cfDNA Chimerism and Somatic Mutation Testing in Early Prediction of Relapse After Allogeneic Stem Cell Transplantation for Myeloid Malignancies
Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Bone Marrow and Peripheral Blood Analysis
2.2. Post-Transplant Consolidation Therapy
2.3. Diagnosis of Relapse
2.4. DNA and RNA Extraction and Sequencing
2.5. Statistical Analysis
3. Results
3.1. Concordance of cfDNA and Bone Marrow Samples
3.2. Correlation of cfDNA Detection with Relapse
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Subject Age, Median (Range) | 59 (27–77) | Donor Age, Median (Range) | 25 (16–56) |
Subject Sex (N) | Donor Sex (N) | ||
Male | 13 | Male | 11 |
Female | 7 | Female | 9 |
Transplant Diagnosis (N) | Donor (N) | ||
Primary AML | 6 | HLA-Matched Sibling | 2 |
Secondary AML | 6 | Haploidentical | 3 |
MDS | 7 | URD Matched | 12 |
CML, Blast Crisis | 1 | URD Mismatched | 3 |
ABO (N) | CMV (Recipient or Donor, N) | ||
Match | 11 | +/+ | 3 |
Minor Mismatch | 3 | +/− | 4 |
Major or Bidirectional Mismatch | 6 | −/+ | 4 |
−/− | 9 | ||
HSC Source (N) | Conditioning Regimen (N) | ||
PBSC | 20 | MA | 6 |
BM | 0 | RIC | 10 |
Non-MA | 4 | ||
GvHD Regimen (N) | |||
Tac + MTX | 3 | Post-Transplant Consolidation (N) | |
Tac, MTX + abatacept | 11 | Yes | 9 |
PTCy | 2 | No | 11 |
PTCy or abatacept | 4 |
Sub No. | DX | Donor/HLA Match | CondReg | GvHD Reg | Post-Transplant Consolidation | Relapse | Current Status | Number of Mutations/Geometric Mean of VAF | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Regimen | Day Started | Y/N | Day | Pre-Transplant BM | Pre cfDNA | Day 28 | Day 56 | Day 84 | Post-Transplant BM | ||||||
001 | AML | URD 10/10 | MA + ATG | MTX | NA | N | Expired, RRT, day 59 | 3/4.58 | 2/20.92 | 5/0.1 | 3/0.51 | ND | ND | ||
002 | t-MDS | URD 10/10 | MA + ATG | MTX + Abat | NA | Y | 170 | Alive, >day 365 | 2/34.42 | 2/42.72 | 3/2.4 | 3/4.02 | 3/2.77 | 2/1.13 | |
003 | MDS | URD 8/10 | NMA | PTCy + Abat | NA | N | Alive, >day 365 | 2/11.04 | 0/NE | 0/NE | 1/2.31 | 0/NE | 0/NE | ||
004 | AML | URD 10/10 | MA + ATG | MTX + Abat | Sorafenib +HMA | 51 | N | Expired, infection, day 357 | 1/44.48 | 1/44.87 | 1/0.5 | 1/0.26 | 0/NE | 1/0.28 | |
005 | t-MDS | URD 10/10 | RIC + ATG | MTX + Abat | HMA +DLI | 121 | N | Alive, >day 365 | 5/3.54 | 16/0.97 | 2/0.54 | 2/0.30 | 2/0.34 | 5/0.37 | |
006 | 2nd-AML (CMML) | URD 10/10 | RIC + ATG | MTX + Abat | NA | N | Alive, >day 365 | 4/37.62 | 4/35.91 | 0/NE | 0/NE | 2/0.11 | 1/2.55 | ||
007 | 2nd-AML (MDS) | URD 10/10 | NMA | PTCy + Abat | NA | Y | 62 | Expired, relapse, day 250 | 8/22.97 | 9/18.72 | 1/0.66 | 6/1.07 | 7/1.52 | 10/4.29 | |
008 | AML | Haplo | RIC | PTCy | Crenolinib +sorafenib | 91 | N | Alive, >day 365 | 0/NE | 0/NE | 0/NE | 0/NE | 0/NE | 0/NE | |
009 | AML | RD 10/10 | RIC + ATG | MTX | HMA +MT401 DLI Group 2 | 76 | Y | 168 | Expired, relapse, day 285 | 2/0.66 | 6/0.84 | 0/NE | 0/NE | 7/0.9 | 4/0.24 |
