Myeloid group
GUIDELINE ON THE USE OF ERYTHROPOIETIN IN MDS
INDICATION
Many patients with MDS require supportive care. The aim of supportive care is to maintain the blood count at a point where quality of life is maintained.
The objective of this guideline is to help clinicians identify groups of MDS patients who might respond to erythropoietin (Epo) and to offer guidance on the management of MDS patients requiring Epo and/or G-CSF.
Investigations prior to starting Epo
• FBC • Creatinine (for estimated GFR) • Serum epo level measured at the Hb nadir prior to transfusion • Ferritin • Fe/TIBC ratio or equivalent (if ferritin<500) • Bone marrow karyotype, blast percentage, ring sideroblast percentage • Record BP
Erythropoietins Products- Either short or long acting Epo may be used.
Short acting Epoetin alpha (Eprex) Epoetin beta (NeoRecormon) Epoetin delta (Dynepo)
Long acting Darbepoetin alpha (Aranesp)
1. Erythropoietin in non-sideroblastic MDS subtypes
Eligibility
• IPSS low or int-1 risk disease
In addition patients should have one or both of the following criteria: • Serum Epo <500 iu/ml • Transfusion requirement < 2 units/month
This is a controlled document and therefore must not be changed 1 of 4 ML.26 Use of Authorised by Leukaemia lead Prof Paresh Vyas March 2017 V. 2.0 Erythropoietin in MDS
Myeloid group
Approximately 50% of this group of MDS patients will have a meaningful response to Epo. Patients outside this group are much less likely to respond.
Patients with MDS and excess sideroblasts should be considered for upfront Epo/GCSF combination (see below)
Dosing
• Epoetin (alpha, beta, delta): 10,000 units weekly initially and uptitrate every 4 weeks to a maximum of 30,000 units. If no response is seen after 8 weeks, consider increasing to 60,000 units once per week and/or adding G-CSF according to schedule below.
OR
• Darbepoetin: 500 mcg every three weeks initially and if no response after 8 weeks increase to 300mcg once every week and consider adding G-CSF according to schedule below.
G-CSF (for patient with inadequate response): Start Filgrastim 300mcg or Lenograstim 263mcg, two to three times per week. Monitor blood count weekly and titrate dose to keep WBC between 6 and 10x109/l.
Response Assessment
An assessment of erythroid response should be made after 8 weeks. If there is a less than 10g/L increase in Hb, the dose of Epo should be increased and G-CSF considered. If there is no response after a further 8 weeks, stop the drugs.
Check BP at each clinic visit
2. Upfront Epo-GCSF (EpoG) combined therapy in sideroblastic subtypes of MDS
Eligibility
Patients with MDS and ring sideroblasts who are IPSS low or int-1 risk with serum epo<500iu/ml and/or transfusion requirement <2 units/month
Dosing
Start with epoietin (alpha, beta, delta) 10,000 units weekly uptitrated 4 weekly to maximum of 30 000units or darbepoietin 500mcg every three weeks with G-CSF added incrementally as described above.
Response Assessment
Check response after 8 weeks, if increment in Hb <10g/L, increase epoietin to 60,000 units weekly or darbepoietin to 300mcg weekly. Re-assess response after 8 weeks, if increment in Hb <10g/L, stop Epo-G. This is a controlled document and therefore must not be changed 2 of 4 ML.26 Use of Authorised by Leukaemia lead Prof Paresh Vyas March 2017 V. 2.0 Erythropoietin in MDS
Myeloid group
Check BP at each clinic visit
3. Follow-up monitoring
• FBC (aim for Hb 100-120g/L, higher Hbs are associated with poorer overall survival). Reduce Epo dose by 25% if rise in Hb is too rapid.
• BP (if systolic >150 or diastolic >100, consider Epo dose reduction of 25%)
• If response to Epo suboptimal consider oral iron (Ferrous Sulphate) 200mg daily
4. Loss of response to Epo
Median duration response is about 24 months. Loss of response to Epo does not necessarily herald transformation but the status of the MDS should be re-evaluated. Stop Epo if response is lost.
This is a controlled document and therefore must not be changed 3 of 4 ML.26 Use of Authorised by Leukaemia lead Prof Paresh Vyas March 2017 V. 2.0 Erythropoietin in MDS
Myeloid group
International prognostic scoring system (IPSS) for MDS
Prognostic Variable Score Value 0 0.5 1.0 1.5 2.0 BM blasts (%) <5 5-10 11-20 21-30
* Karyotype Good Intermediate Poor Cytopenias 0/1 2/3
Scores for risk groups are as follows: Low, 0; INT-1, 0.5-1.0; INT-2, 1.5-2.0; High, > 2.5.
* Good, normal, -Y, del(5q), del(20q); Poor, complex (> 3 abnormalities) or chromosome 7 anomalies; Intermediate, other abnormalities.
References
1. Killick S et al Guidelines for the diagnosis and management of adult myelodysplastic syndromes. British Journal Of Haematology 2014;164:503-25 2. Jädersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellström-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005 Aug 1;106(3):803-11. 3. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.
REVIEW
Name Revision Date Version Review date
Dr Alex Sternberg, Prof Paresh Vyas Re-draft March 2017 v.2.0 March 2019
This is a controlled document and therefore must not be changed 4 of 4 ML.26 Use of Authorised by Leukaemia lead Prof Paresh Vyas March 2017 V. 2.0 Erythropoietin in MDS