scholarly journals Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation By Conventional Microscopy in Multiple Myeloma after High Dose Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3396-3396
Author(s):  
Camille Claracq ◽  
Murielle Roussel ◽  
Benjamin Hébraud ◽  
Michel Attal ◽  
Herve Avet Loiseau ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cells ◽  
Survival Outcomes ◽  
High Dose ◽  
High Dose Therapy ◽  
Impact On Survival ◽  
Bone Marrow Plasma ◽  
Conventional Microscopy

Abstract Impact on Survival Outcomes of Bone Marrow Plasma Cells Percentage and Morphology Evaluation by Conventional Microscopy in Multiple Myeloma after High Dose Therapy. Background: The achievement of at least CR is a crucial step for a long-lasting response and prolonged survival after autologous stem cell transplantation (ASCT) in patients (pts) with multiple myeloma (MM). The current definition of complete remission (CR) or better in MM requires a negative serum and urine immunofixation (IF) and <5% bone marrow plasma cells (BMPCs). Additional prognostic tools are related to sFLC ratio, immunophenotypic and molecular evaluations, when possible. As BMPCs levels could differ if evaluated by BM biopsy or aspirate (the latter supposed to underestimate BMPCs count), we aim to determine a new threshold for PCs in BM aspirate and to determine whether it could be, in association with PCs morphology by standard microscopic evaluation, an easy and cheap surrogate marker for outcome, in the absence of sFLC assay and/or phenotypical-molecular analysis for MRD. Material and Methods: 191 de novo MM pts treated between 2003-2010 in Toulouse's myeloma and BMT center with adequate clinical and biological data were retrospectively studied. Responses were evaluated at day 100 after ASCT in all pts according to IMWG criteria. BM examination comprised PCs count, BM cellularity, and the presence of PCs dysmorphy. Progression free survival (PFS) was calculated from the start of therapy until progression, death or last follow-up. Overall survival (OS) was calculated from the start of therapy until death or last follow-up. The Kaplan-Meier method was used to estimate the survival distribution. Results: Baseline demographics and initial disease characteristics are summarized in table 1. Median follow-up is 6 years. At the completion of ASCT, 49 pts (26%) achieved CR, 89 (47%) VGPR and 41 (21%) PR; 57 pts (30%) had a negative serum IF (sIF). Overall, 151 pts relapsed and 68 died with median PFS and OS of 36 and 99 months, respectively. At D100, median PCs count was 1% (range 0-23%): 1% (0-3%) in CR pts, 1% (0-23%) in VGPR pts, and 1.5% (0-7%) in PR pts. Only 1 pt with negative sIF had 5% BMPCs and a positive urine IF, and was assessed as VGPR. Overall, 55 negative sIF pts had 2% or less BMPCs. The number of 2% of BMPCs was found to be predictive, irrespective of response. Median PFS was 39 vs 21 months if BMPCs is > 2% (p<.001) and median OS was 99 months vs 66 (ns). We further aimed to evaluate the impact of PCs dystrophy on survival outcomes in 176 evaluable pts. PCs dysmorphy was reported in 29 pts including 3 pts in CR, 9 VGPR and 13 PR, respectively. All except 2 pts relapsed, with a median PFS of 26 mo (vs 39, p=.002). Nineteen died with a median OS of 60 mo (vs 101, p=.003). For pts at least in VGPR, median PFS was 26 mo in case of PCs dysmorphy vs 40 mo (p=.004) and median OS was 59 mo vs not reached (p=.005). (see figures) Conclusion: conventional microscopy of BM aspirate is a useful and rapid tool to evaluate the percentage of PCs and their morphology as a first step to assess the residual tumor mass in patients with MM after ASCT, and it constitutes a good predictor for disease progression and survival outcome. These findings have to be confirmed and the exact threshold of PCs remains to be determinate in a large prospective study. Table Characteristics n=191 Sex: M/F, n 109/82 Median age, y (range) 57 (31–68) Isotype, n (%) IgG, IgA, LC 123 (64), 35 (18), 28 (15) ISS stage, n (%) n= 158 I, II, III 85 (54), 40 (25), 33 (21) Median bone marrow plasma cells, % (range) 23 (1-96) Median b2-microglobulin, mg/L (range) 3.1 (1.3–19.4) Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

