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Protein kinase C-beta II (PKC-beta II) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy. This study compared prognostic significance of immunohistochemically determined PKC-beta II expression in de novo DLBCL treated with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy with and without rituximab. Outcomes were assessed in 80 consecutive patients, 48 treated with CHOP, and 32 with rituximab plus CHOP (R-CHOP). PKC-beta II expression correlated with inferior overall survival (OS) and progression-free survival (PFS) in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0-2 adverse factors), but not in the overall patient group unstratified by IPI. PKC-beta II expression correlated with inferior OS and PFS in R-CHOP-treated patients unstratified by IPI status. Immunohistochemically demonstrated PKC-beta II expression thus identified patient subgroups where alternative treatment strategies may confer superior outcome. We now report that PKC-beta II expression has prognostic significance not only for CHOP therapy in low-risk IPI disease, but also for all patients receiving CHOP plus rituximab.

Patients with suspected multiple myeloma should be investigated with screening tests. They may have a paraprotein in the serum, Bence-Jones protein in the urine, or both.

Summary. Alterations in neoplastic cell behaviour responsible for increased production of terminally-differentiated granulocytes during long-term culture of bone marrow in different categories of acute leukaemia and myelodysplasia have been investigated. An increase in neutrophils associated with transition to a morphological picture identical to normal control cultures occurred in 15 of 25 studies on acute leukaemia in contrast to one of six studies on myelodysplastic disorders. An abnormal neoplastic karyotype was employed as a marker for monitoring the course of the neoplastic cell population in 11 studies in which there was progression towards a normal pattern of differentiation. An increase in differentiation was shown by this means to represent increased maturation of cells of the neoplastic process in one study on a myelodysplastic disorder, demonstrating domination of proliferative activity in culture by all of the myelodysplastic disorders examined. Transition towards normal differentiation in nine studies on acute leukaemia, however, correlated with partial or complete replacement of the acute leukaemic cells by normal haemopoietic series in de novo acute leukaemia, and by Ph positive cells in blast crisis of CML. Conversion to morphologically and cytogenetically normal cell populations in five studies on de novo acute leukaemia occurred in four cases which failed to respond to remission-induction therapy, suggesting the selective toxic effect capable of purging acute leukaemic cells from bone marrow operated by a mechanism which lacked cross-resistance to currently-employed cytotoxic agents.

Summary Aims The reported association of glomerular disease with chronic lymphocytic leukaemia (CLL) is rare despite the relative frequency of this type of leukaemia. Hence, we have examined the renal biopsies in three patients with CLL and glomerulonephritis. Methods Renal biopsies were examined by light microscopy, immunofluorescence microscopy and electron microscopy. Results One of two patients with mild impairment of renal function and an active urinary sediment had ultrastructural features of idiopathic type I membranoproliferative glomerulonephritis (MPGN), and the other had features of fibrillary/immunotactoid glomerulonephritis with deposits of IgG and C3. One patient with nephrotic syndrome had characteristic electron microscopic appearances of type III MPGN. In all three there was an association with monoclonal gammopathy. The parameters of glomerular damage improved in association with response to drug treatment of the CLL. Conclusion There is a spectrum of types of MPGN seen in patients with CLL and there appears to be an association with the presence of monoclonal gammopathy. This is the first reported case of type III MPGN in CLL.

The capacity of multiple myeloma cells to generate parathyroid hormone-related protein (PTHrP) has been examined by in situ assessment of PTHrP mRNA and PTHrP protein in myeloma cells of patients in whom the disease was associated with the development of hypercalcaemia. The presence of PTHrP mRNA was evaluated by in situ hybridization using an antisense riboprobe, and PTHrP by immunohistochemistry using a monoclonal antibody, in archival bone marrow trephine specimens from 17 patients. PTHrP mRNA was detected in myeloma cells in 16 of the 17 patients, indicating a high frequency of PTHrP gene expression in myeloma cells in these subjects. PTHrP protein was, on the other hand, detected in the myeloma cells of only five of these patients. The impact of the mercury-based fixation and decalcification procedure used for processing the bone marrow trephine specimens was assessed to determine the influence of this process on the outcome of the immunohistochemical assay for PTHrP. It was shown that this preparative procedure resulted in a marked reduction of immunohistochemically detectable PTHrP, which provides a possible explanation for the lower frequency of positivity for PTHrP in myeloma cells in the bone marrow specimens. The present findings are consistent with the view that PTHrP can be generated in myeloma cells in vivo, and could contribute to osteolysis and hypercalcaemia, as in patients with cancer.

Summary Disseminated enteric human cytopathogenic orphan (echo) virus infection after allogeneic bone marrow transplantation has been reported once previously: a patient developed a fatal infection with the virus being isolated from brain, lung and heart. We report a second case of disseminated echovirus infection in which virus was isolated from the stomach and liver. On this occasion the infection was associated with the development of biopsy-proven acute graft-versus-host disease of the skin, stomach, colon and liver. The infection resolved without sequelae.

