Adult MDS (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
- Recurrent infection
- Dysmorphic features
- 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
- Reticulin stain
- Cytogenetics – performed on at least 25 metaphases
Further Investigations to consider
- Epo level
- PNH screen
- Fanconi anaemia screen
- Mutational analysis if constitutional cause suspected
- HLA typing of patient and siblings if transplant considered
- Parvo, CMV
- 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:
- Supportive Care
- 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
- Supportive care
- 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.