Prognostic impact of bone marrow CD138 immunohistochemistry (IHC) prior to autologous stem cell transplant (ASCT) for multiple myeloma (MM)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8600-8600
Author(s):  
M. C. Foster ◽  
R. Christensen ◽  
J. Egan ◽  
J. Whitley ◽  
W. K. Chiu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Pearson Correlation ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Chi Squared

8600 Background: Low bone marrow plasma cell (BMPC) burden prior to ASCT for MM is associated with favorable outcomes, but is usually determined by morphologic evaluation of marrow aspirates, a method subject to variability in sampling and interpretation. It is unknown if CD138 IHC, a more sensitive measure of BMPC, predicts progression-free survival (PFS), overall survival (OS) or post-ASCT response. Methods: Consecutive patients (n=93) who underwent single ASCT for MM from 2001 to 2008 and had available, stainable bone marrow core biopsies (BMB) obtained <90 days prior to ASCT were included in this single-center retrospective cohort study. BMB and/or clot CD138 IHC staining were reviewed by blinded hematopathologists. Post-ASCT response, PFS, and OS were determined using the International Myeloma Working Group uniform response criteria. Results: Patients were highly cytoreduced prior to ASCT, with 50.5% of pts having 0–5%, 21.5% having 6–10%, 20.4% having 11–20%, and 7.5% having >20% BMPC by CD138 analysis. BMPC% by CD138 IHC correlated with aspirate BMPC% [Pearson correlation coefficient=0.48, 95%CI (0.30, 0.63)]. In 12.6% of patients, BMPC% by CD138 IHC was ≥10% more than the aspirate count. Patients with ≤5% BMPC were more likely to achieve or maintain a CR or VGPR at initial post-ASCT restaging than those with >5% BMPC: Odds Ratio (95% CI) 6.91 (2.12, 22.57), p=. 0005 (chi-squared). With median follow up of 15.4 months for the ≤5% BMPC group and 19.3 months for the >5% BMPC group, 34/93 patients have progressed or died, with no difference between groups. By Kaplan-Meier analysis, PFS was similar regardless of BMPC [3 year estimated PFS (95%CI): ≤5%BMPC, 49.9% (29.4, 70.4) vs. >5%BMPC, 45.5% (26.7, 64.3); HR=1.24 (0.62, 2.49), p=.55, log-rank]. There was no difference in OS [3 year estimated OS (95%CI): ≤5%BMPC, 71.0% (49.7, 92.3) vs. >5%BMPC, 81.8% (66.2, 97.4); HR=0.61 (0.21, 1.78), p=.36, log-rank]. Conclusions: Detection of ≤5% BMPC by CD138 IHC prior to ASCT predicts attainment or maintenance of post-transplant CR/VGPR and correlates with plasma cell morphology. Differences in PFS or OS may emerge with additional follow-up, or if more patients with a higher content of residual plasma cells were transplanted. [Table: see text]

Should CD138 Immunohistochemistry be Standard Recommended Practice for Bone Marrow Evaluation of Plasma Cell Neoplasms?

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S110-S110
Author(s):  
A Vijayanarayanan ◽  
K Inamdar ◽  
M Menon ◽  
P Kuriakose
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Linear Correlation ◽  
Plasma Cells ◽  
Pearson Correlation ◽  
Protein Electrophoresis ◽  
Pearson Correlation Coefficient ◽  
Cell Percentage ◽  
Significant Linear Correlation ◽  
Plasma Cell Neoplasms

