Myelodysplastic Syndrome (MDS) (BSH 2013)
Heterogeneous group of malignant hematopoietic disorders, characterized by dysplastic changes in 1 or more cell lineages, ineffective hematopoiesis and a variable risk of developing AML
4 per 100,000 per year (>30/100,000/year of >70 y.o.)
All patients should be offered a review at a regional expert centre given rarity of disease.
WHO 2016 Classification
Prior chemo/radiotherapy exposure
FHx of MDS/AML or pulmonary/liver fibrosis
Splenomegaly, bruising, bleeding, infections, skin lesions
FBC, Film, Reticulocytes, LDH, Ferritin, B2M, Blood group and Antibody screen
Hep B/C, HIV
MGG stain with assessment of 500 cells inc. 30 megakaryocytes – dysplasia should be present in at least 10% of cells of relevant lineage
Flow cytometry optional – no specific immunophenotype
Iron stain (Prussian Blue / Perls) - >15% ring sideroblasts for MDS-RS
Cytogenetics – performed on at least 25 metaphases
Further Investigations to consider
Fanconi anaemia screen
Mutational analysis if constitutional cause suspected
HLA typing of patient and siblings if transplant considered
Red cell extended phenotyping if chronic transfusion expected
JAK2 if MPN/MDS overlap suspected
Prognosis – IPSS-R
IPSS-R designed for use at diagnosis
The WHO WPSS can be used at any time during the course of the disease
Prognosis - IPSS
Therapy is guided by IPSS (based on blast % / karyotype / No. of cytopenias) , not IPSS-R
Low risk patients = IPSS Low / Intermediate 1 (INT-1)
High risk patients = IPPS INT-2 / High
Irradiated products after ATG or transplant
Transfuse to correct symptomatic anaemia and improve QoL
Consider extended phenotyping for those on chronic transfusion programme
Neutropenia + Infection
GCSF in low risk disease with recurrent infections
Antifungal prophylaxis if receiving active treatment
Thrombocytopenia + Active bleeding
Routine prophylactic transfusion may be appropriate in recurrent bleeding
But not required in stable non-bleeding patients regardless of absolute count
TXA, esp for mucous membrane bleeding
Spiritual and Emotional health needs
Rare disease, difficult to understand, many treatments, poor outlook
Management of Low Risk MDS
Discuss potentially eligible patients w/ allogeneic transplant team early after diagnosis, as early HSCT preferred
Non-transplant options include:
ATG + Ciclosporin - consider in patients <60 y.o. with normal karyotype or trisomy 8
Lenalidomide - consider in 5q- and 1 or fewer other karyotypic abnormalities
Erythropoeitin - add GSCF in siderolblastic variants. Stop after 16 weeks if no response
Consider iron chelation in some low risk patients with a very good prognosis – Desferrioxamine preferred due to experience of use
(Diagnostic note: One additional cytogenetic abnormality is allowed except for chromosome 7 abnormalities, which carry a very poor prognosis. Also, MDS-EB trumps 5q- diagnosis)
Typically presents as refractory anaemia in older women with macrocytosis, thrombocytosis and non-lobulated megakaryocytes (micromegakaryocytes).
Relatively indolent natural history.
Lenalidomide induces a durable transfusion independency, though patients ultimately relapse.
Even during complete cytogenetic response (CCyR) during lenalidomide therapy, morphology demonstrates persistence of non-lobated micomegakaryocytes.
Other Good Prognosis Cytogenetic Subtypes
SF3B1 mutation in MDS with Ring Sideroblasts and thrombocytopenia (MDS/MPN-RS-T)
Management of High Risk MDS
Transplant eligible patients
Early HSCT - Precede by induction chemotherapy if >10% blasts or hypercellular bone marrow
Transplant ineligible patients
Intensive chemotherapy - consider if good PS, minimal co-morbidities, no high risk karytopic abnormalities
Median age 76 years old.
Median survival only 20 months.
Molecular – Poor prognosis with SRSF2 or ASXL1 mutation. TET2 mutation no prognostic signif.
Cytogenetics usually normal
Non-transplant Mx = supportive care +/- hydroxycarbamide. Azacitidine for CMML-2
Other Poor Prognosis Cytogenetic Subtypes
SRSF2 mutation in MDS with Ring Sideroblasts
TP52 mutation adds poor prognosis in all MDS subtypes.