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Bart Barlogie

Publications and source records attributed to Bart Barlogie.

At least 73 records · Page 4Linked to original sources
PubMed2003

The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma.

BACKGROUND: Myeloma cells may secrete factors that affect the function of osteoblasts, osteoclasts, or both. METHODS: We subjected purified plasma cells from the bone marrow of patients with newly diagnosed multiple myeloma and control subjects to oligonucleotide microarray profiling and biochemical and immunohistochemical analyses to identify molecular determinants of osteolytic lesions. RESULTS: We studied 45 control subjects, 36 patients with multiple myeloma in whom focal lesions of bone could not be detected by magnetic resonance imaging (MRI), and 137 patients in whom MRI detected such lesions. Different patterns of expression of 57 of approximately 10,000 genes from purified myeloma cells could be used to distinguish the two groups of patients (P<0.001). Permutation analysis, which adjusts the significance level to account for multiple comparisons in the data sets, showed that 4 of these 57 genes were significantly overexpressed by plasma cells from patients with focal lesions. One of these genes, dickkopf 1 (DKK1), and its corresponding protein (DKK1) were studied in detail because DKK1 is a secreted factor that has been linked to the function of osteoblasts. Immunohistochemical analysis of bone marrow-biopsy specimens showed that only myeloma cells contained detectable DKK1. Elevated DKK1 levels in bone marrow plasma and peripheral blood from patients with multiple myeloma correlated with the gene-expression patterns of DKK1 and were associated with the presence of focal bone lesions. Recombinant human DKK1 or bone marrow serum containing an elevated level of DKK1 inhibited the differentiation of osteoblast precursor cells in vitro. CONCLUSIONS: The production of DKK1, an inhibitor of osteoblast differentiation, by myeloma cells is associated with the presence of lytic bone lesions in patients with multiple myeloma.

Bone Marrow↗
PubMed2003

High heparanase activity in multiple myeloma is associated with elevated microvessel density.

Heparanase is an enzyme that cleaves heparan sulfate chains of proteoglycans, and its expression has been associated with increased growth, metastasis, and angiogenesis of some tumors. Because myeloma tumor cells express high levels of the syndecan-1 heparan sulfate proteoglycan and because these tumors grow as highly vascularized aggregates within the bone marrow, we analyzed the activity, expression, and function of heparanase in myeloma patients. Analysis of heparanase activity in the plasma isolated from bone marrow biopsies of 100 patients reveals 86 positive for heparanase activity and 14 negative. The bone marrow samples can be further divided into three categories of heparanase activity, high activity (42 patients), low activity (44 patients), and negative (14 patients). In contrast to the bone marrow plasma, levels of heparanase activity in peripheral blood plasma of 29 myeloma patients were either negative or low, suggesting that in multiple myeloma, heparanase functions in the local microenvironment of the bone marrow and its activity is not significantly elevated systemically. Immunohistochemistry reveals that patients with high levels of heparanase activity often have tumor cells with intense staining for the enzyme. Interestingly, a marked heterogeneity among tumor cells was noted, with clusters of heavily stained cells surrounded by cells with weak or negative staining for heparanase. Analysis of microvessel density reveals a strikingly higher concentration of vessels in patients with high heparanase activity (78.96 vessels/mm(2)) as compared with patients negative for heparanase activity (25.03 vessels/mm(2)). When human myeloma cells transfected with the cDNA for heparanase are implanted in severe combined immunodeficient (SCID) mice, the resulting tumors exhibited a significantly higher microvessel density than did tumors established with control cells. Thus, expression of heparanase appears to play a direct role in enhancing microvessel density in these myeloma tumors. Because heparanase is known to stimulate angiogenesis, and because high microvessel density is associated with poor prognosis in myeloma, we conclude that heparanase expression likely plays an important role in regulating the growth and progression of myeloma, and that therapies designed to block heparanase activity may aid in controlling this cancer.

Animals↗
PubMed2003

The natural history of respiratory syncytial virus infection in cancer and transplant patients: implications for management.

Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous peripheral blood stem cell transplantation (APBSCT). However, little is known about the natural history of this infection in these patients, and current standard practice, aerosolized ribavirin plus intravenous immunoglobulin (IVIG), is extremely expensive, difficult to use, and not supported by controlled clinical trials. The purpose of this observational study was to determine the frequency, seasonality, morbidity, and mortality of RSV infection in a group of cancer patients receiving cytotoxic chemotherapy with neither ribavirin nor IVIG treatment. During the period of October 3, 1997, through October 14, 1998, 190 cancer patients (median age, 58 years; 71 women) underwent viral nasopharyngeal washing prior to chemotherapy. Multiple myeloma (MM) accounted for most patients (147, 77%). RSV was recovered from cultures taken from 71 patients (37%) throughout the year, although more frequently during fall and winter seasons (P <.001) than spring and summer. Serious respiratory complications developed in 19 (27%) of 71 RSV-positive patients versus 24 (20%) of 119 patients whose RSV cultures were negative (P =.384). The presence of renal failure or increased lactate dehydrogenase (LDH) prior to chemotherapy and the development of mucositis were the only predictive factors for severe respiratory complications. Recovery of RSV from nasopharyngeal washings among cancer patients is common, occurs throughout the year, and does not appear to increase serious morbidity or mortality. RSV infection may not necessarily be a contraindication for APBSCT or an indication for therapy with aerosolized ribavirin and IVIG.

Adult↗
PubMed2003

Treatment of multiple myeloma.

Autologous peripheral blood stem cell (PBSC)-supported high-dose melphalan is now considered standard therapy for myeloma, at least for younger patients. The markedly reduced toxicity of allotransplants using nonmyeloablative regimens (mini-allotransplantations) may hold promise for more widely exploiting the well-documented graft-versus-myeloma (GVM) effect. New active drugs include immunomodulatory agents, such as thalidomide and CC-5013 (Revimid; Celgene, Warren, NJ), and the proteasome inhibitor, PS 341 (Velcade; Millenium, Cambridge, MA), all of which not only target myeloma cells directly but also exert an indirect effect by suppressing growth and survival signals elaborated by the bone marrow microenvironment's interaction with myeloma cells. Among the prognostic factors evaluated, cytogenetic abnormalities (CAs), which are present in one third of patients with newly diagnosed disease, identify a particularly poor prognosis subgroup with a median survival not exceeding 2 to 3 years. By contrast, in the absence of CAs, 4-year survival rates of 80% to 90% can be obtained with tandem autotransplantations. Fundamental and clinical research should, therefore, focus on the molecular and biologic mechanisms of treatment failure in the high-risk subgroup.

Amyloidosis↗
PubMed2003

DTPACE: an effective, novel combination chemotherapy with thalidomide for previously treated patients with myeloma.

PURPOSE: To improve outcome in previously treated patients (at least two cycles of standard therapy) with multiple myeloma, thalidomide was combined with cytotoxic chemotherapy as induction therapy. PATIENTS AND METHODS: The regimen consisted of 4-days of oral dexamethasone, daily thalidomide, and 4 days of continuous-infusion cisplatin, doxorubicin, cyclophosphamide, and etoposide (DTPACE). Response to two cycles of DTPACE for induction was evaluated in 236 patients. Before being treated with DTPACE, 148 patients (63%) had shown progressive disease while receiving standard chemotherapy, and 55 patients (23%) had chromosome 13 abnormalities. RESULTS: The partial remission rate (PR) after two cycles of DTPACE was 32%, with 16% attaining a complete remission (CR) or near-CR (nCR; defined as only immunofixation electrophoresis-positive). Patients with high lactate dehydrogenase (LDH; n = 98) showed a better response than those with normal LDH (n = 138): PR or better, 43% v 27% (P =.01); CR + nCR, 25% v 11% (P =.01). Patients with chromosome 13 abnormalities (n = 55) responded equally well as the other patients (n = 181): PR or better, 35% v 33% (P =.84); CR + nCR, 17% v 15% (P =.73). Patients who received 100% dose of DTPACE for two cycles (n = 115) achieved higher response rates than those with less than 100% dose (n = 121): PR or better, 49% v 17% (P <.0001); CR + nCR, 27% v 6% (P <.0001). CONCLUSION: Combination therapy of oral dexamethasone and thalidomide with infusional chemotherapy is effective as induction therapy before autotransplantation, especially in patients with high-risk features.

Administration, Oral↗
PubMed2003

A phase 2 study of bortezomib in relapsed, refractory myeloma.

