Prognostic factors and staging in multiple myeloma: a reappraisal.

To assess the important factors in the prognosis and staging of multiple myeloma (MM), we have correlated the presenting clinical features of 147 previously untreated patients with MM with the survival duration using multiple regression analyses. We have included the three major available myeloma-staging systems (MSS), ie, Durie-Salmon (DS), Medical Research Council (MRC), and Merlini-Waldenström-Jayakar (MWJ), plus two new variables related to disease activity: the serum beta 2-microglobulin level (S beta 2M) and the instantaneous rate of bone resorption. Our study confirms the validity of the three MSS in the prediction of survival duration, with a slight but significant advantage for the DS MSS.

A unique malignant T-cell lymphoproliferative disorder with neutropenia simulating hairy cell leukemia.

The association of neutropenia with an indolent chronic T-suppressor cell lymphoproliferative disorder (LPD) has been well documented. The morphologic features and course suggest that this is a benign disorder. The authors studied a 58-year-old man with a chronic T-cell LPD, splenomegaly, and neutropenia.

Antitumor activity of bovine cartilage extract (Catrix-S) in the human tumor stem cell assay.

Catrix is an acidic mucopolysaccharide complex derived from bovine tracheal cartilage. The antitumor efficacy of Catrix has been evaluated in the human tumor stem cell assay system using three human tumor cell lines and fresh biopsy specimens from 22 patients with malignant tumors. In vitro efficacy has been demonstrated with high dose continuous exposure Catrix, particularly against the 8226 human myeloma cell line as well as ovarian, pancreatic, colon, testicular, and sarcoma biopsy specimens.

Phase I-II study of 13-cis-retinoic acid in myelodysplastic syndrome.

Eighteen patients with myelodysplastic syndrome received 13-cis-retinoic acid (1.0-mg/kg/day starting dose with 0.5-mg/kg increment escalations) in a phase I-II trial.

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow.

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases.

Anti-fibrinolytic therapy with aminocaproic acid for the control of bleeding in thrombocytopenic patients.

11 courses of EACA were given to 9 acutely ill, severely thrombocytopenic patients (platelet count less than 20 X 10(9)/l). 6 patients were being treated for acute leukaemia while 1 each had cyclical amegakaryocytic thrombocytopenia, dysmyelopoietic syndrome and advanced chronic lymphocytic leukaemia. 8 were refractory to HLA-matched platelets and 1 refused blood product transfusion.

Poly(I,C)-LC as an interferon inducer in refractory multiple myeloma.

Seven patients with refractory multiple myeloma (readily evaluable for response) were treated in a Phase II trial with poly(I,C)-LC using a 3 times per week intravenous schedule. Serial immunologic testing included assessment of natural killer (NK) cell activity, antibody-dependent cytotoxicity, delayed hypersensitivity, and in vitro mitogen responses. One patient had a partial response (PR) of 6-month duration, and 3 other patients had objective responses (less than PR).

Establishment of two new myeloma cell lines from bilateral pleural effusions: evidence for sequential in vivo clonal change.

Two new human myeloma cell lines have been established from a 36-year-old woman with refractory IgG kappa multiple myeloma in whom bilateral malignant pleural effusions developed. The malignant plasma cells from each effusion were set up in a liquid culture using an L-15 medium containing catalase, glutathione, selenous acid, ascorbic acid, insulin, transferrin, additional glutamine hydrocortisone, and 2-mercaptoethanol and designated as M-3 medium. Two IgG kappa cell lines, LB -831 and LB-832, were established and proved to be Epstein-Barr virus negative using the internal repeat sequence DNA probe.

Chemohormonal therapy for advanced breast cancer with tamoxifen, adriamycin, and cyclophosphamide (TAC).

Combined chemohormonal therapy is an attractive therapeutic strategy for the treatment of Stage IV breast cancer. Between 1977 and 1979, the authors evaluated a new chemohormonal therapy program in 63 evaluable women with advanced breast cancer who previously had not received cytotoxic chemotherapy or tamoxifen. The chemohormonal therapy consisted of 21- to 28-day cycles of tamoxifen (10 mg orally twice daily), Adriamycin (doxorubicin) (40 mg/m2 intravenously on day 1) and cyclophosphamide (200 mg/m2 orally on days 3-6) (TAC).

Danazol-induced factor VIII and IX bypassing activity in hemophiliacs.

Danazol, a synthetic androgen reported to increase factor VIII and IX activity levels, was given to 6 hemophiliacs. With danazol therapy (600 mg/da) the APTTs shortened by 30-45% of pre-treatment times. However, the activity levels of the deficient factors did not increase significantly nor consistently with the APTT change.

CALLA-positive myeloma: an aggressive subtype with poor survival.

