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Prognosis in multiple myeloma (MM) is related to the establishment of an immunologically and kinetically characteristic plateau phase. Patients who present with this state may not benefit from immediate chemotherapy. We assessed 20 patients with MM who were staged according to the Salmon and Durie classification at diagnosis and monitored throughout the course of their disease. Patients with a lambda paraprotein and a kappa/lambda lymphocyte ratio in the blood greater than 4.0 were considered to demonstrate light chain isotype suppression (LCIS). Similarly, patients with a kappa paraprotein and a kappa/lambda ratio of less than 0.55 were also considered to have LCIS (1). 14 patients had LCIS; of these, 6 were classified as stage IA, 2 as stage IB, 3 as stage IIA, and 3 as stage IIIA. 6 patients did not have LCIS; 3 were classified as stage IIA, 1 as stage IIIA and 2 as stage IIIB. 10 patients with LCIS were assessed for treatment benefit following administration of melphalan and prednisone, as defined by a fall in the serum paraprotein level of greater than 50% over 6 months. In 8 patients the serum paraprotein levels did not fall, and the patients remained in good health without clinical deterioration. Thus LCIS at presentation may indicate patients in whom treatment can be safely deferred or in whom aggressive therapy is not indicated.

Twenty nine cases of plasmocytic spinal cord tumors which were responsible for neurological troubles were collected over the 19 year period between 1962 and 1981. In 25 of the cases, spinal cord compression was the first sign of the tumor. In 4 of the cases, spinal cord compression was a secondary complication of an already known tumor. The various problems associated with this pathological process are discussed. The neurological problem is fairly straight forward: whether the compression is the first sign of the tumor, and whether it is a secondary complication, it must be surgically removed. Subsequent radiotherapy and chemotherapy are advisable. The oncogenous problem is more delicate. If the plasmocyte is a solitary tumor, and surgical removed is complete, the patient is, in theory, "heated", but should be regularly seen an outpatient basis. On the other hand, a multiple myeloma may first show it self as a spinal cord tumor, where as the patient is in reality suffering from a generalized disease.

It is difficult to compare the results of treatment obtained in different trials in myelomatosis because different sets of diagnostic criteria are used, and because the criteria by which patients are deemed eligible for entry vary. Thus the composition of different series of patients varies considerably. Furthermore, the outcome of treatment is recorded in different ways. Uniformity in the diagnostic categories entered would reduce the variance in survival between different trials: for example, trials in myelomatosis should exclude patients with monoclonal gammopathy of uncertain significance, non-progressive or indolent myeloma, extramedullary plasmacytoma, and plasma-cell leukaemia. The subdivision into simple prognostic groupings such as those proposed by the Medical Research Council is helpful in interpreting the survival patterns in different trials in which the proportions of patients in different prognostic groups are likely to vary. These groupings and other staging systems do not correlate with responsiveness to treatment. Rapid responders fare worse than slow responders, and this might provide a basis for a second randomisation to test whether a change in treatment could benefit the rapid responders.

In a retrospective study of 202 cases of multiple myeloma (MM) were studied cyto- and histomorphologically. In 62 cases only bone marrow smears, in 60 only histological preparations and in 80 both types of material were available. According to the differentiation of myeloma cells, a plasmocytic (n = 127), a mixed cellular (n = 35) and a plasmoblastic type (n = 32) could be distinguished. Besides, 8 cases with predominance of giant cells were found (giant cell MM). The comparative cytological and histological typing into the four types of MM proved to be reproducible. The medium survival time and survival curves of the described types showed a statistically significant difference. The survival times were 39.7 months with the plasmocytic type, 16.1 months with the mixed cellular type, and 9.8 months with the plasmoblastic type. The prognostic relevance of the morphological classification was supported by the frequency of extramedullary infiltrates (20% in the plasmocytic, 67% in the mixed cell, 69% in the plasmoblastic and 100% in the giant cell type).

We measured plasma cell labeling indices (LI) in 52 patients with monoclonal gammopathies. Cytoplasmic reactivity with polyspecific or kappa- and lambda-specific light chain anti-Ig reagents identified monoclonal plasma cells, plasmablasts, and lymphocytoid plasma cells. Among newly diagnosed untreated patients, a high immunofluorescence LI distinguished those with multiple myeloma (MM) from those with stable monoclonal gammopathies (P less than 0.002). Among treated patients with MM, those in the plateau phase of the disease had low LI, whereas patients in the relapse phase or early in treatment had high LI. The immunofluorescence LI correctly classified three more patients with newly diagnosed MM than did the tritiated thymidine LI technique. LI specific for the neoplastic plasma cells resulted in excellent discrimination of patients with active disease. Because results are easily and rapidly obtained, this technique is useful clinically.

