scholarly journals Preventing relapse after haematopoietic stem cell transplantation for acute leukaemia: the role of post-transplantation minimal residual disease (MRD) monitoring and MRD-directed intervention

2017 ◽  
Vol 179 (2) ◽  
pp. 184-197 ◽  
Author(s):  
Xiao-Dong Mo ◽  
Meng Lv ◽  
Xiao-Jun Huang
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Acute Leukaemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Residual Disease ◽  
Haematopoietic Stem Cell ◽  
Post Transplantation ◽  
Minimal Residual

Detectable Minimal Residual Disease before Haematopoietic Stem Cell Transplantation Predicts Extremely Poor Prognosis in Children with Acute Lymphoblastic Leukaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2037-2037
Author(s):  
Katerina Muzikova ◽  
Eva Fronkova ◽  
Lucie Sramkova ◽  
Leona Reznickova ◽  
Renata Formankova ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factor ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Residual Disease ◽  
Clonal Evolution ◽  
Haematopoietic Stem Cell ◽  
Minimal Residual

Abstract The level of minimal residual disease (MRD) prior to allogeneic haematopoietic stem cell transplantation (HSCT) was shown to be an independent prognostic factor for the outcome of paediatric patients with high-risk acute lymphoblastic leukemia (ALL). Retrospective studies which used (semi-)quantitation of clone-specific immunoglobulin/T-cell receptor (Ig/TCR) rearrangements documented feasibility and practicality of such an approach. Recently, this approach was disputed by Imashuku et al (BMT 2003) due to great occurrence of the clonal evolution and generally high MRD levels prior HSCT in their cohort. In our prospective study, MRD before and after HSCT was monitored in a cohort of 36 children with ALL consecutively transplanted in our centre between VIII/2000 and VII/2004. We used a quantitative real-time PCR approach introduced and standardised by European Study Group on MRD in ALL. In 25 of 36 patients MRD level prior HSCT was assessed (9 patients lacked adequately sensitive Ig/TCR target; two lacked analysable DNA prior HSCT). Seventeen patients were MRD-negative prior HSCT (including two with MRD level below the quantitative range 10(−4)) and 8 were MRD-positive up to 9x10(−2). In the MRD-positive subgroup, 7 events (6 relapses) occurred post-transplant in striking contrast to only one relapse in MRD-negative subgroup (EFS log-rank p<0.0001). MRD proved to be the only significant prognostic factor in a multivariate analysis (p<0.0001). Adoptive immunotherapy including donor lymphocyte infusions in patients with adverse dynamics of MRD after HSCT had only limited and/or temporary effect. Clonal evolution did not present a problem precluding MRD monitoring in any of patients suffering a post-transplant relapse. We show that MRD quantitation using clonal Ig/TCR rearrangements represents a feasible approach for the risk assessment in paediatric ALL patients undergoing allogeneic HSCT. However, our ability to respond to detectable MRD levels after HSCT and to avert an impending relapse is very limited. The change of the approach to MRD-positive patients prior HSCT is necessary because of very questionable benefit of HSCT in these children. Supported by grants MSM0021620813, FNM 9735 and GAUK 62/2004.

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).

Methods and role of minimal residual disease after stem cell transplantation

2018 ◽  
Vol 54 (5) ◽  
pp. 681-690 ◽  
Author(s):  
Marco Ladetto ◽  
Sebastian Böttcher ◽  
Nicolaus Kröger ◽  
Michael A. Pulsipher ◽  
Peter Bader
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Cell Transplantation ◽  
Residual Disease ◽  
Minimal Residual

Minimal Residual Disease (MRD) Evaluation by Flow Cytometry in Acute Leukemia Patients Undergoing Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1103-1103
Author(s):  
Maria-Belen Vidriales ◽  
Jose J. Pérez ◽  
Consuelo López-Berges ◽  
Norma C. Gutierrez ◽  
Juana Ciudad ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Acute Leukaemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Allogeneic Transplantation ◽  
Minimal Residual

Abstract Investigation of minimal residual disease (MRD) in acute leukemias by immunophenotyping is increasingly used for disease monitoring. Most MRD studies using flow cytometry techniques have focused on patients treated with conventional chemotherapy, while information on its value in patients undergoing allogeneic transplantation is scanty. The aim of the present study is to evaluate whether or not immunophenotypical assessment of MRD could also be a valuable tool in patients undergoing allogeneic transplantation for acute leukaemia. For that purpose we have analysed the level of MRD before and after (month +3) transplantation, by multiparameter flow cytometry, in a series of 38 acute leukaemia patients (26 ALL cases -20 cases in 1st CR and 6 in 2nd CR- and 12 AML cases -all of them in 1st CR), that showed an aberrant immunophenotype at diagnosis. Although the level of MRD in the BM obtained before transplantation showed a tendency to predict RFS, differences did not reached statistical significance. By contrast, the evaluation of the BM obtained 3 months after allo-transplantation had significant prognostic value. Thus, patients with low MRD levels (&lt;0.05% for ALL and &lt;0.2% for AML) (n=17) had a significantly longer RFS than patients with MRD positive (median RFS: 40 vs 16 months) (p=0.001). Multivariate analysis showed that the immunological evaluation of MRD after transplantation had independent prognostic value for RFS in acute leukaemia, together with age, WBC count, and cytogenetics. Our results suggest that immunological analysis of MRD should be included in the follow-up evaluation of acute leukaemia patients undergoing allogeneic stem cell transplantation.

