Monitoring for relapse with an artificial intelligence (AI)-powered peripheral blood-based tool called AlloHeme demonstrated greater sensitivity in predicting relapse after hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) than standard donor engraftment (chimerism) or measurable residual disease testing. Findings from a 2-year analysis of the ACROBAT study were presented during the 2026 Transplantation & Cellular Therapy Tandem Meetings of ASTCT and CIBMTR.1
“The ACROBAT results suggest that blood-based AlloHeme monitoring offers a simple, effective strategy for identifying relapse risk and enabling early intervention [in patients with acute myeloid leukemia and myelodysplastic syndrome],” said presenting author Ran Reshef, MD, MSc, Professor of Medicine at Columbia University and Director of Cell Therapy, Blood and Marrow Transplantation Program at Herbert Irving Comprehensive Cancer Center.
Background and Study Methods
Dr. Reshef explained that existing tools for monitoring relapse and measurable residual disease have limitations. For example, short tandem repeat–polymerase chain reaction–based chimerism testing may be useful for assessing engraftment, but it is not leukemia-specific and has limited sensitivity. Multiparametric flow cytometry is rapid and widely available but cannot be standardized because it is highly operator-dependent, has limited sensitivity, and requires bone marrow sampling.2
“We clearly need a tool that is highly sensitive, universal, and ideally noninvasive,” Dr. Reshef said.
Researchers conducted a prospective, observational cohort study to evaluate AlloHeme, a blood-based, next-generation sequencing–driven multi-analyte test, for detecting relapse after transplantation in patients with acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.
In the ACROBAT study, 285 patients were enrolled and monitored for relapse for up to 2 years after HCT, with testing performed biweekly for the first 3 months, monthly for the next 3 months, and quarterly from months 9 through 24. The assay’s performance was assessed at 24 months using leave-one-out cross-validation to evaluate its robustness.
The ACROBAT results suggest that blood-based AlloHeme monitoring offers a simple, effective strategy for identifying relapse risk and enabling early intervention [in patients with acute myeloid leukemia and myelodysplastic syndrome].— RAN RESHEF, MD, MSC
Tweet this quote
Testing involved peripheral blood sampling with next-generation sequencing of more than 400 single-nucleotide polymorphisms, supported by a proprietary AI algorithm. Dr. Reshef explained that the algorithm incorporates whole-blood chimerism and sorted myeloid cell chimerism (CD33) to detect early relapse. At least two consecutive tests were required to generate a definitive positive or negative result.
The study focused on patients with acute myeloid leukemia or myelodysplastic syndrome, yielding an analytical cohort of 198 participants. (Too few patients with acute lymphoblastic leukemia experienced relapse to be evaluated for the study.) Of these, 40 experienced disease relapse, 14 withdrew or were lost to follow-up, 26 had nonrelapse mortality, and 118 completed 2 years of follow-up. Dr. Reshef noted that this cohort was representative of a standard transplant population.
Results
Patients who tested positive with AlloHeme at 2, 3, or 6 months posttransplant were significantly more likely to relapse than those who tested negative, “indicating that the positive test is an excellent marker of impending relapse,” Dr. Reshef said.
At 2 months posttransplant, the hazard ratio (HR) for relapse was 5.9 (95% confidence interval [CI] = 2.1–16.8; P < .001); at 3 months, it was 6.3 (95% CI = 2.6–15.4; P < .001); and at 6 months, 11.9 (95% CI = 5.0–28.2; P < .001).
For relapse or death, the HR was 5.2 at 2 months (95% CI = 2.5–11.2; P = .010), 6.2 at 3 months (95% CI = 3.1–12.4; P < .001), and 4.1 at 6 months (95% CI = 1.7–9.6; P < .001).
In terms of assay performance, 43 patients had a positive AlloHeme result; of these, 9 (21%) did not experience relapse. Among the 115 patients with a negative result, 6 (5%) relapsed.
The test achieved 85% sensitivity and 92% specificity, with a positive predictive value of 79% and a negative predictive value of 95%. The area under the receiver operating characteristic curve was 0.89 and was consistent across subgroups. Dr. Reshef noted that these findings were based on a median of 11 tests per patient, rather than the protocol-defined 14, as compliance with the recommended testing schedule was challenging. He commented that assay performance might have improved with better compliance, more frequent testing, and longer follow-up.
