Presence Of Abnormal Plasma Cells In Peripheral Stem Cell Harvest Products Predict Early Relapse Following Autologous Stem Cell Transplantation In Patients With Multiple Myeloma

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.

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

Clinical Medicine Insights Oncology ◽

10.4137/cmo.s16835 ◽

2014 ◽

Vol 8 ◽

pp. CMO.S16835 ◽

Cited By ~ 5

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.

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

Bone Marrow Transplantation ◽

10.1038/bmt.2016.74 ◽

2016 ◽

Vol 51 (8) ◽

pp. 1143-1145 ◽

Cited By ~ 5

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

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

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2012.069 ◽

2012 ◽

Vol 4 (1) ◽

pp. e2012069 ◽

Cited By ~ 2

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.

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Pulmonary Lymphangitic Spread of Multiple Myeloma as Early Relapse after Autologous Stem Cell Transplantation

Case Reports in Hematology ◽

10.1155/2021/5590975 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Bicky Thapa ◽

Gulrayz Ahmed ◽

Meera Mohan ◽

Volodymyr Shponka ◽

Parameswaran Hari

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Clinical Outcome ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Lung Involvement ◽

Early Relapse ◽

First Relapse ◽

Pleural Involvement

Clinical relapses early after autologous stem cell transplantation portrays an inferior clinical outcome. Early relapse in this setting with extramedullary disease (EMD) of lung involvement in multiple myeloma is rare. To our knowledge, this is the first reported case of lymphangitic spread of myeloma with pulmonary parenchymal and pleural involvement occurring at first relapse.

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

Blood ◽

10.1182/blood.v112.11.1702.1702 ◽

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<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.

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Significance of Salvage Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma: A Nationwide Retrospective Study in Japan

Acta Haematologica ◽

10.1159/000484652 ◽

2018 ◽

Vol 139 (1) ◽

pp. 35-44 ◽

Cited By ~ 3

Author(s):

Tsuyoshi Muta ◽

Toshihiro Miyamoto ◽

Tomohiko Kamimura ◽

Yoshinobu Kanda ◽

Masaharu Nohgawa ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Retrospective Study ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Performance Status ◽

Staging System ◽

Early Relapse ◽

Time To Relapse

Autologous stem cell transplantation (ASCT) has been employed for patients with relapsed multiple myeloma (MM) after up-front ASCT. The present retrospective study aimed to examine the survival benefit from salvage ASCT. Among 446 patients with relapsed MM after up-front single ASCT, 70 patients received salvage ASCT, the employment of which reduced the risk of mortality after relapse (p = 0.041). Using the parameters before initial ASCT, the advantage of salvage ASCT compared to standard therapy was confirmed in the subgroup with an international staging system stage of I or II (p = 0.040), good performance status (PS; p = 0.043), or no/mild renal comorbidity (p = 0.029). The advantage of salvage ASCT was also confirmed in the subgroup excluding those with early relapse within 7 months after initial ASCT (p = 0.026). Among patients who received salvage ASCT, a favorable prognosis is apparent for those with a time to relapse after initial ASCT of longer than 24 months. The overall survival after salvage ASCT was favorable excluding patients with the following factors: early relapse, poor PS, moderate/severe renal comorbidity, and progressive disease (p < 0.001). In conclusion, our results reinforced the evidence for encouraging salvage ASCT for eligible patients.

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Early Relapse After Autologous Stem Cell Transplantation in Multiple Myeloma is Still Prognostic in The Era of Novel Agents

Medical Laboratory Technology Journal ◽

10.31964/mltj.v0i0.281 ◽

2020 ◽

Vol 6 (2) ◽

pp. 92

Author(s):

Semih Başcı ◽

Tuğçe Nur Yiğenoğlu ◽

Bahar Uncu Ulu ◽

Mehmet Bakırtaş ◽

Derya Şahin ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Novel Agents ◽

Treatment Modalities ◽

Induction Treatment ◽

Early Relapse ◽

The Impact

Significant improvements in the prognosis of Multiple Myeloma(MM) have recently observed in the era of novel agents. Induction treatment, including new agents followed by conditioning regimen and upfront autologous stem cell transplantation(ASCT), has been accepted as the standard treatment approach for newly diagnosed eligible MM patients. Despite novel agents, upfront ASCT is still superior to conventional chemotherapy alone. Previous studies revealed that the duration between ASCT and relapse had predicted overall survival(OS), and meantime, it was widely used to determine the potential benefit from a second ASCT. However, the majority of the data collected reflects the treatment modalities before novel agents. In this study, we aimed to investigate the impact of post-transplantation early relapse(ER) on survival in the era of novel agents. The results of 155 MM patients that underwent ASCT at our center between January 2010 and May 2018 were analyzed retrospectively. The median follow-up duration was 20 months in the ER group, 27 months in the non-ER group, and 24 months in all patients. 33.3% of patients in the ER group and 71.4% of patients in the non-ER group were alive at the time of analysis. Median OS was 20.77±3.66 months in the ER group and 40.89±4.21 months in the non-ER group. We found a statistically significant relationship between the ER and the poor OS (p:<0.001). Our study reveals that in the era of novel agents, ER still related to poor survival. Therefore, comprehensive studies needed to develop new strategies for early relapsed patients.

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