnosis. Our AML patients had a reduced frequency of abnormalities in chromosome No. 5 or 7 and an increased frequency of abnormalities in chromosome No. 8 compared with studies reported in other countries (p = 0.01). This difference suggests that in New Zealand AML might be caused by factors different from those operating in more industrialized centers.

Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients

PURPOSE To retrospectively study the prophylaxis of invasive aspergillosis in neutropenic patients and to relate the frequency of this fungal disease to any causal or modifying factors that could be identified. PATIENTS AND METHODS Between 1977 and 1988, 130 patients underwent 158 intensive treatment episodes to control acute leukemia, lymphoma, and aplastic anemia, and the frequency of complicating aspergillus infection was determined. RESULTS Proven invasive aspergillus infections occurred in 22 cases, 12 of which were fatal. Invasive aspergillosis was suspected in a further 16 cases and all these patients recovered with amphotericin B treatment. Colonization by Aspergillus in the absence of clinically significant infection was seen in 31 treatment episodes. Invasive aspergillosis involved mainly the upper and lower respiratory tract and skin. Control of the infection was closely related to the control of the underlying disease, with subsequent return of normal marrow function and resolution of neutropenia. The incidence of aspergillus infection has decreased dramatically since 1985, most probably due to the introduction of intranasal amphotericin B. This occurred despite the persistence of aspergillus spores in the hematology ward air during the 1986 to 1988 period. CONCLUSION Intranasal aerosolized amphotericin B may protect against invasive aspergillosis, even when neutropenic patients are cared for in conventional wards without HEPA filtration.

Does multisomy of chromosome 1q confer a proliferative advantage in B-cell acute lymphoblastic leukemia?

Two patients fulfilled the clinical and hematologic criteria for B‐cell acute lymphoblastic leukemia: the malignant cells had L3 morphology, bore B‐cell markers, and carried the specific t(8;14) translocation. The leukemic cells of one patient were tetrasomic for lq, and those of the other patient showed several separate cell lines with complete or partial trisomy of lq. In the latter patient it appeared that a break close to the heterochromatin of lq produced an unstable chromosome end which formed associations with the telomeres of at least seven other chromosomes. It is suggested that multisomy of lq gives tumor cells a proliferative advantage and is secondary to the basic neoplastic event.

Essential thrombocythaemia and the Philadelphia chromosome

Six adult patients presented with clinical features of essential thrombocythaemia. Five of the patients, although Ph‐positive, have maintained these features without evidence of leukaemia; in one case for 9 years. A sixth patient developed leukaemic blast crisis following a persistently high platelet count over 4 years. Her cells were Ph‐negative, but hybridization of gene probes to chromosomes in situ and to leukaemic DNA showed that the abl oncogene had moved to the breakpoint cluster region (bcr) on the normal chromosome 22. This patient has the same molecular gene change as occurs in some cases of Ph‐negative chronic myeloid leukaemia (CML) whose leukaemic cells likewise show no evidence of chromosomal translocation. Molecular studies are essential for the correct diagnosis of these patients. The Ph genomic lesion appears to have a range of leukaemic expression which includes thrombocythaemia as well as chronic myeloid leukaemia and acute lymphatic leukaemia.

Ph-negative chronic myeloid leukaemia

An analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph‐positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c‐abl and bcr genes as is seen in Ph‐positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph ‘molecular defect’but lacks the Philadelphia chromosome is no different from Ph‐positive CML.

Invasive aspergillosis in severely neutropenic patients over 18 years: impact of intranasal amphotericin B and HEPA filtration

The impact of intranasal amphotericin B and high-efficiency particulate air (HEPA) filtration on the incidence of invasive aspergillosis was reviewed in patients from 1977 to 1994 undergoing intensive chemotherapy. Overall, the incidence of proven invasive aspergillosis was reduced from 24.4% (1977-1984) to 7.1% (1985-1991) (P < 0.001) following the introduction of intranasal prophylaxis, but when probable cases of aspergillosis were included and lymphoma cases excluded, there was no change in incidence. Following the introduction of HEPA filtration, patient exposure to aspergillus spores as measured by air sampling was markedly reduced and there were no new cases of invasive aspergillosis. HEPA filtration proved effective in reducing invasive aspergillosis and has allowed increasingly aggressive treatment regimens to be introduced.

Richter's syndrome with identification of marker chromosomes.

A case is presented of a man with Richters syndrome with diffuse histiocytic lymphoma following a ten‐year history of untreated chronic lymphatic leukemia. He did not respond to therapy. The lymphoma cells had 61 chromosomes with aneuploidy of 13 chromosomes and 11 structurally altered chromosomes. Only chromosomes 8, 9, 12, 14, and 18 were diploid and without abnormality. Significantly, part of chromsome 1q was duplicated as in the partial trisomy of 1q reported to characterize a number of hematologic neoplasms. A large marker chromosome with subterminal centromere was a tandem duplication of chromosome 4q. Cancer 46:135–138, 1980.

Haemostasis in heat stroke.

Summary. A patient with moderately severe heat stroke was studied with particular attention to changes in haemostasis. Activation of fibrinolysis, a probable failure of hepatic synthesis of coagulation factors and severe thrombocytopenia were observed, but there was no definite evidence for disseminated intravascular coagulation (DIC). It is suggested, however, that in heat stroke of greater severity the more extensive tissue breakdown may lead to DIC. If DIC is superimposed on the above changes in haemostasis it is likely to be both sudden and overwhelming.

The tissue distribution of the 3α-fucosyl-N-acetyl lactosamine determinant recognized by the CD15 monoclonal antibodies CMRF-7 and 27

&NA; Two monoclonal antibodies, CMRF‐7 and 27, which react with cells of the granulocytic series, were obtained from hybridomas cloned from separate fusions. Biochemical studies indicate that both antibodies are of the CD15 group and react with the antigenic determinant 3α‐fucosyl‐N‐acetyl lactosamine (hapten X) expressed on some glycolipids and several different granulocyte glycoproteins with a wide range of molecular weights. The antigen was found on some promyelocytes and more differentiated granulocytes, including neutrophils and some eosinophils, but not basophils. Monocytes, lymphocytes, and erythrocytes were negative for CMRF‐7 but neuraminidase treatment revealed “cryptic” sites on monocytes and some lymphoid cells. The antibody CMRF‐7 reacted with the majority of acute myeloid leukemia blasts in the FAB categories M2‐M5 but less frequently with M1 blasts and was positive with only 5/43 acute lymphoid leukemias. Immunoperoxidase staining of other normal human tissues indicates that this determinant is found on a range of epithelial cells in skin, the gastrointestinal tract and the genitourinary system. In addition some parts of the central nervous tissue and some endocrine organs stained with these antibodies.

Abnormal chromosome 16 in clonogenic eosinophils from a case of acute myeloid leukemia (FAB,M2)

A case of acute myeloid leukemia (AML, FAB M2) is described in which the leukemic karyotype showed several numerical and structural cytogenetic abnormalities including an abnormal chromosome 16 with breakpoint at band q22, monosomy for chromosomes 5 and 7, and a single pair of double minute chromosomes. There was no patient history of treatment for a previous malignancy or occupational exposure to mutagens. Bone marrow eosinophilia was seen at presentation for refractory anemia with excess blasts in transformation and when AML was diagnosed. When bone marrow buffy coat cells were cultured in soft agar in the presence of colony stimulating factor, 19% of the colonies and 20% of the clusters were of eosinophils. Cytogenetic examination of pooled eosinophil colonies showed the marker chromosomes that identified the leukemic population.