BACKGROUND: Bortezomib, a boronic acid dipeptide, is a novel proteasome inhibitor that has been shown in preclinical and phase 1 studies to have antimyeloma activity. METHODS: In this multicenter, open-label, nonrandomized, phase 2 trial, we enrolled 202 patients with relapsed myeloma that was refractory to the therapy they had received most recently. Patients received 1.3 mg of bortezomib per square meter of body-surface area twice weekly for 2 weeks, followed by 1 week without treatment, for up to eight cycles (24 weeks). In patients with a suboptimal response, oral dexamethasone (20 mg daily, on the day of and the day after bortezomib administration) was added to the regimen. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. RESULTS: Of 193 patients who could be evaluated, 92 percent had been treated with three or more of the major classes of agents for myeloma, and in 91 percent, the myeloma was refractory to the therapy received most recently. The rate of response to bortezomib was 35 percent, and those with a response included 7 patients in whom myeloma protein became undetectable and 12 in whom myeloma protein was detectable only by immunofixation. The median overall survival was 16 months, with a median duration of response of 12 months. Grade 3 adverse events included thrombocytopenia (in 28 percent of patients), fatigue (in 12 percent), peripheral neuropathy (in 12 percent), and neutropenia (in 11 percent). Grade 4 events occurred in 14 percent of patients. CONCLUSIONS: Bortezomib, a member of a new class of anticancer drugs, is active in patients with relapsed multiple myeloma that is refractory to conventional chemotherapy.

Adult↗
PubMed2003

Telomerase and telomere length in multiple myeloma: correlations with disease heterogeneity, cytogenetic status, and overall survival.

We have investigated the significance of telomerase activity (TA) and telomere length (TL) in multiple myeloma (MM). The analyses were undertaken on CD138+ MM cells isolated from the marrow of 183 patients either at diagnosis or in relapse. There was heterogeneity in telomerase expression; 36% of the patients had TA levels comparable to those detected in normal plasma cells, and 13% of patients had levels 1- to 4-fold greater than in a neuroblastoma cell line control. The TL of MM cells was significantly shorter than that of the patients' own leukocytes; in 25% of patients, the TL measured less than 4.0 kbp. Analysis of TL distribution indicated selective TA-mediated stabilization of shorter telomeres when mean TL fell below 5.5 kbp. Unusually long (10.8-15.0 kbp) telomeres were observed in 7 patients, and low TA was observed in 5 of 7 patients, suggesting the operation of a TA-independent pathway of telomere stabilization. A strong negative correlation existed between TA and TL or platelet count. TL negatively correlated with age and with interleukin-6 (IL-6) and beta2-microglobulin levels. Various cytogenetic abnormalities, including those associated with poor prognosis, strongly correlated with TA and, to a lesser extent, with short TL. High TA and short TL defined a subgroup of patients with poor prognosis. At 1 year the survival rate in patients with TA levels lower than 25% of neuroblastoma control and TL greater than 5.5 kbp was 82%, whereas in patients with higher TA and shorter TL the survival rate was 63% (P =.004). The 2-year survival rate for patients with TA levels lower than 25% was 81%, and it was 52% in those with higher TA levels (P <.0001).

Adult↗
PubMed2003

Continuous absence of metaphase-defined cytogenetic abnormalities, especially of chromosome 13 and hypodiploidy, ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression.

Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo-13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy II, overexpression of cell cycle genes distinguished CA from no CA, especially in cases of del(13) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells.

Two common features in human immunodeficiency virus infection and acquired immunodeficiency syndrome, rheumatoid arthritis, and hematologic malignancies including multiple myeloma are elevated serum levels of beta(2)-microglobulin (beta(2)M) and activation or inhibition of the immune system. We hypothesized that beta(2)M at high concentrations may have a negative impact on the immune system. In this study, we examined the effects of beta(2)M on monocyte-derived dendritic cells (MoDCs). The addition of beta(2)M (more than 10 microg/mL) to the cultures reduced cell yield, inhibited the up-regulation of surface expression of human histocompatibility leukocyte antigen (HLA)-ABC, CD1a, and CD80, diminished their ability to activate T cells, and compromised generation of the type-1 T-cell response induced in allogeneic mixed-lymphocyte reaction. Compared with control MoDCs, beta(2)M-treated cells produced more interleukin-6 (IL-6), IL-8, and IL-10. beta(2)M-treated cells expressed significantly fewer surface CD83, HLA-ABC, costimulatory molecules, and adhesion molecules and were less potent at stimulating allospecific T cells after an additional 48-hour culture in the presence of tumor necrosis factor-alpha and IL-1beta. During cell culture, beta(2)M down-regulated the expression of phosphorylated mitogen-activated protein (MAP) kinases, extracellular signal-related kinase (ERK), and mitogen-induced extracellular kinase (MEK), inhibited nuclear factor-kappaB (NF-kappaB), and activated signal transducer and activator of transcription-3 (STAT3) in treated cells, all of which are involved in cell differentiation and proliferation. Thus, our study demonstrates that beta(2)M at high concentrations retards the generation of MoDCs, which may involve down-regulation of major histocompatibility complex class I molecules, inactivation of Raf/MEK/ERK cascade and NF-kappaB, and activation of STAT3, and it merits further study to elucidate the underlying mechanisms.

