An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults

Abstract

Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation.

Persistence of immunophenotypically aberrant CD34+ myeloid progenitors is frequent in bone marrow of patients with myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms treated with hypomethylating agents

“…HMAs have also shown promising results in patients with low-risk MDS 5–7. Responses to HMAs are assessed based on haematological improvement (HI), reduction of the bone marrow (BM) blast count and cytogenetic response following the criteria proposed by the International Working Group (IWG) for MDS8 or MDS/MPN 9. It is noteworthy that patients may require several (4–6) months to achieve a response to HMAs, and this response can improve over time 10.…”

CMML: Clinical and molecular aspects

“…CMML may present with general symptoms akin to those seen in patients with non-CML MPN such as PMF [4]. To date there is no validated questionnaire for CMML patients, but recent biological findings suggest that plasma levels of inflammatory cytokines can also be elevated in CMML [28], paving the way for dedicated therapeutic intervention such as JAK inhibition [29].…”

“…Progress in this direction is ongoing, with for instance a recent proposal for consensus response criteria in CMML [4], that have been retrospectively validated (Duchmann et al, in press). Akin to MDS, it is tempting to stratify CMML as high-risk and low-risk disease, with high-risk cases requiring disease-modifying interventions, and low-risk disease eligible for symptomatic treatment aiming mostly at dampening myeloproliferation or improving cytopenias in MP-CMML and MD-CMML, respectively.…”

Myelodysplastic Syndromes

“…The genetics, biology, and clinical approach to MDS/MPN are distinct from those of MDS without proliferative features and are not discussed further herein. 16 …”