In order to assess the prognostic value of rapid tumor mass reduction in responding multiple myeloma (MM) patients, 100 consecutive patients were analyzed, and bone marrow plasma cell kinetic characteristics were evaluated at diagnosis. Forty-two patients obtained a tumor mass reduction greater than or equal to 50% with three cycles of chemotherapy and within 3 months (early responder myeloma [ERM]), and 23 in greater than 3 months (slow responder myeloma [SRM]). Survival rates in these two groups were not statistically different (P = .07). The labeling index (LI) of bone marrow plasma cells was significantly higher in ERM patients than in SRM patients (1.8 +/- 2.0 v 0.8 +/- 0.7, P = .006). The LI was used to separate the ERM patients into two well-defined subgroups. ERM patients with a LI greater than or equal to 2% showed a median survival of 16.4 months, whereas ERM patients with a LI less than 2% did not reach the median survival at 46.9 months (P less than .0044). Remission duration was also significantly different: 12.2 months in the high LI subgroup and 26.3 months in the low LI subgroup (P less than .0025). Early response itself does not correspond to shorter remission duration and shorter survival, but it is a poor prognostic factor if associated with a high plasma cell proliferative activity.

A panel of five haematologists has examined, without consultation or prior knowledge of the diagnosis, blood films and bone marrow smears from 456 patients with a diagnosis of leukaemia. A diagnostic classification which recognized various subtypes of acute myelogenous leukaemia was used but no attempt was made to subdivide acute lymphoblastic leukaemia. Complete agreement with the initial diagnosis was low (56.4%) and was particularly poor (45.7%) when the patient had one of the forms of acute leukaemia. However, disagreements which would have involved the patient in a change of treatment were unusual (2.0%). We conclude that a high degree of diagnostic agreement for patients with leukaemia is unlikely from morphological classifications alone.

Sera from 244 patients with haematological malignancies were examined for beta 2-microglobulin (beta 2m) levels. There were 142 leukaemias, 32 malignant lymphomas, three immunoblastic lymphomas, two pseudolymphomas and 65 multiple myelomas. Culture supernatants from various established cell lines were also tested. The phenotype facilitating beta 2m shedding from the cell surface appeared to be independent of the specific IgG heavy chain allotypes; however, a myeloma group with normal serum beta 2m levels showed a significant association with the specific Gm allotypes. The determination of serum beta 2m levels can provide valuable information on the proliferative stage of the disorders, the effectiveness of chemotherapy, and be a diagnostic aid for blastic crisis in chronic myelocytic leukaemias, and for subtyping lymphoid malignancies.

Clinical trials of myeloma treatment are reviewed. 7618 patients are described in nine Tables (some patients appear in more than one). Most randomized trials and trials of non-staged myeloma yield no statistically significant differences between the combinations of alkylators, vinca alkaloids, nitrosoureas, anthracyclines, epipodophyllotoxins, procarbazine and/or steroids used. Intensive combination treatment induces response in an average of 3 months and seems superior to monotherapy in stage III, in which the early mortality is reduced from 45% to 10%. No studies were found showing any evidence for superiority of intensive treatment in stage I. Alternating chemotherapy combinations do not delay refractoriness. No evidence was found that maintenance treatment prolongs survival in responding patients.

Sixty-eight patients with plasmacytic neoplasia and osteosclerotic lesions were analyzed. Men predominated in this series. Mean age was 55.3 years and 26 patients were younger than 51 years at diagnosis. Early onset of disease was statistically different from multiple myeloma in general. Thirty patients had peripheral polyneuropathy and often neurological manifestations preceded other symptoms. Skeletal pain was less common, whereas hepatomegaly, splenomegaly, and lymphadenopathy were more common than in myeloma in general. Incidence of azotemia, hypercalcemia, high ESR, and anemia was lower than in myeloma. In one fourth of the patients, the number of skeletal lesions did not exceed three. Mean survival was less than 20 months from first symptom and 12 months from diagnosis. Mortality was related sometimes to polyneuropathy. Thus, in several aspects, plasmacytic neoplasia with osteosclerotic lesions is different from the classical multiple myeloma.

We report the outcome of the statistical analysis of 50 myeloma patients, making a comparison of the prognosis value of the staging systems proposed by Durie and Salmon and, more recently by Merlini, Waldenström and Jayakar. Moreover, we studied the relationship between initial percentage of bone marrow plasma cells and prognosis. All patients had a complete follow-up and received the same treatment. We excluded our cases of non excreting and solitary myeloma. The staging system proposed by Durie and Salmon still has the best prognosis significance. The system proposed by Merlini, Waldenström and Jayakar does not allow a staging of the patients in rigourous conditions. The absence of a relationship between initial bone marrow plasmocytosis and prognosis corroborates the poor reliability of this staging system.