Abstract Introduction/Objective Myeloma diagnosis by a pathologist requires 10% plasma cells (PC) or a biopsy proven plasmacytoma in addition to myeloma defining events. PC% &gt; 60% is a biomarker of malignancy under this definition. WHO allows for assesment of plasma cell percentage either by aspirate count or by CD138 immunohistochemistry (IHC). There is lack of consensus on aspirate smear adequacy for PC% estimation. Uneven distribution of plasma cells, hemodilution and/or patchy infiltration can lead to gross underestimation. We compared PC% by aspirate count and CD138 IHC and established corelation with serum protein electrophoresis (SPEP) values. Methods 67 myeloma cases were included after excluding cases with suboptimal or inadequate aspirate smears. Two hematopathologists evaluated the diagnostic marrow (therapy naive) for PC% by aspirate count and CD138 IHC on biopsy/clot section. Corresponding SPEP and Free light chain (FLC) values were obtained. Correlation coefficent was calculated using Pearson correlation coefficient (GraphPad Prism). Results The Ig subtypes included IgG (41/67) and IgA (17/67). 12 cases had available FLC values. Both average and median PC% by CD138 IHC was considerably higher (50%, 52%) compared to aspirate count (29%, 21%). However, PC% by aspirate smear count and CD138 IHC demonstrated a significant linear correlation (r=0.71, p60% by CD138 (and not by aspirate count). Conclusion CD138 IHC based PC% is consistently higher, nevertheless, statistically significant linear corelation is observed between aspirate count PC% and CD138 IHC. A significant linear correlation is observed between CD138 IHC and SPEP (IgG and IgA), however, no such correlation is observed with aspirate count. More cases were diagnosed as myeloma (11%) and higher propotion of cases (35%) had biomarker of malignancy i.e. PC% &gt;60% by CD138 IHC. Based on these findings, we propose estimation of PC% by CD138 immunostain be a recommended standard practice for better clinicopathologic and biologic correlation.

Daratumumab (DARA) maintenance or observation (OBS) after treatment with bortezomib, thalidomide and dexamethasone (VTd) with or without DARA and autologous stem cell transplant (ASCT) in patients (pts) with newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 2.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8004-8004
Author(s):  
Philippe Moreau ◽  
Pieter Sonneveld ◽  
Keyword(s):  
Interim Analysis ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Complete Response ◽  
Autologous Stem Cell Transplant ◽  
Second Primary ◽  
Cell Transplant ◽  
Open Label ◽  
Depth Of Response

8004 Background: D-VTd plus ASCT was approved for transplant-eligible (TE) NDMM based on part 1 of CASSIOPEIA. We report a prespecified interim analysis of CASSIOPEIA part 2: DARA maintenance vs OBS in pts with ≥partial response (PR) in part 1, regardless of induction/consolidation (ind/cons) treatment. Methods: CASSIOPEIA is a 2-part, randomized, open-label, phase 3 study in TE NDMM. Pts received 4 cycles ind and 2 cycles cons with D-VTd or VTd. 886 pts who achieved ≥PR were rerandomized to DARA 16 mg/kg IV Q8W for up to 2 yr (n = 442) or OBS (n = 444) until progressive disease per IMWG. Pts were stratified by ind (D-VTd vs VTd) and depth of response (minimum residual disease [MRD] status and post cons response ≥PR). Primary endpoint was progression-free survival (PFS) after second randomization. This interim analysis assessed efficacy and safety after 281 PFS events. A preplanned hierarchical procedure tested key secondary endpoints: time to progression (TTP), ≥complete response (CR), MRD negativity rates by NGS and overall survival (OS). Results: At median follow-up of 35.4 mo, median PFS was not reached (NR) with DARA and 46.7 mo with OBS (HR 0.53; 95% CI 0.42–0.68; P <0.0001). PFS advantage for DARA was consistent across most subgroups. However, a prespecified analysis showed significant interaction with ind/cons treatment arm ( P< 0.0001). PFS HR for DARA vs OBS was 0.32 (95% CI 0.23–0.46) in the VTd arm and 1.02 (0.71–1.47) in the D-VTd arm. Median TTP was NR for DARA vs 46.7 mo for OBS (HR 0.49; 95% CI 0.38–0.62; P <0.0001). More pts in the DARA vs OBS arm achieved ≥CR (72.9% vs 60.8%; OR 2.17; 95% CI 1.54–3.07; P <0.0001). MRD negativity (in ≥CR pts at 10-5) was 58.6% with DARA vs 47.1% with OBS (OR 1.80; 95% CI 1.33–2.43; P= 0.0001). Median OS was NR in either arm. Most common (≥2.5%) grade 3/4 adverse events (AEs) with DARA vs OBS were pneumonia (2.5% vs 1.4%), lymphopenia (3.6% vs 1.8%), and hypertension (3.0% vs 1.6%). Serious AEs occurred in 22.7% (DARA) vs 18.9% (OBS) of pts; the most common (≥2.5%) was pneumonia (2.5% vs 1.6%). 13 (3.0%) pts discontinued DARA due to an AE. The rate of infusion-related reactions was 54.5% (DARA-naïve pts) and 2.2% (prior DARA pts); 90% were grade 1/2.Second primary malignancies occurred in 5.5% (DARA) vs 2.7% (OBS) of pts. Conclusions: CASSIOPEIA part 2 demonstrated a clinical benefit of DARA maintenance in TE NDMM pts, with significantly longer PFS for DARA vs OBS. With current follow-up, maintenance PFS benefit appeared only in pts treated with VTd as ind/cons. Pts who received D-VTd ind/cons with or without DARA maintenance achieved similar PFS; longer follow-up is needed for PFS2 and OS. DARA significantly increased deeper response and MRD negativity rates vs OBS, and was well tolerated with no new safety signals. Clinical trial information: NCT02541383.

