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Multiple Myeloma Patients (multiple + myeloma_patient)
Selected AbstractsMultiple myeloma patients receiving large volume leukapheresis efficiently yield enough CD34+ cells to allow double transplantsJOURNAL OF CLINICAL APHERESIS, Issue 1 2009A.C. Zubair Abstract Current protocols for myeloma patients require more than one autologous transplant. We performed a retrospective study to determine the cost-effectiveness of large volume leukapheresis (LVL) compared with standard volume leukapheresis (SVL) collection when two transplants are required. We evaluated 87 patients who underwent a cumulative total of 260 LVL and SVL collections. The median product volume per collection was 356 ml for LVL, and this was significantly higher than the median product volume per collection for SVL (median 149.5 ml, P < 0.001). The median total CD34+ cell yield/kg was 6.4 × 106 for LVL and 5.2 × 106 for SVL. This difference was statistically significant (P = 0.005). Because the target CD34+ cell dose for a single transplant was 3 × 106/kg at our institution, overall the LVL yields enough CD34+ cells that could allow for two transplants. Therefore, more patients in the LVL group were able to undergo a potential second transplant. Because of the reserved cells for a second transplant, LVL patients received significantly less CD34+ cell/kg per transplant than the patients in SVL group (P = <0.001). As a result, LVL group had statistically significant but clinically insignificant delay in neutrophil (P = <0.001) and platelet (P = 0.02) engraftments. Additionally, using LVL instead of SVL to collect ,6 × 106/kg CD34+ cells may potentially save $7,497 per patient. We therefore conclude that LVL is the method of choice for collection of multiple myeloma patients when two transplants are anticipated. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Multiple myeloma patients with CKS1B gene amplification have a shorter progression-free survival post-autologous stem cell transplantationBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2006Hong Chang Summary The prevalence and prognostic relevance of recurrent gains of CKS1B (cyclin kinase subunit 1B) gene at chromosome 1q21 region was investigated by interphase fluorescence in situ hybridisation in a cohort of 99 multiple myeloma (MM) patients treated with intensive chemotherapy followed by autologous stem cell transplantation. CKS1B amplification (3,8 CKS1B signals) was detected in 31of 99 (31%) patients and was associated with deletions of p53 (P = 0·003) and 13q (P = 0·039) but not with translocation t(11;14) or t(4;14). CKS1B amplification was associated with bone marrow plasmacytosis (P = 0·02), but there was no correlation with patient age, gender, disease stage, lytic bone lesions, albumin, creatinine, C-reactive protein or beta-2 microglobulin levels. Patients with CKS1B amplification had a significantly shorter progression-free survival than those without such amplification (18·5 vs. 25·7 months, P = 0·035). Likewise, a shorter overall survival (44·8 months vs. not reached) was observed; however, the difference did not reach statistical significance (P = 0·20). Seven patients had paired bone marrows obtained at diagnosis and at relapse, the percentage of cells with CKS1B amplification and the level of amplification were significantly increased in the relapse marrows. In this cohort of patients, CKS1B was frequently amplified in MM and may represent genetic instability associated with disease progression. [source] Four crystal forms of a Bence-Jones proteinACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2005Debora L. Makino Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40,years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P43212 and P212121, with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3,Å, diffract to 1.5 and 1.9,Å, respectively. Two closely related trigonal forms, both belonging to space group P3121 with unit-cell parameters a = b = 154.3,Å but differing by a doubling of the c axis, one 46.9,Å and the other 94.0,Å, diffract to 2.9 and 2.6,Å resolution, respectively. The trigonal crystal of short c -axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of fibrils common to certain storage diseases. [source] Plasmacytoma in a multiple myeloma patientBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Mathieu Jablonski No abstract is available for this article. [source] Therapeutic approaches for newly diagnosed multiple myeloma patients in the era of novel drugsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Fortunato Morabito Abstract The treatment of