Adult MDS (2013)

Intro

-       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

mds who.png

 

Diagnosis

 

History

-       Prior chemo/radiotherapy exposure

-       FHx of MDS/AML or pulmonary/liver fibrosis

-       Recurrent infection

Examination

-       Dysmorphic features

-       Splenomegaly, bruising, bleeding, infections, skin lesions

Bloods

-       FBC, Film, Reticulocytes, LDH, Ferritin, B2M, Blood group and Antibody screen

-       Hep B/C, HIV

Marrow

-       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

IPSS-R.jpeg

 

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

Source:  Blood Ref

Source: Blood Ref

 

Supportive Care

 

Transfusion

-       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

 

General Approach

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

 

5q- Syndrome

 

(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

 

General Approach

 

Transplant eligible patients

- Early HSCT - Precede by induction chemotherapy if >10% blasts or hypercellular bone marrow

 

Transplant ineligible patients

- Supportive care

- Azacitidine

- Intensive chemotherapy - consider if good PS, minimal co-morbidities, no high risk karytopic abnormalities

 

CMML

 

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.