Adverse Prognostic Impact of Bone Marrow Microvessel Density in Multiple Myeloma

Introduction: Multiple myeloma (MM) is a heterogeneous malignant plasma cell (PC) disorder and the survival ranges from several months to > 10-years. Several risk stratification systems such as the Revised International Staging System (R-ISS) have been developed. PET/CT allows the direct assessment of metabolic tumor burden in various malignancies. Therefore, metabolic tumor volume (MTV) and total lesion glycolysis (TLG), which are volumetric parameters applicable to PET/CT, are emerging tools for MM prognostication. This study was aimed to determine the value of MTV and TLG using PET/CT in the prognostication and in combination with various hematologic parameters such as bone marrow PC (BMPC) percentages and circulating tumorous PCs (CPCs) to identify the patients with high-risk features. Methods: A total of 196 consecutive patients with newly diagnosed MM (NDMM) who underwent baseline whole-body PET/CT between January 2009 and June 2019 at Kameda Medical Center, Kamogawa-shi, Japan, were retrospectively analyzed. PET/CT was performed using dedicated PET/CT scanners (Discovery ST Elite Performance; GE Healthcare, Milwaukee, USA). The standard uptake value (SUV) was normalized according to the injected dose and lean body mass. The baseline SUVmax of all lesions was recorded, and the highest value was considered as the SUVmax of the patient. MTV was defined as the myeloma lesions volume visualized on PET/CT scans with SUV greater than or equal to the fixed absolute threshold of SUV = 2.5. TLG was calculated as the sum of the product of average SUV (SUVmean) and MTV of all lesions. Computer‐aided analysis of PET-CT images for MTV and TLG calculations was performed using an open-source software application of Metavol (Hokkaido University, Sapporo, Japan). The CPCs were measured using an 8-color flowcytometry and reported as the percentage per total mononuclear cells using the monoclonal antibodies of CD19, 38, 45, 56, 117, 200, κ, λ, and CD138. The BMPC was calculated by counting the percentages of CD138-stained PCs among the all nucleated cells on bone marrow biopsy samples. Eleven patients (13.8%) were excluded because the MTV data could not be retrieved. Ultimately, 185 patients were included in our analysis. Written informed consent was obtained from all patients. Results: Among the 185 patients, 28 patients (15.1%) were negative for avid lesion on PET/CT. Whole-body MTV and TLG ranged from 0 to 2440.7 mL, with a median of 34.2 mL and from 0 to 12582.4 g, with a median of 97.0 g, respectively. The best cut-off values of MTV and TLG that discriminate the survival using a receiver-operating-characteristic curve analysis were 56.4 mL and 166.4 g, respectively. The overall survival (OS) and progression-free survival (PFS) of patients with a lower cut-off value of MTV (≤56.4 mL) had better survival with not reached (NR) and 37.3 months as compared to those with a higher cut-off value (>56.4 mL) that reached 52.9 and 23.8 months, respectively (p=0.003 and 0.019). Similarly, the OS and PFS of patients with a lower cut-off value of TLG (≤166.4 g) showed better survivals with NR and 37.3 months as compared to those with a higher cut-off value (>166.4 g) that reached 54.3 and 28.8 months, respectively (p=0.0047 and 0.012). Next, we explored the prognostic impact of the clinical variables including MTV or TLG, CPCs, and BMPC. High levels of CPCs and BMPCs levels were defined as ≥0.018% of the total mononuclear cells and BMPCs of ≥57%, respectively. Univariate analysis showed that age≥70, serum creatinine≥2.0 mg/dL, R-ISS stage 3, higher cut-off value of MTV, and higher cut-off value of TLG were the associated with shorter OS. To measure the tumor volume with accuracy, we combined BMPC or CPCs and MTV or TLG. On multivariate analysis, age≥70 and the combination of higher cut-off value of MTV or TLG and high level of BMPC percentage were significantly associated with shorter OS [Hazard Ratio (HR) 2.12, p=0.038, HR 2.66, p=0.027 and HR 2.57, p=0.029, respectively] and PFS (Not assessed, HR 2.52, p=0.018 and HR 2.7, p= 0.011, respectively) (Figure 1). Conclusion: Our findings demonstrated that MTV and TLG calculated from pretreatment PET/CT were useful for risk stratification in patients with NDMM when combined with BMPC. The prognostic performance of the combined high-burden of TLG or MTV and high levels of BMPC were independent of the established risk factors. Disclosures Matsue: Novartis Pharma K.K: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Ono Pharmaceutical: Honoraria.