newly diagnosed multiple myeloma (MM) has evolved rapidly over recent years. The availability of new effective drugs with novel mechanisms of action, such as thalidomide, lenalidomide and bortezomib in the last decade, has resulted in a new scenario expected to impact favorably on the outcome of patients with MM. The introduction of new drugs in the treatment of patients eligible for autologous stem cell transplantation (ASCT) has allowed for a significant increase of complete response rate with a positive impact on progression-free survival. In patients not eligible for ASCT, randomized trials have shown that both thalidomide and bortezomib when combined with melphalan and prednisone (MP) are superior to MP and are now considered the standard of care. Ongoing trials are assessing whether MP plus lenalidomide or the combination of lenalidomide plus dexamethasone should be considered an attractive treatment option, while additional studies are needed to determine the role of routine maintenance or consolidation therapy with these new drugs. This new therapeutic armamentarium in light of adequate prophylaxis and supportive care allows clinicians to greatly improve the survival perspectives for both young and elderly patients. In this review, we report updated data for the front-line therapy of MM, examining the role of new drugs either when administered as induction therapy before ASCT in younger patients or when combined with alkylating agents for the treatment of older patients. The most relevant articles on therapy of MM published from November 1982 to January 2010 (selected through PubMed), and recent meeting abstracts were used as sources for this review. [source] What changes in health-related quality of life matter to multiple myeloma patients?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2010A prospective study Abstract Objective: To determine the clinical significance of changes in quality-of-life scores in patients with multiple myeloma (MM), we have estimated the minimal important difference (MID) for the health-related quality-of-life instrument, the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30. The MID is the smallest change in a quality-of-life score considered important to patients. Methods: Between 2006 and 2008, 239 patients with MM completed the EORTC QLQ-C30 at inclusion (T1) and after 3 months (T2). At T2, a structured quality-of-life interview was also performed. MIDs were calculated by using mean score changes (T2,T1) for patients who in the interview stated they had improved, deteriorated or were unchanged. MIDs were also estimated by the receiver-operating characteristic (ROC) curve method as well as by calculation effect sizes using standard deviations of baseline scores. Results: MIDs varied slightly depending on the method used. Patients stating in the interview that they had ,improved' or ,deteriorated' had a corresponding change in EORTC QLQ-C30 score ranging from 6 to15 (improvement) and from 9 to17 (deterioration) (scale range 0,100). The ROC analysis indicated that changes in score from 7 to17 represent clinically important changes to patients. The effect size method suggested 5,6 to be a small and 11,15 to be a medium change. Conclusion: Calculation of MIDs as mean score changes or by ROC analysis suggested that a change in the EORTC QLQ-C30 score in the range of approximately 6,17 is considered important by patients with MM. These MIDs are closer to a medium effect size than to a small effect size. Our findings imply that mean score changes smaller than 6 are unlikely to be important to the patients, even if these changes are statistically significant. [source] Long-term effects of idiotype vaccination on the specific T-cell response in peripheral blood and bone marrow of multiple myeloma patientsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Amir Osman Abdalla Abstract Objectives:, To elucidate long-term effects of idiotype (Id) vaccination on Id-specific T cells of multiple myeloma (MM) patients and compare Id-specific T-cell responses of peripheral blood with those of bone marrow (BM). Materials and methods:, Id-specific T-cell responses of peripheral blood mononuclear cells (PBMC) were compared with those of BM mononuclear cells (BMMC) in 10 MM patients vaccinated with the Id protein at a median time of 41 months since the last immunization. The PBMC responses at late follow-up were also compared with those during active immunization. The responses were assessed by a proliferation assay, enzyme-linked immunospot (ELISPOT) (,-interferon), cytometric bead array (CBA) for secreted cytokines and quantitative real-time