Impact of pretransplant measurable residual disease on the outcome of allogeneic hematopoietic cell transplantation in adult monosomal karyotype AML

Abstract

Allogeneic hematopoietic cell transplantation (HCT) is often unsuccessful for monosomal karyotype (MK) acute myeloid leukemia (AML). To what degree failures are associated with pretransplant measurable residual disease (MRD)-a dominant adverse risk factor-is unknown. We therefore studied 606 adults with intermediate-or adverse-risk AML in morphologic remission who underwent allogeneic HCT between 4/2006 and 1/2019. Sixty-eight (11%) patients had MK AML, the majority of whom with complex cytogenetics. Before HCT, MK AML patients more often tested MRD pos by multiparameter flow cytometry (49% vs. 18%; P<0.001) and more likely had persistent cytogenetic abnormalities (44% vs. 13%; P<0.001) than non-MK AML patients. Three-year relapse/overall survival estimates were 46%/43% and 72%/15% for MRD neg and MRD pos MK AML patients, respectively, contrasted to 20%/64% and 64%/38% for MRD neg and MRD pos non-MK AML patients, respectively. After multivariable adjustment, MRD pos remission status but not MK remained statistically significantly associated with shorter survival and higher relapse risk. Similar results were obtained in several patient subsets. In summary, while our study Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Conditioning Intensity, Pre-Transplant Flow Cytometric Measurable Residual Disease, and Outcome in Adults with Acute Myeloid Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

“…Consistent with previous reports from our institution [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ], patients testing MRD pos at the time of HCT had a substantially higher risk of relapse and shorter RFS and OS than MRD neg patients ( Table 2 ). Among MRD pos patients, 3-year estimates of relapse risk, RFS and OS were similar across the 3 conditioning intensities ( Table 2 and Figure 2 ).…”

“…higher 3-year estimates of RFS and OS than patients who received RIC or NMA conditioning, whereas 100-day NRM rates were similar for the three different conditioning intensities. Consistent with previous reports from our institution [16][17][18][19][20][21][22][23][24], patients testing MRD pos at the time of HCT had a substantially higher risk of relapse and shorter RFS and OS than MRD neg patients ( Table 2). Among MRD pos patients, 3-year estimates of relapse risk, RFS and OS were similar across the 3 conditioning intensities ( Table 2 and Figure 2).…”

“…Information on post-transplant outcomes was captured via the Long-Term Follow-Up Program through medical records from our outpatient clinic and local clinics that provided primary care for patients in addition to records obtained on patients on research studies. In previous publications, we have reported partial results from 667 of the 743 patients included in this study cohort [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Patients were treated either on Institutional Review Board-approved research protocols (all registered with ) or on standard treatment protocols.…”

Measurable residual disease (MRD) testing for acute leukemia in EBMT transplant centers: a survey on behalf of the ALWP of the EBMT

“…Confirming these findings, a recent meta-analysis including data from 19 articles reported between 2005 and 2016 demonstrated that detectable MRD (regardless of MRD methodology, MRD threshold, and conditioning regimen intensity) at transplantation predicted for higher relapse incidence and worse OS in allo-HCT patients [15]. Interestingly, detectable MRD has remained predictive of allo-HCT outcome in patients with monosomal karyotype (which is associated with a particularly poor prognosis by itself [16]) [17]. Thus, incorporating pretransplant MRD as an additional parameter in large transplant registry databases, though challenging, is of special importance.…”

Use of Measurable Residual Disease to Evolve Transplant Policy in Acute Myeloid Leukemia: A 20-Year Monocentric Observation

“…In our opinion, such a conception appears even more solid in a time when the availability of new, non-chemotherapeutic agents will theoretically allow to design specific transplant protocols, including maintenance, to prevent relapse in these pre-alloHCT MRD positive patients [ 33 ]. The idea to resume maintenance strategies appears particularly appealing in situations, such as the presence of complex or monosomic karyotype, TP53 mutations or high/very high pre-transplant MRD levels, in which GVL alone may fail to keep residual AML under control [ 34 ]. This may well explain why our AR category did not benefit from alloHCT.…”