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Clinical application of next-generation sequencing-based monitoring of minimal residual disease in childhood acute lymphoblastic leukemia - Journal of Cancer Research and Clinical Oncology

Background Next-generation sequencing (NGS) is an emerging technology that can comprehensively assess the diversity of the immune system. We explored the feasibility of NGS in detecting minimal residual disease (MRD) ..... see more

Source : https://link.springer.com/article/10.1007/s00432-022-04151-6


Conclusion: NGS is more sensitive than MFC and RQ–PCR for MRD measurement. B-ALL children with ≧2 clonal rearrangements detected by NGS before treatment are difficult to switch to negative MRD after chemotherapy.

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MRD in Venetoclax-Based Treatment for AML: Does it Really Matter?

The prognosis of newly diagnosed patients with acute myeloid leukemia is still unfavorable in the majority of cases within the intermediate and mainly adverse genetic risk group but also in ..... see more

Source : https://www.frontiersin.org/articles/10.3389/fonc.2022.890871/full


Relevance: We here review and discuss more recent data on the minimal residual disease interpretation and role in AML patients treated with venetoclax-based combinations.

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Molecular Measurable Residual Disease Assessment before Hematopoietic Stem Cell Transplantation in Pediatric Acute Myeloid Leukemia Patients: A Retrospective Study by the I-BFM Study Group - PubMed

Hematopoietic stem cell transplantation (HSCT) is a curative post-remission treatment in patients with acute myeloid leukemia (AML), but relapse after transplant is still a challenging event. In recent year, several ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35884834/


Conclusion/Relevance: Here, we propose the first collaborative retrospective I-BFM-AML study assessing qPCR-MRD values in pretransplant bone marrow samples of 112 patients with a diagnosis of AML ….These data support the PCR-based approach playing a clinical relevance in AML transplant management.

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Clinical Impact of Measurable Residual Disease in Acute Myeloid Leukemia - PubMed

Measurable residual disease (MRD) has emerged as a primary marker of risk severity and prognosis in acute myeloid leukemia (AML). There is, however, ongoing debate about MRD-based surveillance and treatment. ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35892893/


Conclusion: Several studies address the implications of MRD on treatment selection and hematopoietic stem cell transplant, including patient candidacy, conditioning regimen, and transplant type. More prospective, randomized studies are needed to guide the application of MRD in the treatment of AML, particularly in transplant.

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Circulating DNA in the neoadjuvant setting of early stage colon cancer

Abstract While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this ..... see more

Source : https://www.tandfonline.com/doi/abs/10.1080/0284186X.2022.2101023?journalCode=ionc20


Conclusion/Relevance: While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy …. This is the first study of ctDNA in the neoadjuvant setting...

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Patient-Specific Assays Based on Whole-Genome Sequencing Data to Measure Residual Disease in Children With Acute Lymphoblastic Leukemia: A Proof of Concept Study - PubMed

Risk-adapted treatment in acute lymphoblastic leukemia (ALL) relies on genetic information and measurable residual disease (MRD) monitoring. In this proof of concept study, DNA from diagnostic bone marrow (BM) of ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35865473/


Conclusion/Relevance: The results suggest that our approach to design molecular assays, together with ddPCR quantification, is a technically feasible option for accurate MRD quantification and that cfDNA may contribute valuable information regarding MRD and low-grade CNS involvement.

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ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group - PubMed

Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35809752/


Relevance: Circulating tumour DNA (ctDNA) assays conducted on plasma are rapidly developing a strong evidence base for use in patients with cancer. The European Society for Medical Oncology convened an expert working group to review the analytical and clinical validity and utility of ctDNA assays.

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Novel Treatments for Pediatric Relapsed or Refractory Acute B-Cell Lineage Lymphoblastic Leukemia: Precision Medicine Era

With the markedly increased cure rate for children with newly diagnosed pediatric B-cell acute lymphoblastic leukemia (B-ALL), relapse and refractory B-ALL (R/R B-ALL) remain the primary cause of death worldwide ..... see more

Source : https://www.frontiersin.org/articles/10.3389/fped.2022.923419/full


Conclusion/Relevance: To date, the prognosis of pediatric patients with R/R B-ALL has been enhanced markedly thanks to the development of novel drugs. This article reviews the new advancements of several promising strategies for pediatric R/R B-ALL.

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Defibrotide Prophylaxis of Sinusoidal Obstruction Syndrome in Adults Treated With Inotuzumab Ozogamicin Prior to Hematopoietic Stem Cell Transplantation

Sinusoidal Obstruction Syndrome (SOS) is a life threatening HSCT complication and it can rapidly evolve in Multiple Organ Dysfunction Syndrome, with a mortality exceeding 80%. Early treatment with defibrotide is ..... see more

Source : https://www.frontiersin.org/articles/10.3389/fonc.2022.933317/full


Relevance: Sinusoidal Obstruction Syndrome (SOS) is a life threatening HSCT complication and it can rapidly evolve in Multiple Organ Dysfunction Syndrome, with a mortality exceeding 80%. Early treatment with defibrotide is the leading factor for efficacy. Its prophylactic use is recommended in the pediatric setting, but its value isn’t...

