Figure 3.
MD Anderson Cancer Center institutional algorithm to manage patients with high-risk AML after alloHSCT outside of a clinical trial. The presented algorithm is adopted from MDACC’s institutional guidelines to help identify patients who may be candidates for cell therapy post-alloHSCT and to structure the clinical decision-making process that feeds into the management of this hard-to-treat patient population. As a general rule, we propose an individualized risk-stratified approach that takes into account both pretransplant clinical features (eg, remission status, molecular and cytogenetic risk profile, comorbidities, chemorefractory disease), transplant-associated aspects (eg, graft type, donor source, conditioning regimen, degree of HLA disparity, type of GvHD prophylaxis), and posttransplant parameters including the emergence and severity of aGvHD, MRD markers, and chimerism studies. Whenever possible, patients should be evaluated for inclusion into a clinical trial to benefit from novel innovative treatment strategies. Outside of clinical trials, patients should be treated on protocols whenever possible. Candidates for DLI should be discussed at a patient management conference. (1) MRD studies should be performed in accordance with Food and Drug Administration guidance and based on either multiparameter flow cytometry, reverse transcriptase-quantitative polymerase chain reaction (PCR), allele-specific oligonucleotide PCR (ASO-PCR), or targeted NGS. Assessment of MRD levels should be performed longitudinally (ie, both pre- and posttransplant) to provide the highest degree of sensitivity and specificity in detecting clinically relevant leukemia-driving clones taking into account the manufacturer’s guidance for the specific diagnostic test used. Results should be carefully interpreted in light of the test’s inherent sensitivity and specificity as well as diagnostic limitations arising from clonal evolution and clonal heterogeneity. (2) Chimerism assessment is done on peripheral blood or bone marrow. Due to the lack of unequivocal data and the concern of inducing GvHD, our institutional guidelines preclude any conclusions regarding the use of preemptive cell therapy based on mixed T-cell chimerism studies only.