polymerase chain reaction (QRT-PCR) for cytokine gene expression. Results:, At the late testing time, an Id-specific response was detected in PBMC of five patients (ELISPOT, CBA, QRT-PCR) and in BMMC of four patients (CBA, QRT-PCR). A response in both compartments was noted only in three patients. The cytokines gene profile was consistent with a predominance of Th2 cells [interleukin (IL)-4, IL-5, IL-10]. Comparison of the Id-specific responses of PBMC during active immunization with those at the late follow-up showed that the frequency and magnitude of the responses had decreased significantly by time (proliferation/ELISPOT) (P < 0.02) and shifted at the gene level from a Th1 to a Th2 profile (P < 0.05). Conclusion:, Id-specific T cells may decline overtime and shift toward a Th2 response and may be found at a similar frequency of patients in blood and BM. [source] Absence of veno-occlussive disease in a cohort of multiple myeloma patients undergoing autologous stem cell transplantation with targeted busulfan dosageEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2006A. Clopés Abstract:,Background:,Plasma concentrations of oral busulfan (BU) were measured in multiple myeloma (MM) patients undergoing autologous peripheral blood stem cell transplantation (ASCT) with a double alkylating conditioning protocol in order to individualise doses of BU based on individual pharmacokinetic parameters and to reduce toxicities related to BU exposure. Patients and methods:,Forty-four consecutive patients with MM participating in the co-operative Spanish protocol were prospectively evaluated. Conditioning regimen prior to autologous infusion consisted of BU followed by melphalan. BU pharmacokinetic parameters were estimated for each patient after the first dose based on measured concentrations and subsequent doses were modified as necessary to achieve target exposure. Results:,Mean BU exposure (AUCss) (±DS) before dosage modification range from 3192 to 12 180 ng h/mL. Twenty-six out of 44 (59%) patients required dose adjustment. None of the patients developed hepatic veno-occlusive disease (VOD). Grade , II oropharyngeal mucositis was observed in the majority of patients (95%) and the severity of mucositis increased with increasing average steady-state BU plasma concentration. There were four treatment-related deaths: two patients died from multiorgan failure and two of respiratory infections. Of the remaining 40 patients, 15 were in complete remission with negative immunofixation, 21 in partial remission and four in stable disease 3 months after ASCT. Conclusions:,The results of the present study show the variability in BU pharmacokinetic parameters and suggest the possible relationship between toxicities and BU exposure. Individualising BU dosage in MM patients undergoing ASCT we observed the absence of VOD. [source] Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5-6 2001Lene Meldgaard Knudsen Abstract:Background: Cells belonging to the malignant clone are found in the peripheral blood in myeloma patients. In order to minimise the content of tumour cells in the stem cell product it is crucial to perform stem cell harvest at a time when tumour cells in the peripheral blood are at a minimum. Objective: The aim of the study was to compare the mobilisation kinetics of normal CD34+ cells and myeloma plasma cells during mobilisation with either G-CSF alone or high-dose cyclophosphamide (HDCy) plus G-CSF. Design and methods: Morning blood samples were drawn each day during mobilisation from start of G-CSF or HDCy and to the end of leukapheresis, and were analysed by flow cytometry for content of CD34+ cells and myeloma plasma cells (CD38+ + CD45,). Tumour cells were also estimated by a patient-specific real-time polymerase chain reaction (PCR) method based on the 5, nuclease TaqMan technology. Results: Flow cytometry data from 16 patients showed concomitant mobilisation of CD34+ cells and myeloma plasma cells. Seven patients were mobilised twice; first with G-CSF alone and then with HDCy plus G-CSF. There was no difference between the two mobilisation regimens regarding tumour cell mobilisation kinetics. Real-time PCR was performed in one patient and confirmed the mobilisation of tumour cells at the time when CD34+ blood cells were at a maximum. Conclusions: Tumour cells are mobilised to the peripheral blood at the same time as CD34+ cells in multiple myeloma patients after priming with both G-CSF alone and HDCy in combination with G-CSF. [source] Urinary N-telopeptide levels in multiple myeloma patients, correlation with Tc-99m-sestaMIBI scintigraphy and other biochemical markers of disease