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Safety and efficacy of blinatumomab in Japanese adult and pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: final results from an expansion cohort - PubMed

Background The safety and efficacy of blinatumomab, a CD19/CD3 BiTE® (bispecific T-cell engager) molecule, was evaluated in an expansion cohort of the phase 1b/2 study (NCT02412306) in Japanese adult (n=14) ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35790143/


Conclusion: Blinatumomab was safe and efficacious in Japanese patients with relapsed/refractory BCP ALL.

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Novel CD19 chimeric antigen receptor T cells manufactured next-day for acute lymphoblastic leukemia - Blood Cancer Journal

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need ..... see more

Source : https://www.nature.com/articles/s41408-022-00688-4


Relevance: Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured...

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Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia - BMC Genomics

Background T cell acute lymphoblastic leukemia (T-ALL) defines a group of hematological malignancies with heterogeneous aggressiveness and highly variable outcome, making therapeutic decisions a challenging task. We tried to discover ..... see more

Source : https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-022-08688-1


Conclusion: Overall, our investigations led to the discovery of a homogenous group of leukemic cells with profound alterations of their biology. It also resulted in an accurate predictive tool that could significantly improve the management of T-ALL patients.

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Comparisons of Long-Term Survival and Safety of Haploidentical Hematopoietic Stem Cell Transplantation After CAR-T Cell Therapy or Chemotherapy in Pediatric Patients With First Relapse of B-Cell Acute Lymphoblastic Leukemia Based on MRD-Guided Treatment

Measurable residual disease (MRD) positivity before haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an independent prognostic factor in determining outcomes in patients with B-cell acute lymphoblastic leukemia (ALL). In this ..... see more

Source : https://www.frontiersin.org/articles/10.3389/fimmu.2022.915590/full


Conclusion: Our study suggests that CAR-T therapy effectively eliminates pre-HSCT MRD, resulting in better survival in the context of haplo-HSCT.

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Punctual and kinetic MRD analysis from the Fondazione Italiana Linfomi MCL0208 phase III trial in mantle cell lymphoma

Research Article | Simone Ferrero, Daniele Grimaldi, Elisa Genuardi, Daniela Drandi, Gian Maria Zaccaria, Beatrice Alessandria, Marco Ghislieri, Martina Ferrante, Andrea Evangelista, Barbara Mantoan, Gabriele De Luca, Piero Maria Stefani, ..... see more

Source : https://ashpublications.org/blood/article/doi/10.1182/blood.2021014270/485688/Punctual-and-kinetic-MRD-analysis-from-the


Conclusion: MRD is a powerful predictor over the entire natural history of MCL and suitable for models with continuous adaptation of patient risk.

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Prognostic Impact and Phenotype of Residual Acute Myeloid Leukemia Stem Cells - PubMed

Background: Leukemia stem cells (LSCs) have been demonstrated to be more therapy-resistant than leukemic blast cells reflecting measurable residual disease (MRD). CD34+CD38- cell frequency is an independent factor for relapse ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35704721/


Relevance: Leukemia stem cells (LSCs) have been demonstrated to be more therapy-resistant than leukemic blast cells reflecting measurable residual disease (MRD). CD34 CD38- cell frequency is an independent factor for relapse prediction and could therefore be used in the future to improve MRD assessment in acute myeloid leukemia (AML). This...

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Droplet Digital PCR - A new view on minimal residual disease quantification in acute lymphoblastic leukaemia - PubMed

Real-time quantitative polymerase chain reaction (qPCR) using T-cell receptor/immunoglobulin gene rearrangements has been used as gold standard for minimal residual disease (MRD) monitoring in acute lymphoblastic leukaemia (ALL) for more ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35691569/


Conclusion: The prospective study demonstrates that ddPCR outperforms qPCR with a significantly better quantitative limit of detection and sensitivity. The number of critical MRD estimates below quantitative limit was reduced by 6- and by 3-fold in the retrospective and prospective cohorts, respectively. Furthermore, the concordance of...

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Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma - PubMed

doi: 10.1200/JCO.21.01365. Online ahead of print. 1 Clinica Universidad de Navarra, Cancer Center Universidad de Navarra (CCUN), Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigacion Sanitaria de Navarra (IDISNA), ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35666958/


Conclusion: Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.

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High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma - PubMed

doi: 10.1200/JCO.21.01393. Online ahead of print. 1 SSD Clinical Trial in Oncoematologia e Mieloma Multiplo, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35666982/


Conclusion: In multiple myeloma, increasing levels of CTC above an optimal cutoff represent an easy-to-assess, robust, and independent high-risk factor. The achievement of MRD negativity is the most important factor that modulates their negative prognostic impact.

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Isatuximab plus carfilzomib and dexamethasone versus carfilzomib and dexamethasone in elderly patients with relapsed multiple myeloma: IKEMA subgroup analysis - PubMed

In this subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285), we evaluated efficacy and safety of the anti-CD38 monoclonal antibody isatuximab (Isa) in combination with carfilzomib-dexamethasone (Isa-Kd) vs ..... see more

Source : https://pubmed.ncbi.nlm.nih.gov/35653225/



Conclusion: In conclusion, Isa-Kd provides a consistent benefit vs Kd in elderly patients, with a manageable safety profile, and represents a new treatment option for patients with relapsed MM, independent of age.

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Conclusion: Patients with complete remission and negative MRD exhibited significantly higher overall survival when compared to patients having MRD positivity (P value 0.027). Conclusion: MRD is a powerful predictor of outcome in ALL and its positivity at different time points is associated with poor prognostic factors as well as survival...