High Dose Melphalan with Autologous Stem Cell Transplantation Overcomes Poor Prognosis of Primary Amyloidosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1350-1350
Author(s):  
Simrit Parmar ◽  
Mubeen Khan ◽  
Gabriela Rondon ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Plasma Cells ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematologic Response ◽  
Bone Marrow Plasma ◽  
Organ Response ◽  
High Dose Melphalan

Abstract Abstract 1350 Background: Systemic Primary AL Amyloidosis is a rare but potentially fatal disease resulting from tissue deposits of amyloid fibrils derived from monoclonal immunoglobulin light chains. High-dose melphalan followed by autologous hematopoietic stem cell transplant (auto HCT) is associated with hematologic and organ responses and improved survival. Methods: In this retrospective analysis we identified 46 patients with primary AL amyloidosis who received auto HCT between 01/1998 to 05/2010 at MDACC. Organ responses were determined using Amyloidosis Consensus Criteria. Results: The median age at auto HSCT was 56 years (34-74) where 61% were males and 35% were older than 60 years of age. 61% had lambda light chain restriction and only 4% had cytogenetic abnormalities. Disease characteristics are summarized in Table 1. The median time from diagnosis to auto HCT was 6.6 months (2.2-29.4 months). 22 pts (47.8%) had one organ, 19 pts (41.3%) had 2 organ and 4 pts (8.7%) had 3 organ involvement. 11 pts (23.9%) had heart and 35 pts (76.1%) had kidney involvement. The median follow up from the time of diagnosis was 22.4 months and from time of auto HCT was 16.7 months. High dose Melphalan dose was 200mg/m2 in 24 pts (52%) and 140mg/m2 in 22 (47.8%). There were 4 early deaths and 4 pts whose follow up was less than 3 months and their response was not assessed. Out of the 38 evaluable patients, the post-transplant organ responses were as follows ≥PR 25(66%), ≥stable disease 35(92%) (Table2). The hematologic responses were: CR=5 (13%), ≥VGPR=10(26%), ≥PR=26 (68%), ≥SD=37(97%). One patient had progressive disease. There was a correlation between organ response and hematologic response (chi square;p<10-3). The day-100 treatment related mortality (TRM) was 8.7% and 1-yr TRM was 13%. The median progression-free (PFS) and overall survival (OS) from auto HCT was 73.8 months and not reached (from transplant). The median PFS and OS from diagnosis were 93 months and 59.8 months respectively. In multivariate analysis, heart involvement (p=0.01), female sex (p=0.011), age ≥60 years (p=0.002), bone marrow plasma cells≥10% (p=0.043) and Beta-2 microglobulin>3.5mg/l (p=0.02) were associated with poor OS. Improved OS correlated with organ response (52.6 vs 11.4 months; p=0.01) and hematologic response (52.6 vs.6.1months; p=0.002). Hemoglobin <10 g/dl (p=0.047), bone marrow plasma cells≥10% (p=0.043) and age≥60 years (p=0.075) were associated with shorter PFS. Hematologc response (p=0.48) and organ response (p=0.12) were not associated with improved PFS. Conclusion: In this analysis the outcome of patients with primary systemic AL amyloidosis was durable with auto HCT with acceptable mortality risk and improved survival. Disclosures: No relevant conflicts of interest to declare.

Serum Free Light Chain Ratio in Distinguishing Smoldering Multiple Myeloma From Active Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3948-3948
Author(s):  
Jeremy T Larsen ◽  
Shaji Kumar ◽  
S. Vincent Rajkumar
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Predictive Value ◽  
Plasma Cells ◽  
Organ Damage ◽  
End Organ Damage ◽  
Cut Point ◽  
Smoldering Multiple Myeloma ◽  
Bone Marrow Plasma

