The Quantification of Minimal Residual Disease Pre‐ and Post‐Unmanipulated Haploidentical Allograft by Multiparameter Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia

Wang, Xinyu; Fan, Qiao‐Zhen; Xu, Lei; Wang, Yu; Zhang, Xiao-Hui; Chen, Huan; Chen, Yuhong; Wang, Feng-Rong; Han, Wei; Sun, Yu‐Qian; Yan, Chen‐Hua; Tang, Fei‐Fei; Liu, Yanrong; Mo, Xiao‐Dong; Liu, Kai-Yan; Huang, Xiao‐Jun; Chang, Ying‐Jun

doi:10.1002/cyto.b.21840

Cited by 22 publications

(24 citation statements)

References 49 publications

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“…Consistent with previous studies, [ 14 , 16 – 20 , 23 , 25 , 64 ] our study showed that patients with post-MRD + suffered higher CIR and poorer survival than post-MRD − patients. In addition, we also found that post-MRD + at different time points was related to a higher incidence of relapse and a lower probability of LFS and OS, which was consistent with the results of Bader et al .…”

Section: Discussionsupporting

confidence: 93%

“…A previous study [ 18 ] also showed that the positive MRD at the time points, including days +30, +60, +90, +180, and +365 after allo-SCT, were inversely correlated with event-free survival and positively correlated with CIR in pediatric ALL. More recently, we reported the association of both quantitative and qualitative pre-transplantation MRD (pre-MRD) [ 11 ] as well as post-transplantation MRD (post-MRD) [ 25 ] with increased CIR and inferior survival in patients with ALL who underwent haploidentical allograft transplantation.…”

Section: Introductionmentioning

confidence: 99%

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A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Cao

Zhou

Liu

et al. 2021

Chinese Medical Journal

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Background For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. Methods A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. Results All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR ( P < 0.001, P = 0.004, and P < 0.001, respectively) and worse LFS ( P < 0.001, P = 0.017, and P < 0.001, respectively), and OS ( P < 0.001, P = 0.009, and P < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 ( P < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score. Conclusion This new risk score system might stratify patients with different risks of relapse, which could guide treatment.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

Cao

Zhou

Liu

et al. 2021

Chinese Medical Journal

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“…The pooled results evidenced a higher relapse risk (hazard ratio 3.26; p < 0.05) and lower RFS (hazard ratio 2.53; p < 0.05) in patients with positive pre-transplant MRD in comparison to those with negative MRD. Further studies published 2018–2020 in different transplant settings (related and unrelated donor or haploidentical HCT) and mixed age populations with large percentages of AYA, confirmed the unfavorable prognostic role of pre-HCT MRD pos , with a relapse incidence of 32–73% vs. 19.7–24% in pre-HCT MRD neg subsets [ 85 , 86 , 87 , 88 , 89 , 90 , 91 ]. Thus, achieving an MRD neg status before HCT in MRD pos patients should improve the overall transplantation outcome.…”

Section: Mrd In Aya Ph− Allmentioning

confidence: 79%

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

Tosi

Spinelli

Leoncin

et al. 2021

Cancers

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In many clinical studies published over the past 20 years, adolescents and young adults (AYA) with Philadelphia chromosome negative acute lymphoblastic leukemia (Ph− ALL) were considered as a rather homogeneous clinico-prognostic group of patients suitable to receive intensive pediatric-like regimens with an improved outcome compared with the use of traditional adult ALL protocols. The AYA group was defined in most studies by an age range of 18–40 years, with some exceptions (up to 45 years). The experience collected in pediatric ALL with the study of post-induction minimal residual disease (MRD) was rapidly duplicated in AYA ALL, making MRD a widely accepted key factor for risk stratification and risk-oriented therapy with or without allogeneic stem cell transplantation and experimental new drugs for patients with MRD detectable after highly intensive chemotherapy. This combined strategy has resulted in long-term survival rates of AYA patients of 60–80%. The present review examines the evidence for MRD-guided therapies in AYA’s Ph− ALL, provides a critical appraisal of current treatment pitfalls and illustrates the ways of achieving further therapeutic improvement according to the massive knowledge recently generated in the field of ALL biology and MRD/risk/subset-specific therapy

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“…transplantation outcomes in patients with T-ALL. In addition, we also tried to establish a risk score principally based on the dynamic peri-HSCT MRD combined with other parameters, such as remission status pre-HSCT and onset of chronic GVHD demonstrated by others [12,26,27] and us [2,16,19] , which might provide better relapse risk determination for T-ALL patients.…”

mentioning

confidence: 99%

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

Wang

et al. 2021

CURR MED SCI

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SummaryWe performed a retrospective analysis to investigate dynamic peri-hematopoietic stem cell transplantation (HSCT) minimal/measurable residual disease (MRD) on outcomes in patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 271 patients were enrolled and classified into three groups: unchanged negative MRD pre- and post-HSCT group (group A), post-MRD non-increase group (group B), and post-MRD increase group (group C). The patients in group B and group C experienced a higher cumulative incidence of relapse (CIR) (42% vs. 71% vs. 16%, P<0.001) and lower leukemia-free survival (LFS) (46% vs. 21% vs. 70%, P<0.001) and overall survival (OS) (50% vs. 28% vs. 72%, P<0.001) than in group A, but there was no significant difference in non-relapse mortality (NRM) among three groups (14% vs. 12% vs. 8%, P=0.752). Multivariate analysis showed that dynamic peri-HSCT MRD was associated with CIR (HR=2.392, 95% CI, 1.816–3.151, P<0.001), LFS (HR=1.964, 95% CI, 1.546–2.496, P<0.001) and OS (HR=1.731, 95% CI, 1.348–2.222, P<0.001). We also established a risk scoring system based on dynamic peri-HSCT MRD combined with remission status pre-HSCT and onset of chronic graft-verses-host disease (GVHD). This risk scoring system could better distinguish CIR (c=0.730) than that for pre-HSCT MRD (c=0.562), post-HSCT MRD (c=0.616) and pre- and post-MRD dynamics (c=0.648). Our results confirm the outcome predictive value of dynamic peri-HSCT MRD either alone or in combination with other variables for patients with T-ALL.

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The Quantification of Minimal Residual Disease Pre‐ and Post‐Unmanipulated Haploidentical Allograft by Multiparameter Flow Cytometry in Pediatric Acute Lymphoblastic Leukemia

Cited by 22 publications

References 49 publications

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation

MRD-Based Therapeutic Decisions in Genetically Defined Subsets of Adolescents and Young Adult Philadelphia-Negative ALL

Predictive Value of Dynamic Peri-Transplantation MRD Assessed By MFC Either Alone or in Combination with Other Variables for Outcomes of Patients with T-Cell Acute Lymphoblastic Leukemia

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