Outcome and Minimal Residual Disease Monitoring in Patients with t(16;21) Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Patients with t(16;21) acute myelogenous leukemia (AML) who receive chemotherapy have poor outcomes. The treatment efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) must be identified, and the usefulness of minimal residual disease (MRD) monitoring requires evaluation. Fourteen consecutive patients with t(16;21) AML undergoing allo-HSCT at our institution were included in this study. Translocation liposarcoma- ETS-related gene (TLS-ERG) transcript levels were serially monitored for a median of 15 months (range, 3-51 months) after allo-HSCT. Eight patients relapsed, 7 patients died from relapse-related causes, and 1 patient died from a non-relapse-related cause. The 2-year cumulative incidence rates of relapse, disease-free survival, and overall survival after HSCT were 66.2%, 30.8%, and 46.2%, respectively. Of the 3 patients who received an HLA-matched sibling transplant, 2 relapsed, and 1 (33.3%) was in hematologic complete remission (CR) but died of nonrelapse mortality, whereas 5 of 11 patients (45.5%) who received haploidentical transplantation were in CR and were alive. Two of 6 patients with undetectable TLS-ERG at the time of allo-HSCT relapsed, at 14 and 15 months, and 3 of 4 PCR-positive patients relapsed, at a median of 10 months after HSCT. Four patients with continually low post-HSCT TLS-ERG levels (mostly <.01%) remained alive and in CR. The TLS-ERG levels of all 8 patients who relapsed were significantly increased before the relapse, exceeding 1.0% in all 7 patients who experienced hematologic relapse. In total, 7 patients received modified donor lymphocyte infusion (DLI), and 1 patient received IFN-α. All 7 patients with a TLS-ERG level >5.0% at the time of intervention experienced an increase or a brief decrease in TLS-ERG level, followed by an increase, and 6 relapsed, whereas the TLS-ERG level of 1 patient with a TLS-ERG level <1.0% at intervention decreased to undetectable. Therefore, t(16;21) AML is an indication for allo-HSCT. Among the HSCT recipients, 30.8% responded to treatment with CR. TLS-ERG transcript levels reflect MRD and might predict relapse and guide effective intervention.

The RTK–RAS signaling pathway is enriched in patients with rare acute myeloid leukemia harboring t(16;21)(p11;q22)/FUS::ERG

“…In comparison, Pan et al 1 conducted a retrospective study of patients with FUS::ERG AML and found that HSCT could improve OS but not leukemia-free survival. Alternatively, Qin et al 4 demonstrated that 5 of 11 patients with AML harboring FUS::ERG who underwent haploidentical transplantation were alive without relapse. The heterogeneity of the chemotherapy regimen and supportive care, as well as the small sample size in each study, might account for such inconsistent results.…”

“…This suggested that traditional chemotherapy failed to eradicate leukemic cells in these patients, which might partially explain the limited effect of HSCT in our study. 4 , 17 …”

“… 1 – 3 However, published results regarding the role of allogeneic hematopoietic stem cell transplantation (HSCT) in these patients are discordant. 1 , 4 …”

Single-cell immune landscape of measurable residual disease in acute myeloid leukemia

“…Patients also monitored MRD at the 1, 2, 3, 4.5, 6, 9, and 12 month after preemptive IFN-α treatment and at 6-month intervals thereafter. MRD-positivity was defined when a single BM sample tested positive for leukemia-associated aberrant immune phenotypes (LAIPs) and/or different from normal (DfN) by multiparameter flow cytometry (MFC) 22 or one of the following molecular markers: RUNX1-RUNX1T1 31 , CBFβ-MYH11 32 , KMT2A 33,34 , TLS-ERG 35 , DEK-NUP214 36 , BCR-ABL 37 , or NPM1 mutations A, B, and D 38 using realtime quantitative polymerase chain reaction (PCR) (Supplementary Methods).…”

The effect of varicella-zoster virus reactivation on the long-term outcomes of patients undergoing allogeneic hematopoietic stem cell transplantation

“…Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an efficient therapy that contains the potential to cure hematologic malignancies. Although the incidence of post-transplant relapse is now being lowered by monitoring minimal residual disease [ 1 ], creating risk-based preventative strategies [ 2 ], and optimizing donor lymphocyte infusions (DLI) [ 3 ], relapse continues to be the leading contributory factor to death in individuals following transplantation. Furthermore, because the preconditioning of allo-HSCT leaves the body in a condition of extreme immunodeficiency and years of B- and T-lymphocytopenia after transplantation [ 4 – 6 ], infectious complications remain a difficult challenge to deal with following allo-HSCT.…”