Detailed immunotyping was carried out on 21 direct myeloma bone marrow aspirates and eight human myeloma cell lines. Four previously untreated common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma patients were identified and six of eight cell lines (75%) were also positive. CALLA positivity, as part of an immature B phenotype, was found to correlate with very aggressive clinical disease: median survival six months v 56 months for the CALLA-negative group.

Effect of danazol on coagulation parameters and bleeding in hemophilia.

Danazol was given orally at a dose of 600 mg/day to six hemophiliacs for eight to 14 weeks. All patients showed a significant decrease in activated partial thromboplastin time (APTT) beginning with the first measurement (two weeks) and persisting until use of the drug was discontinued. However, a corresponding increase in the deficient factor activity could not be consistently demonstrated.

Proliferative characteristics and sister chromatid exchange (SCE) of colony-forming cells (CFU-S) in acute myelogenous leukemia.

Sister chromatid exchange (SCE) and cell cycle progression of colony-forming cells (CFU-S) from patients with acute myelogenous leukemia were studied using bromodeoxyuridine (BrdU) incorporation and sister chromatid differential staining. The mean SCE rate of CFU-S was 7.99, which is similar to that reported for human peripheral blood lymphocytes.

Acute myelogenous leukaemia modulated by B12 deficiency: a case with bone marrow blast cell assay corroboration.

A patient is described who appeared to demonstrate modulation of acute myelogenous leukaemia with vitamin B12 deprivation. Support for this observation was obtained via an in vitro bone marrow blast cell assay. The addition of B12 to this patient's bone marrow in vitro significantly stimulated the colony forming ability of the blast cells.

Bone marrow monosomy 7: hematologic and clinical manifestations in childhood and adolescence.

The hematologic manifestations and clinical course are described for six children and adolescents with bone marrow monosomy 7. One child with secondary acute myelogenous leukemia had monosomy 7 plus a marker chromosome; the remaining patients had marrow monosomy 7 as the only karyotypic abnormality. The hematologic abnormalities were diverse, but the majority of patients had a smoldering preleukemic or myeloproliferative phase.

Serum beta 2-microglobulin in the initial staging and subsequent monitoring of monoclonal plasma cell disorders.

Serum beta 2-microglobulin (beta 2-M) measurements were carried out in 97 patients with monoclonal plasma cell disorders. Twenty-six (87%) of 30 patients with monoclonal gammopathy of undetermined significance (MGUS) had increased beta 2-M levels and serial follow-up in seven patients showed a progressive increase with time. Of the 63 patients with active myeloma, pretreatment serum beta 2-M values were available in 25 for correlation with pretreatment stage.

Tumor growth stimulation in vitro by interferons.

Interferons (IFNs) are a family of polypeptides originally identified as antiviral substances. Subsequently, other properties of interferons were recognized, including inhibition of cell proliferation, and effects on the immune response and on expression of surface antigens. In this paper we present evidence that interferons, even the highly purified cloned IFNs, can stimulate clonogenic tumor growth in vitro.

Serum beta2 microglobulin and survival duration in multiple myeloma: a simple reliable marker for staging.

Previous reports have shown serum beta2 microglobulin (SB2M) to be a reliable marker for evaluation of presenting tumour mass, response to chemotherapy and prognosis of patients with multiple myeloma (MM). In the current study, SB2M was evaluated and correlated by bivariate and multivariate regression analyses with the main presenting clinical features, response to chemotherapy and survival duration of 115 untreated myeloma patients. In the bivariate analysis, there was a clear correlation between SB2M and myeloma stage (P = 0.

[OKT-8+ suppressor T-lymphocytes are increased in patients with stable multiple myeloma].

T-lymphocyte subpopulations were studied in 68 patients with monoclonal gammopathies and 27 age-matched healthy controls using the monoclonal antibodies (mAb) OKT-3, OKT-4 and OKT-8. 13 patients had untreated multiple myeloma (MM), 51 had MM and were receiving intermittent pulse chemotherapy or were in remission and followed up without treatment. Four patients had a monoclonal gammopathy of unknown significance (MGUS).

Alternating combination chemotherapy and levamisole improves survival in multiple myeloma: a Southwest Oncology Group Study.

Previously untreated patients with multiple myeloma were entered on a randomized clinical trial to determine whether the use of alternating combination chemotherapy, including vincristine, doxorubicin, alkylating agents, and prednisone (160 patients) was more effective than conventional chemotherapy with melphalan and prednisone (77 patients), and whether the addition of the immunomodulating agent levamisole to maintenance chemotherapy enhanced the survival of patients achieving remission. The treatment groups were well matched for all major factors. The more aggressive chemotherapy was more effective at inducing remission, with a significantly higher proportion of patients achieving at least 75% tumor mass regression (53% with alternating combinations versus 32% with melphalan-prednisone, p = 0.