Bcl-2 protein expression is not related to short survival in multiple myeloma.

The oncoprotein bcl-2 can be expressed in malignant plasma cells and might play a role in the prevention of corticosteroid-mediated apoptosis, thereby prolonging survival of the myeloma cells. We retrospectively investigated whether bcl-2 expression in bone marrow plasma cells measured by two-color fluorescence for immunoglobulin light chains would be related to survival duration in patients suffering from multiple myeloma. In all patients the large majority of plasma cells expressed bcl-2 (median 91%, range 74-100%). Contrary to our expectations, a tendency was observed toward higher percentages bcl-2+ plasma cells in patients with a long survival (more than 5 years, n = 9) vs patients who died from refractory myeloma within a year of diagnosis (n = 7). This tendency was found even when analysis was extended to include four patients in the short diagnosis group (n = 11) who had received chemotherapy prior to bone marrow examination.

Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status.

To determine the incidence of monoclonal gammopathies (MG) in relation to the aging process as such, and to evaluate the influence of disease on the occurrence of MG, we studied 439 elderly subjects aged 75-84 years. These individuals were categorized into 4 groups on the basis of their health status. There was a group of "optimally healthy" elderly, a group of "apparently healthy" residents of homes for the aged, a group of geriatric outpatients and a group of randomly chosen inpatients from a general hospital. Whereas no MG were detected in a control group of healthy young subjects aged 25-34 years, the frequency of MG in the aged groups ranged from 11% in the "optimally healthy" aged group to 38% in the inpatients group. In a tentative classification according to possible cause, most of the MG belonged to the pathogenetic category of immunodeficiency. There was a clear association of the occurrence of monoclonal gammopathies of this category with the health status.

The interaction between the Lewis blood group system and HLA-matching in renal transplantation.

A retrospective study was initiated to investigate the influence of recipients' Lewis subtype and HLA-matching on cadaveric kidney graft outcome. A total of 1111 patients receiving a first cadaveric kidney graft were analyzed. No difference in one-year graft survival was found between Lewis-negative (73%, n = 133) and Lewis-positive (73%, n = 978) recipients. Further subdivision of the study group into HLA-A,-B well-matched (0 or 1 mismatches [MM]) and poorly matched (2, 3, or 4 MM) revealed a strong deleterious effect of HLA-A,-B mismatching in the Lewis-negative group only. One year graft survival in Lewis-negative HLA-A,-B poorly matched (2, 3, or 4 A,B MM) patients was 60% (n = 67) versus 86% (n = 66) in the Lewis-negative HLA-A,-B well-matched (0 or 1 A,B MM) group (P = 0.004). For the Lewis-positive group the one-year graft survival rates were 72% (2, 3, or 4 A,B MM; n = 498) and 74% (0 or 1 A,B MM; n = 480), respectively (P = n.s.). The additional beneficial effect of HLA-DR matching again turned out to be strongest in the Lewis-negative group. In Lewis-negative, HLA-DR (0 MM) and -A,-B well-matched recipients (n = 36) graft survival was 94% versus only 64% in the Lewis-negative, DR matched, A,-B mismatched (2, 3, or 4 A,B MM) group (n = 25; P = 0.09). In the Lewis-positive, HLA-DR 0 mismatched group the one-year survival rates were 78% (0 or 1 A,B MM; n = 240) and 73% (2, 3, or 4 A,B MM; n = 253), respectively (P = 0.05). Our data suggest that donor recipient selection should not be based on Lewis matching per se. However, since Lewis-negative patients are at high risk of graft failure when receiving HLA mismatched kidneys, they should preferentially receive optimally HLA matched grafts.

Cranial nerve palsy as the presenting feature of secondary plasma cell leukemia.

A patient with IgA lambda multiple myeloma (MM) developed plasma cell leukemia (PCL), presenting as oculomotor nerve palsy. The cerebrospinal fluid (CSF) contained plasma cells, which double stained with fluoresceinated anti-IgA and anti-lambda antisera. The palsy was most probably due to meningeal myelomatosis. The neurologic disorder appeared to be refractory to the therapy used, although plasma cells disappeared from the peripheral blood. Secondary plasma cell leukemia is a rare complication of MM, usually occurring in the terminal stage of the disease. Those patients may be eligible for central nervous system (CNS) prophylaxis, as is commonly performed in patients with other types of leukemia.

Light chain types of IgD in human bone marrow and serum.

One of the unexplained features of human IgD is its preferential expression with either kappa or lambda light chains in different situations. While the membrane IgD on B lymphocytes shows a predominance of the kappa type, about 90% of all known IgD myeloma proteins and 87% of normal IgD producing plasma cells in spleens of healthy individuals were shown to belong to the lambda type. Very little is known of the kappa/lambda light chain distribution of normal polyclonal IgD in the serum and in the bone marrow plasma cells. In this study, the kappa/lambda representation of IgD in bone marrow plasma cells and in the serum of 25 adult persons (two healthy and 23 suffering from various nonmalignant diseases) was investigated. The kappa/lambda ratio of IgD+ bone marrow plasma cells showed a large variation among the individuals of this group, in 84% of the cases being below 1.0. While about 1/3 of the investigated subjects had 80% or more of IgD of the lambda type (kappa/lambda ratio below 0.2), most showed a kappa/lambda ratio of IgD higher than that, with four persons exhibiting a clear cut predominance of IgD of the kappa type. A positive correlation (Spearman's correlation co-efficient, P = 0.005) between the percentages of IgD+ plasma cells and their kappa/lambda ratio was found. Semiquantitative evaluation of the kappa/lambda composition within the serum IgD by immunoselection was in agreement with the kappa/lambda ratio of IgD+ plasma cells in all individual cases.