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MM-375: Prognostic Impact of Multiple Myeloma Cytogenetic Abnormalities on Outcome of Autologous Bone Marrow Transplantation: A Single-Center Experience

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/s2152-2650(20)30957-5 ◽

2020 ◽

Vol 20 ◽

pp. S309

Author(s):

May Denewer ◽

Sameh Shamaa ◽

Mohamed Samra ◽

Yasser El-Nahass EL-Nahass ◽

Emad Azmy

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

Prognostic Impact ◽

Single Center ◽

Single Center Experience ◽

Autologous Bone

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Prognostic Significance of Morphological Evaluation of Tumor Cells in Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.4889.4889 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4889-4889

Author(s):

Mohammed Al-sahmani ◽

Irena Trnavska ◽

Monika Antosova ◽

Libuse Antosova ◽

Jarmila Kissova ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Treatment Response ◽

Plasma Cell ◽

Diagnostic Procedures ◽

Lower Number ◽

Lower Percentage ◽

Type I ◽

Prognostic Impact ◽

Type Ii

Abstract Abstract 4889 Multiple myeloma (MM) is the second most common hematological malignancy. It is caused by clonal proliferation of terminally differentiated cells of B-lineage. Morphology assessment including the determination of plasma cell percentage in the bone marrow remains one of the basic diagnostic procedures even in the era of genomics. The objective of this study was to evaluate the prognostic impact of the presence of different plasma cell morphological subtypes on overall treatment response and long-term survival. We also analyzed whether this parameter can be correlated to other conventional prognostic/predictive markers. Our cohort consisted of 139 newly diagnosed MM patients who subsequently underwent autologous transplantation (AT) within the 4W and CMG 2002 clinical trials in a single center. Percentage of plasma cell subtypes in the bone marrow was evaluated based on the progressive nucleolus analysis, assessment of nuclear chromatin, and the nucleus/cytoplasm (N/C) ratio. A combination of these elements permits differentiation of eight subtypes P000-P111 and four subclassifications. Mature plasma cells (P000, P001) were found in 42.4% of patients; type I proplasmocytes (P010, P011, P100) in 38.1% of patients; and type II proplasmocytes (P101, P110) in 19.4% of patients. For patients undergoing AT, there was a statistically significant association between the presence of P000 subtype and overall treatment response whereas group of patients with overall therapeutic response ORR has lower number of mature plasma cell (P000 subtype) than patients without treatment response (median 24.0% vs. 36.0%, p = 0.032). Patients with <10% bone marrow infiltration by mature plasmocytes (P000 subtype) had shorter overall survival compared with patients with P000 percentage of ≥37% (46.8 months vs. 77.8 months; p = 0.020). The presence of <3% proplasmocytes (P110 subtype) was associated with longer time to progression compared with P110 ≥31% infiltration (median: 54.6 months vs. 22.4 months; p=0.045). Patients in ISS stage 1 or 2 had lower percentage of P010 (type I) proplasmocytes than patients in stage 3 (11.5% vs. 23.0%; p=0.030). In contrast, higher infiltration of P100 (type I) proplasmocytes and P101 (type II) proplasmocytes was observed in patients in 1-2 ISS stage compared with stage 3 patients (12.0% vs. 6.5%; p=0.015 for P100 and 1.0% vs. 0.0%; p=0.046 for P101). Patients without deletion of 13q14 chromosome had higher bone marrow percentage of mature P000 plasmocytes than patients with deletion of 13q14 (35% vs. 13%; p=0.014). Deletion of 13q14 was also associated with lower number of type II P110 proplasmocytes (36.5% vs. 6.0%; p=0.012). Despite advances in high-tech genomic technologies, evaluation of plasmocyte infiltration of the bone marrow still belongs to basic diagnostic procedures in MM and further morphological subtyping of plasmocytes should provide important prognostic information for MM patients treated by autologous stem cell transplantation. Supported by grants MSM 0021622434, MŠMT LC06027, MZCR NR9225-3 and IGA NR9225-3. Disclosures No relevant conflicts of interest to declare.