010 | 2nd-AML | Haplo | NMA | PTCy + Abat | NA | Y | 52 | Expired, relapse, day 125 | 3/8.14 | 3/23.98 | 3/0.64 | 2/19.28 | 2/33.48 | 4/5.92 | |
011 | 2nd-AML (MDS) | URD 9/10 | RIC | PTCy + Abat | HMA | 88 | N | Alive, >day 365 | 3/19.83 | 3/9.66 | 1/1.59 | 1/3.40 | 1/6.32 | 0/NE | |
012 | MDS | URD 10/10 | MA + ATG | MTX + Abat | NA | Y | 167 | Alive, relapse, day 347 | 4/7.67 | 11/5.68 | 5/0.62 | 3/0.04 | 7/0.36 | 4/0.46 | |
013 | MDS | URD 10/10 | RIC + ATG | MTX + Abat | NA | Y | 139 | Alive, >day 365 | 1/48.78 | 5/2.50 | 1/0.26 | 2/1.63 | 2/1.60 | 2/4.23 | |
015 | AML | RD 10/10 | MA | MTX | Midostaurin + gilteritinib | 35 | N | Alive, >day 365 | 0/NE | 0/NE | 1/36.07 | 1/30.3 | 1/31.2 | 2/0.94 | |
016 | MDS | URD 10/10 | RIC + ATG | MTX + Abat | HMA | 89 | N | Expired, sepsis, day 268 | 1/33.18 | 5/1.46 | 1/0.98 | 1/0.03 | 1/0.06 | 0/NE | |
017 | CML | URD 10/10 | RIC | MTX + Abat | Imatinib | 52 | N | Alive, >day 365 | 1/6.66 | 3/3.78 | 0/NE | 1/0.21 | 0/NE | 0/NE | |
018 | 2nd-AML (BrCa) | URD 10/10 | RIC | MTX + Abat | NA | N | Alive, >day 365 | 6/1.42 | 8/0.63 | 2/0.57 | 0/NE | 0/NE | ND | ||
019 | 2nd AML (MF) | Haplo | NMA | PTCy | NA | N | Alive, >day 365 | 9/5.79 | 6/9.43 | 3/0.18 | 5/0.54 | 2/0.23 | 1/0.06 | ||
020 | AML | URD 10/10 | MA + ATG | MTX + Abat | NA | N | Alive, >day 365 | 5/4.11 | 7/1.71 | 1/0.97 | 1/0.37 | 0/NE | 1/0.37 | ||
021 | MDS | URD 10/10 | RIC + ATG | MTX + Abat | Sorafenib | 77 | N | Alive, >day 365 | 2/0.69 | 4/1.20 | 0/NE | 1/0.11 | 1/0.11 | 0/NE |
Sub No | Relapse (Y/N) | Pre-Transplant BM | VAF | Pre-Transplant cfDNA | VAF | Day 84 BM | VAF | Day 84 cfDNA | VAF |
---|---|---|---|---|---|---|---|---|---|
001 | N | DNMT3a SRSF2 IDH1 | 15.85 4.66 1.3 | DNMT3A SRSF2 | 28.57 15.38 | ND | ND | ||
002 | Y | TP53 HNF1A | 48.34 24.54 | TP53 HNF1A | 63.57 28.71 | TP53 HNF1A | 2.5 0.51 | TP53 HNF1A | 3.19 0.84 |
003 | N | BCOR KMT2D | 13.85 8.8 | Neg | Neg | Neg | |||
004 | N | DNMT3A | 44.48 | DNMT3A | 44.87 | DNMT3A | 0.28 | Neg | |
005 | N | TP53 PPM1D CHEK2 NOTCH3 PPM1D | 5.2 2.18 7.53 3.95 1.66 | TP53 PPM1D CHEK2 NOTCH3 PPM1D BRAF PPM1D CARD11 KMT2A PMS1 CDK12 PBRM1 TP53 KEAP1 CARD11 KMT2C | 5.53 5.13 4.76 2.79 0.67 5.97 3.23 0.76 0.7 0.58 0.56 0.52 0.35 0.21 0.18 0.11 | KMT2A GATA3 MAP3Ki4 TET2 KRCC2 | 0.19 0.95 0.47 0.37 0.21 | TP53 PPM1D | 0.37 0.32 |
006 | N | TET2 EZH2 ASXL1 TET2 | 52.71 47.1 33.71 23.92 | TET2 EZH2 ASXL1 TET2 | 49.13 36.36 34 27.4 | ASXL1 | 2.55 | TET2 TET2 | 0.25 0.05 |
007 | Y | SRSF2 ASXL1 NRAS MTOR MTOR MTOR KDM6A ARAF | 55.44 50.62 41.9 31.37 30.0 27.27 6.15 4.17 | SRSF2 ASXL1 NRAS MTOR MTOR MTOR FH GNAQ IRF4 | 45.55 48.27 48.59 40.26 38.3 36.09 2.71 4.17 4.11 | SRSF2 ASXL1 NRAS MTOR MTOR MTOR GNAS GNAS GNAS BCL6 | 9.4 10.24 7.63 0/73 0.48 0.8 10.41 8.46 8.67 13.43 | SRSF2 ASXL1 NRAS MTOR MTOR FH DNMT3A | 5.62 8.29 4.46 0.55 0.31 1.85 0.27 |
008 | N | Neg | Neg | Neg | Neg | ||||
009 | Y | TET2 NRAS | 0.28 1.54 | TET2 TET2 WT1 NFKBIA NRAS FLT3-ITD | 5.78 1.38 0.83 0.6 0.39 0.23 | TET2 WT1 NFKBIA FLT3-ITD | 0.15 0.69 0.25 0.14 | TET2 WT1 NFKBIA NRAS FLT3-ITD WT1 WT1 | 2.73 3.02 3.77 0.13 2.4 0.12 0.41 |