Monitoring of Minimal Residual Disease After Allogeneic Stem Cell Transplantation In Relapsed Childhood ALL Allows The Identification Of Impending Relapse - Results Of The ALL BFM SCT 2003 Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1995-1995
Author(s):  
Peter Bader ◽  
Hermann Kreyenberg ◽  
Arend von Stackelberg ◽  
Cornelia Eckert ◽  
Meisel Roland ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Allogeneic Stem Cell Transplantation ◽  
Cumulative Incidence ◽  
Residual Disease ◽  
Post Transplantation ◽  
Post Transplant ◽  
Minimal Residual

Abstract Purpose Monitoring of minimal residual disease (MRD) after allogeneic stem cell transplantation (allo-SCT) by quantitative real-time PCR (qRT-PCR) of rearranged Ig- and TCR-genes may highlight patients with highest risk for relapse to whom pre-emptive treatment may be offered. Patients and Methods In the prospective phase 3 trial ALL-SCT-BFM-2003 (recruitment period 09/2003 to 09/2011; time point of analysis May 2013), MRD was assessed in bone marrow immediately on days +30, +60, +100, +200 and +365 post transplantation in 115 patients. Of these, 48 were male and 67 were female patients. All received a myeloablative conditioning regimen with TBI and VP 16. Patients received their transplant in CR2 (n=94), CR3 (n=21), CR4 (n=1) or NR (n=2). The transplantations were performed with bone marrow from matched sibling donors (MSD, n=23), matched unrelated donors (MUD, n=71) or with T-cell depleted stem cells from mismatched donors (MMD, n=21). Fifty-four patients were younger than 10 and 61 patients were older than 10 years at the time of transplant. Standardized quantification of MRD was performed according to the guidelines of the Euro-MRD-Group and MRD results were not released to the clinicians. Results The total group of patients showed a pEFS of 0.52±0.10; cumulative incidence of relapse (CIR) and cumulative incidence of treatment related mortality (CI TRM) was 0.41±0.11 and 0.19±0.09, respectively. In 76 patients, MRD could also be assessed prior to transplant: patients who were MRD negative (n=41) had a three year pEFS of 0.62±0.04, patients with a MRD load of <10E-3 (n=28) of 0.49±0.14 and none of the patients who were MRD positive >1E-3 survived their disease. MRD values post transplant were analyzed as time-dependent covariates. When analyzed either for the different time points or for the highest MRD value post transplant, MRD results had always significant influence on survival. Taken the highest MRD value post transplant, probabilities of pEFS and CIR were 0.65±0.11 and 0.23±0.09 for MRD negative patients (n=72), 0.36±0.18 resp. 0.75 ±0.18 for patients with MRD <10-3 (n=36) compared to 0.00±0.0 and 1.0±0.0 in patients who developed MRD ≥10-3 leukemic cells (n=07) (pEFS, P<0.0001; CIR, P<0.0001). In multivariate cox regression analysis, MRD prior and post transplantation, as well as indication for SCT, significantly influenced the probability of survival. It is noteworthy, that all patients who developed a MRD load of >10E-3 at any time after transplant finally developed relapse and died. However, 49% of patients who became MRD positive <10E-3 did not necessarily develop frank relapse. Here, dynamic evolution needs to be considered as 9/15 patients with an MRD load of <10E-3 at day 200 survived. However, if MRD was not cleared by day 365 all patients finally relapsed. Conclusion Assessment of MRD post transplant allows the identification of patients with impending relapse. All patients who developed MRD >10E-3 at any time post transplant finally relapsed. Therefore, MRD may serve as an endpoint for further pre-emptive therapies. Acknowledgment This trial was supported by the “Deutsche Knochenmarkspender Datei” (DKMS). Disclosures: No relevant conflicts of interest to declare.

scholarly journals Study protocol of a pilot study evaluating feasibility and acceptability of a psychosexual intervention for couples postallogeneic haematopoietic stem cell transplantation

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039300
Author(s):  
Brindha Pillay ◽  
Maria Ftanou ◽  
David Ritchie ◽  
Yvonne Panek-Hudson ◽  
Michael Jefford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Sexual Dysfunction ◽  
Stem Cell Transplantation ◽  
Relationship Satisfaction ◽  
Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Post Transplantation ◽  
Allogeneic Hsct

IntroductionSexual dysfunction is one of the most common side effects of allogeneic haematopoietic stem cell transplantation (HSCT) for haematological cancers. Problems can persist between 5 and 10 years post-transplant and impact mood, couple intimacy and relationship satisfaction. Few intervention studies, however, target sexual dysfunction in patients post-HSCT. This pilot study aims to examine the feasibility and acceptability of implementing a psychosexual intervention for HSCT survivors and their partners post-transplantation.Methods and analysisFifteen allogeneic HSCT survivors and their partners will be recruited. Patients who are more than 3 months post-transplantation will be sent invitation letters describing the couples’ psychosexual intervention that will be offered through this study. The intervention will comprise two components: (1) psychosexual education about medical and behavioural treatment options for sexual dysfunction delivered by a haematology nurse consultant; (2) emotionally focused therapy-based relationship education programme for couples delivered by a clinical psychologist (four sessions of 1.5 hours each). Couples who consent to participate will be administered a series of measures assessing mood, relationship satisfaction and sexual dysfunction preintervention and post-intervention, as well as satisfaction with the intervention postintervention. Feasibility of the intervention will be examined via recording enrolment rate, adherence, compliance with completing outcome measures and fidelity of intervention delivery.Ethics and disseminationEthics approval has been obtained at the Peter MacCallum Cancer Centre in Melbourne, Australia. Results will be presented at national and international conferences and published in a peer-reviewed journal so that in can be accessed by clinicians involved in the care of allogeneic HSCT patients. If this intervention is found to be feasible and acceptable, its impact will be examined in a future randomised controlled trial and subsequently implemented as part of routine care in the allogeneic HSCT population.

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