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Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis

Acta Haematologica ◽

10.1159/000478085 ◽

2017 ◽

Vol 138 (2) ◽

pp. 77-84 ◽

Cited By ~ 5

Author(s):

Panagiotis Ntellas ◽

Konstantinos Perivoliotis ◽

Katerina Dadouli ◽

Georgios K. Koukoulis ◽

Maria Ioannou

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Overall Survival ◽

Clinical Outcome ◽

Confidence Interval ◽

Microvessel Density ◽

Prognostic Value ◽

Meta Analysis ◽

End Point ◽

Secondary Outcomes

Background/Aims: Bone marrow (BM) angiogenesis is considered a hallmark of multiple myeloma (MM) development and progression, and can be quantified with the use of microvessel density (MVD). The purpose of this study is to provide a review and a meta-analysis of the current literature regarding the prognostic value of MVD in the overall survival (OS) of MM patients. Methods: MEDLINE was screened for studies evaluating the OS of MM patients with regard to their MVD count in BM trephine. The pooled hazard ratio (HR) and its associated 95% confidence interval (CI) among MM patients with a high and low MVD count was the primary end point. Secondary outcomes included odds ratios (OR) for 12-, 36-, and 60-month survival. Results: Ten eligible trials were identified for the analysis of the primary end point and 9 for the secondary end points. Pooled HR for OS was 1.85 (95% CI: 1.25-2.73, p = 0.002). The pooled OR of survival were 1.59 (95% CI: 1.02-2.46, p = 0.04) at 12 months, 2.90 (95% CI: 1.68-5.03, p = 0.0001) at 36 months, and 3.42 (95% CI: 2.41-4.85, p < 0.00001) at 60 months, in favor of the low MVD group. Conclusion: This meta-analysis provides persuasive evidence that MVD has significant impact on the clinical outcome of MM patients.

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Clinical and Prognostic Impact of (11;14)(q13;q32) Translocation on Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2019-130809 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5507-5507

Author(s):

