Residual Disease
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2021 ◽  
Vol 75 ◽  
pp. 102040
Sara Makkeyah ◽  
Ayat Manzour ◽  
Azza Tantawy ◽  
Ashraf Mohamed ◽  
Fatma Ebeid ◽  

2021 ◽  
Vol 9 (1) ◽  
Hong Ding ◽  
Juan Xu ◽  
Zhimei Lin ◽  
Jingcao Huang ◽  
Fangfang Wang ◽  

AbstractMultiple myeloma (MM) is a treatable plasma cell cancer with no cure. Clinical evidence shows that the status of minimal residual disease (MRD) after treatment is an independent prognostic factor of MM. MRD indicates the depth of post-therapeutic remission. In this review article, we outlined the major clinical trials that have determined the prognostic value of MRD in MM. We also reviewed different methods that were used for MM MRD assessment. Most important, we reviewed our current understanding of MM MRD biology. MRD studies strongly indicate that MRD is not a uniform declination of whole MM tumor population. Rather, MM MRD exhibits unique signatures of cytogenetic aberration and gene expression profiles, unlike those of MM cells before therapy. Diagnostic high-risk MM and low-risk MM exhibited a diversity of MRD features. Clonal evaluation may occur at the MRD stage in MM. The dynamics from the diagnostic MM to MRD correlate with the disease prognosis. Lastly, on the aspect of omics, we performed data-based analysis to address the biological features underlying the course of diagnostic-to-MRD MM. To summarize, the MRD stage of disease represents a critical step in MM pathogenesis and progression. Demonstration of MM MRD biology should help us to deal with the curative difficulties.

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1889
Linda J. Hong ◽  
Sandy Huynh ◽  
Joy Kim ◽  
Laura Denham ◽  
Mazdak Momeni ◽  

Background: Adenocarcinoma in situ (AIS) of the cervix, is increasing in incidence, particularly in women of reproductive age. Fertility preservation is often desired. In a predominantly Hispanic population, we sought to determine the incidence of occult cervical cancer co-existing with AIS, and evaluate how conization margin status correlates with residual disease upon hysterectomy. Methods: A retrospective study utilizing a comprehensive cancer center database was conducted. Data from patients with histologically proven AIS of the cervix were abstracted. Results: Of 47 patients that met the criteria, 23 (49%) were Hispanic, 21 (45%) were White, two (4%) were Asian, and one (2%) was Black. The median age was 37. Forty-two patients underwent cervical conizations; 13/42 (48%) had positive margins upon conization; 28/42 (67%) underwent hysterectomies. Furthermore, 6/13 (46%) patients with positive conization margins had residual disease in hysterectomy specimens, with 2/13 (15%) found to have invasive cancer. In contrast, 0/14 (0%) of patients with negative margins had residual disease (p = 0.036, Chi-squared 4.41, df = 1). In total, 2/27 (7%) patients who underwent hysterectomies had invasive cancer (7%). Conclusions: Positive margins upon cervical conization for AIS of the cervix were correlated with a relatively high rate of residual AIS and occult invasive cancer. Negative conization margins were correlated with no residual disease. Those patients may be candidates for fertility-sparing treatment.

PLoS Medicine ◽  
2021 ◽  
Vol 18 (10) ◽  
pp. e1003794
Beryne Odeny

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1872
Agnieszka Krzywdzińska ◽  
Bartosz Puła ◽  
Anna Czyż ◽  
Beata Krzymieniewska ◽  
Jolanta Kiernicka-Parulska ◽  

Minimal residual disease (MRD) status is now considered as one of the most relevant prognostic factors in multiple myeloma (MM) while MRD negativity became an important endpoint in clinical trials. Here, we report the results of the first study evaluating the reproducibility of high-sensitivity flow cytometry MM MRD assessment in four laboratories in Poland. EuroFlow protocols for instrument setting standardization and sample preparation in MM MRD assessment were implemented in each laboratory. In the inter-laboratory reproducibility study, 12 bone marrow samples from MM patients were distributed and processed in participant laboratories. In the inter-operator concordance study, 13 raw data files from MM MRD measurements were analyzed by five independent operators. The inter-laboratory study showed high 95% overall concordance of results among laboratories. In the inter-operator study, 89% of MRD results reported were concordant, and the highest immunophenotype interpretation differences with regard to expression of CD27, CD45, CD81 were noticed. We confirmed the applicability and feasibility of the EuroFlow protocol as a highly sensitive method of MRD evaluation in MM. Results of our inter-center comparison study demonstrate that the standardization of MM MRD assessment protocols is highly desirable to improve quality and comparability of results within and between different clinical trials.