Hyperimmunoglobulinaemia D and periodic fever: a new syndrome.

Six patients of Dutch ancestry with a long history of recurrent attacks of fever of unknown cause were found to have a high serum IgD level and a large number of plasma cells with cytoplasmic IgD in the bone marrow. Because the clinical picture in some ways resembled that of familial Mediterranean fever (FMF), sera of patients with FMF were also investigated; only one of eight such patients had a raised serum IgD.

Paraproteinaemia plus osteolytic lesions in typical hairy-cell leukaemia.

Most cases of hairy-cell leukaemia (HCL) involve proliferations of neoplastic B lymphocytes. In rare cases, M-proteins or osteolytic lesions have been documented in patients with HCL. In this study two patients with typical HCL are reported in whom both paraproteinaemia and osteolytic lesions of the femoral neck developed. In one of the patients the production of the M-protein by hairy cells could be established. In the other patient, at autopsy no signs of myeloma were found. The hairy cells from inside the osteolytic lesion had the same immunological phenotype as hairy cells from the peripheral blood, the spleen, and other parts of the bone marrow. These cases once more confirm the B-cell nature of many cases of HCL, and show that hairy cells can have functional capacities usually attributed to much more mature B lymphocytes, i.e. plasma cells.

Primary plasma cell leukaemia. A case report and a review of the literature.

A case history of a patient with primary plasma cell leukaemia is presented. Analysis of serum showed an IgD lambda paraprotein, and lambda-light-chains were found in the urine. Immunofluorescence studies of a bone marrow aspirate revealed intracytoplasmatic IgD of lambda-type in plasma cells. Moreover J-chain could be demonstrated in these plasma cells. A complete remission of the disease, with disappearance of the paraprotein, was obtained following treatment with a combination of cyclophosphamide, vincristine and prednisone. 12 months later, the patient developed multiple extramedullary plasmocytoma lesions in the skin. After treatment with cyclophosphamide, vincristine, doxorubicin and prednisone, another remission was achieved. The literature on the clinical features and the response to chemotherapy of primary plasma cell leukemia is reviewed.

Cell markers in hairy cell leukemia studied in cells from 51 patients.

To determine the maturation arrest of the neoplastic cells of hairy-cell leukemia (HCL) and the spectrum of the surface markers on these cells, a series of 51 patients with this disease was studied. The cells of all but two of the patients showed monoclonal surface Ig with respect to light chains. In about one-third of the cases, only gamma heavy chain determinants were present on the cells; the majority carried multiple heavy chain determinants as documented by the application of different fluorochromes. Two patients each showed two different clones of cells, both of the same light chain type. In one of these two patients, two paraproteins were present in the serum. Intracytoplasmic Ig was found in only 4 of 39 cases, in all instances being IgM. All cases studied concerned cells with FclgG receptors; however, the density of this receptor varied. FcIgM receptors also showed a spectrum of density, with some cases showing very few FcIgM-positive cells. Receptors C3 were not observed on the hairy cells. Serum immunoglobulin levels were normal or increased. Paraproteins were found in the sera of 4 of 38 patients. These data suggest that HCL is a neoplasm of B lymphocytes. The neoplastic cells are probably arrested at a more mature stage than the cells of chronic lymphocytic leukemia. The multiple isotypes on the cells indicate a block at the "switch" phase from the small micro-carrying lymphocyte to the larger Ig-producing lymphocyte or plasma cell.

Increased levels of IgG4 subclass in 5 patients with acquired respiratory disease.

5 sera from a series of more than 1,000 serum samples from hospitalized patients tested by immunoelectrophoresis were selected for further examination because of a disproportional increase in the anodic part of IgG. A marked polyclonal increase in IgG4 subclass level was detected in each of these sera. While the patients suffered from a variety of diseases (e.g. Loeffler's syndrome, leiomyosarcoma, periarteritis nodosa, chronic bronchitis, and mycosis fungoides, respectively), they all had an acquired respiratory disease as the only common clinical denominator.

IgG subclasses in rhesus-D immunization. Effects of weekly small volume plasmapheresis.

The IgG subclass composition was determined of the anti-D antibodies present in the serum of 22 women who had a history of severe rhesus-D immunization and who weekly underwent small volume plasmapheresis during their current pregnancy. There was no correlation between the subclass patterns of IgG anti-D antibodies and the degree of illness of the child; the good clinical results obtained with the small volume plasmapheresis could not be explained by a consistent change in the anti-D IgG subclass composition.

Chronic lymphocytic leukaemia and IgG heavy chain disease.

A 64-year-old woman who has suffered from chronic lymphocytic leukaemia since 1976 is discussed. In 1978, an abnormal protein component was found in her serum by means of immunoelectrophoresis. Using the techniques of immunoselection of the serum immunoglobulins and immunofluorescence of the bone marrow cells, it was demonstrated that this component consists of IgG1 heavy chains only. The native protein, COL, consisted of a dimer linked by disulphide bonds of a molecular weight of 80 000 daltons. Its monomeric unit had a molecular weight of 40 000 daltons, as determined by SDS-polyacrylamide gel electrophoresis after reduction with 2-mercaptoethanol. Protein COL was not produced by the leukaemic cells (which bore IgM-lambda on their membrane) but by a morphologically distinct clone of lymphoid cells. After therapy with chlorambucil, the level of the heavy chain disease protein in the serum decreased substantially.