Brief Abstract Protein kinase C beta II expression in diffuse large B-cell lymphoma has prognostic significance not only for CHOP therapy in low-risk International Prognostic Index disease but also for all patients receiving CHOP plus rituximab. Full Abstract Introduction Protein kinase C beta II (PKCbII) expression has been reported to indicate inferior prognosis in diffuse large B-cell lymphoma (DLBCL) treated with anthracycline-based chemotherapy. Aim To compare the prognostic significance of immunohistochemically determined PKCbII expression in de novo DLBCL treated with CHOP chemotherapy (cyclophosphamide/doxorubicin/vincristine/prednisone) with and without rituximab. Patients and Methods 80 consecutive patients treated at St. Vincent's Hospital with de novo DLBCL, 48 treated with CHOP, and 32 with R-CHOP (rituximab plus CHOP), were studied using immunohistochemistry for PKCbII on diagnostic tissue samples. Staining results were correlated with patient characteristics and clinical outcome. Overall survival (OS) and progression-free survival (PFS) were determined by the Kaplan-Meier method, and comparisons were determined by the log-rank test. Results PKCbII expression correlated with inferior OS and PFS in CHOP-treated patients with low-risk International Prognostic Index (IPI) disease (0–2 adverse factors) but not in the overall patient group unstratified by IPI. PKCbII expression significantly correlated with inferior OS and PFS in R-CHOP—treated patients unstratified by IPI status. Conclusion PKCbII expression has prognostic significance not only for CHOP therapy in low-risk IPI disease but also for all patients receiving R-CHOP. Immunohistochemically demonstrated PKCbII expression thus identified patient subgroups in which alternative treatment strategies might confer superior outcome.

Summary: Very high serum muramidase concentrations in the absence of renal impairment can serve as a marker of a number of haematological neoplastic disorders, and several cases are described where the presence of these disorders was indicated by this means before the diagnosis could be established on morphological grounds. The suitability of the muramidase assay for this purpose was supported by observations that muramidase concentrations in excess of approximately five times the mean normal value were correlated closely with either chronic granulocytic, acute monocytic or myelomonocytic leukaemia, myelofibrosis or polycythaemia vera. These neoplastic disorders appeared to be effectively distinguished by this criterion from other haematological and inflammatory disorders including reactive monocytic and granulocytic states which produced lesser elevation of the muramidase concentration. On the basis of the present experience, it is suggested that estimation of the serum muramidase concentration is particularly useful in the investigation of suspected leukaemia in refractory sideroblastic anaemia, persistent monocytosis, and pancytopenic states with cellular bone marrow where the morphological picture is difficult to interpret.

A case is described in which polycythaemia vera was found to co-exist with chronic lymphatic leukaemia at the time of presentation. This case can be added to five other reported cases of an association between polycythaemia vera and well-differentiated lymphocytic neoplasia, and adds further emphasis to the tendency for dual presentation, which has now occurred in all but one of these cases. One explanation is that the association is due to chance, but the tendency for dual presentation raises the possibility that the overall picture reflects neoplastic involvement of stem cells with capacity to differentiate into the lymphoid as well as the erythroid, myeloid and megakaryocytic series.

Summary Analysis of the bone marrow karyotype in 109 consecutive untreated patients with acute lymphoblastic leukemia (ALL) by the G-banding technique revealed the presence of a translocation between specific sites on the long arms of chromosomes 4 and 11, [t(4;11) (q21;q23)] in 3 adults and 2 children. Splenomegaly was present in all patients, marked leukocytosis in 4, and retinal hemorrhages in the absence of significant mucocutaneous bleeding in 3. Complete remission defined by conventional morphological criteria was achieved with combination chemotherapy in all instances, but the duration of remission was brief in 3. Three patients were studied in relapse, and clonal evolution was found to have occurred in 2. Analysis of our data in conjunction with other published reports suggests this specific karyotypic abnormality characterizes a small subgroup of ALL in which there is a strong association with recognized clinical and laboratory indices of poor prognosis, inparticular its frequent occurrence in children under the age of 2.5 yr. There is a propensity to undergo clonal evolution, and the possibility exists that such a development is associated with poor prognosis

The clinical course of a patient with chronic hepatitis and previous ulcerative colitis who subsequently developed pure red cell aplasia (PRCA) is described. The PRCA remitted initially with corticosteroid therapy. A subsequent relapse responded to cyclophosphamide therapy following splenectomy. This was followed by a fatal third episode of red cell aplasia associated with megakaryocyte aplasia.

Serum lysozyme concentrations were assayed in a variety of haemopoietic disorders. Abnormal lysozyme levels were found to be associated with disorders of specific haemopoietic cell lines, and the investigation was directed particularly toward evaluating the usefulness of the enzyme level in the diagnosis of marrow dyscrasias where diagnosis on morphological grounds was in doubt, such as in the 'preleukaemic' state. Chronic myeloid leukaemia and myelofibrosis were both found to be associated with elevated serum lysozyme levels (30-120 μg./ml.). This occurred in myelofibrosis despite peripheral pancytopenia, suggesting that ineffective myelopoiesis might occur in this condition. Cytologically distinct myelomonocytic leukaemias were associated with high levels of lysozyme (164-180 μg./ml.); however, several cases of acute leukaemia with predominantly myeloblastic or promyelocytic features had significantly elevated levels. Therefore leukaemias with increased lysozyme were not restricted to one morphological category. Enzyme levels in these patients accurately reflected the response of the leukaemic marrow infiltration to therapy and provided a more reliable index of progress than peripheral blood examination. Monocytosis in bacterial infections produced marginally elevated lysozyme levels which were thus considerably lower than in leukaemic states. Despite the marked monocytosis in infectious mononucleosis the level was less than in bacterial infections. The assay was of value in certain cases of marrow dyscrasia as an early index of leukaemic transformation. While enzyme levels were normal in uncomplicated refractory sideroblastic anaemia, in 3 cases elevated serum lysozyme heralded the onset of overt myelomonocytic leukaemia or a myeloproliferative disorder with a leukaemoid peripheral blood picture.