Myelodysplastic Syndrome (MDS) Low Risk

Haematological Pathway

for

South Wales Cancer Network

Document Control Sheet

Organisation / South Wales Cancer Network
Specialty/Project / Haematological Site Specific Group
Document Title / Myelodysplastic Syndrome (MDS) Low Risk Haematological Pathway
Document Number / 05/007
Version / Author/s / Ratified by
1.0 / Dr W Ingram
Dr J Kell / Dr C Fegan
Approved by / Approval date / Date of next review
South Wales Haematology Cancer Network Group / 8.1.14 / 8.1.15

Low Risk Myelodysplastic Syndrome (IPSS Low/Int-1)

NSAG Patient Care Pathway

Demographics

-The overall incidenceof MDS is 4 per 100,000 increasing to >30 per 100,000 in patients over 70 years old.

Diagnosis

-Full blood count with differential WBC including monocyte count

-Blood film analysis

-Reticulocyte count

-Bone Marrow aspirate and trephine biopsy

  • Morphology
  • Flow cytometry quantification of blast population
  • Iron stain
  • Reticulin stain
  • Cytogenetic analysis

-Additional investigations:

  • EPO level (if Hb <100 g/l)
  • JAK2 status (in suspected cases of MDS/MPN overlap syndromes)
  • PNH screen
  • CMV, Hepatitis B/C, HIV

Staging and Prognostication

-WHO classification of MDS

-Both the IPSS and the WPSS should be documented at diagnosis. IPSS-R can be used for prognostication, but not to guide therapy

-Additional investigations to aid prognostic stratification:

  • Ferritin

Information Required at MDT

-The WHO classification should be documented at MDT.

-The IPSS and WPSS (If available the IPSS-R may be recorded)

-All essential diagnostic information and any relevant additional investigations should be recorded.

Treatment

All new MDS cases should be discussed at an MDT.

All MDS patients should be evaluated for suitability for entry into local/regional clinical trials.

Further support for patients can be accessed via the MDS Patient Forum (

Supportive Care

-Supportive care remains the mainstay of treatment for the majority of patients with Low/Int-1 risk MDS.

-Local guidelines should be followed with respect to antimicrobial prophylaxis in neutropenic patients.

-Red cell transfusions for symptomatic anaemia.

-Platelet support for symptomatic thrombocytopenia.

-G-CSF may be considered for patients with low risk disease and recurrent infections.

-ESAs and iron chelation are discussed in further detail below.

Iron chelation

-The BCSH task force has taken the view that it cannot routinely recommend iron chelation in MDS as only limitedsurvival data has been reported in retrospective studies.

-Entry into clinical trials is strongly encouraged.

-A pragmatic view has been taken to consider iron chelation for patients with good prognosis MDS (RA/RARS/del(5q)) or those who may be considered for allogeneic transplantation.

-Ferritin >1000 ng/l or >20 units transfused red cells with ongoing transfusion need should trigger iron chelation therapy in suitable patients.

-Desferrioxamine is first line therapy with Deferasirox recommended for patients intolerant of desferrioxamine. Deferiprone could be considered in patients with normal baseline neutrophil counts.

Erythropoietin Stimulating Agents (ESA)

-ESA therapy should be considered for anaemic MDS patients with IPSS score of Low or Int-1 who fulfil the below criteria for predicting response (Score 0 and 1).

-Non-sideroblastic phenotypes should start with EPO or DA alone. Start EPO at 30,000 units per week for eight weeks, if no response increase to 60,000 units per week or 30,000 units twice per week for a further 8 weeks. Alternatively start DA at 300ug once every 14 days or 150ug once every 7 days, if no response after eight weeks increase to 300ug per week for a further 8 weeks.

-For sideroblastic phenotypes (RARS and RCMD-RS) ESA should be combined with G-CSF starting at 300ug per week in 2/3 divided doses (or 105ug 2/3 times per week) increasing to 300ug three times per week in non-responders. Aim for doublingof WBC if < 1.5 x 109/l or WBC 6-10 x 109/l.

-The haemoglobin should not be allowed to rise above 12g/dl.

Predictive response to ESA: Score 0 = 74%, Score 1 = 23%, Score 2 =7%

Transfusion need / Point / S-EPO / Point
<2 units RBC/month / 0 / <500 U/l / 0
≥2 units RBC/month / 1 / ≥500 U/l / 1

Immunosuppressive Therapy

-ATG (horse) followed by ciclosporin may be considered in patients withLow/INT-1 MDS who are less than 60 years of age and have a normal karyotype or trisomy 8.

-Ciclosporin therapy alone may be considered for older patients particularly in cases with hypocellular BM or associated autoimmune phenomena.

MDS with del(5q)

-Supportive care including transfusions, ESAs and iron chelation are as described above.

-Lenalidomide has recently been licensed within Europe and under review by NICE. Access to this agent within Wales is currently only available via the IPFR route whilst awaiting NICE review.

-Selected patients with del(5q) and IPSS Low/INT-1 may be candidates for allogeneic stem cell transplantation. These include lenalidomide treated patients who fail to achieve transfusion independence, those losing their response, or patients with transfusion dependence not considered suitable for lenalidomide.

Allogeneic Stem Cell Transplantation

-Allo-SCT is the only treatment with proven curative potential.

-All newly diagnosed MDS patients eligible for SCT should be referred for discussionat the Myeloid MDT held at UHW.

Monitoring

-Monitoring should be tailored according to the patients’ symptoms and degree of blood count abnormality.

-Ferritin should be monitored in patients potentially suitable for iron chelation or allo-HSCT.

Discharge

-Patients with a confirmed diagnosis of MDS should remain under the care of a haematologist.

Reference

BCSH Guideline: Guidelines for the Diagnosis and Management of Adult Myelodysplastic Syndromes (Awaiting publication)

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Myelodysplastic Syndrome (MDS) Low Risk1