Outcomes and Treatments of Relapsed AL Amyloidosis Following Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1858-1858 ◽  
Author(s):  
Rahma Warsame ◽  
Soo-Mee Bang ◽  
Shaji K. Kumar ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Treatment Options ◽  
Autologous Stem Cell Transplant ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Post Transplant

Abstract Abstract 1858 Systemic light chain amyloidosis (AL amyloidosis) is a condition where clonal plasma cells produce misfolded insoluble immunoglobulin light chains that deposit in various organs causing progressive organ dysfunction. Chemotherapy and autologous stem cell transplant (ASCT) when eligible is the standard treatment options for patients with AL amyloidosis. There are several studies who report long term outcomes of patient post ASCT. However, there is a paucity of literature describing the outcomes of patients who have received ASCT but have relapsed. We performed a retrospective study to assess the outcomes and treatment regimens employed following relapse after ASCT. Between 1996 and 2009, 410 patients received ASCT at the Mayo Clinic as first line therapy. Of those 410 patients 42 patients died within 3 months of transplant, 64 patients died without documented relapse, 158 patients were alive without documented progression, and 146 patients had documented progression. Those 146 patients are the subject of our study. The median time to hematologic relapse was 2 years (range: 0.2–15.5 years). At relapse, 59 patients were treated with IMiD based therapy, 36 with alkylator based therapy, 24 with bortezomib, 15 with steroids, and 5 with second ASCT. The respective hematologic response rates were 58%, 33%, 50%, 53%, and 60%. The remaining six patients were not evaluable for response for one other following reasons: organ transplants; no further therapy; inevaluable disease. With a median post relapse follow up of 3.6 years, the median overall survival (OS) from the first post ASCT relapse was 4.6 years. The median post transplant follow up was 6.1 years, the median OS for these patients was 7.3 years from the time of transplant. These data provide novel information about outcomes after SCT relapse, which should be useful not only for patients and doctors but also for investigators designing studies for salvage therapies post-transplant. Disclosures: No relevant conflicts of interest to declare.

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

Definition of a high-risk population among patients with AL amyloidosis not undergoing autologous stem cell transplantation using bone marrow plasmacytosis and the presence of CRAB.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8516-8516
Author(s):  
Taxiarchis Kourelis ◽  
Morie Gertz ◽  
Martha Lacy ◽  
Francis Buadi ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Autologous Stem Cell Transplant ◽  
Bone Lesions ◽  
High Risk Population ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Beta 2 Microglobulin