activityHEMATOLOGICAL ONCOLOGY, Issue 1 2003M. G. Alexandrakis Abstract Urinary cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a sensitive and specific marker of bone resorption in multiple myeloma (MM). In this study, we measured the levels of NTx in 30 newly diagnosed MM patients and 25 controls. We examined its association with the overall score of skeletal involvement measured by Tc-99m-MIBI scintigraphy and other biochemical markers of bone disease (tumour necrosis factor a (TNF-a), serum calcium and creatinine). We further studied the correlation of NTx with the stage of disease (according to Durie,Salmon criteria) and bone marrow infiltration by plasma cells. High levels of NTx, bone marrow infiltration, TNF-,, calcium and creatinine were noted at advanced stages of disease (p,<,0.05). NTx and TNF-a were found at significantly higher concentrations in patients with a high overall score (3 and 4) in Tc-99m-sestaMIBI in comparison to a low score (0, 1 and 2; p,<,0.05). Positive correlations were found between NTx and TNF-a, as well as between bone infiltration and TNF-a or calcium. In conclusion, NTx is a useful marker for the monitoring of bone resorption in MM and correlates with imaging findings on Tc-99m-sestaMIBI and other biochemical markers of disease activity. Copyright © 2002 John Wiley & Sons, Ltd. [source] Proliferative activity of plasma cells is the most relevant prognostic factor in elderly multiple myeloma patientsINTERNATIONAL JOURNAL OF CANCER, Issue 5 2004R. García-Sanz Abstract Although multiple myeloma (MM) is predominantly a disease of the elderly, few studies have focused on the identification of prognostic factors in this group of patients. Four hundred twenty five MM patients >65 years were uniformly treated with chemotherapy (MP or VCMP/VBAD). Multivariate analysis identified 4 factors with independent unfavorable prognostic influence: high percentage of S-phase bone marrow plasma cells (>2.5%); elevated ,2 microglobulin (B2M) (>4 mg/L); age >80 years old; and LDH serum levels (above normal limit). The S-phase value was the most powerful independent prognostic factor to discriminate subgroups of patients with different prognosis. Thus, 3 main risk categories could be identified according to S-phase values: ,1%, 1,3% and >3%, with median survivals of 34, 22 and 12 months, respectively (p < 0.0001). Our study also proved the value for elderly patients of the recently developed International Score System (ISS) based on B2M and albumin. Furthermore, the number of S-phase cells helped to subdivide the ISS III Group identifying a subset of patients with very poor prognosis defined by an additional high S-phase, who displayed a median survival of only 8 months. These results demonstrate that elderly patients can be accurately classified according to prognosis, which may be particularly valuable when comparing the efficacy of new treatment strategies. Moreover, our results underline the high prognostic value of proliferative activity of PC, a parameter that should be considered in routine laboratory investigations of MM. © 2004 Wiley-Liss, Inc. [source] Detecting methylation patterns of p16, MGMT, DAPK and E-cadherin genes in multiple myeloma patientsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2010O. OZALP YUREGIR Summary Multiple myeloma (MM) is a B-cell neoplasia characterized by the clonal proliferation of plasma cells. Besides known genetic abnormalities, epigenetic changes are also known to effect MM pathogenesis. DNA methylation is an epigenetic mechanism that silences genes by adding methyl groups to cytosine-guanine dinucleotides at the promoter regions. In this study, the methylation status of four genes; p16, O6-methyl guanine DNA methyl transferase (MGMT), death-associated protein kinase (DAPK) and E-cadherin (ECAD); at the time of diagnosis was investigated using methylation-specific polymerase chain reaction (MS-PCR). In the 20 cases studied; methylation of the promoter regions of p16, MGMT, DAPK and ECAD genes was detected in 10%, 40%, 10% and 45% of the cases, respectively. In 65% (13/20) of cases, at least one of the genes studied had promoter methylation; while 35% of cases (7/20) had methylated promoters of more than one gene. There was a significant correlation between promoter hypermethylation of MGMT and the presence of extramedullary involvement; but for the other genes no correlation was found regarding disease properties like age, disease stage, clinical course and the presence of lytic bone lesions. Determining the methylation profiles of genes in MM, could lead to a new understanding of the disease pathogenesis and