Cytoplasmic immunoglobulin content in multiple myeloma

Journal of Clinical Investigation (Impact Factor: 13.77). 09/1985; 76(2):765-9. DOI: 10.1172/JCI112033
Source: PubMed

ABSTRACT Bone marrow cells of 82 patients with multiple myeloma were subjected to flow cytometric analysis of DNA and cytoplasmic immunoglobulin (CIg) content using propidium iodide and direct immunofluorescence assays. Except for two patients with nonsecretory myeloma, there was conformity in the immunoglobulin type derived from immunoelectrophoresis and plasma cell CIg staining. One patient with nonsecretory myeloma exhibited monotypic CIg staining, while the second showed no reaction. In eight patients with IgG lambda myeloma, the same tumor cells contained both lambda and kappa light chains, suggesting the productive rearrangement of both light chain genes. 14 patients with previously unrecognized plasma cells of low RNA content, all of whom were resistant to chemotherapy, were identified by CIg staining. By revealing previously unrecognized plasma cells with low RNA content, CIg analysis identified more patients with treatment-refractory myeloma.

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Available from: Mark A Pershouse, Aug 13, 2014
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    • "These tests were performed before initiating protocol therapy, monthly until initiation of consolidation therapy and then every 3–6 months. Bone marrow aspirates and biopsies were examined morphologically and by flow cytometry to evaluate nuclear DNA content and cytoplasmic immunoglobulin prior to each of the four protocol phases and then at least annually as well as at relapse (Barlogie et al, 1985). Cytogenetic studies were also performed and cytogenetic abnormalities recorded among 20 Giemsa-banded metaphases (Sawyer et al, 1995). "
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    ABSTRACT: Total therapy 3 incorporated bortezomib into a melphalan-based tandem transplant regimen for 303 newly diagnosed patients with myeloma. Induction chemotherapy prior to and consolidation chemotherapy after transplants each consisted of two cycles of VTD-PACE (bortezomib, thalidomide, dexamethasone and 4-d continuous infusions of cis-platin, doxorubicin, cyclophosphamide, etoposide); 3-year maintenance comprised monthly cycles of VTD in the first and TD in the remaining years. The median age was 59 years (age >64 years, 28%). A minimum of 20 x 10(6) CD34 cells/kg was collected in 87% of patients; 83% completed both transplants, and only 5% suffered a treatment-related death. At 24 months, 83% had achieved near-complete remission, which was sustained in 88% at 2 years from its onset. With a median follow-up of 20 months, 2-year estimates of event-free and overall survival were 84% and 86% respectively. The 44 patients who experienced an event more often had a high-risk gene array profile, cytogenetic abnormalities and indicators of high lactate dehydrogenase, beta-2-microglobulin, creatinine and International Staging System stage. Toxicities of grade > 2 included thrombo-embolic events in 27% and peripheral neuropathy in 12%. Results of this phase-2 study demonstrated that bortezomib could be safely combined with multi-agent chemotherapy, effecting near-complete remission status and 2-year survival rates in more than 80% of patients.
    British Journal of Haematology 07/2007; 138(2):176-85. DOI:10.1111/j.1365-2141.2007.06639.x · 4.96 Impact Factor
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    • "Recently, abnormalities of chromosome 13 (mainly complete and partial deletions of the long arm), found to be present in 16% of untreated patients, were recognized as the major adverse disease feature with high-dose therapy (HDT) (Tricot et al, 1995) and, subsequently, also with standard-dose therapy (SDT) (Seong et al, 1998). While proliferation-independent genetic measurements such as DNA flow cytometry (Barlogie et al, 1985) and, in recent years, interphase fluorescence hybridization (FISH) have revealed aneuploidy in virtually all patients with active MM (Drach et al, 1995; Tabernero et al, 1996; Zandecki et al, 1996), abnormal metaphases are obtained only in about one-third of newly diagnosed patients (Dewald et al, 1985; Gould et al, 1988; Sawyer et al, 1995). Cytogenetic abnormalities (CA) are typically complex in MM and represent a hallmark of this disease, involving many chromosomes that are altered both numerically and structurally (Rao et al, 1998; Sawyer et al, 1998a, 2001). "
