Dr Manoj Raghavan speaks to Suzy about the 2016 revised WHO classification of MDS and gives some hints about what is likely to be coming in the revised BSH guideline.
Dr Manoj Raghavan
Classification – see link below for full definitions.
Cytopenias defined as haemoglobin <100g/L, platelet count <100 x109/L, neutrophils <1.8 x109/L. These differ to the cytopenia thresholds in the IPSS-R.
– MDS with single or multilineage dysplasia (MDS-SLD; MDS-MLD)
– MDS with ringed sideroblasts with single or multilineage dysplasia or isolated del(5q) (MDS-RS-SLD; MDS-RS-MLD; MDS with isolated del(5q))
– MDS with excess blasts 1 or 2 (MDS-EB-1; MDS-EB-2)
– MDS unclassifiable (1% blood blasts; SLD and pancytopenia; based on defining cytogenetic abnormality; refractory cytopenia of childhood)
MDS defining cytogenetic abnormalities (no change from 2008 classification) whereby MDS may be diagnosed even in the absence of diagnostic morphological dysplasia.
|Unbalanced abnormalities||Balanced abnormalities|
|−7 or del(7q)||t(11;16)(q23;p13.3)|
|−5 or del(5q)||t(3;21)(q26.2;q22.1)|
|i(17q) or t(17p)||t(1;3)(p36.3;q21.1)|
|−13 or del(13q)||t(2;11)(p21;q23)|
|del(12p) or t(12p)||t(6;9)(p23;q34)|
Complex = 3 or more of the above
SF3B1 mutation in MDS-RS only require 5% RS to make a diagnosis; prognosis is better. DNMT3A, ASXL1, TET2 lower risk of progression and commonly found with ageing; P53 higher risk of progression.
MDS mimics include haematinic deficiencies, other nutritional deficiencies e.g. zinc, copper, increased cell turnover for other reasons e.g. immune cytopenias, drug effects e.g. methotrexate, HIV.
Generally a diagnosis requires cytopenias and dysplasia in at least one lineage involving >10% cells with evidence of clonality (see full classification for complete diagnostic criteria)
ICUS – idiopathic cytopenia of indeterminate significance – cytopenias, insufficient dysplasia to diagnose MDS and insufficient evidence of clonality (i.e. diagnostic criteria for other diagnoses not met)
CCUS – clonal cytopenia of indeterminate significance – cytopenias with evidence of clonality, but insufficient dysplasia to diagnose MDS
CHIP – clonal haematopoiesis of indeterminate potential – evidence of clonality in the absence of cytopenias and dysplasia
G (giemsa) banding – looking at chromosomes to assess for translocations/missing material
FISH (fluorescence in situ hybridisation) – looks for specific additions/losses
DNA panels – look at more or fewer copy numbers at particular loci indicating losses or gains of parts of chromosomes. May be done by SNP (single nucleotide polymorphism) arrays. Won’t identify balanced translocations, as DNA quantity will be the same. However in MDS these are rare. Can be done on peripheral blood (although the sensitivity will be lower than when done on marrow).
Need to weigh risks of treatment against the life expectancy for individual patients. IPSS and IPSS-R based on blasts, cytogenetics and cytopenias help stratify into risk groups (link below).
Red cell transfusion support guided by quality of life and symptoms, individualised. Swings in haemoglobin may be more important than the value of the haemoglobin. Rh and K matched
Iron chelation: consider in younger patients with low risk disease and long life expectancy. Risk of liver and renal side effects. TELESTO trial – desferasirox (Exjade)
Platelet support – generally for bleeding/symptoms. tPO mimetics may reduce bleeding risk without improving mortality. Concerns regarding risk of fibrosis have been largely disbanded.
Neutropenia – PRN GCSF for infections.
Azacitidine is the only licensed treatment for patients not fit for induction chemo/HSCT for those with 10-30% blasts. AZA001 study: Best supportive care or chemotherapy vs azacitidine. 2.5y OS with aza vs 1.5y for other treatments. Median survival 18m in patients on azacitidine in real life studies. Given as OP, tolerated well even in older patients.
High risk patients suitable for transplant: aim to get blast count <10% prior to HSCT. Induction chemotherapy is with AML agents.
MDS with del(5q) – treat with epo or if unsuccessful lenalidomide, which can induce cytogenetic remissions and reduce transfusion dependence. May select out TP53 mutations. Good prognosis if isolated del(5q) (NB lenalidomide only licensed in patients with isolated del(5q)).