8516 Background: There is consensus that light chain amyloidosis (AL) patients with CRAB criteria (abnormal calcium or renal function, anemia or lytic bone lesions) also have multiple myeloma (MM). These patients are typically excluded from AL trials; however, AL patients with >= 10% bone marrow plasma cells (BMPC) in the absence of CRAB are included in trials along with AL with < 10% BMPC. We postulated that the currently used dichotomy may be incorrect and examined the spectrum of AL with and without MM. Methods: We identified 1,272 patients with AL seen within 90 days of diagnosis, between January 1, 2000, and December 31, 2010. We defined the population of patients with coexisting MM based on the existence of CRAB (AL-CRAB-MM). Patients without CRAB were divided into two groups, AL-only (<10% BMPC) and AL-PC-MM (>=10% BMPC). Results: Among the 1,272 patients, 117 (9%) had AL-CRAB-MM, 476 (37%) had AL-PC-MM, and 679 (53%) had AL only. Their respective median overall survivals (OS) were 16.2, 15.8, and 28.4 months (p<0.0001). Autologous stem cell transplant (ASCT) was performed in 203 (30%), 138 (29%) and 23 (20%) patients respectively. Since the outcomes of AL-CRAB-MM and AL-PC-MM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, AL-CRAB-MM and AL-PC-MM retained negative prognostic value independent of age, cardiac stage, prior autologous stem cell transplant (ASCT), beta 2 microglobulin, and dFLC. We next considered whether patients received ASCT as part of their treatment. For those patients who never received ASCT, the 5-year OS were 19%, 14%, and 31%, p<0.001, for AL-CRAB-MM, AL-PC-MM, and AL only respectively. In contrast, for those patients who received ASCT, the respective 5-year OS were 46%, 56%, and 73%, p<0.001. Conclusions: AL patients with >=10% BMPCs have a poor prognosis similar to patients with AL-CRAB-MM and should therefore be considered as AL with MM.

scholarly journals Clinical Significance of Spatial Heterogeneity in Newly Diagnosed and Relapsed Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1607-1607
Author(s):  
Maximilian Merz ◽  
Lei Wei ◽  
Qiang Hu ◽  
Almuth Maria Anni Merz ◽  
Jie Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Board Of Directors ◽  
Clinical Significance ◽  
Stem Cell Transplant ◽  
Plasma Cells ◽  
Cell Transplant ◽  
Specific Detection ◽  
Advisory Committees ◽  
Pet Ct