2021 ◽  
Vol 11 ◽  
Jinliang Yu ◽  
Zhiyuan Sheng ◽  
Shuang Wu ◽  
Yushuai Gao ◽  
Zhaoyue Yan ◽  

The recurrence of glioma is a difficult problem in clinical treatment. The molecular markers of primary tumors after resection cannot fully represent the characteristics of recurrent tumors. Here, abundant tumor DNA was detected in tumor in situ fluid (TISF). We report that TISF-derived tumor DNA (TISF-DNA) can detect genomic changes in recurrent tumors and facilitate recurrence risk analysis, providing valuable information for diagnosis and prognosis. The tumor DNA in TISF is more representative and sensitive than that in cerebrospinal fluid. It reveals the mutational landscape of minimal residual disease after glioma surgery and the risk of early recurrence, contributing to the clinical management and clinical research of glioma patients.

2021 ◽  
Vol 22 (20) ◽  
pp. 10916
Despina Fotiou ◽  
Foteini Theodorakakou ◽  
Efstathios Kastritis

Systemic AL amyloidosis is a rare complex hematological disorder caused by clonal plasma cells which produce amyloidogenic immunoglobulins. Outcome and prognosis is the combinatory result of the extent and pattern of organ involvement secondary to amyloid fibril deposition and the biology and burden of the underlying plasma cell clone. Prognosis, as assessed by overall survival, and early outcomes is determined by degree of cardiac dysfunction and current staging systems are based on biomarkers that reflect the degree of cardiac damage. The risk of progression to end-stage renal disease requiring dialysis is assessed by renal staging systems. Longer-term survival and response to treatment is affected by markers of the underlying plasma cell clone; the genetic background of the clonal disease as evaluated by interphase fluorescence in situ hybridization in particular has predictive value and may guide treatment selection. Free light chain assessment forms the basis of hematological response criteria and minimal residual disease as assessed by sensitive methods is gradually being incorporated into clinical practice. However, sensitive biomarkers that could aid in the early diagnosis and that could reflect all aspects of organ damage and disease biology are needed and efforts to identify them are continuous.

Juliette Lambert ◽  
Jerome Lambert ◽  
Xavier Thomas ◽  
Jean-Baptiste Micol ◽  

WT1 overexpression is frequently identified in acute myeloid leukemia (AML) and has been reported as a potential marker for measurable residual disease (MRD) monitoring. Here, we evaluated the value of post-induction WT1 MRD level as a prognostic factor, as well as the interaction between post-induction WT1 MRD response and the effect of allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR). In the ALFA-0702 trial, AML patients aged 18 to 59 years had a prospective quantification of WT1 MRD. Occurrence of a WT1 MRD ratio >2.5% in bone marrow or >0.5% in peripheral blood was defined as MRDhigh, while ratio under these thresholds was defined as MRDlow. The prognostic value of MRD after induction chemotherapy was assessed in 314 patients in first CR by comparing the risk of relapse, the relapse-free survival (RFS) and the overall survival (OS). Interaction between MRD response and allo-SCT effect was evaluated in patients by comparing the influence of allo-SCT on the outcomes of patients with MRDhigh and MRDlow. We showed that MRDhigh patients after induction had a higher risk of relapse and a shorter RFS and OS. MRD response remained of strong prognostic value in the subset of 225 patients with intermediate/unfavorable-risk AML, eligible for allo-SCT, since MRDhigh patients had a significantly higher risk of relapse resulting in worse RFS and OS. Effect of allo-SCT was higher in MRDlow patients than in MRDhigh patients but not statistically different. Early WT1 MRD response highlight a population of high-risk patients in need of additional therapies.

Alejandro Medina ◽  
Cristina Jiménez ◽  
Noemí Puig ◽  
María Eugenia Sarasquete ◽  
Juan Flores-Montero ◽  

Context.— Minimal residual disease (MRD) is a major prognostic factor in multiple myeloma, although validated technologies are limited. Objective.— To standardize the performance of the LymphoTrack next-generation sequencing (NGS) assays (Invivoscribe), targeting clonal immunoglobulin rearrangements, in order to reproduce the detection of tumor clonotypes and MRD quantitation in myeloma. Design.— The quantification ability of the assay was evaluated through serial dilution experiments. Paired samples from 101 patients were tested by LymphoTrack, using Sanger sequencing and EuroFlow's next-generation flow (NGF) assay as validated references for diagnostic and follow-up evaluation, respectively. MRD studies using LymphoTrack were performed in parallel at 2 laboratories to evaluate reproducibility. Results.— Sensitivity was set as 1.3 tumor cells per total number of input cells. Clonality was confirmed in 99% and 100% of cases with Sanger and NGS, respectively, showing great concordance (97.9%), although several samples had minor discordances in the nucleotide sequence of rearrangements. Parallel NGS was performed in 82 follow-up cases, achieving a median sensitivity of 0.001%, while for NGF, median sensitivity was 0.0002%. Reproducibility of LymphoTrack-based MRD studies (85.4%) and correlation with NGF (R2 > 0.800) were high. Bland-Altman tests showed highly significant levels of agreement between flow and sequencing. Conclusions.— Taken together, we have shown that LymphoTrack is a suitable strategy for clonality detection and MRD evaluation, with results comparable to gold standard procedures.

Wael Khair

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