Abstract Abstract 3948 Background: Smoldering multiple myeloma (SMM) is an asymptomatic precursor disease of multiple myeloma, and is defined by excess bone marrow plasma cells and monoclonal protein without evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions [CRAB]). The identification of SMM patients with more aggressive underlying disease remains a challenge. We hypothesize that SMM is a clinical entity comprised of both premalignant, high-risk MGUS and early multiple myeloma in transition to malignant disease, which may be differentiated with the use of the serum FLC (FLC) ratio. Methods: This was a retrospective analysis of 586 patients with newly diagnosed SMM from 1970–2010 with available stored serum samples around the time of diagnosis to be utilized for quantification of FLC ratios. SMM was defined by the International Myeloma Working Group 2003 definition; serum M-protein ≥ 3 g/dL and/or ≥ 10% bone marrow plasma cells with no evidence of CRAB features. The immunoglobulin FLC assay (Binding Site, U.K.) was used for testing. The FLC ratio was calculated as κ/λ (reference range 0.26–1.65). The involved/uninvolved FLC ratio was recorded to simplify the reporting of data. Receiver Operating Characteristics (ROC) curves were created to assess the ability of the FLC ratio to discriminate patients who progressed to symptomatic multiple myeloma (MM) in the first 2 years or at any point during follow-up versus patients without evidence of progression. Patients with less than 24 months follow-up without progression were censored. The optimal diagnostic cut-point for FLC involved/uninvolved ratio to identify patients with progressive disease from the ROC curve was >88.6 (equivalent to <0.011 or >88.6). For ease of clinical application, the optimal value for involved/uninvolved FLC ratio was rounded to >100. Time to progression (TTP) from date of the initial FLC to active MM was calculated using Kaplan-Meier analysis and compared to patients with a high (>100) and low (<100) involved/uninvolved FLC ratio at time of SMM diagnosis. TTP within 24 months of the initial FLC was also calculated. Results: During the study period, 54% of patients progressed to active MM. On ROC analysis, a cut-point of >100 corresponded to a sensitivity of 25% (95% CI, 20.5–30.4) and specificity of 99.3% (97.3–99.9), with positive likelihood (+LR) ratio of 33.9 (38.1–41.0), negative likelihood ratio (−LR) of 0.75 (0.2–3.0), positive predictive value (PPV) of 97.6 (91.5–99.7) and negative predictive value of 53.0 (48.5–57.4). Using the ROC to assess progression to MM within 24 months (Figure 1), sensitivity was 29.6% (23.5–36.4), specificity 94.5% (91.7–96.5), +LR 5.36 (4.3–6.6), -LR 0.75 (0.5–1.1), PPV 85.8 (77.7–91.8), and NPV 54.3 (49.8–58.9). Median TTP to active MM in the FLC >100 group was 15 months (9–17) versus 52 months (44–60) in the FLC <100 group (p <.0001) [Figure 2]. In the FLC ratio >100 group, progression at 1 year was 47%, 76% at 2 years, and 90% at 3 years. Only 25% of the FLC <100 patients had progressed at 2 years. The most common progression event was bone disease (42%), followed by anemia (26%), renal impairment (23%), and hypercalcemia (5%). Conclusion: Elevation of the FLC ratio >100 (or <0.01) is highly specific for the future development of active MM, with 76% of these patients developing end-organ damage requiring therapy within 2 years. Risk of transformation to MM in the FLC <100 group was similar to previously reported rates of 10% per year for the first 5 years. Development of an FLC ratio >100 is associated with increasing disease burden and in this study behaved in a malignant fashion rather than a precursor state. The FLC is a simple and useful predictor of progression to MM in SMM, and patients with FLC ratios of <0.01 or >100 within the first 2 years of SMM diagnosis should be monitored especially closely. Future studies are needed to determine optimum cutoffs for FLC ratio to where a change in definition of MM could be considered. Disclosures: No relevant conflicts of interest to declare.

The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3396-3396 ◽  
Author(s):  
Robert Kyle ◽  
Ellen Remstein ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
M Protein ◽  
Cell Content ◽  
Bone Marrow Plasma ◽  
M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were &gt; 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein &lt; 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells &lt; 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p &lt; 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p &lt; 0.001) and reduction of uninvolved immunoglobulins (p &lt; 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

The impact of body mass index on the risk of early progression of smoldering multiple myeloma to symptomatic myeloma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8032-8032
Author(s):  
Wilson I. Gonsalves ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Martha Lacy ◽  
Francis Buadi ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Multiple Myeloma ◽  
Bone Marrow ◽  
Body Mass ◽  
Plasma Cells ◽  
Progression Rate ◽  
Early Progression ◽  
Bone Marrow Plasma ◽  
The Impact