The effect of bone marrow plasma cell morphology at diagnosis on survival time was evaluated in 66 patients with multiple myeloma. According to the morphologic classification multiple myeloma was categorized as plasmacytic, plasmacytic/plasmablastic, or plasmablastic. The plasmablastic myeloma had an estimated median survival of 9 months compared with 42 months for plasmacytic/plasmablastic myeloma. Median survival of plasmacytic myeloma has not yet been attained. Plasma cell morphology at diagnosis is an important predictor of survival duration in patients with multiple myeloma. These parameters provide information required for decisions on treatment modalities.

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation, primarily in bone marrow, of a clone of plasma cells. The nature of the stem cells feeding the tumoral compartment is still unknown. To investigate this special point, we have studied the phenotypes of nine well-known human myeloma cell lines (HMCLs) and compared them with those of normal lymphoblastoid cell lines (LCLs). Twenty-four clusters of differentiation involved in B lymphopoiesis were investigated using a panel of 65 monoclonal antibodies (MoAbs). For each cluster, the percentage of positive cells and the antigen density were determined, giving rise to a "quantitative phenotype". We thus classified the HMCLs into two different groups: those with cytoplasmic mu chains (c mu+) and those without (c mu-). In the first (c mu+) group, comprising seven cell lines, the HMCLs had a phenotype of pre-B/B cells close to that of Burkitt's lymphoma cell lines. They expressed low densities of surface mu chains, without detectable cytoplasmic or surface light chains. Three of them were infected with the Epstein Barr virus (EBV). These c mu+ HMCLs bore most of the B-cell antigens except CD23. They expressed the CALLA antigen (CD10) and lacked the plasma-cell antigen PCA1. In contrast, LCLs expressed surface light chains, high densities of CD23, low densities of PCA1 antigen, and no CD10 antigen. The c mu- HMCLs had a plasma-cell phenotype, lacking most of the B-cell antigens and expressing high densities of PCA1 antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of multiple myeloma detected by the first symptom of severe postextraction bleeding was presented. Although laboratory data showed severe anemia, rouleaux formation of erythrocytes, abnormal hemostatic parameters, elevated erythrocyte sedimentation rate and hyperglobulinemia, no involvement of bones such as the jaws, skull, ribs or sternum was demonstrated roentgenologically. Final diagnosis obtained by immunoelectrophoresis was Ig A . K type myeloma. During a therapeutic period with melphalan and predonine, bleeding from the extracted wound was repeated. 2 months after the onset of the first symptoms, the patient died of systemic bleeding. Autopsy findings revealed many hemorrhagic sites in the lungs, stomach, kidney and bladder and the existence of plasma cell-like tumor cells in the bone marrow of lumber vertebra and sternum.

The diagnosis of multiple myeloma (MM) is often made in an advanced phase when using the established criteria. Derived from the modern diagnostic procedures used in malignant lymphomas, an alternative diagnostic strategy in MM is proposed. The prognostic value of a histologic classification of MM has been demonstrated, based on bone marrow biopsies of 577 myeloma patients. Furthermore, the infiltration volume in the biopsy proved to be an important prognostic parameter and complements the used clinical staging system. The different possibilities of a reliable follow-up of myeloma patients are shown.

Since multiple myeloma has a heterogenous character in its pathophysiology, it is clinically classified according to various kinds of factors. Therefore, in the treatment of multiple myeloma, it is important to select efficacious regimens considering the different progress or modes of the diseases as defined by both Durie and Salmon's staging systems and tumor distribution classifications. In this review, the correlation between the response to chemotherapy and survival was analyzed and demonstrated to be significant when we used new response criteria, namely the serum albumin and M-protein levels after the treatment. The new criteria should be applied to determine a prognosis and improve survival. Recently, there has been progress in treatments involving high-dose melphalan combined with autologous bone marrow transplantation for refractory or relapsed myeloma patients. This treatment is anticipated to prolong survival.

A group of 193 multiple myeloma (MM) patients consisting of cases treated only symptomatically (1959-63) or by nonsystematic monotherapy with Cyclophosphamide or Melphalan (1963-76) and of a subgroup given systematic polychemotherapy and intensive supportive treatment (1976-84) were evaluated for the practical applicability and prognostic relevance of three staging systems. The clinical staging system of Durie and Salmon and the quantitative system of Salmon and Wampler have proved in both subgroups of various periods and with different therapeutic approaches to be well applicable in the clinic allowing the patients to be divided into three prognostically different groups according to the size of the tumor mass. Merlini, Waldenström and Jayakar's staging system has likewise shown relationship to prognosis though the patients could be divided only into two prognostically different groups. It is evident that a deeper knowledge of MM requires nowadays a more comprehensive, complex and prognostically more relevant classification system.