Daisuke Miura ◽

Kentaro Narita ◽

Ayumi Kuzume ◽

Rikako Tabata ◽

Toshiki Terao ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Tumor Cells ◽

Clinical Characteristics ◽

Mononuclear Cells ◽

Plasma Cells ◽

Stage Iii ◽

Prognostic Impact ◽

Cd20 Expression ◽

The Impact

Introduction. Translocations involving chromosome 14 at band q32, the immunoglobulin heavy chain (IgH) locus, are considered to be the most important initiating events for the development of multiple myeloma (MM). Among the IgH translocations in MM, t(11;14)(q13;q32) is the most frequently reported, and associated with a lymphoplasmacytic morphology. This translocation have been traditionally considered as standard-risk chromosomal abnormality compared to other translocations such as t(4;14) or t(14;16), although some controversies on the prognostic impact of this translocation still remain. This study aimed to clarify the clinical and prognostic impact of t(11;14) in Japanese patients in relation to other clinical variables such as immunophenotype of the tumor cells, other cytogenetic abnormalities, and use of stem cell transplantation (SCT). Patients and methods. Among the 244 consecutive patients with newly diagnosed MM, treated at Kameda Medical Center between April 2009 and July 2019, 234 patients, having cytogenetic analysis data (including t(11;14), t(4;14), t(14;16), and del(17p) by interphase fluorescence in situ hybridization (iFISH)) fully available, were included in this study. Data regarding the patients' clinical and laboratory characteristics, including the International Staging System (ISS), immunophenotype of the tumor cells, baseline circulating plasma cells (CPCs), treatment responses, disease progression, and survival status, were collected. iFISH was performed with CD138-purified bone marrow plasma cells, and the cut off values for translocation were ≥ 10% and for del(17p) ≥ 20%. Using multicolor flow cytometry, surface marker analysis of bone marrow samples and quantification of pre-treatment CPCs on peripheral blood mononuclear cells were simultaneously performed. CPCs were reported as the percentage of total mononuclear cells. Patients were considered to be negative for clonal CPCs at a sensitivity of 10−4 (0.01%) clonal plasma cells for all events evaluated. Results. The incidence of patients harboring t(11;14) was 24.4% (n = 57); t(11;14) was detected significantly high in light-chain-only subtypes (P < 0.001). We compared clinical characteristics of patients carrying t(11;14) with others. Myeloma cells with t(11;14) were associated with negative expression of CD56 (P < 0.001), CD117 (P = 0.046), and CD200 (P = 0.006), and positive expression of CD20 (P = 0.01) and CD81 (P = 0.035). Patients with t(11;14) were associated with positive CPCs (P = 0.011). In order to focus on the impact of t(11;14), we divided the patients into 4 groups: (A) no specific cytogenetic abnormality listed above (n = 137), (B) t(11;14) group (n = 57), (C) t(4;14) or t(14;16) group (n = 29), and (D) del(17p) only (n = 10), and the clinical characteristics and survival of the patients were compared across the three groups (A), (B), and (C). Almost all the patients (> 95%) in this cohort received bortezomib-based therapy. Median progression-free survival (PFS) and overall survival (OS) of patients in (A), (B), and (C) groups were 55.6, 34.2, and 30.2 months (m) (A vs. B, P = 0.036, and A vs. C, P = 0.031), and not reached, 51.2, and 79.8 m (A vs. B, P = 0.11, and A vs. C, P = 1.00), respectively. However, patients harboring t(11;14) were further divided into CD20-positive and -negative groups, the latter having poor prognosis (36.1 vs. 26.7, P = 1.0 for median PFS, and not reached vs. 44.2, P = 0.029 for median OS). Compared to other groups, patients without CD20 expression had significantly shorter OS (vs. A, vs. B, P = 0.024, 0.035, respectively), whereas those with CD20 expression tended to have longer OS, without statistical significance (Figure 1).Univariate analysis revealed ISS stage III, creatinine > 2.0 mg/dL, use of SCT, t(11;14) without CD20 expression, and age ≥ 70 years to be associated with shorter OS, whereas multivariate analysis demonstrated ISS stage III, use of SCT, and t(11;14) without expression CD20 (HR 1.88; 95% CI 1.10-3.21; P = 0.021) to be independent prognostic factors for poor OS. Conclusions. Our findings demonstrated that patients harboring t(11;14) had distinct clinical and immunophenotypic characteristics, two subsets of the disease entities with a clearly different survival according to CD20 expression. Disclosures Matsue: Ono Pharmaceutical: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Novartis Pharma K.K: Honoraria; Celgene: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria.

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Stromal Cell IL-8 Production Is Increased in MM and May Impact Both Tumor Cells and the Microenvironment.

Blood ◽

10.1182/blood.v106.11.2508.2508 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2508-2508

Author(s):