Abstract Introduction Malignant plasma cells (PC) in multiple myeloma (MM) are not homogeneously distributed in the bone marrow and spatial genomic heterogeneity is an evolving concept in MM. PC for histopathology, cytogenetic and molecular analyses and minimal residual disease (MRD) assessment are usually obtained from the iliac crest. This might introduce bias into diagnostic procedures since focal lesions (FL) occur in more than 80% of patients. Methods In April 2019, we initiated a prospective trial to compare findings from imaging-guided biopsies of FL detected by PET/CT and paired standard sampling from the posterior iliac crests (IC) in patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). Bone marrow aspirates from FL and paired IC samples were analyzed with next-generation flow (NGF) for phenotypic and MRD assessment (sensitivity level 10 -5) post therapy where applicable. PC from both locations were isolated using anti-CD138 magnetic beads and subjected to whole-exome sequencing (WES). Last year, we reported on longitudinal assessment of spatiotemporal immunogenomic heterogeneity in this cohort (https://doi.org/10.1182/blood-2020-142622). With a longer follow-up, we report clinical significance of the respective findings. Results In total, 18 patients (10 NDMM, 8 RRMM) underwent bone marrow aspirates from the IC and imaging-guided biopsies of paired FL. Para-medullary disease (PMD) was observed in 4 patients (1 NDMM, 3 RRMM). Unshared mutations from WES between both locations were identified in every patient. In 12 out of 18 patients (8 NDMM and 4 RRMM), less than 20% of mutations were unshared between IC and FL. Patients with &gt;20% unshared mutations had RRMM and/or a history of PMD. The prognostic significance of unshared mutations was emphasized by lesion-specific detection of high-risk mutations (e.g. TP53) and copy number variations (e.g. gains/losses of Chr 1 and del(17p)). To investigate whether unshared mutations might be accessible for therapeutic interventions, the Drug Gene Interaction Database was queried. More interactions were found in FL (n=886) compared to IC (n=505). Furthermore, we showed spatially divergent existence of PC that contribute to resistance, e.g. against proteasome inhibition through mutations in proteasome subunit PSMC3. Next, we investigated whether MRD assessment from IC and FL provides congruent results. In three patients with MRD-negative IC bone marrow aspirates, we obtained clinically relevant divergent results from FL biopsies. In a patient in complete response (CR) after 5 cycles RVD (Lenalidomide, Bortezomib, Dexamethasone), autologous stem cell transplant (ASCT) and 5 years of lenalidomide maintenance, follow-up PET/CT showed a single new FL in the caudal right ilium. While NGF showed persistent MRD-negativity in the ICt, NGF from the FL revealed monocloncal PC. Since there were no other signs of progressive disease, the patient was followed with close surveillance. Repeat PET/CT after 5 months showed progression of the FL. Serological evaluation confirmed relapse from CR and systemic treatment was initiated. In another patient with MRD-negative IC bone marrow aspirate after 4 cycles RVD, imaging-guided biopsy of a T10 residual FL showed monoclonal PC. Mass spectrometry of supernatants from IC aspirates showed persistence of monoclonal protein in each patient. Second primary malignancies (SPM) were detected by imaging-guided biopsies: Multiple PET-positive FL occurred in a MRD-negative patient after 4 cycles of RD, ASCT and 3 years lenalidomide maintenance. NGF confirmed MRD-negativity in IC and FL aspirates. NGF detected no malignant cells in the peripheral blood but B-lymphoblasts were detected in one of the PET-positive FL. Allogeneic stem cell transplant was performed after induction therapy and there is no detectable MM or B-acute lymphoblastic leukemia. Conclusions We demonstrate clinical significance of spatial heterogeneity in NDMM and RRMM through site-specific detection of mutations and chromosomal aberrations associated with adverse outcome and drug susceptibility. Our findings showing divergent results from MRD assessments in bone marrow and FL underline the critical role of whole-body imaging for follow-up of patients in remission. Sampling plasma cells solely from the IC limits the ability for complete clinical decision-making. Disclosures Merz: Sanofi: Honoraria; Janssen: Honoraria; BMS: Honoraria; Hexal: Honoraria; GSK: Honoraria. Barnidge: The Binding Site: Current Employment. McCarthy: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird: Honoraria, Membership on an entity's Board of Directors or advisory committees; Juno: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Hillengass: Beijing Life Oasis Public Service Center: Speakers Bureau; Beijing Medical Award Foundation: Speakers Bureau; Skyline: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Oncotracker: Membership on an entity's Board of Directors or advisory committees; Curio Science: Speakers Bureau; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Axxess Network: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees.

Autologous stem cell transplantation versus no transplant in patients above 70 with multiple myeloma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20509-e20509
Author(s):  
Christopher Lemieux ◽  
Lori S. Muffly ◽  
David Joseph Iberri ◽  
Andrew Rezvani ◽  
Robert Lowsky ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival ◽  
First Line Therapy ◽  
Included Patient

e20509 Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m2 (75%, n = 40) and 140 mg/m2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients < 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]

t(11;14) Is Infrequent in Long-Term Myeloma Survivors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4890-4890
Author(s):  
Hong Chang ◽  
Sara Samiee ◽  
Xiao Ying Qi ◽  
Qi Long Yi ◽  
A. Keith Stewart
Keyword(s):  
Stem Cell ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Chain Gene ◽  
Cell Transplant ◽  
Cell Transplants ◽  
Gene Switch ◽  
Chromosome 13Q