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    ABSTRACT: Cytogenetic abnormalities (CA), especially of chromosome 13, have been used to identify a subgroup of previously untreated multiple myeloma (MM) patients with very poor prognosis despite high-dose therapy (HDT). We examined the prognostic implications of CA in 1000 MM patients receiving melphalan-based tandem autotransplants (median follow-up, 5 years). Negative consequences for both overall survival (OS) and event-free survival (EFS) in the presence of any CA were confirmed, especially when detected within 3 months of HDT. In the context of standard prognostic factors (SPF), 'MM-MDS' (MM karyotype that contains, in addition, CA typical of MDS) imparted a poor OS and EFS, after adjusting for any CA and all individual CA. One-year mortality was also high, especially for the MM-MDS subgroup with trisomy 8 within a MM signature karyotype (87%vs 34% in its absence, P < 0.001). No patient remained event free 5 years post transplant in the presence of these baseline high-risk CA. However, certain trisomies (e.g. chromosomes 7 and 9) and del 20 had favourable clinical consequences. The higher risk that is associated with CA compared with SPF justifies routine cytogenetic studies in all patients with MM at diagnosis and whenever additional treatment decisions are considered, such as in planning HDT either for initial response consolidation, at the time of primary unresponsiveness to induction therapy, or at relapse.
    British Journal of Haematology 08/2003; 122(3):430-40. DOI:10.1046/j.1365-2141.2003.04455.x · 4.96 Impact Factor
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    • "The diploid karyotype in the remaining patients is thought to be derived from normal haematopoietic precursors. Using DNA flow cytometry (Barlogie et al, 1985; San Miguel et al, 1995) and, more recently, fluorescence in situ hybridization (FISH) (Drach et al, 1995; Flactif et al, 1995; Shaughnessy et al, 2000; Debes et al, 2001) and comparative genomic hybridization (CGH) (Perez-Simon et al, 1998) for interphase genetic analysis, chromosome abnormalities seem to be universal in MM (Drach et al, 1995; Zandecki et al, 1996). CA 13, consisting mainly of monosomy 13 but also of deletion 13q and translocations involving 13q, is present in no more than 15% of patients and was the first consistent genetic abnormality associated with poor prognosis in the context of both standard (Seong et al, 1998) and high-dose therapies (Tricot et al, 1995; Barlogie et al, 1999; Desikan et al, 2000). "
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    ABSTRACT: Cytogenetic abnormalities of chromosome 13 (CA 13) and those detected by fluorescence in situ hybridization (FISH 13) have both been associated with poor prognosis in multiple myeloma (MM) patients. The prognostic implications of CA, FISH 13 and other standard laboratory parameters were examined in the first 231 patients enrolled in Total Therapy II, an intensive cytotoxic chemotherapy programme with tandem autotransplants. Three-year projections of event-free survival (EFS) and overall survival (OS) were 71% and 77% respectively. CA 13 was detected in 14% and significantly correlated with FISH 13 (present in 51%), tumour burden, proliferative activity and lactic dehydrogenase (LDH). Both EFS and OS were significantly shorter in patients with CA 13, FISH 13, LDH >or= 190 U/l, beta2 microglobulin >or= 4 mg/l and C reactive protein >or= 4.0 mg/l; other CA was an additional risk factor for OS. Two-thirds of CA 13 patients were identified by FISH 13 and plasma-cell-labelling index (PCLI) >or= 0.4%; however, PCLI failed to identify additional risk groups in FISH subsets. Although present in considerably fewer patients, CA 13 imparted more rapid relapse (61% at 3 years) and death (43% at 3 years) than FISH 13 (38% and 35%; P = 0.02 and 0.1 respectively) and should be part of the initial work-up of patients with MM.
    British Journal of Haematology 02/2003; 120(1):44-52. DOI:10.1046/j.1365-2141.2003.03948.x · 4.96 Impact Factor
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