Michael Kline ◽

Kathleen Donovan ◽

Linda Wellik ◽

Christopher Lust ◽

Wendy Jin ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Tumor Cells ◽

Cell Lines ◽

Microvessel Density ◽

Stromal Cells ◽

Stromal Cell ◽

Cell Clone ◽

Angiogenic Factor ◽

Antibody Array

Abstract Background: Multiple myeloma (MM) is an incurable hematological malignancy characterized by the expansion of a plasma cell clone that localizes to the bone marrow. Stromal cells residing in the bone marrow respond to signals from MM cells and other cell types by producing cytokines and other proteins that stimulate tumor cell growth, survival, adhesion, migration, and drug resistance. We have examined the proteins produced by stromal cells in response to stimulation by bone marrow from patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and MM. Furthermore, we have begun analyzing the properties of one of these proteins, the pro-angiogenic chemokine IL-8, in MM. Methods: Bone marrow aspirates from patients with MGUS (n=3), SMM (n=7), and MM (n=6) were cultured for 48 hours, and the culture supernatants were incubated with stromal cells for an additional 48 hours. Protein levels were analyzed using antibody array and ELISA. Microvessel density (MVD) was determined as a measure of angiogenesis in patient bone marrow samples using CD34 staining. Flow cytometry analysis of MM cell lines and patient bone marrow samples was performed using monoclonal antibodies against IL-8 receptors CXCR1 and CXCR2. Results and Conclusion: We observed a significant increase in stromal cell IL-8 production stimulated by bone marrow cells from patients with active myeloma and a subset of SMM patients (16.67 ± 9.82 ng/ml) in comparison to bone marrow of patients with MGUS and all other SMM patients (0.55 ± 0.17 ng/ml; P=0.0004). Use of an IL-1 inhibitor and recombinant IL-1β demonstrated that IL-8 production was dependent upon IL-1β signaling. Increased BM microvessel density correlated with stimulation of stromal cell IL-8 production (P=0.0005). Furthermore, the majority of MM cell lines (7/9) and MM patient plasma cells were found to express IL-8 receptors CXCR1 and CXCR2. In addition to its function as a pro-angiogenic factor, IL-8 may directly influence MM cells through its CXCR1 and CXCR2 receptors. We conclude that stromal cell IL-8 production parallels MM disease activity, is IL-1β induced, correlates with bone marrow angiogenesis, and may influence MM disease via impact upon both the microenvironment and tumor cells.

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Inhibiting the IGF-1 Receptor Tyrosine Kinase with Picropodophillin: An In Vitro and In Vivo Study in the 5T33MM Mouse Model.

Blood ◽

10.1182/blood.v104.11.640.640 ◽

2004 ◽

Vol 104 (11) ◽

pp. 640-640

Author(s):

Karin Vanderkerken ◽

Eline Menu ◽

Thomas Stromberg ◽

Hendrik De Raeve ◽

Kewal Asosingh ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Mouse Model ◽

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Microvessel Density ◽

Kinase Inhibitor ◽

High Dose

Abstract Multiple myeloma (MM) represents a B-cell malignancy, characterized by monoclonal proliferation of plasma cells in the bone marrow (BM) and is associated with osteolysis and angiogenesis. Insulin-like growth factor-1 (IGF-1), produced by the BM stromal cells, has been described as an important factor in the survival, proliferation and migration of MM cells. The latter process is involved in the homing of the MM cells to the BM. IGF-1 also induces VEGF secretion by the MM cells, thus stimulating angiogenesis in the BM. As IGF-1 is a pleiotropic factor in MM, therapeutic strategies targeting the IGF-1R may be effective as anti-tumor treatments. In this work we investigated the effect of an IGF-1 receptor tyrosine kinase inhibitor (picropodophyllin or PPP1) in the murine, syngeneic 5T33MM model of multiple myeloma. This mouse model is representative for the human disease and can combine in vitro and in vivo studies. We first investigated the effects of PPP on the MM cells in vitro. We and others have previously demonstrated that IGF-1 induced ERK activation, involved in VEGF secretion and proliferation. When the 5T33MM cells were preincubated with 1microM PPP, Western blot analysis demonstrated the blocking of this activation. Furthermore, when the 5T33MM cells were preincubated with PPP for 30 min, IGF-1 induced VEGF secretion and proliferation of the 5T33MM cells were completely blocked. Next, we used the tyrosine kinase inhibitor PPP in vivo. 5T33MM cells were injected intravenously in C57BLKaLwRij mice and the development of the disease was monitored by measuring the serum paraprotein concentration. Mice were either treated with a low (17mM, IP, twice a day) or a high dose of PPP (50mM, IP, twice a day) or with the vehicle (DMSO/oil 9/1) from the day of injection with 5T33MM onward. At week 3, vehicle controls showed signs of morbidity and were sacrificed. The presence of tumor was measured by assessing serum paraprotein concentrations and determining the proportion of idiotype positive cells in the BM by flow cytometry. Angiogenesis was assessed by measuring the microvessel density on CD31 stained paraffin sections. The tumor burden in the bone marrow in the PPP treated mice was 77% lower than in vehicle treated animals (p< 0,0001) and the serum paraprotein concentration was 90% lower (p< 0,0001). The microvessel density in the BM of the PPP treated group was reduced by 60% (p< 0,02). In a separate survival experiment the mice were either treated with the vehicle or with the high dose (50mM) of PPP, from the time of tumor injection. Kaplan-Meier analysis demonstrated a significant increase in survival after treatment with PPP when compared with vehicle (28 vs. 18 days, p<0,001). These data demonstrate that the IGF-1RTK inhibitor PPP possesses strong anti-tumor activity, as demonstrated both in vitro and in vivo in a syngeneic model of multiple myeloma, and may therefore be an effective therapeutic candidate for MM treatment.

