Clinical value of pre‐transplant minimal residual disease in childhood lymphoblastic leukaemia: the results of the <scp>F</scp>rench minimal residual disease‐guided protocol

Gandemer, Virginie; Pochon, Cécile; Oger, Emmanuel; Dalle, Jean‐Hugues; Gautier, Michel; Schmitt, Claudine; Berranger, Eva de; Garrigue, Claire; Cavé, Hélène; Cayuela, Jean‐Michel; Grardel, Nathalie; Macintyre, Elizabeth; Margueritte, Geneviève; Méchinaud, Françoise; Rorhlich, Pierre; Lutz, Patrick; Deméocq, F.; Schneider, Pascale; Plantaz, Dominique; Poirée, Marilyne; Bordigoni, Pierre

doi:10.1111/bjh.12749

Cited by 31 publications

(32 citation statements)

References 50 publications

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“…This confirms the major role of antithymocyte globulin as part of GvHD prophylaxis in patients transplanted from unrelated donors. 11 We also report a low rate of TRM compared with other series where average TRM reaches 20-25%, 25,29,30,34 even though a large variability (7-45%) is possible. 27,35,38,39 Our results suggest that close monitoring of CsA therapy may permit a substantial reduction of GvHD-related mortality.…”

Section: Discussionsupporting

confidence: 49%

“…Second, as this study is monocentric, patients in this study did not receive various combinations of immunosuppressive agents as usually reported. 25,28,30,35,54 MRD before HSCT had no prognostic value in our cohort. The DFS of patients with negative or positive MRD before HSCT was similar.…”

Section: Discussionmentioning

confidence: 53%

“…This contrasts with previous studies where DFS was about two times lower in patients with pretransplant detectable MRD. 25,27,[55][56][57] However, MRD could not be measured in all patients in our study. Thus, for those patients for whom data were available, only a few had positive MRD.…”

Section: Discussionmentioning

confidence: 72%

“…DFS usually reported in children transplanted for high-risk leukemia from sibling or unrelated donors vary between 50 and 70%. 25,[27][28][29][30][31][32][33]40 Weiss et al 37 report a similar DFS (84%) using CsA alone as GVHD prophylaxis but in patients transplanted only from MSDs. 37 They also used CsA while targeting a lower and narrower TBC range (80-130 ng/mL) compared with those usually recommended (100-200 ng/mL).…”

Section: Discussionmentioning

confidence: 85%

“…The MRD positivity was defined as ⩾ 10 − 3 . [22][23][24][25] Statistical analysis All statistical analyses were performed using SPSS for Windows (version 11.0; SPSS, Chicago, IL, USA). Pearson's χ 2 tests were used to compare possible differences in qualitative variables between groups of patients.…”

Section: Mrd Analysismentioning

confidence: 99%

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Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Bleyzac

Cuzzubbo

Rénard

et al. 2016

Bone Marrow Transplant

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There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽ 120 ng/mL versus 43% with concentration 4120 ng/mL (Po 0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾ 10 − 3 and in those with MRD o 10 − 3 before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 85%

Section: Mrd Analysismentioning

confidence: 99%

See 3 more Smart Citations

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Bleyzac

Cuzzubbo

Rénard

et al. 2016

Bone Marrow Transplant

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Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts

Zhao

Liu

et al. 2019

American J Hematol

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This study evaluated the effects of pretransplantation minimal residual disease (pre-MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical stem cell transplantation (haplo-SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry. Both in the entire cohort of patients and in subgroup cases with T-ALL or B-ALL, patients with positive pre-MRD had a higher incidence of relapse (CIR) than those with negative pre-MRD in MSDT settings (P < 0.01 for all). Landmark analysis at 6 months showed that MRD positivity was significantly and independently associated with inferior rates of relapse (HR, 1.908; P = 0.007), leukemia-free survival (LFS) (HR, 1.559; P = 0.038), and OS (HR, 1.545; P = 0.049). The levels of pre-MRD according to a logarithmic scale were also associated with leukemia relapse, LFS, and OS, except that cases with MRD <0.01% experienced comparable CIR and LFS to those with negative pre-MRD. A risk score for CIR was developed using the variables pre-MRD, disease status, and immunophenotype of ALL. The CIR was 14%, 26%, and 59% for subjects with scores of 0, 1, and 2-3, respectively (P < 0.001). Three-year LFS was 75%, 64%, and 42%, respectively (P < 0.001). Multivariate analysis confirmed the association of the risk score with CIR and LFS.The results indicate that positive pre-MRD, except for low level one (MRD < 0.01%), is associated with poor outcomes in patients with ALL who underwent unmanipulated haplo-SCT.

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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

Wang

Fan

et al. 2019

Cytometry Part B Clinical

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BackgroundThis study aimed to determine the impact of the pre‐ and post‐minimal residual disease (MRD) status as well as the peri‐transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts.MethodsA retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry.ResultsPediatric ALL patients with pre‐MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre‐MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post‐MRDneg group, patients with post‐MRDpos experienced higher CIR (81.0% vs. 15.9%, P < 0.001), inferior LFS (14.3% vs. 66.9%, P < 0.001) and OS (19.1% vs. 66.9%, P < 0.001). In regard to peri‐MRD kinetics, compared with the MRD‐decreasing group and MRDneg/MRDneg group, MRD‐increasing group had higher CIR, lower probabilities of LFS and OS (P < 0.001). Compared to pre‐MRDneg/post‐MRDneg group, a higher CIR was found in the pre‐MRDpos/post‐MRDpos group (66.7% vs. 12.5%, P < 0.001), pre‐MRDpos/post‐MRDneg group (32.0% vs. 12.5%, P = 0.016), and pre‐MRDneg/post‐MRDpos group (91.7% vs. 12.5%, P < 0.001). A lower incidence of LFS and OS were found in pre‐MRDpos/post‐MRDpos group and pre‐MRDneg/post‐MRDpos group than in pre‐MRDneg/post‐MRDneg group (P < 0.05). Multivariate analyses confirmed the association of pre‐MRD status, post‐MRD status, and peri‐MRD kinetics with outcomes (P < 0.05).ConclusionsThe results indicate that, in the pediatric ALL subgroup, not only pre‐MRD status or post‐MRD status but also peri‐SCT MRD dynamics, were associated with an increased CIR after haploidentical allografts. Patients are put into different risk group based on MRD kinetics versus single time MRD status. © 2019 International Clinical Cytometry Society

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Clinical value of pre‐transplant minimal residual disease in childhood lymphoblastic leukaemia: the results of the French minimal residual disease‐guided protocol

Abstract: SummaryMinimal residual disease (MRD) is a major predictive factor of the cure rate of acute lymphoblastic leukaemia (ALL). Haematopoietic cell transplantation is a treatment option for patients at high risk of relapse.

Cited by 31 publications

References 50 publications

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Minimal residual disease status determined by multiparametric flow cytometry pretransplantation predicts the outcome of patients with ALL receiving unmanipulated haploidentical allografts

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

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