MRD evaluation of AML in clinical practice: are we there yet?
MRD evaluation of AML in clinical practice: are we there yet? Hematology Am Soc Hematol Educ Program. 2019 Dec 06;2019(1):557-569 Authors: Freeman SD, Hourigan CS Abstract MRD technologies increase our ability to measure response in acute myeloid leukemia (AML) beyond the limitations of morphology. When applied in clinical trials, molecular and immunophenotypic MRD assays have improved prognostic precision, providing a strong rationale for their use to guide treatment, as well as to measure its effectiveness. Initiatives such as those from the European Leukemia Network now provide a collaborative knowledge-based framework for selection and implementation of MRD assays most appropriate for defined genetic subgroups. For patients with mutated-NPM1 AML, quantitative polymerase chain reaction (qPCR) monitoring of mutated-NPM1 transcripts postinduction and sequentially after treatment has emerged as a highly sensitive and specific tool to predict relapse and potential benefit from allogeneic transplant. Flow cytometric MRD after induction is prognostic across genetic risk groups and can identify those patients in the wild-type NPM1 intermediate AML subgroup with a very high risk for relapse. In parallel with these data, advances in genetic profiling have extended understanding of the etiology and the complex dynamic clonal nature of AML, as well as created the opportunity for MRD monitoring using next-generation sequencing (NGS). NGS AML MRD detection can stra...
High-resolution genome-wide SNP-arrays detect large chromosomal aberrations including copy-neutral loss of heterozygosity (CNLOH), which is not captured in conventional cytogenetics.
We previously demonstrated poor outcomes of patients with acute myeloid leukemia (AML) with antecedent myeloproliferative neoplasms (MPN) undergoing allogeneic hematopoietic stem cell transplantation (HCT) (Gupta et al, BBMT, 2019; abstract 140). In particular, we did not find any difference in outcomes of patients who received transplant “in remission” defined as blood and bone marrow blasts
BMT CTN 0901 enrolled patients with MDS (N=54) or AML (N=218) (median age of 55 years) who had
The WHO 2016 AML-MRC designation applies to AML patients (pts) with a history of myelodysplastic syndrome (MDS) or MDS/myeloproliferative neoplasm, a MDS-related cytogenetic abnormality, or multilineage dysplasia in>50% of ≥2 cell lineages in the absence of NPM1 or biallelic CEBPA mutations. AML-MRC pts typically have a poor prognosis after induction chemotherapy. CPX-351 (Vyxeos®; daunorubicin and cytarabine liposome for injection), a dual-drug liposomal encapsulation of cytarabine [C] and daunorubicin [D] at a sy nergistic ratio, is approved by the FDA and EMA for the treatment of adults with newly diagnosed th...
Acute myeloid leukemia bearing a RUNX1 gene mutation (RUNX1+ AML) has been proposed as a provisional entity in the 2016 WHO classification. Clinically, it has been associated with inferior response rates and outcome after conventional chemotherapy. Accordingly, RUNX1+ AML is allocated in the unfavorable prognostic category of the 2017 European Leukemia Net classification. Following allogeneic stem cell transplantation (alloSCT), RUNX1 was an unfavorable factor in one study in MDS/secondary AML, while data in de novo AML are scarce.
In QuANTUM-R, the once-daily, oral, highly potent and selective FLT3 inhibitor Q improved clinical benefit vs SC (median overall survival [mOS], 6.2 vs 4.7 mo [HR, 0.76 (95% CI, 0.58-0.98); P = .02]) in R/R FLT3-ITD AML (NCT02039726). Before randomization, 25% (Q) and 23% (SC) of pts had 1 prior HSCT.
Relapse of leukemic cells that do not express the antigen targeted by chimeric antigen receptor (CAR) is still a risk. As is the potential for targeting hematopoietic stem cells (HSCs) that share the same antigen expression, off-tumor on-target toxicity. Further, CAR T cells that bind different epitopes of the same antigen can have different tumor-killing efficacies. Therefore, we screen murine single chain variable fragment (scFv) based for indirect affinity to identify a CAR that targets Acute myeloid leukemia (AML), while minimizing toxicities.
For patients with refractory or high-risk hematologic malignancies, like acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplant (Allo-HSCT) is a potentially curative approach. Morbidities and mortality associated with current conditioning regimens limit the use of this curative procedure. As a result, many eligible patients do not consider transplant and 2/3 of those transplanted are only able to tolerate a reduced intensity conditioning regimen, which is associated with increased relapse rates (Scott, J Clin Onc 2017).
Relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) following an allogeneic stem cell transplant has a bleak prognosis with no standard for treatment identified. Current literature suggests combining hypomethylating agents (HMA) with a donor lymphocyte infusion (DLI) as salvage therapy to reduce disease burden and induce a graft versus leukemia (GVL) effect. At our institution, this salvage therapy option is being used for this population, peaking interest in our experience to date.
The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy.