scholarly journals Assessment of tumoral plasma cells in apheresis products for autologous stem cell transplantation in multiple myeloma

2016 ◽  
Vol 51 (8) ◽  
pp. 1143-1145 ◽  
Author(s):  
S Wuillème ◽  
A Lok ◽  
N Robillard ◽  
P Dupuis ◽  
V Stocco ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cells

Flow Cytometric Disease Monitoring in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation: A Retrospective Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5014-5014
Author(s):  
Hong Liu ◽  
Constance M. Yuan ◽  
Raul C. Braylan ◽  
Myron N. Chang ◽  
John R. Wingard ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cells ◽  
Flow Cytometric ◽  
Before And After

Abstract The persistence of abnormal neoplastic plasma cells (APC) detectable in the bone marrow by flow cytometry at more than 3 months after autografting for multiple myeloma (MM) has been reported to predict early disease progression. In this study, we retrospectively reviewed the flow cytometric data from bone marrow aspirates of MM patients before and after autologous stem cell transplantation (ASCT). Light scatter properties and CD38 expression were used to identify plasma cells, and CD19/CD45/CD56 further distinguished normal plasma cells (NPC) from APC. Conventional response criteria (Blade criteria) and survival data were also collected. Forty-seven (47) patients treated with the same conditioning regimen were screened. Median follow up from ASCT was 19 months. After ASCT, 66% (31/47) patients achieved complete remission (CR)/very good partial remission (VGPR), as compared to only 36% (17/47) prior to ASCT. In 39 patients with data before and after ASCT, all 39 (100%) had a detectable abnormal plasma cell population identified phenotypically by flow cytometry prior to ASCT. Of these patient, 18/39 (46%) had greater than 30 APC and these patients had significantly shorter PFS independent of other covariates (1-sided P=0.036, 2 sided P=0.072, logrank). Twenty-six out of 39 patients (67%) also had detectable NPC. Following ASCT, the number of patients with detectable NPC increased to 35/39 (89%), while 3/39 (8%) had no detectable NPC and 1/39 (3%) had neither NPC or APC. The proportion of APC decreased significantly after transplant (81% prior to transplant vs. 59% post-transplant, P=0.008, 2 tailed t-test). Patients with a APC to NPC ratio < 1 post transplant has higher PFS rate at 2 year (54%) when compared to patients with higher APC/NPC ratio (29% PFS at 2 year), however, the difference is not statistically significant. In addition to the presence of APC, the ratio of APC to NPC, age, beta-2 microglobulin levels, and the presence of normal immunoglobulin levels were analyzed. Patients who achieved CR/VGPR after transplant had significantly longer PFS (23 months vs. 11 months, P=0.03). All other covariates were not found to be significant. Because only 10 deaths were observed, covariate analysis for OS was not feasible. In conclusion, the recovery of NPC after ASCT is seen in a substantial propotion of patients with a trend towards better PFS in patients with low APC/NPC ratio. On the other hand, the presence of a significant population of APC (> 30) prior to transplant appears to correlate with poorer PFS in MM patients.

scholarly journals Tandem Autologous Stem Cell Transplantation for Multiple Myeloma Patients Based on Response to Their First Transplant—A Prospective Phase II Study

2014 ◽  
Vol 8 ◽  
pp. CMO.S16835 ◽  
Author(s):  
Michael Byrne ◽  
Donya Salmasinia ◽  
Helen Leather ◽  
Christopher R. Cogle ◽  
Amy Davis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Phase Ii ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Prospective Phase

In this prospective phase II clinical trial, multiple myeloma (MM) patients were randomized to receive a second (tandem) autologous stem cell transplantation (ASCT) based on whether they achieved a partial response or worse (≤PR) following initial ASCT (ASCT1). Patients who achieved a very good partial response or better (≥VGPR) had salvage ASCT at relapse. Seventy-five patients received conditioning therapy and ASCT1. A total of 44 patients (59%) achieved ≥VGPR, whereas 31 patients entered ≤PR and were offered tandem ASCT. In all, 20 patients agreed to tandem ASCT. Demographic and clinical characteristics were similar between the two cohorts except for median lactate dehydrogenase (LDH) ( P = 0.0141) and percentage of marrow plasma cells before ASCT1 ( P = 0.0047), both lower in the ≥VGPR group. Intent to treat analysis showed that patients who achieved ≥VGPR to ASCT1 had a trend toward improved progression-free survival (PFS) (37 vs. 26 months, P = 0.078) and superior overall survival (OS) (not reached vs. 50 months, P = 0.0073). Patients with ≤PR who declined tandem transplantation had shortened PFS (20 vs. 28 months, P = 0.05) but similar OS (53 vs. 57.5 months, P = 0.29) compared to those who received it. Thus, a favorable clinical response to ASCT1 identifies a low-risk group with superior long-term prognosis despite similar PFS.

scholarly journals UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

2012 ◽  
Vol 4 (1) ◽  
pp. e2012069 ◽  
Author(s):  
Patrizia Tosi ◽  
Manuela Imola ◽  
Mianulli Anna Maria ◽  
Simona Tomassetti ◽  
Anna Merli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cells ◽  
Standard Of Care ◽  
New Drugs ◽  
High Dose ◽  
Hematopoietic Stem

Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

Loss of Chromosome 1p21 Band Is Associated with Disease Progression and Poor Survival in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1702-1702
Author(s):  
Hong Chang ◽  
Connie Qi ◽  
Allan Jiang ◽  
Wei Xu ◽  
Young Trieu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Risk Factor ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Independent Risk Factor ◽  
Plasma Cells ◽  
Cell Transplant