Antigens, CD↗
PubMed2003

Toward the identification of distinct molecular and clinical entities of multiple myeloma using global gene expression profiling.

Multiple myeloma (MM) is a poorly understood and uniformly fatal malignancy of antibody-secreting plasma cells (PC). Although several key molecular events in disease initiation or progression have been confirmed (such as 14q32 translocations) or implicated (chromosome 13 deletion), a unifying mechanism of myelomagenesis has proved elusive. Furthermore, while MM is generally indistinguishable morphologically, the disease exhibits tremendous variability in its clinical course, with some patients surviving only months and others many years, suggesting that MM is composed of distinct clinical entities. As abnormal gene expression is central to most, if not all cancers, high-throughput global gene expression profiling has become a powerful tool to investigate the molecular biology and clinical behavior of malignancy. Here we discuss recent progress made in the development of molecular-based diagnostics and prognostics for MM through the dissection of the transcriptome of PCs from healthy individuals and patients with MM and other PC dyscrasias.

Cell Differentiation↗
PubMed2003

Prognostic factors in allogeneic transplantation for patients with high-risk multiple myeloma after reduced intensity conditioning.

OBJECTIVES: The aim of this study was to identify prognostic factors for outcome of high-risk patients with multiple myeloma after allogeneic transplantation prepared by reduced intensity conditioning (RIC). MATERIALS AND METHODS: Data from 45 consecutive patients (median age 52 years, range 38-68), who received grafts from a sibling (n = 34) or unrelated donor (n = 11) were analyzed. Fourteen patients received an RIC allotransplant while chemosensitive (>/=partial remission [PR]), whereas 31 chemoresistant patients (<PR) had either relapsed (n = 28) or were refractory (n = 3) after one or more autografts; of these 28 patients, 4 had secondary myelodysplasia concurrent with relapse. Of the 14 chemosensitive patients, 12 received an RIC allotransplant as consolidation after an autotransplant (AT). RESULTS: Twenty-nine (64%) were in a complete remission (CR) or near CR, 5 were in PR, and 5 had progressive disease. Twenty-five patients died, 17 of transplant-related complications, 7 of progressive disease, and 1 of a nontransplant-related cause. With a median follow-up of 15 months, the following factors were significantly associated with a better event-free survival (EFS) probability at 3 years: chemosensitive disease (64% vs 12%), pretransplant performance score (PS, Zubrod) </=2 (36% vs 0%), CR + near CR post transplant (36% vs 0%), and presence of chronic graft-vs-host disease (GVHD; 29% vs 0%). The same factors and absence of grade III to IV acute GVHD (52% vs 0%) were significant for a better overall survival (OS). On multivariate analysis including only pretransplant factors, both chemosensitive response and PS </=2 were significant for overall survival and event-free survival (p < 0.01). When response to RIC allotransplant and GVHD were added to the model, chronic GVHD was significant for better event-free survival, with an odds ratio of 1.5 (p < 0.01). CONCLUSIONS: Our data suggest that although RIC allotransplant induces high rates of CR and near CR, even in refractory disease, it appears to result in a durable response only if it is applied early in the disease in high-risk patients, when they still are chemosensitive and have an adequate PS.

Adult↗
PubMed2003

Interpreting the molecular biology and clinical behavior of multiple myeloma in the context of global gene expression profiling.

Multiple myeloma (MM) is a rare but uniformly fatal malignancy of antibody-secreting plasma cells (PCs). Although several key molecular events in disease initiation or progression have been confirmed (e.g. FGFR3/MMSET activation) or implicated (e.g. chromosome 13 deletion), the mechanisms of MM development remain enigmatic. Importantly, although generally being indistinguishable morphologically, MM exhibits a tremendous degree of variability in clinical course, with some patients surviving only months and others many years. However, current laboratory parameters can account for no more than 20% of this outcome variability. Furthermore, the means by which current drugs impart their anti-MM effect are also mostly unknown. In addition, the mechanisms by which MM cells contribute to serious comorbidities, such as osteopenia and/or focal lytic lesions of bone, are also poorly understood. Finally, very little knowledge exists concerning the molecular events leading to benign hyperplasia and/or overt malignancy of PCs. Given that abnormal gene expression lies at the heart of most, if not all, cancers, high-throughput global gene expression profiling has become a powerful tool for investigating molecular biology and clinical behavior of diseases. Here, we discuss recent progress made in addressing many of the above issues through the molecular dissection of the transcriptome of normal PCs and MM.

Cell Differentiation↗
PubMed2003

Prognostic impact of cytogenetic and interphase fluorescence in situ hybridization-defined chromosome 13 deletion in multiple myeloma: early results of total therapy II.

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.

Aged↗
PubMed2003

Mobilization of CD34+ cells in elderly patients (>/= 70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen.

The mobilization of peripheral blood stem cells was studied in 984 multiple myeloma patients, including 106 patients aged >/= 70 years. Increasing age correlated inversely with CD34+ yield (P < 0.0001), but also with >/= 12 months of prior standard chemotherapy (P = 0.0001), < 200 x 10(9)/l platelets (P = 0.0006) premobilization and mobilization with growth factors only (P = 0.0001). After controlling for these age covariates, multivariate analysis identified </= 12 months standard therapy and platelet count >/= 200 x 10(9)/l premobilization as favourable variables (both P < 0.0001), while increasing patient age remained an unfavourable factor (P = 0.0009). With both favourable variables, 85% of elderly patients collected >/= 4 x 10(6)/kg CD34+ cells in a median of one collection. The effect of age was incremental with no age threshold showing acceleration in the decline of CD34+ yield. Chemotherapy significantly increased CD34+ yield compared with growth factors only. However, the subgroup of patients with > 12 months prior therapy and premobilization platelet count < 200 x 10(9)/l mobilized as many CD34+ cells with granulocyte colony-stimulating factor (G-CSF) alone as with chemotherapy and haematopoietic growth factors. Increasing patient age had no effect on post-transplant neutrophil recovery, but significantly delayed platelet recovery (>/= 50 x 10(9)/l) if < 2 x 10(6)/kg CD34+ cells were infused, but this effect was eliminated completely with infusion of >/= 4 x 10(6)/kg CD34+ cells. Increasing age adversely affected CD34+ yield even with limited premobilization therapy, indicating that early collection is important in elderly patients.

Adult↗
PubMed2003

Infection--an underappreciated cause of bone pain in multiple myeloma.

Bone pain, especially back pain, is a common presenting feature of myeloma patients. We report three multiple myeloma patients with exacerbations of back pain and referred shoulder pain resulting from vertebral infections. Two patients were treated with surgery, and one patient had computerized tomography-guided percutaneous needle aspiration for diagnostic purposes. All three patients received a prolonged course of antibiotics. Vertebral infection resolved with this treatment in all three patients without any recurrence. Previous dexamethasone therapy, together with an episode of bacteraemia, appears to be a predisposing factor for vertebral infection. Magnetic resonance imaging enabled the diagnosis in all three patients.

Aged↗
PubMed2003

MDS-type abnormalities within myeloma signature karyotype (MM-MDS): only 13% 1-year survival despite tandem transplants.

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.

Antineoplastic Agents, Alkylating↗
PubMed2003

A new staging system for multiple myeloma patients based on the Southwest Oncology Group (SWOG) experience.

We aimed to develop and evaluate a staging system for multiple myeloma (MM) based on easily obtained laboratory measures. The Durie-Salmon stage is most commonly used and is an effective system of patient stratification for clinical trial research. However, the criteria are complex and many laboratory parameters are required to properly stage patients. In this analysis, we focused on two common measures with prognostic importance in MM: serum beta2 microglobulin (beta2m) and serum albumin. Pre-study data on 1555 previously untreated MM patients enrolled on four recent South-west Oncology Group (SWOG) phase III trials were used in the analysis. Staging models were developed and validated using regression tree methods for survival outcomes. SWOG stages were defined as: stage 1, beta2m < 2.5 mg/l (14% of patients, median overall survival of 55 months); stage 2, 2.5 </= beta2m < 5.5 (43% of patients, median overall survival of 40 months); stage 3, beta2m >/= 5.5 and albumin >/= 30 g/l (32% of patients, median overall survival of 24 months); and stage 4, beta2m >/= 5.5 and albumin < 30 g/l (11% of patients and median overall survival of 16 months). This staging scheme was also predictive of event-free survival, first-year mortality and long-term (>/= 5 years) event-free survival. We conclude that although the SWOG stage does not represent a new prognostic marker for MM (cytogenetics, FISH), it could provide a simple alternative to the Durie-Salmon stage for patients with previously untreated MM. Additional evaluation in other MM patient populations is needed to confirm results.

Adult↗