8032 Background: Human adipocytes can contribute directly to the in vitro growth and progression of multiple myeloma (MM) cell lines. Clinically, an elevated body mass index (BMI) has been associated with an increased risk of MGUS and a shorter time to progression (TTP) of MGUS to MM. However, the impact of BMI on the risk of early progression to MM from a more advanced plasma cell disorder such as smoldering MM (SMM) remains unknown. Methods: This study included patients (pts) with a known or new diagnosis of SMM evaluated at the Mayo Clinic, Rochester from January 2000-December 2010. Pts were classified based on their BMI as: normal (< 25) and elevated (>/= 25) BMI. Progression to symptomatic MM was defined by the development of hypercalcemia, renal insufficiency, anemia or lytic bone lesions. Results: There were 306 pts with a diagnosis of SMM who were included in this analysis. The median follow up was 106 months. There were 203 (66%) pts who progressed to symptomatic MM at last follow up. The median BMI of the group was 27.5 (Range: 17.2 – 56.4). There were 228 (75%) pts with an elevated BMI. There were 76 (28%) pts who had myeloma defining events (MDEs) such as a serum free light chain ratio > 100 or > 60% clonal bone marrow plasma cells at initial evaluation. MDEs were present in 17% and 33% of pts with a normal and elevated BMI respectively (P = 0.011). The median TTP of SMM to MM in pts with a normal and elevated BMI was 64 and 36 months respectively (P = 0.0006). The 2-year progression rate of SMM to symptomatic MM in pts with a normal and elevated BMI was 16% and 42% respectively (P < 0.0001). Upon limiting the analysis to only SMM pts without MDEs at initial evaluation (N =187), the 2-year progression rate to symptomatic MM with a normal and elevated BMI was 15% and 33% respectively (P = 0.013). In a multivariable model, only elevated BMI (P = 0.004) and increasing clonal bone marrow plasma cells (P = 0.001) was statistically significant in predicting for a 2-year progression to MM. Conclusions: SMM pts with an elevated BMI appear to have a higher risk of early progression to MM than those with a normal BMI. This study provides evidence of a potentially modifiable risk factor for the progression of SMM to MM and warrants confirmation in larger studies.

scholarly journals Multiple myeloma: circulating lymphocytes that express plasma cell antigens

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 352-356
Author(s):  
GJ Ruiz-Arguelles ◽  
JA Katzmann ◽  
PR Greipp ◽  
NJ Gonchoroff ◽  
JP Garton ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Peripheral Blood Lymphocytes ◽  
Tumor Burden ◽  
B Cell Differentiation ◽  
Blood Lymphocytes ◽  
Bone Marrow Plasma

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1–3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

scholarly journals Prognostic value of bone marrow angiogenesis in patients with multiple myeloma undergoing high-dose therapy

2004 ◽  
Vol 34 (3) ◽  
pp. 235-239 ◽  
Author(s):  
S Kumar ◽  
M A Gertz ◽  
A Dispenzieri ◽  
M Q Lacy ◽  
L A Wellik ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Prognostic Value ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Delphi-Panel Analysis of Appropriateness of High-Dose Therapy and Bone Marrow Autotransplants in Newly Diagnosed Multiple Myeloma

1999 ◽  
Vol 33 (5-6) ◽  
pp. 511-519 ◽  
Author(s):  
Robert Peter Gale ◽  
Rolla Edward Park ◽  
Robert W. Dubois ◽  
Kenneth C. Anderson ◽  
William M. Audeh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Delphi Panel ◽  
High Dose ◽  
Panel Analysis ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy

Abstract 4762: Deficient double strand breaks repair of bone marrow plasma cells correlates with better clinical outcome of multiple myeloma patients

2014 ◽  
Author(s):  
Maria Gkotzamanidou ◽  
Masood Shammas ◽  
Evangelos Terpos ◽  
Sathees C. Raghavan ◽  
Kenneth C. Anderson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Outcome ◽  
Plasma Cells ◽  
Double Strand Breaks ◽  
Strand Breaks ◽  
Bone Marrow Plasma

Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies

2000 ◽  
Vol 18 (5) ◽  
pp. 947-947 ◽  
Author(s):  
Ivana N. M. Micallef ◽  
Debra M. Lillington ◽  
John Apostolidis ◽  
John A. L. Amess ◽  
Michael Neat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cell ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Progenitor ◽  
Acute Myelogenous ◽  
Cell Support

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q−, 15 had −7/7q−, seven had −18/18q−, seven had −13/13q−, and four had −20/20q−. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

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