The interference of genetic associations in establishing the prognostic value of the immunophenotype in acute myeloid leukemia
CYTOMETRY PART B-CLINICAL CYTOMETRY
Authors: van Solinge, Thomas S.; Zeijlemaker, Wendelien; Ossenkoppele, Gert J.; Cloos, Jacqueline; Schuurhuis, Gerrit J.
Abstract
BackgroundIn acute myeloid leukemia controversy exists about the role of immunophenotyping of the blasts at diagnosis as a potential prognostic factor. MethodsWe retrospectively analyzed immunophenotypic marker expression on blasts in relation to genetic aberrancies and survival data of 684 patients. All patients were included in different studies from the HOVON/SAKK Consortium. ResultsMarkers CD2, CD7, CD11b, CD19, CD22, and CD56 all appeared to be associated with one or more established prognostic genetic aberrancies. In the overall population, differences in univariate survival analyses were observed for CD2, CD11b, and CD22. After correcting these survival differences for currently used risk profile data, only CD11b expression remained of prognostic value for poor overall survival (OS) and event-free survival (EFS). CD11b expression turned out to be an independent factor for poor OS and EFS in the subgroup of patients who lacked cytogenetic and molecular aberrancies. ConclusionsIn this study, we demonstrate that associations between immunophenotypic markers and genetic aberrancies interfere with the prognostic properties of immunophenotypic markers. Such may account for most of the previously reported prognostic impact of these markers. Only CD11b expression remained as an independent prognostic marker. (c) 2017 International Clinical Cytometry Society
Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies
BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
Authors: Cooper, Mathew L.; DiPersio, John F.
Abstract
At present, the only curative therapy for patients with T-cell malignancies is allogeneic stem cell transplant, which has associated risks and toxicities. Novel agents have been tried in relapsed T-cell acute lymphoblastic leukemia (T-ALL), but only one, with 20%-30% complete remission rates, has been approved by the US Food and Drug Administration. T-ALL is a heterogeneous disease, but it has universal overexpression of CD7 as well as several other T-cell markers, such as CD2 and CD5. T cells engineered to express a chimeric antigen receptor (CAR) are a promising cancer immunotherapy. Such targeted therapies have shown great potential for inducing both remissions and even long-term relapse-free survival in patients with B-cell leukemia and lymphoma. UCART7 for CD7(+) T-cell malignancies is in development for treatment of relapsed T-ALL in children and adults. It may also have potential in other CD7(+) hematologic malignancies that lack both effective therapies and targeted therapies. The challenges encountered and progress made in developing a novel fratricide-resistant "off-the-shelf" CAR-T (or UCART7) that targets CD7(+) T-cell malignancies are discussed here.