scholarly journals Donor-derived CD19-targeted T cell infusion induces minimal residual disease-negative remission in relapsed B-cell acute lymphoblastic leukaemia with no response to donor lymphocyte infusions after haploidentical haematopoietic stem cell transplantation

2017 ◽  
Vol 179 (4) ◽  
pp. 598-605 ◽  
Author(s):  
Yuhong Chen ◽  
Yifei Cheng ◽  
Pan Suo ◽  
Chenhua Yan ◽  
Yu Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
Lymphoblastic Leukaemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Residual Disease ◽  
Haematopoietic Stem Cell ◽  
Minimal Residual ◽  
Donor Lymphocyte Infusions

scholarly journals Minimal Residual Disease Prior to and After Haematopoietic Stem Cell Transplantation in Children and Adolescents With Acute Lymphoblastic Leukaemia: What Level of Negativity Is Relevant?

2021 ◽  
Vol 9 ◽  
Author(s):  
Pietro Merli ◽  
Marianne Ifversen ◽  
Tony H. Truong ◽  
Hanne V. Marquart ◽  
Jochen Buechner ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Acute Lymphoblastic Leukaemia ◽  
Minimal Residual Disease ◽  
Lymphoblastic Leukaemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Residual Disease ◽  
Haematopoietic Stem Cell ◽  
Minimal Residual

Minimal residual disease (MRD) assessment plays a central role in risk stratification and treatment guidance in paediatric patients with acute lymphoblastic leukaemia (ALL). As such, MRD prior to haematopoietic stem cell transplantation (HSCT) is a major factor that is independently correlated with outcome. High burden of MRD is negatively correlated with post-transplant survival, as both the risk of leukaemia recurrence and non-relapse mortality increase with greater levels of MRD. Despite growing evidence supporting these findings, controversies still exist. In particular, it is still not clear whether multiparameter flow cytometry and real-time quantitative polymerase chain reaction, which is used to recognise immunoglobulin and T-cell receptor gene rearrangements, can be employed interchangeably. Moreover, the higher sensitivity in MRD quantification offered by next-generation sequencing techniques may further refine the ability to stratify transplant-associated risks. While MRD quantification from bone marrow prior to HSCT remains the state of the art, heavily pre-treated patients may benefit from additional staging, such as using 18F-fluorodeoxyglucose positron emission tomography/computed tomography to detect focal residues of disease. Additionally, the timing of MRD detection (i.e., immediately before administration of the conditioning regimen or weeks before) is a matter of debate. Pre-transplant MRD negativity has previously been associated with superior outcomes; however, in the recent For Omitting Radiation Under Majority age (FORUM) study, pre-HSCT MRD positivity was associated with neither relapse risk nor survival. In this review, we discuss the level of MRD that may require pre-transplant therapy intensification, risking time delay and complications (as well as losing the window for HSCT if disease progression occurs), as opposed to an adapted post-transplant strategy to achieve long-term remission. Indeed, MRD monitoring may be a valuable tool to guide individualised treatment decisions, including tapering of immunosuppression, cellular therapies (such as donor lymphocyte infusions) or additional immunotherapy (such as bispecific T-cell engagers or chimeric antigen receptor T-cell therapy).

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