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Bone Marrow Microcirculation Parameter Amplitude A of Contrast-Enhanced Dynamic MRI Is a Prognostic Factor for Progressive Multiple Myeloma for Patients with Low Beta2-Microglobulin.

Blood ◽

10.1182/blood.v106.11.5062.5062 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5062-5062

Author(s):

Jens Hillengass ◽

Klaus Wasser ◽

Axel Benner ◽

Stefan Delorme ◽

Christian Zechmann ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Prognostic Factor ◽

Prognostic Value ◽

International Standards ◽

High Temporal Resolution ◽

Significant Prognostic Factor ◽

Prognostic Impact ◽

Newly Diagnosed ◽

Contrast Enhanced

Abstract Introduction: We have previously shown that contrast-enhanced dynamic magnetic resonance imaging (dMRI) microcirculation parameters Amplitude A and distribution rate constant kep are significantly increased in patients with multiple myeloma (MM) compared to healthy controls and correlate with osteolytic bone involvement. Furthermore an elevated Amplitude A is associated with a high plasmacell-infiltration and increased microvessel density in bone marrow. We now evaluated the prognostic value of changes in microcirculation of bone marrow as detected by dMRI for overall (OAS) and event free survival (EFS) in patients with MM. Methods: Between 1999 and 2001 62 patients with progressive MM requiring chemotherapy according to international standards (6 newly diagnosed patients, 56 patients with relapse or refractory disease) were investigated with dMRI of the lumbar spine. OAS and EFS were updated for all patients in February 2005. The estimated median follow up was 4.5 years. All patients underwent standardized dMRI with high temporal resolution (T1w-turboFLASH) before start of therapy. The contrast uptake was quantified using a two compartment model with the output parameters Amplitude A and distribution constant rate kep reflecting bone marrow microcirculation. To examine the prognostic value of the findings of dMRI we used the Proportional Hazards model as proposed by Cox. Results: We recorded a correlation with borderline significance (p-value 0.1) between Amplitude A and EFS. We did not find a correlation of dMRI parameters with OAS. The multivariable analysis of Beta2-Microglobulin, age, Lactat Dehydrogenase (LDH) and Albumin revealed Beta2-Microglobulin as the only statistically significant prognostic factor for EFS in this group of patients. When patients were classified according to high or low Beta2-Microglobulin, Amplitude A was able to provide significant additional information characterizing EFS. Patients with low Beta2-Microglobulin and increased Amplitude A had significant shorter EFS than patients with low Beta2-Microglobulin and low Amplitude A. Conclusion: Our investigations indicate that dMRI parameter Amplitude A which reflects the increased bone marrow microcirculation and angiogenesis is a novel prognostic factor for progressive multiple myeloma in patients with low Beta2-Microglobulin. So a more precise differentiation of patients may be possible through dMRI. The prognostic impact of dMRI for newly diagnosed myeloma patients and patients with monoclonal gammopathie with undetermined signifikance will now be evaluated in a prospective study.