AlloHeme detected relapse a median of 41 days before clinical relapse (range, 19–85 days). The mean time was 101 days (standard deviation, 153 days). No significant difference in lead time was observed between the groups of patients with acute myeloid leukemia and myelodysplastic syndrome.
Comparative Context
Compared with real-world approaches for detecting relapse, the ACROBAT study showed that AlloHeme performed better. Real-world chimerism testing showed a sensitivity of 60% (P < .05) and a median lead time of 0 days, whereas next-generation sequencing-based chimerism testing had a sensitivity of 53% and a median lead time of 16 days, according to the study authors.
Compared with real-world measurable residual disease testing, AlloHeme demonstrated superior performance. Bone marrow–based multiparametric flow cytometry had a sensitivity of 54% (P < .05) and a negative predictive value of 85%, whereas molecular measurable residual disease testing had a sensitivity of 48% (P < .05) and a negative predictive value of 82%. Overall, measurable residual disease testing had a sensitivity of 57% (P < .05) and a negative predictive value of 85%.
DISCLOSURE: Dr. Reshef reported a consulting or advisory role with Gilead Sciences, Bayer, Incyte, Sanofi, TScan, Orca Bio, Pierre Fabre Pharmaceuticals, CareDx, Sana Biotechnology, Sail Biomedicines, and Autolus. Dr. Reshef also reported receiving research funding from Atara Biotherapeutics, Incyte, Sanofi, Immatics, AbbVie, Takeda, Gilead Sciences, CareDx, TScan, Cabaletta, Synthekine, BMS, J&J, Allogene, Genentech, Vittoria Therapeutics, AstraZeneca, Kinomica, Sonoma Bio, Arecellx, and Imugene.
REFERENCES
1. Reshef R, Ciurea SO, Sobecks RM, et al: Acrobat Interim Results: Peripheral Blood-Based Alloheme Test Enables Robust Relapse Surveillance in Post-HCT AML and MDS Patients. 2026 Transplantation & Cellular Therapy Tandem Meetings of ASTCT and CIBMTR. Abstract 61. Presented February 6, 2026.
2. Haaksma LH, Cloos J, de Leeuw DC: Flow cytometric and molecular MRD in AML: current methods, clinical applications and challenges. Leuk Lymphoma 66:2357-2368, 2025.
Answering the Audience
After presenting the ACROBAT trial results at the 2026 Transplantation & Cellular Therapy Tandem Meetings of ASTCT and CIBMTR, Ran Reshef, MD, MSc, answered audience questions that provided further clarification of the findings.
Dr. Reshef explained that comparisons between AlloHeme and other chimerism tests did not align with the study’s protocol-defined time points for relapse assessment. Instead, results for each test were based on real-world data from participating centers.
He also explained that when AlloHeme was applied to bone marrow samples instead of peripheral blood, testing was performed less frequently, making consecutive testing more challenging.
Several audience members asked about the false-positive and false-negative results observed in the trial. Dr. Reshef noted that several relapse cases were clustered during periods when AlloHeme testing was less frequent. “I feel that missed testing or lower frequency of testing could be responsible for false negatives,” he said.
Dr. Reshef also noted that some cases of graft-vs-host disease and infections may have contributed to false positives, adding that these findings continue to be explored.
Session co-chair Phuong T. Vo, MD, Associate Professor, Clinical Research Division, Fred Hutch Cancer Center, asked what interventions clinicians might consider based on these results, given that the lead time ranged from 41 days to about 1 year. Dr. Reshef responded that how the test should be used in practice requires further study in future clinical trials, with the goal of developing intervention strategies and recommendations tied to the assay. “I do think that even if you’re getting several months of a heads up, and you know that there is such a high probability for a patient to relapse, it would still trigger an intervention. It would be nice to know what the individual lead time would be because then you might tailor the interventions a little bit differently…but we don't yet have sufficient data to discover what that individual time frame would be,” he said.
He also commented that AlloHeme is expected to serve as a complementary tool alongside measurable residual disease, next-generation sequencing, and other assays helping to reduce false positives and negatives and provide a more comprehensive picture.
The future cost of CareDx’s AlloHeme remains unknown, but Dr. Reshef noted that the planned turnaround time for results from the blood-based test is 3 days, with initial testing recommended at day 30 post-transplant. However, he emphasized that no real-world data currently support this approach, as it remains experimental.