guide the assessment of treatment options. [source] Multiple myeloma patients receiving large volume leukapheresis efficiently yield enough CD34+ cells to allow double transplantsJOURNAL OF CLINICAL APHERESIS, Issue 1 2009A.C. Zubair Abstract Current protocols for myeloma patients require more than one autologous transplant. We performed a retrospective study to determine the cost-effectiveness of large volume leukapheresis (LVL) compared with standard volume leukapheresis (SVL) collection when two transplants are required. We evaluated 87 patients who underwent a cumulative total of 260 LVL and SVL collections. The median product volume per collection was 356 ml for LVL, and this was significantly higher than the median product volume per collection for SVL (median 149.5 ml, P < 0.001). The median total CD34+ cell yield/kg was 6.4 × 106 for LVL and 5.2 × 106 for SVL. This difference was statistically significant (P = 0.005). Because the target CD34+ cell dose for a single transplant was 3 × 106/kg at our institution, overall the LVL yields enough CD34+ cells that could allow for two transplants. Therefore, more patients in the LVL group were able to undergo a potential second transplant. Because of the reserved cells for a second transplant, LVL patients received significantly less CD34+ cell/kg per transplant than the patients in SVL group (P = <0.001). As a result, LVL group had statistically significant but clinically insignificant delay in neutrophil (P = <0.001) and platelet (P = 0.02) engraftments. Additionally, using LVL instead of SVL to collect ,6 × 106/kg CD34+ cells may potentially save $7,497 per patient. We therefore conclude that LVL is the method of choice for collection of multiple myeloma patients when two transplants are anticipated. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Erythropoiesis stimulating agents are associated with reduced survival in patients with multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008Eirini Katodritou The impact of erythropoiesis-stimulating agent (ESA) on cancer patients' survival has recently become a matter of extensive discussion. Studies in solid tumors demonstrated that ESA adversely affects survival. This issue has not been sufficiently studied in patients with multiple myeloma. In this study, which included 323 multiple myeloma patients followed in our Institution between 1988 and 2007, we demonstrated by using a proportional hazards model including multiple covariates (age, LDH, Hb, platelets, serum creatinine, ISS score, ,2 microglobulin, and ESA administration) that ESA administration is associated with reduced survival (hazards ratio: 1.88, 95% CI: 1.28,2.77). Anemia, which is considered a predictor for survival, platelets, serum creatinine, ISS score, and LDH, were not significant, whereas, age and ,2 microglobulin confirmed their predicting value in the multivariate analysis. With a median follow-up of 31 months (range 1,238), the median survival of patients in the ESA group was 31 months (95% CI: 25,37), whereas in the group without ESA administration it was 67 months (95% CI: 55,79) (P < 0.001). The median progression-free survival for patients in the ESA group was 14 months (95% CI: 12,16), and for the group without ESA it was 30 months (95% CI: 24,36) (P < 0.001). These results indicate that ESA may have a detrimental impact on MM patients' outcomes and, thus, in this context, they should be used with rigorous criteria. © 2008 Wiley-Liss, Inc. Am. J. Hematol., 2008. [source] Community experience with bortezomib in patients with multiple myelomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2007Adedayo A. Onitilo Abstract Community practice experience allows a nonselective care of patient using information derived from a more controlled clinical trial environment. We present our community experience with multiple myeloma patients with advanced age, long disease duration since diagnosis, advanced stage, multiple prior therapies including stem cell transplantation, co-morbidities, and other poor prognostic features, such as low albumin, high B-2 microglobulin, renal failure, and the presence of poor risk chromosomal abnormalities. Our response rates are comparable to those from clinical trials. Bortezomib is well tolerated in this population of multiple myeloma patients with the exception of infection adverse events that are generally mild grade 1,2. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] short report: High levels of serum angiogenic growth factors in patients with AL amyloidosis: comparisons with normal individuals and multiple myeloma patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2010Efstathios Kastritis Summary Serum levels of five angiogenic cytokines were evaluated in 82 patients with primary systemic amyloidosis (AL). Angiopoietin-1, vascular endothelial growth factor, basic fibroblast growth factor and angiogenin were higher in AL patients than in controls (n = 35) and newly-diagnosed, symptomatic, myeloma patients (n = 35). Angiopoetin-1/Angiopoetin-2 ratio was lower in AL compared to controls but higher than in myeloma patients. Angiopoetin-2 correlated with cardiac dysfunction indices; however, none of the angiogenic growth factors was prognostically significant. The increased angiogenic cytokine levels observed in AL seem to represent either a toxic effect of amyloid fibrils or light chains, or a compensatory response to organ dysfunction. [source] TP53 deletion is not an adverse feature in multiple myeloma treated with total therapy 3BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2009John D. Shaughnessy Summary Contrary to Total Therapy (TT) 2 for multiple myeloma patients, FGFR3, translocation bore no adverse effects on outcome in TT3 with added bortezomib. Del TP53, another poor-risk feature in TT2 and present in 10% of 441 patients treated, was examined for its prognostic consequences in TT3. Not affecting rate or duration of complete response, TP53 haplo-insufficiency also did not compromise, in the 83% with genomically defined low-risk myeloma, survival or event-free survival. FGFR3+ and FGFR3, molecular subgroups fared worse in the presence of del TP53 when applying TT2 but not TT3. Thus, the prognostic implications of del TP53 were protocol-, genome-defined risk- and molecular subgroup-dependent. [source] Bortezomib is associated with better health-related quality of life than high-dose dexamethasone in patients with relapsed multiple myeloma: results from the APEX studyBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2008Stephanie J. Lee Summary Health-related quality of life (HRQL) was prospectively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire , Core (QLQ-C30) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group,Neurotoxicity (NTX) side-effects questionnaires were administered at baseline and every 6 weeks up to 42 weeks. Patients receiving bortezomib (1·3 mg/m2, days 1, 4, 8 and 11 for eight 3-week cycles, then days 1, 8, 15 and 22 for three 5-week cycles; n = 296) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone (40 mg/d, days 1,4, 9,12, and 17,20 for four 5-week cycles, then days 1,4 only for five 4-week cycles; n = 302), plus significantly better physical health, role, cognitive, and emotional functioning scores, lower dyspnoea and sleep symptom scores, and better NTX questionnaire score, using multiple imputation to account for missing data. Results were similar using available-data analyses. Sensitivity analyses suggested that improved HRQL with bortezomib is at least partially explained by improved survival. These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone, consistent with the better clinical outcomes seen with bortezomib. [source] Pathogenic ATM mutations occur rarely in a subset of multiple myeloma patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2008Belinda Austen Summary Ataxia Telangiectasia (A-T) patients have biallelic inactivation of the ATM gene and exhibit a 200-fold-increased frequency of lymphoid tumours. ATM mutations have been found in a number of adult lymphoid malignancies but there is no data on the occurrence of ATM mutations in multiple myeloma tumours. The purpose of our work was to investigate the occurrence of ATM mutations in multiple myeloma and to this end we screened 45 sporadic cases for ATM mutations using denaturing high-performance liquid chromatography analysis and DNA sequencing. Pathogenic ATM mutations were identified in 2/45 of the myelomas compared with a published estimate of ATM mutant allele frequency in the UK population of 2/521 (P = 0·033). One was the missense mutation 7181C>T which was then modelled in an expression system and the S2394L protein shown to have no ATM kinase activity. The second myeloma had the pathogenic ATM splice site mutation IVS40-1G>C leading to loss of exon 41. We also report a 48-year-old ataxia telangiectasia patient who developed multiple myeloma. Taken together our study suggests that ATM mutation may play a role in the pathogenesis of a subset of multiple myelomas. [source] Serum pleiotrophin levels are elevated in multiple myeloma patients and correlate with disease statusBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2006Howard S. Yeh Summary Pleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparin-binding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple myeloma (MM) patients when compared with healthy subjects (P < 0·0001). Serum levels of this protein significantly increased during progression of disease, and decreased during response to anti-MM therapy (P < 0·001). These results suggest that serum PTN may be a new biomarker for monitoring the disease status and therapeutic response of MM patients. [source] Serum MUC-1 as a marker of disease status in multiple myeloma patients receiving thalidomideBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Linda Mileshkin No abstract is available for this article. [source] Serum MUC-1 as a marker of disease status in multiple myeloma patients receiving thalidomide , Response to mileshkin et al.BRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Stefano Luminari No abstract is available for this article. [source] Soluble urokinase-type plasminogen activator receptor (suPAR) as an independent factor predicting worse prognosis and extra-bone marrow involvement in multiple myeloma patientsBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2003Gian Matteo Rigolin Summary. The urokinase-type plasminogen activator (uPA) system, which consists of a proteinase (uPA), a receptor (uPAR or CD87) and inhibitors, is involved in proteolysis, cell migration, tissue remodelling, angiogenesis and cell adhesion. Recent findings suggest that malignant plasma cells express uPA and uPAR. The expression of these factors could represent a process by which myeloma plasma cells interact with the bone marrow (BM) environment and influence important biological events such as bone matrix degradation, plasma cell invasion and homing and, possibly, clinical evolution. We evaluated uPAR (CD87) and its soluble form (suPAR) in 49 multiple myeloma (MM) patients and correlated their expression and levels with clinico-biological characteristics of the disease. Flow cytometric analysis demonstrated that CD87 was expressed in all MM patients. High CD87 expression was associated with higher intensity of expression of CD56 (P = 0·038), CD38 (P = 0·058) and CD138 (P = 0·054) and CD45bright positivity (P = 0·014). suPAR levels correlated positively with soluble serum CD138 (P = 0·001), creatinine (P = 0·001), beta2 -microglobulin (P < 0·001), disease stage (P = 0·017) and extra-BM involvement (P = 0·002). In the 46 evaluable patients, multivariate analysis showed that high levels of suPAR (P = 0·0214) and disease stage (P = 0·0064) were predictive of extra-BM involvement. In multivariate Cox analysis, 13q deletion (P = 0·0278), high soluble serum CD138 (P = 0·0201) and high suPAR (P = 0·0229) were the only parameters that independently affected survival. We conclude that CD87 is expressed on myeloma plasma cells and that suPAR, which predicts extra-BM involvement and poor prognosis, possibly represents a molecule with a relevant role in the biology of MM. [source] Autologous stem cell transplantation in elderly multiple myeloma patients over the age of 70 yearsBRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2001Ashraf Badros The feasibility and efficacy of autologous stem cell transplantation (auto-SCT) in patients aged ,,70 years was analysed. Newly diagnosed (n = 34) and refractory multiple myeloma (n = 36) patients were studied. The median age was 72 years (range: 70,82·6). CD34+ cells were mobilized with chemotherapy and granulocyte colony-stimulating factor (G-CSF) (n = 35) or G-CSF alone (n = 35), yielding medians of 11·8 × 106 versus 8 × 106cells/kg respectively (P = 0·007). Because of excessive mortality (16%) in the first 25 patients who received melphalan 200 mg/m2 (MEL-200), the dose was subsequently decreased to 140 mg/m2 (MEL-140). Median times to absolute neutrophil count (ANC) > 0·5 × 109/l and to platelets >,20 × 109/l were 11 and 13 d respectively. Thirty-one patients (44%) received tandem auto-SCT. Complete remission (CR) was 20% after the first SCT and 27% after tandem SCT. Median CR duration was 1·5 years and was significantly longer for patients with ,,12 months of prior chemotherapy (2·6 versus 1·0 years, P = 0·0008). The 3-year event-free survival (EFS) and overall survival (OS) (+ standard error, SE) were projected at 20% + 9% and 31% + 10% respectively. Tandem SCTs positively affected EFS (4·0 versus 0·7 years; P = 0·003) and OS (4·0 versus 1·4 years; P = 0·02) compared with single auto-SCT. In conclusion, MEL-140 is less toxic and appears equally as efficacious as MEL-200 in elderly patients. The benefits of tandem SCT in this patient population need further evaluation in a randomized trial. [source] |