Abstract The translocation t(11;14) involving immunoglobulin heavy chain gene switch region and cyclin D1 is the most common IgH translocation (15–20%) in multiple myeloma (MM). MM patients with t(11;14) are considered to have a better prognosis when treated with either conventional chemotherapy or autologous stem cell transplant. In contrast, patients with chromosome 13q deletions (40–50% of patients) have a poor prognosis. To address whether long-term survivors of MM more frequently harbor a t(11;14) but not 13q deletions, we used cytoplasmic Ig-enhanced interphase fluorescence in situ hybridization (cIg-FISH) to evaluate clonal plasma cells for t(11;14) and 13q status from 20 long-term survivor MM cases. These patients met the diagnostic criteria for MM before May of 1996 and have survived more than 8 years. The 11 male and 9 female had a median age of 52 (range 39–62) at diagnosis. Eleven had IgG, 6 IgA, 2 free light chains, and 1 non-secretory. Of the 20 patients, 17 received autologous stem cell transplants. The median duration between diagnosis and transplant was 24 months (range 5–149), the median progression free survival (PFS) after transplant was 32 months (range, 1–62). One patient died 3 years after transplant and 10 years after diagnosis. The 19 other patients remain alive. Translocation t(11;14) was detected in only one of 20 patients with 94% of clonal plasma cells involved. This patient had PFS of 20 months after transplant and is alive 3 years post-transplant and 10.5 years after diagnosis. Chromosome 13q deletions were detected in only 3 cases (15%). Despite its association with a better prognosis, our results indicate that t(14;14) is infrequent in long-term myeloma survivors. As anticipated, 13q deletions were infrequent.

Cyclin D1 Immunohistochemistry Identifies a Subset of Plasma Cell Myeloma with Superior Overall Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4854-4854
Author(s):  
James R. Cook ◽  
Eric D. Hsi ◽  
Raymond R. Tubbs ◽  
Sarah Worley ◽  
Mohamad A. Hussein
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Plasma Cell ◽  
Plasma Cells ◽  
D1 Protein ◽  
Progression Free Survival ◽  
Plasma Cell Myeloma ◽  
Free Survival ◽  
Cyclin D1 Protein

Abstract The expression of Cyclin D1 is dysregulated in approximately half of cases of plasma cell myeloma due to translocations, aneusomy, or other abnormalities. Recent studies using quantitative mRNA analysis have suggested that increased Cyclin D1 mRNA expression is associated with a favorable prognosis. Previous attempts to examine the significance of cyclin D1 protein expression by immunohistochemistry have been hampered by the use of antibodies with weak staining and high background. In this study, we employ a newly available, commercial antibody that gives superior staining in B5 fixed tissues. We performed immunohistochemistry for Cyclin D1 on bone marrow core biopsies from a series of 44 newly diagnosed plasma cell myeloma patients who were uniformly treated on a Phase II study of rituxan, melphalan and prednisone. 22 patients (50%) were positive for Cyclin D1, defined as any plasma cells with positive nuclear staining. Cyclin D1 positive and negative cases displayed no significant differences in the initial levels of β2m (3.6±0.5 mg/L vs. 3.5±0.5 mg/L, p=0.860), number of bone marrow plasma cells (63±5.5% vs. 47±6.2%, p=0.063), or proportion of cases classified as SWOG stage 3-4 (2 of 22 (9%) vs. 5 of 22 (23%), p=0.412). The cyclin D1 positive cases displayed a superior overall survival with an estimated 3-year survival of 95% for Cyclin D1 positive cases versus 56% for Cyclin D1 negative cases (p=0.032). The cyclin D1 positive cases also displayed a trend towards better progression-free survival (median progression free survival of 15.7 months for Cyclin D1 positive versus 12.8 months for Cyclin D1 negative, p=0.13). In a Cox proportional hazards regression model, used to compare the effect of Cyclin D1 protein expression on overall survival time while adjusting for stage, the Cyclin D1 positive patients continued to show a strong trend to better overall survival (p=0.062). This study demonstrates that cyclin D1 immunohistochemistry, which could be readily performed in most pathology laboratories, is capable of identifying a subset of plasma cell myeloma with a favorable survival. Additional studies are ongoing to determine if these results can be generalized to other forms of therapy. If confirmed, routine cyclin D1 immunohistochemistry at the time of diagnosis may offer important prognostic information that could identify lower risk patients for whom less intensive therapies might be appropriate.

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.

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