Serum beta 2-microglobulin, serum creatinine and bone marrow plasma cells in benign and malignant monoclonal gammopathy

Serum beta 2-microglobulin concentrations were determined in samples of 65 patients with benign or malignant monoclonal gammopathy. In the group of patients suffering from multiple myeloma or Waldenstr?m's macroglobulinemia the mean beta 2-microglobulin level was significantly higher than in the group with benign monoclonal gammopathy. Values above 3 mg/l were highly indicative of malignant disease and observed in 50% of the myeloma patients. Serum creatinine levels were significantly correlated to beta 2-microglobulin levels. However, mean creatinine concentrations did not significantly differ between the two groups of patients. Plasma cells and lymphoplasmocellular elements containing cytoplasmic immunoglobulin were counted in bone marrow samples of all patients. The counts, expressed in percent of nucleated bone marrow cells, allowed a good discrimination between the benign and the malignant group of patients. Bone marrow from patients with multiple myeloma or macroglobulinemia contained more, from patients with benign monoclonal gammopathy less than 17% plasma cells. No significant correlation was noticed between the extent of this plasmocytic bone marrow infiltration and serum beta 2-microglobulin or creatinine levels.     

Beta2-microglobulin and bone marrow plasma cell involvement predict complete responders among patients undergoing blood cell transplantation for myeloma.

We studied the prognostic value of clinical and laboratory variables, measured before blood cell transplantation, in predicting complete response among patients undergoing autologous blood cell transplantation for relapsed or primary refractory myeloma. Sixty-seven patients who underwent transplantation for relapsed or primary refractory myeloma were studied. The overall response rate was 90%, and the complete response rate was 33%. Low beta2-microglobulin (< or =2.7 mg/l) was associated with a significantly better complete response rate compared with high levels (54 vs 19%, P = 0.002). Similarly, the complete response rate was 39% when the bone marrow plasma cell percentage was low (<40%) and 21% with greater involvement (P = 0.04). Complete response rate was 50% when beta2-microglobulin and bone marrow plasma cell percentage were low, 36% if either was high, and 12% when both were high (P = 0.01). Median survival measured from initial diagnosis of myeloma was 51 months. Overall survival after transplantation was better among responders who achieved complete response than those who did not: median survival, 24 vs 11 months, P = 0.04 (log-rank) and 0.009 (Gehan-Wilcoxon). Attainment of a complete response independently predicted better survival in a multivariate analysis. beta2-Microglobulin and bone marrow plasma cell percentage predict complete responders among patients undergoing transplantation for myeloma.     

Bone marrow angiogenesis and its correlation with other disease characteristics in multiple myeloma in stage I versus stage II-III

PURPOSE: We studied bone marrow angiogenesis in different stages of multiple myeloma according to the Durie and Salmon classification and its correlations with other disease characteristics. METHODS: Sixty-five immunohistochemical CD34-stained, paraffin-embedded bone marrow biopsies of multiple myeloma patients and 12 controls were studied. The mean number of microvessels per area in each sample was determined as the microvessel density (MVD). In addition, plasma cell infiltration of the bone marrow, serum beta2-microglobulin, immunoglobulin levels, C-reactive protein, and serum calcium concentration were measured in 22 patients with stage I multiple myeloma and in 43 patients in stage II-III. RESULTS: In myeloma patients, the bone marrow MVD was significantly higher than in controls (P<0.001). In 43 patients with stage II-III multiple myeloma, MVD was significantly higher than in 22 patients with stage I (median MVD 46 and 21 vessels/mm(2), respectively, P=0.005). Additionally, in stage II-III the bone marrow MVD correlated positively with the bone marrow plasma cell infiltration (r=0.55, P<0.001) and the serum beta2-microglobulin level (r=0.53, P<0.001), while in stage I patients no correlation could be found. CONCLUSIONS: Angiogenesis is significantly increased in stage II-III myeloma in comparison to stage I. In stages II-III, bone marrow angiogenesis is correlated with plasma cell infiltration and serum beta2-microglobulin levels.     

Comparison of plasma cell infiltration in bone marrow biopsies and aspirates in patients with multiple myeloma

In 54 patients with multiple myeloma plasma cell infiltration was compared in bone marrow biopsies and aspirates. In 48% of cases plasma cell infiltration was comparable, in 48% infiltration in the aspirate was lower than in the biopsy. In only two cases more plasma cells were found in the aspirate. Eleven patients (20%) had less than 20% plasma cells in the aspirate and more than 50% in the biopsy. Underestimation of plasma cell load especially seems to occur in patients with a focal growth pattern of multiple myeloma or when strong fibrosis is present. 69% of patients with stage III, according to Durie & Salmon (1975), and 76% of patients with a high beta 2-microglobulin had more than 50% plasma cells in the biopsy, indicating that these parameters, which are based on tumour load, are influenced by other factors as well. The bone marrow biopsy is of superior value for direct estimation of the tumour load in multiple myeloma compared to bone marrow aspirates. A prospective study is needed to determine its prognostic significance.     

Relationship between bone marrow angiogenesis and plasma cell infiltration and serum β2-microglobulin levels in patients with multiple myeloma

There is growing evidence that angiogenesis is important not only in solid tumors but also in hematological malignancies. Recently, we found that bone marrow angiogenesis is a prognostic factor for disease-related survival in patients with multiple myeloma. In this report, we addressed the question of whether the microvessel density in bone marrow biopsies is correlated to other myeloma parameters, e.g., serum beta2-microglobulin (beta2-MG) and plasma cell infiltration in the bone marrow. In 22 multiple myeloma patients, immunohistochemical, CD34-stained, paraffin-embedded bone marrow biopsies before and after chemotherapy were studied. Microvessels were counted in 400x magnification, and the mean number of vessels per area in each sample was noted as the microvessel density (MVD). Pretreatment bone marrow MVD (median: 44, range: 11-175 vessels/mm2) correlated significantly with the bone marrow plasma cell infiltration (median: 30%, range: 5-90%, r = 0.642, P=0.001) and beta2-MG (median: 2.74, range: 1.4-26.1 mg/l, r = 0.749, P < 0.0005). In contrast, there was no correlation between posttreatment MVD and plasma cell infiltration or beta2-MG (median: MVD 31, range: 0-221 vessels/mm2, median plasma cell infiltration: 15%, range: 5-80%, r = 0.229, P = 0.306 and median beta2-MG: 2.65, range: 1-27.6 mg/l, r = -0.042, P = 0.853). These findings show that the strong correlations between bone marrow MVD and plasma cell infiltration as well as serum beta2-MG levels disappear after chemotherapy. The underlying mechanisms need further investigations.     

The sensitivity of CD138 immunostaining of bone marrow trephine specimens for quantifying marrow involvement in MGUS and myeloma, including samples with a low percentage of plasma cells

Accurate quantification of plasma cells in bone marrow samples is essential for the diagnosis, classification and prognosis of plasma-cell dyscrasias. Published comparisons between aspirate/trephine morphology, flow cytometry and immunohistochemistry are lacking. Bone marrow plasma cells from 100 patients with plasma cell myeloma or monoclonal gammopathy of undetermined significance were quantified by a 500-cell differential count on Romanowsky-stained aspirate slides, flow-cytometry gating of CD38bright+/CD138+ cells, hematoxylin and eosin trephine section examination and CD138 trephine immunohistology. The results of quantification by the different methods were compared. Compared to other methods, CD138 trephine immunohistology consistently demonstrated greater plasma-cell infiltration. Immunohistology is the most sensitive method for assessment of plasma-cell infiltration at diagnosis or post-therapy, especially in patients with minimal bone marrow involvement.     

Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed multiple myeloma

Adverse prognostic factors in multiple myeloma include advanced age, number of prior therapies, and higher International Staging System (ISS) disease stage. In the international, randomised, phase-3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study, bortezomib demonstrated significantly longer time to progression (TTP), higher response rates and improved survival compared with high-dose dexamethasone in patients with relapsed multiple myeloma following one to three prior therapies. In this APEX subgroup analysis, efficacy of bortezomib and dexamethasone was compared in elderly (age > or =65 years) and high-risk (>1 prior line of therapy; ISS stage II/III; refractory to prior therapy) patients. Bortezomib demonstrated substantial clinical activity in these patients. Response rate (34-40% vs. 13-19%), including complete response rate (5-8% vs. 0-1%), was significantly higher with bortezomib versus dexamethasone in all four subgroups. Similarly, median TTP was significantly longer with bortezomib versus dexamethasone, and 1-year survival probability was significantly higher in all subgroups. As in the total APEX population, rates of grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated patients aged > or =65 years and with >1 prior line, while rates of serious adverse events were similar; toxicities generally proved manageable. Bortezomib should be considered an appropriate treatment for elderly and high-risk patients with relapsed multiple myeloma.     

Amplification of cyclin D1 gene in multiple myeloma: clinical and prognostic relevance

Approximately 30% of myeloma patients express cyclin D1 RNA and protein. The low incidence of translocation t(11; 14) detected by conventional cytogenetics suggests that the up-regulation of cyclin D1 protein might result from other mechanisms as well as from gene amplification. Therefore, the frequency and the clinical and prognostic implications of cyclin D1 amplification were examined. We highly purified myeloma cells from bone marrow by magnetic cell sorting and analysed 50 myelomas by fluorescence in situ hybridization (FISH) using probes specific for cyclin D1 and 20 samples by immunoblotting to detect cyclin D1 expression. The amplification of cyclin D1 gene was found in 19 of 50 analysed patients and was associated with expression of cyclin D1 protein. The amplification correlated significantly with the bone marrow infiltration, plasma cell morphology and labelling index as well as serum beta2-microglobulin, C-reactive protein (CRP) and creatinine levels. In univariate analysis, the amplification of the cyclin D1 gene was a significantly unfavourable parameter with regard to overall survival (P = 0.0064) and progression-free survival (P = 0. 0005). In multivariate analysis, cyclin D1 amplification and serum beta2-microglobulin were independent and well-suited parameters for predicting survival. The detection of cyclin D1 amplification seems to be of promising prognostic value in multiple myeloma.     

Early chemosensitivity to VAD regimen predicts a favorable outcome after autologous stem cell transplantation in multiple myeloma

We report that early chemosensitivity, defined by a greater than 50% reduction of M-component and plasma-cell marrow infiltration, after 2 cycles of VAD was correlated with a favorable outcome following autologous stem cell transplantation in 46 patients with newly diagnosed multiple myeloma submitted to high-dose therapy.     

Chromosome 1 abnormalities in elderly patients with newly diagnosed multiple myeloma treated with novel therapies

Multiple myeloma is a plasma cell disorder characterized by malignant plasma cell infiltration in the bone marrow, serum and/or urine monoclonal protein and organ damage. The aim of this study was to investigate the impact of chromosome 1 abnormalities in a group of elderly patients (>65 years) with newly diagnosed multiple myeloma enrolled in the GIMEMA-MM-03-05 trial and treated with bortezomib, melphalan and prednisone or bortezomib, melphalan, prednisone and thalidomide followed by bortezomib and thalidomide maintenance. We also evaluated the link between chromosome 1 abnormalities and other clinical, genetic and immunophenotypic features by a multivariate logistic regression model. Interphase fluorescence in situ hybridization on immunomagnetically purified plasma cells and bone marrow multiparameter flow cytometry were employed. A multivariate Cox model showed that chromosome 1 abnormalities, age >75 years and a CD19⁺/CD117⁻ immunophenotype of bone marrow plasma cells were independent risk factors for overall survival in elderly patients with newly diagnosed multiple myeloma. Moreover, a detrimental effect of thalidomide, even when administered in association with bortezomib, was observed in patients with abnormal chromosome 1 as well as in those with 17p deletion, while the benefit of adding thalidomide to the bortezomib-melphalan-prednisone regimen was noted in patients carrying an aggressive CD19⁺/CD117⁻ bone marrow plasma cell immunophenotype. This trial was registered at www.clinicaltri-als.gov as #{"type":"clinical-trial","attrs":{"text":"NCT01063179","term_id":"NCT01063179"}}NCT01063179.     

Treatment response to bortezomib in multiple myeloma correlates with plasma hepatocyte growth factor concentration and bone marrow thrombospondin concentration

Multiple myeloma (MM) is associated with increased rate of bone marrow angiogenesis. Increased concentration of hepatocyte growth factor (HGF) is associated with poor prognosis in patients treated with conventional chemotherapy or thalidomide. We have shown previously that decreased level of thrombospondin, an angiogenesis inhibitor, correlates with poor response to high‐dose chemotherapy. The aim of our current study was to evaluate association between therapeutic response to bortezomib and thrombospondin and HGF levels. Peripheral blood plasma concentration of HGF and bone marrow plasma concentration of thrombospondin were measured in patients with MM prior to the initiation of bortezomib therapy. Overall, 58 patients were enrolled, 44/58 (76%) of them with relapsed disease. Treatment outcomes were analyzed for possible associations with pretreatment HGF and thrombospondin levels. Patients who achieved complete response had significantly higher pretreatment HGF levels and lower pretreatment thrombospondin levels than others. More than 70% of patients with low pretreatment HGF and high pretreatment thrombospondin concentrations achieved very good partial response or complete response, in contrast to only 20% of patients with high HGF and low thrombospondin levels. High pretreatment thrombospondin and low pretreatment HGF concentrations are associated with therapeutic response to bortezomib in patients with MM.     

Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management

DISEASE OVERVIEW: Multiple myeloma is malignant plasma-cell disorder that accounts for ～10% of all hematologic malignancies. DIAGNOSIS: The diagnosis requires (1) 10% or more clonal plasma cells on bone marrow examination or a biopsy-proven plasmacytoma plus (2) evidence of end-organ damage felt to be related to the underlying plasma cell disorder. RISK STRATIFICATION: Patients with 17p deletion, t(4;14), t(14;16), t(14;20), and karyotypic deletion 13 or hypodiploidy are considered to have high-risk myeloma. All others are considered to have standard-risk disease. RISK-ADAPTED THERAPY: Standard-risk patients are treated with nonalkylator-based therapy such as lenalidomide plus low-dose dexamethasone (Rd) followed by autologous stem-cell transplantation (ASCT). If patients are tolerating the induction regimen treatment well, an alternative strategy is to continue initial therapy after stem-cell collection, reserving ASCT for first relapse. High-risk patients are treated with a bortezomib-based induction followed by ASCT and then bortezomib-based maintenance. Patients not eligible for ASCT can be treated with Rd for standard risk disease or a bortezomib-based regimen if high-risk features are present. To reduce toxicity, when using bortezomib, the once-weekly dose is preferred; similarly, when using dexamethasone, the low-dose approach (40 mg once a week) is preferred, unless there is a need for rapid disease control. MANAGEMENT OF REFRACTORY DISEASE: Patients with indolent relapse can be treated first with lenalidomide, bortezomib, or alkylators plus low-dose corticosteroids. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. The most promising new agents in development are pomalidomide and carfilizomib.     

Myeloma cells exhibit an increase in proteasome activity and an enhanced response to proteasome inhibition in the bone marrow microenvironment in vivo

The proteasome inhibitor bortezomib has a striking clinical benefit in patients with multiple myeloma. It is unknown whether the bone marrow microenvironment directly contributes to the dramatic response of myeloma cells to proteasome inhibition in vivo. We have used the well‐characterized 5TGM1 murine model of myeloma to investigate myeloma growth within bone and response to the proteasome inhibitor bortezomib in vivo. Myeloma cells freshly isolated from the bone marrow of myeloma‐bearing mice were found to have an increase in proteasome activity and an enhanced response to in vitro proteasome inhibition, as compared with pre‐inoculation myeloma cells. Treatment of myeloma‐bearing mice with bortezomib resulted in a greater reduction in tumor burden when the myeloma cells were located within the bone marrow when compared with extra‐osseous sites. Our results demonstrate that myeloma cells exhibit an increase in proteasome activity and an enhanced response to bortezomib treatment when located within the bone marrow microenvironment in vivo. Am. J. Hematol., 2009. © 2009 Wiley‐Liss, Inc.     