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Soft-Tissue Plasmacytomas in Multiple Myeloma: Incidence, Mechanisms of Extramedullary Spread, and Treatment Approach

Journal of Clinical Oncology ◽

10.1200/jco.2011.34.9290 ◽

2011 ◽

Vol 29 (28) ◽

pp. 3805-3812 ◽

Cited By ~ 166

Author(s):

Joan Bladé ◽

Carlos Fernández de Larrea ◽

Laura Rosiñol ◽

María Teresa Cibeira ◽

Raquel Jiménez ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Soft Tissue ◽

Chemokine Receptors ◽

Experimental Studies ◽

Disease Recurrence ◽

Myeloma Cell ◽

Response To Therapy ◽

High Dose ◽

Prognostic Impact

We provide an overview on soft-tissue extramedullary plasmacytomas (EMPs) in multiple myeloma (MM). We reviewed the incidence of EMPs in MM, myeloma bone marrow homing, possible mechanisms of extramedullary spread, and prognosis and response to therapy. The incidence of EMPs is 7% to 18% at MM diagnosis and up to 20% at relapse. The current notion that EMPs are more frequent after treatment with novel agents remains to be proven, especially considering that different patterns of disease recurrence can emerge as patients live longer in the era of novel drugs. Bone marrow genetic abnormalities are not associated with extramedullary spread per se, which also suggests that microenvironmental interactions are key. Possible mechanisms of extramedullary spread include decreased adhesion molecule expression and downregulation of chemokine receptors. EMPs usually show plasmablastic morphology with negative CD56 expression. High-dose therapy with autologous stem-cell transplantation (ASCT) can overcome the negative prognostic impact of extramedullary disease in younger selected patients. EMPs do not typically respond to thalidomide alone, but in contrast, responses to bortezomib have been reported. The incidence of EMPs in patients with MM is high and is associated with poor outcome in patients treated conventionally. A potential first-line treatment option seems to be a bortezomib-containing regimen followed by ASCT, whenever possible. Experimental studies on the mechanisms of myeloma cell adhesion, myeloma growth at extramedullary sites, and drug sensitivity are priorities for this area of continuing therapeutic challenge.

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Bone Marrow Plasma Cell Assessment before Peripheral Blood Stem Cell Mobilization in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

BioMed Research International ◽

10.1155/2014/982504 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Sung-Eun Lee ◽

Jae-Ho Yoon ◽

Seung-Hwan Shin ◽

Ki-Seong Eom ◽

Yoo-Jin Kim ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Stem Cell ◽

Peripheral Blood ◽

Plasma Cells ◽

Peripheral Blood Stem Cell ◽

Blood Stem Cell ◽

Prognostic Impact ◽

Bone Marrow Plasma ◽

Pbsc Mobilization

The current definition of complete response (CR) in multiple myeloma (MM) includes negative serum and urine immunofixation (IFE) tests and <5% bone marrow plasma cells (BMPCs). However, many studies of the prognostic impact of pretransplant response have not included BMPCs. We evaluated the prognostic impact of BMPC assessment before peripheral blood stem cell (PBSC) mobilization on subsequent transplant outcomes. BMPCs were assessed by CD138, kappa, and lambda immunostaining in 106 patients. After a median followup of 24.5 months, patients with <5% BMPCs had a significantly better progression-free survival (PFS) compared to those with ≥5% BMPCs(P=0.005). Patients with <5% BMPCs + serologic CR showed superior PFS compared to those with <5% BMPCs + serologic non-CR(P=0.050)or ≥5% BMPCs + serologic non-CR(P=0.001). Interestingly, the prognostic impact of BMPCs was more apparent for patients who did not achieve a serologic CR(P=0.042)compared to those with a serologic CR(P=0.647). We concluded that IFE negativity and <5% BMPCs before PBSC mobilization were important factors to predict PFS in patients with MM undergoing ASCT. Particularly, a significant impact of <5% BMPCs was observed in patients who did not achieve IFE negativity.

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