How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European LeukaemiaNet

Abstract

Resistance to therapeutic agents is a major factor in the failure of cancer treatments. In leukemia, the resistant cells remaining in the bone marrow and/or peripheral blood constitute minimal residual disease and are detectable by highly sensitive assays when the patient appears to be in complete remission. Early detection of the expansion of residual cells permits clinical intervention with the aim of reversing the proliferation of resistant leukemic cells. Therefore, accurate and precise measurement of minimal residual disease can greatly enhance optimization of oncology patients' clinical management. This notion is supported by a large body of data among chronic myeloid leukemia patients, but minimal residual disease detection and monitoring is increasingly applied to other types of leukemia, and is starting to be a factor in decision-making for some therapeutic trials in childhood acute lymphoblastic leukemia. Here, from the solid ground of minimal residual disease detection in chronic myeloid leukemia, the current state of the art and development of molecular techniques in other leukemias and the growing field of multiparameter flow cytometry are reviewed in two separate parts reporting on the respective advances, advantages and pitfalls of these emerging methods.Key words: minimal residual disease, leukemia, flow cytometry, standardization, monitoring. LeukaemiaNet. Haematologica 2009;94:1135-1150. doi:10.3324/haematol.2008 Citation: Béné MC and Kaeda JS. How and why minimal residual disease studies are necessary in leukemia: a review from WP10 and WP12 of the European

Escalating-dose HLA-mismatched DLI is safe for the treatment of leukaemia relapse following alemtuzumab-based myeloablative allo-SCT

“…14,21 However, these protocols were established in the context of HLA-matched sibling 22 and fully MUD transplants. 9,10 Whilst there is an increasing literature on transplant regimens permitting the use of MMUD as a source of stem cells, the safety of DLI in this setting remains largely unclear. Existing studies comprise mainly small data sets on modified DLI regimens, and more work is therefore needed to establish the safety of such an approach.…”

“…10 A starting dose of 1 Â 10 6 T cells/kg was given followed by increasing doses at 3-6 monthly intervals (1 Â 10 6 , 1 Â 10 7 , 5 Â 10 7 and 1 Â 10 8 T cells/kg) in the absence of GVHD. 12 All patients had stopped immunosuppression prior to administration of DLI.…”

“…8 However, the combination of T-cell depletion and increasingly sensitive methods of minimal residual disease detection results in early relapse detection. 9,10 DLI is a safe and powerful strategy to treat post-HSCT relapse in sibling and MUDtransplant recipients. [11][12][13][14] Indeed registry data suggest that between 16 and 40% of patients undergoing HSCT will receive post-transplant DLI for the treatment of relapse or mixed chimerism.…”

Validation of cell‐based fluorescence assays: Practice guidelines from the ICSH and ICCS – part IV – postanalytic considerations

“…In reporting MRD, the immunophenotype of the remaining neoplastic clone identified is compared with that observed in prior studies for several key reasons: (a) describing the clone in reference to normal counterparts; (b) noting possible antigen drift; and (c) lineage switch in undifferentiated and mixed phenotype leukemia; all of which have potential therapeutic implications (12). Any immunophenotypic aberrancy identifying the clone must be included in the report and a comment made on comparison to prior studies.…”

The European LeukemiaNet: achievements and perspectives

“…WP10 has closely collaborated with the clinical groups regarding the development of flow-cytometry for the diagnosis and monitoring of minimal residual disease, 38 particularly in MDS. 19 • A major challenge for the cytogenetics working-group (WP 11) has been the harmonization of techniques and the identification of cryptic and complex chromosome aberrations.…”