Multiple myeloma: clinical features and indications for therapy

Multiple myeloma is a malignant plasma-cell proliferative disease with an expected 15,270 new cases and 11,070 deaths in the USA in 2004 alone. This accounts for 1% of all malignancies and slightly more than 10% of all hematologic malignancies in Caucasians and 20% in African Americans. The diagnosis is based on the presence of bone pain, anemia, and plasma-cell infiltrate in the bone marrow or within bone lesions. It is essential that the spectrum of plasma-cell proliferative disorders be recognized: monoclonal gammopathy of undetermined significance (MGUS), smoldering (asymptomatic) multiple myeloma (SMM), and active (symptomatic) MM. These distinctions affect important management decisions. Other related disorders include primary systemic amyloidosis, POEMS syndrome, and acquired Fanconi syndrome.     

Characterisation of haematological profiles and low risk of thromboembolic events with bortezomib in patients with relapsed multiple myeloma

Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (< or =3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation.     

A retrospective analysis of bortezomib therapy for Japanese patients with relapsed or refractory multiple myeloma: β2-microglobulin associated with time to progression

Bortezomib is approved for the treatment of patients with relapsed or refractory multiple myeloma (MM), but only a few clinical studies for Japanese patients who were treated with bortezomib have been reported. We retrospectively analyzed 40 patients with relapsed or refractory MM who have received bortezomib at three collaborating centers in Miyagi prefecture in Japan. All the patients have been received bortezomib in combination with dexamethasone. Responses were determined using International Myeloma Working Group uniform response criteria. The overall response was observed in 30 patients (75%), including very good partial response in 8 patients (20%), and partial response in 22 patients (55%). The median time to disease progression was 8.7 months, and the median overall survival has not been reached. The factors affecting time to disease progression were International Staging System stage, serum β2-microglobulin level, and number of treatment cycles. The most common grade 3 and 4 adverse events were thrombocytopenia (50%), peripheral neuropathy (25%), leukopenia (25%), and herpes zoster infection (25%). Thus, bortezomib is well tolerated and effective for Japanese patients with relapsed or refractory MM. Our results suggest that serum β2-microglobulin level may be a marker of prognosis on bortezomib therapy for patients with relapsed or refractory MM although further studies are needed.     

Multiple myeloma: 2012 update on diagnosis, risk-stratification, and management

DISEASE OVERVIEW: Multiple myeloma accounts for ～10% of all hematologic malignancies. DIAGNOSIS: The diagnosis requires 10% or more clonal plasma cells on bone marrow examination or a biopsy proven plasmacytoma plus evidence of end-organ damage felt to be related to the underlying plasma-cell disorder. RISK STRATIFICATION: Patients with 17p deletion, t(14;16), t(14;20), or high-risk gene expression profiling signature have high-risk myeloma. Patients with t(4;14) translocation, karyotypic deletion 13, or hypodiploidy are considered to have intermediate-risk disease. All others are considered to have standard-risk myeloma. RISK-ADAPTED THERAPY: Standard-risk patients are treated with nonalkylator-based therapy such as lenalidomide plus low-dose dexamethasone (Rd) followed by autologous stem-cell transplantation (ASCT). An alternative strategy is to continue initial therapy after stem-cell collection, reserving ASCT for first relapse. Intermediate-risk and high-risk patients are treated with a bortezomib-based induction followed by ASCT and then bortezomib-based maintenance. Patients not eligible for ASCT can be treated with Rd for standard risk disease, or with a bortezomib-based regimen if intermediate-risk or high-risk features are present. To reduce toxicity, when using bortezomib, the once-weekly subcutaneous dose is preferred; similarly, when using dexamethasone, the low-dose approach (40 mg once a week) is preferred, unless there is a need for rapid disease control. MANAGEMENT OF REFRACTORY DISEASE: Patients with indolent relapse can be treated first with two-drug or three-drug combinations. Patients with more aggressive relapse often require therapy with a combination of multiple active agents. The most promising new agents in development are pomalidomide and carfilizomib.     

VAD chemotherapy for refractory multiple myeloma

Thirty-four patients with refractory multiple myeloma were treated with 4-d continuous infusions of vincristine and adriamycin in combination with 4-d pulsed high-dose dexamethasone (VAD). Of 31 evaluable patients, 16 entered a complete remission (50%) and three a partial remission (10%). No difference in response rate was observed between primary refractory and relapsed patients. The median response duration was 9 months and the median survival of the responding patients was 12 months versus 4 months for the non-responders. Ten patients have currently survived longer than 360 d, of which six are stable in complete remission without therapy. All responding patients showed a remarkable improvement of their performance status and 70% of these patients became pain-free. Bacterial infection was the major complication and was probably due to the intensive corticosteroid programme. Severe myelosuppression was rarely observed. Irrespective of the response to VAD, a high beta 2-microglobulin of 4 micrograms/ml or more was a bad prognostic parameter. As early relapses were seen especially in this group of patients, in the patients with a plasma-cell LI% of 3 or more, and in patients with previous anthracyclin treatment, early consolidation, with, for instance, high dose melphalan, might improve the prognosis for these patients.     

Deletion of 13q14 remains an independent adverse prognostic variable in multiple myeloma despite its frequent detection by interphase fluorescence in situ hybridization

Interphase fluorescence in situ hybridization (FISH) studies of chromosomal region 13q14 were performed to investigate the incidence and clinical importance of deletions in multiple myeloma (MM). Monoallelic deletions of the retinoblastoma-1 (rb-1) gene and the D13S319 locus were observed in 48 of 104 patients (46.2%) and in 28 of 72 (38.9%) patients, respectively, with newly diagnosed MM. FISH studies found that 13q14 was deleted in all 17 patients with karyotypic evidence of monosomy 13 or deletion of 13q but also in 9 of 19 patients with apparently normal karyotypes. Patients with a 13q14 deletion were more likely to have stage III disease (P =.022), higher serum levels of beta(2)-microglobulin (P =.059), and a higher percentage of bone marrow plasma cells (P =.085) than patients with a normal 13q14 status on FISH analysis. In patients with a deletion of 13q14, myeloma cell proliferation (Ki-67) was markedly increased (22.0% +/- 6.9% compared with 15.6% +/- 8.2% in patients without the deletion; P =.0008). Evaluation of bromodeoxyuridine incorporation in 5 patients revealed that both rb-1-deleted and rb-1-normal MM subpopulations were proliferative. The presence of a 13q14 deletion on FISH analysis was associated with a significantly lower rate of response to conventional-dose chemotherapy (40.8% compared with 78. 6%; P =.009) and a shorter overall survival (24.2 months compared with > 60 months; P <.005) than in patients without the deletion. Multivariate analysis of prognostic factors confirmed the independent predictive value of 13q14 deletions for shortened survival. In conclusion, deletions of 13q14 are frequently detected by interphase FISH in patients with newly diagnosed MM, correlate with increased proliferative activity, and represent an independent adverse prognostic feature in MM. (Blood. 2000;95:1925-1930)     

Role of cytogenetics in the prognosis of patients with multiple myeloma

The aim of the study was to evaluate the clinical and prognostic significance of cytogenetic abnormalities in multiple myeloma patients. Cytogenetic studies were performed in 95 myeloma patients aged 31-82 (median 64) prior to chemotherapy. The GTG and CBG chromosome banding were performed and chromosomal abnormalities were described according to International System for Human Cytogenetic Nomenclature ISCN (1995). An abnormal karyotype was observed in 29% myeloma patients. Patients with an abnormal karyotypes showed various numerical and structural aberrations with hyperdiploidy in 39%, hypodiploidy in 39% and pseudodiploidy in 18% of patients. Monosomy of chromosome 13 was present in 29% of patients with an abnormal karyotype. Multiple myeloma patients with chromosomal abnormalities had more advanced disease than those with normal karyotype (82% vs 57% had stage III myeloma). beta 2-microglobulin and LDH levels were higher and hemoglobin level was significantly lower in patients with an abnormal karyotype. The plasma cell involvement of bone marrow was significantly higher in these patients. Overall survival was significantly shorter of patients with abnormal karyotypes (median 24 months vs 18 months), particularly of patients with monosomy of chromosome 13 (median 14 months). Cytogenetic studies are helpful to evaluate the prognosis and treatment options in multiple myeloma patients.