010 | Y | SRSF2 MPL IDH2 | 18.93 4.31 6.61 | SRSF2 MPL IDH2 | 37.89 23.93 15.2 | SRSF2 MPL IDH2 KMT2C | 36.08 0.54 16.24 3.87 | SRSF2 IDH2 | 31.04 36.11 |
011 | N | TP53 TET2 PDGFRB | 31.54 16.72 14.79 | TP53 TET2 PDGFRB | 5.26 8.62 19.86 | Neg | PDGFRB | 6.32 | |
012 | Y | AXIN1 SF3B1 ASXL1 ASXL1 AMER1 | 16.83 17.7 6.4 4 8.05 | AXIN1 SF3B1 ASXL1 ASXL1 AMER1 H3F3A EGFR RUNX1 KMT2C ASXL1 | 34.8 33.02 3.03 3.01 2.14 17.7 3.46 2.61 1.79 1.4 | AXIN1 SF3B1 RUNX1 KMT2B | 0.25 0.49 0.28 1.68 | AXIN1 SF3B1 AMER1 EGFR RUNX1 KMT2C KMT2C | 0.5 0.35 0.05 0.36 0.28 0.48 1.86 |
013 | Y | Neg | TP53 TET2 NOTCH1 TET2 | 43.38 0.78 0.47 0.19 | NF2 | 0.37 | TP53 | 0/37 | |
015 | N | Neg | Neg | KMT2B DNMT3A | 1.25 0.7 | Neg | |||
016 | N | SF3B1 | 33.18 | SF3B1 TNFRSF14 KMT2D DNMT3A MAP3K1 | 43.33 1.48 0.83 0.33 0.26 | Neg | SF3B1 | 0.06 | |
017 | N | ASXL1 | 6.66 | ASXL1 CEBPA DNMT3A | 12.81 5.2 0.81 | Neg | Neg | ||
018 | N | ALK SRSF2 TET2 SRSF2 DDX41 | 0.97 0.8 0.51 0.29 1.82 | ALK SRSF2 TET2 SF3B1 SF3B1 ALK FGFR4 | 1.46 0.17 0.2 0.21 0.34 0.44 0.35 | ND | Neg | ||
019 | N | CALR U2AF1 ASXL1 GNAS KRAS RUNX1 GALNT12 TP31 GRIN2A | 39.23 38.39 34.88 20.25 20.11 2.04 0.87 0.6 0.32 | CALR U2AF1 ASXL1 GNAS KRAS RUNX1 | 17.76 15.04 19.57 12.98 12.92 0.8 | ASXL1 | 0.06 | CALR U2AF1 | 0.29 0.18 |
020 | N | DMNT3A. NF1 ASXL1 TET2 SMC3 | 32.74 4.4 2.52 3.72 0.87 | DMNT3A. NF1 ASXL1 TET2 SMC3 PDGFRB KMT2C | 33.87 4.27 3.64 2.2 0.4 0.4 0.23 | DNMT3A | 0.37 | DNMT3A | 0.36 |
021 | N | DNMT3A DNMT3A | 1.02 0.47 | DNMT3A DNMT3A CBL NFI I | 1.38 1.01 1.03 1.46 | Neg | CBL | 0.11 |
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Rowley, S.D.; Albitar, M.; Baker, M.F.; Ali, A.; Kaur, S.; Suh, H.C.; Goy, A.; Donato, M.L. cfDNA Chimerism and Somatic Mutation Testing in Early Prediction of Relapse After Allogeneic Stem Cell Transplantation for Myeloid Malignancies. Cancers 2025, 17, 625. https://doi.org/10.3390/cancers17040625
Rowley SD, Albitar M, Baker MF, Ali A, Kaur S, Suh HC, Goy A, Donato ML. cfDNA Chimerism and Somatic Mutation Testing in Early Prediction of Relapse After Allogeneic Stem Cell Transplantation for Myeloid Malignancies. Cancers. 2025; 17(4):625. https://doi.org/10.3390/cancers17040625
Chicago/Turabian StyleRowley, Scott D., Maher Albitar, Melissa F. Baker, Alaa Ali, Sukhdeep Kaur, Hyung C. Suh, Andre Goy, and Michele L. Donato. 2025. "cfDNA Chimerism and Somatic Mutation Testing in Early Prediction of Relapse After Allogeneic Stem Cell Transplantation for Myeloid Malignancies" Cancers 17, no. 4: 625. https://doi.org/10.3390/cancers17040625
APA StyleRowley, S. D., Albitar, M., Baker, M. F., Ali, A., Kaur, S., Suh, H. C., Goy, A., & Donato, M. L. (2025). cfDNA Chimerism and Somatic Mutation Testing in Early Prediction of Relapse After Allogeneic Stem Cell Transplantation for Myeloid Malignancies. Cancers, 17(4), 625. https://doi.org/10.3390/cancers17040625