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Early relapse prediction after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia (ALL) using lineage-specific chimerism analysis.

ABSTRACT: Relapse is a major cause of treatment failure after hematopoietic stem cell transplantation (HSCT) for acute leukemia. Here, we report a monocentric retrospective study of all HSCTs for B cell acute lymphoblastic leukemia (ALL) performed during the years 2005-2021 (n = 138, including 51 children), aiming to identify the optimal use of lineage-specific recipient-donor chimerism analysis for prediction of relapse. In adults, relapse was associated with increased recipient chimerism in CD3⁺ bone marrow cells sampled at least 30 days before a relapse. Relapse could be predicted with a sensitivity of 73% and a specificity of 83%. Results were similar for children but with a higher recipient chimerism cutoff. Additionally, adults that had at least one chimerism value <0.12% in CD3⁺ peripheral blood cells within the first 60 days after HSCT had 89% probability of being relapse-free after 2-years compared to 64%. Results were similar for children but again necessitating a higher chimerism cutoff. These results suggest that high-sensitive lineage-specific chimerism analysis can be used for (1) early ALL relapse prediction by longitudinal chimerism monitoring in CD3⁺ bone marrow cells and (2) relapse risk stratification by analyzing CD3⁺ blood cells early post-HSCT.

SUBMITTER: Lindahl H

PROVIDER: S-EPMC9713209 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Early relapse prediction after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia (ALL) using lineage-specific chimerism analysis.

Lindahl Hannes H Valentini Davide D Vonlanthen Sofie S Sundin Mikael M Björklund Andreas T AT Mielke Stephan S Hauzenberger Dan D

EJHaem 20220919 4

Relapse is a major cause of treatment failure after hematopoietic stem cell transplantation (HSCT) for acute leukemia. Here, we report a monocentric retrospective study of all HSCTs for B cell acute lymphoblastic leukemia (ALL) performed during the years 2005-2021 (<i>n</i> = 138, including 51 children), aiming to identify the optimal use of lineage-specific recipient-donor chimerism analysis for prediction of relapse. In adults, relapse was associated with increased recipient chimerism in CD3<s ...[more]

PMID: 36467849

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Project description:Background: Disease relapse is a primary cause of treatment failure after hematopoietic stem cell transplantation in the treatment of malignancy. Consolidation therapy early after transplantation may reduce this risk, but it is difficult to administer in the setting of various post-transplant complications. We proposed that testing donor cell chimerism and for persistent minimal residual disease (MRD) with next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA) early after transplantation would identify those patients at higher risk of relapse who would possibly benefit from consolidation therapy. Methods: We enrolled 20 subjects with known tumor-associated somatic mutations into this prospective pilot study, testing plasma samples before and at 28, 56, and 84 days after transplantation. Pre- and post-transplant bone marrow samples were also analyzed. All samples were subjected to an agnostic, commercially available panel covering 302 genes. Results: Significantly more mutations (p < 0.0001) were detected in the plasma cfDNA than in the bone marrow cells in pre-transplant testing (92 versus 61 mutations, respectively), most likely reflecting sampling variation when bone marrow was used. Two subjects were negative for MRD in staging studies immediately before transplants. Most (19/20) subjects had intermittent or sustained MRD detected in post-transplant plasma cfDNA testing, albeit with much lower average variant allele frequencies (VAFs). Six out of 20 subjects suffered relapses within 12 months after transplantation, and all 6 could be identified by adverse-risk driver mutations that persisted after transplantation. No patients who cleared the adverse-risk mutations relapsed. Donor chimerism using cfDNA fell for all relapsed patients and contributed to the identification of patients at early risk for relapse. Conclusions: These data demonstrate that testing plasma cfDNA for persistent leukemia-associated somatic mutations and donor chimerism as early as 28 days after transplantation will identify a subset of patients with high-risk mutations who are at high risk of relapse. This early assessment of relapse risk may facilitate modifications to the treatment plan, reducing the risk of treatment failure.

Dataset Information

Early relapse prediction after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia (ALL) using lineage-specific chimerism analysis.

Publications

Early relapse prediction after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia (ALL) using lineage-specific chimerism analysis.

Similar Datasets

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