Abstract Amplifications involving chromosome 1q and deletions involving 1p are frequent events in multiple myeloma (MM). The pathogenesis and clinical significance of these anomalies are largely unknown. As karyotyping and SNP based mapping analysis identify a minimal common deletion region involving the 1p21 locus, we investigated the prevalence and prognostic significance of del(1p21) in a cohort of 235 MM patients undergoing highdose therapy and autologous stem cell transplant at our institution. Fluorescence in situ hybridization combined with cytoplasmic light chain detection (cIg-FISH) was used to evaluate clonal plasma cells for 1p21 deletion as well as other myeloma-associated chromosomal abnormalities. In addition, 1p21 status was evaluated in 16 patients with of monoclonal gammopathy of undetermined significance (MGUS) and 41 patients with plasma cell leukemia (PCL). CIg-FISH detected hemizygous 1p21 deletions in 18% of the MM, 34% of PCL but none of the MGUS cases. In MM, the median percentage of clonal plasma cells harboring del(1p21) was 55% (range 20–95%). The presence of 1p21 deletions was strongly correlated with 1q21amplification (p=0.01), and marginally correlated with del(p53) (p=0.05) or t(4;14) (p= 0.06), but not with del(13q) or t(11;14). There was no association between del (1p21) and other biological factors including age, gender, Hb, albumin, C-reactive protein, beta-2 microglobulin level, isotype or bone marrow plasmacytosis. The median follow-up in this cohort was 36 months. Patients with 1p21 deletions had significantly shorter progression-free (median 14.2 vs. 25.4 months, p&lt;0.001) and overall survivals (median 39.4 vs. 82.3 months, p=0.001) than those without such deletions. In multivariate analysis, del(1p21) was an independent risk factor for progression free (p= 0.003) and overall survivals (p=0.013) after adjusting for del(13q), del(p53), t(4;14) and 1q21 amplification. 1q21 amplification was significant risk factor in univariant analysis for either progression-free or overall survivals, but did not remain as an independent risk factor in multivariant model adjusting for other genetic risk factors. Our results indicate that del(1p21) is an independent poor prognostic factor associated with disease progression in MM. We recommend include this genetic aberration as part of a routine work-up in the risk-stratification of MM patients receiving autologous stem cell transplantation.

The Reason Why High-Dose Melphalan Followed by Autologous Stem-Cell Transplantation Produces Good Response in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5201-5201
Author(s):  
Yoshiaki Kuroda ◽  
Akira Sakai ◽  
Yoshiko Okikawa ◽  
Shoso Munemasa ◽  
Yuta Katayama ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Plasma Cells ◽  
High Dose ◽  
Myeloma Cells ◽  
Before And After ◽  
High Dose Melphalan

Abstract Multiple myeloma (MM) is the result of a clonal proliferation of plasma cells. And myeloma cells have been shown to be heterogeneous with regard to their morphology and biological character. Recently, correlations between molecular subtypes and prognosis have been identified as a good prognosis with t(11;14) and a poor prognosis with t(4;14) and t(14;16) besides chromosome 13 abnormalities. But it is still unclear how those molecular events work on the prognosis of MM patients. And it is difficult to find the heterogenesity of myeloma cells in each MM case by molecular analysis. Twenty years ago Greipp et al. classified myeloma cells as mature, intermediate, immature and plasmablastic type, and then they showed that plasmablastic morphology is an independent predictor of poor survival rate after autologous stem-cell transplantation. On the other hand, Kawano et al. classified myeloma cells into three types by their phenotype (Huang N, Blood82: 3721, 1993, Kawano MM, Blood82: 564, 1993); immature (MPC1−, CD49e−, CD45−/+), intermediate (MPC1+, CD49e−, CD45−), and mature (MPC1+, CD49e+/−, CD45+). This classification according to the phenotype is good correlation with that by morphology. And they indicated that immature myeloma cells have activity of proliferation. We analyzed both phenotypic and morphological findings of myeloma (plasma) cells consecutively before and after chemotherapy in 23 MM cases in order to find what kind of drug might be useful to reduce the main population of heterogeneous myeloma cells. The phenotypic and morphological analysis were performed before and after ten-cycles of melphalan-predonine (MP) in 2 cases, three or four-cycles of vincristine-doxorubicin-dexamethasone (VAD) in 10 cases, high-dose cyclophosphamide (HD-CPA) for stem cell harvest after three or four cycles of VAD in 5 cases, high-dose melphalan followed by autologus stem-cell transplantation (HD-Mel+ASCT) in 6 cases, and administration of thalidomide at least for two months in 7 cases. First, total myeloma cells decreased after VAD, however, immature myeloma cells increased relatively (9/10). Second, HD-CPA was not effective in reducing myeloma cells furthermore after VAD (5/5). Third, HD-Mel+ ASCT could reduce immature myeloma cells clearly (4/6). In particular, a less than 5% reduction of immature myeloma cells after this course were important for the long duration of good response, but the residue of immature myeloma cells was a predictor of progressive disease (PD). Interestingly, MP was also useful to reduce immature myeloma cells (2/2). Finally, thalidomide was effective in reducing mature and intermediate myeloma cells (3/6), but not effective in immature myeloma cells. In conclusion, melphalan, if it is high-dose, has more effects on immature myeloma cells compared with those of other drugs, which might be a reason of the superiority of HD-Mel+ASCT over conventional treatment in terms of the response rate and event-free survival.

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