Review Explores Adoption of New MRD Monitoring Method

Evidence exists that partial tandem duplication levels from the MLL gene (MLL-PTD) are known indicators of poor prognosis in small groups of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following allogeneic hematopoietic stem cell transplant (allo-HSCT),^1,2 and a new review³ explored using them to monitor for minimal residual disease status to predict disease relapse.

Writing in BMC Cancer, the authors noted, “Allo-HSCT is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for MRD monitoring in transplant patients remains unknown.”

Peking University People’s Hospital provided retrospective data on 48 patients with MLL-PTD AML (n = 33; 20 females) or MDS-EB (n = 15; 11 males) who underwent allo-HSCT at the facility, with their MLL-PTD measured at various time points—diagnosis, prior to allo-HSCT, several times after allo-HSCT—using real-time quantitative polymerase chain reaction (PCR). A cutoff level of detectable MLL-PTD/ABL greater than 0.08% indicated a positive MLL-PTD result, the authors wrote.

Overall, at the 3-year mark after allo-HSCT, the investigators saw the following mean (SD) incidence rates:

• Cumulative incidence of relapse (CIR): 13.7% (5.2%)
• Overall survival (OS): 67.8% (6.9%)
• Disease-free survival (DFS): 68.1% (6.8%)
• Treatment-related mortality (TRM): 20.3% (6.1%)

ROC curve analysis additionally produced the authors’ optimal cutoff value for prediction of relapse after allo-HSCT, MLL-PTD > 1.0%, for which statistical differences in the above 4 indicators (all P < .001) were seen at the 3-year mark compared with using MLL-PTD < 1.0%:

• CIR: 75.0% (15.3%) vs 0% (P < .001)
• OS: 25.0% (15.3%) vs 80.7% (6.6%) (P < .001)
• DFS: 25.0% (15.3%) vs 80.7% (6.6%) (P < .001)
• TRM: 0% vs 19.3% (6.6%) (P = .277)

During the follow-up period (median, 26 [range, 0.7-56.0] months), the AML group had 7 treatment-related and 6 hematological relapse–related deaths; 2 patients died from the MDS-EB group.

When discussing their findings, the authors noted that although PCR-based gene detection methods have proven effective as a monitoring tool among patients with AML, most of this group still lack “effective, specific MRD molecular markers.” Physicians, they emphasized, need to watch more closely for posttransplant relapse among patients with MLL-PTD/ABL > 1%. It may also be necessary to shorten the MRD monitoring interval, they wrote.

“Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden,” the authors concluded. “The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.”

Due to the small size of their study cohort of patients with MLL-PTD AML, they stress the need for ongoing research to confirm their findings.

Reference

1. Choi SM, Dewar R, Burke PW, Shao L. Partial tandem duplication of KMT2A (MLL) may predict a subset of myelodysplastic syndrome with unique characteristics and poor outcome. Haematologica. 2018;103(3):e131-e134. doi:10.3324/haematol.2017.185249

2. Sun Q-Y, Ding L-W, Koeffler HP. Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). Leukemia. 2017;31(1):1-10. doi:10.1038/leu.2016.160

3. Kong J, Gao M-G, Qin Y-Zm et al. Monitoring of post-transplant MLL-PTD as minimal residual disease can predict relapse after allogeneic HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome.BMC Cancer. Published online January 3, 2022. doi:10.1186/s12885-021-09051-5