The authors observed one case of plasmocytic reticulosis which was noticable by its strictly left unilateral localisation, involving the face, the underscapular region, the shoulder and the elbow, the leg with an important augmentation of the left foot. Histologically, dense plasmocytic infiltration can be observed without anomalies. Electron microscopy confirmes the presence of plasmocytes at any stage of activity without monstruosities. This observation can not be classified in the forms that are actually described: Klüken's and Simonis' plasmocytic reticulosis, plasmocytomas with osseous and medullar lesions, extramedullar plasmocytoma.

Monoclonal immunoglobulin from 138 patients with multiple myeloma (MM) showed that 68 patients were of IgG type, 23 of IgA type,33 of BJ type, 6 of IgD type, one of IgM type, 5 of nonsecreting type and the remaining 2 of IgA and IgG double monoclonal type. Urinary Bence Jones protein was tested with concentrated urine specimen with a positive rate of 75%. Classification of light chain revealed the ratio of oK/L being 1.09:1. The difference of distribution of K or L among IgG, IgA BJ types was no significant. 31 cases with monoclonal gammapathies of undetermined significance (MGUS) were also analyzed in this study. There were some difficulties in the differential diagnosis of MGUS and MM,but a significant difference was present in the plasma cell percentage of bone marrow smear of the two groups. Dynamic investigation in this series showed that patients with percentage of plasma cell less than 10% persisting for a long duration are likely to have MGUS only.

The degree of medullary infiltration by plasmocytes has a prognostic value which completes the clinical classifications proposed in multiple myeloma. Beyond a 50 p. cent medullary infiltration, the mean survival of the patients is significantly shorter (p less than 0.02) than survival of patients presenting less than 50 p. cent medullary infiltration. The degree of medullary infiltration is unrelated to the stage of Durie and Salmon classification, but is correlated to the degree of differentiation of the plasmocytes.

Bone marrow biopsies of 674 patients with multiple myeloma (MM) were processed for diagnostic evaluation. Histologic variables were correlated with the clinical features to determine factors of value in predicting prognosis. Four of these were used to classify MM into six histologic types: Marschalko type; small cell type; cleaved type; polymorphous type; asynchronous type; and blastic type. These six types were subsequently combined into three prognostic grades: low, intermediate, and high, analogous to the malignant lymphomas. The quantity of plasma cell burden in the biopsy proved to be a useful criterion for histologic staging of MM, supplementing any clinical staging system in use. Both these parameters, grade and stage, provide information required for decisions on treatment modalities, while the effects of therapy can be monitored by sequential biopsies.

Analyses of prognostic factors have allowed the design of staging systems in different haematological disorders. In a series of 220 patients with multiple myeloma, univariate analysis showed that nine parameters had a significant adverse effect on survival; poor performance status (Karnowsky scaling system less than 70%), infections before diagnosis, renal impairment (assessed either by creatinine clearance greater than 2 mg dl-1 or urea greater than 40 mg dl-1), serum calcium (greater than 10 mg dl-1), severe anaemia (less than 8.5 g dl-1), the presence of Bence-Jones proteinuria, failure to achieve complete remission, more than 40% plasma cells in bone marrow and a low paraprotein index (monoclonal component/% plasma cells: P less than 0.09). In addition, this index correlated significantly with all the other prognostic factors except performance status. The best combination of disease characteristics selected by means of the Cox regression proportional hazards method were performance status and creatinine levels. Additionally, by factor analysis of principal components we obtained a regression equation that included creatinine levels, haemoglobin, performance status and paraprotein index. Using this it was possible to separate the series of patients into three risk categories: A (65 patients), B (69 patients) and C (65 patients) with a median survival of 41, 24 and 12 months, respectively. The model provided similar results to those of the British Medical Research Council, whereas the staging systems proposed by Durie and Salmon, Merlin et al. and Carbone et al. had a lower discriminant value in our series.

Lymph nodes of 46 autopsy cases regarded clinically on the basis of bone marrow and blood film findings as chronic lymphoid leukaemia were reinvestigated. Considering the new reclassification of malignant lymphomas only 38 per cent of the cases have shown histologic pattern of chronic lymphoid leukaemia. 28 per cent out of the remaining 62 proved to be lymphoplasmocytic immunocytoma, 10 per cent centroblastic-centrolytic ML and 8 per cent centrocytic ML.

Mouse myeloma cells in continuous culture were cloned in soft agar. The clones were assayed for their ability to synthesize heavy and light chains of gamma globulin by immunoprecipitation directly in the agar. A minor population secreting only light chains was identified. The two cell types were recloned and a low incidence of conversion of 7S to light-chain production was demonstrated. This technique can be used to isolate rare variants of cells secreting specific macromolecules.