Myelodysplasia

Lead: Rena Buckstein
Date of last revision: Sept 1, 2020

Terms of use: These guidelines are a statement of consensus of the OCC Hematology site group regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult the Guidelines is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. Use of this site and any information on it is at your own risk.

Myelodysplastic Syndromes constitute a heterogeneous group of bone marrow stem cell disorders characterized by ineffective hematopoiesis, clonal instability and a propensity to develop AML. While only 1/3 of patients develop AML, expected actuarial survival is curtailed by more than 50% due to complications of cytopenias and functional cell defects with 85% of patients dying because of MDS. It is a disease with a median age at diagnosis of 74 and in 10% of patients, germline predisposition may be detected. 80% develops as a de-novo/primary disease and 20% develops secondary to prior exposure to chemotherapy and or radiotherapy. Up to 10% of patients will have inherited factors such as constitutional genetic disorders associated with MDS (Down syndrome, trisomy 8 mosaicism, familial monosomy 7), congenital neutropenia (Kostmann syndrome), dyskeratosis congenita, shwachman diamond syndrome, diamond blackfan syndrome, DNA repair defects (Fanconi’s anemia, ataxia telangiectasia, blood syndrome, xeroderman pigmentosum) and neurofibromatosis.¹

Diagnostic Work Up

Patient history and examination

• Detailed family history at least 2 generations back, including cancer, bone marrow failure, liver/lung disorders or early deaths.
• Prior chemotherapy or irradiation, occupational exposure, alcohol-use, concomitant medication.
• Tendency for bleeding or infection.
• Complete physical examination including spleen size
• Detailed transfusion history

Classification

• MDS should be classified according to the WHO 2016 classification² (appendix).

Blood tests

• WBC, differential, hemoglobin, platelet count, red blood cell indices (MCV, RDW) and reticulocyte count.
• Vitamin B12 and Serum Copper (if clinically relevant- eg GI malabsorption, severe malnutrition, gastric bypass or excess zinc supplementation)
• Beta-2 microglobulin
• Blood group and phenotyping (RH, Kell)
• Ferritin, TIBC, LDH, bilirubin, haptoglobin, DAT (Coombs test), ALT, alkaline phosphatase, albumin, uric acid, creatinine, S-erythropoietin, S-protein electrophoresis.
• Screening for HIV, hepatitis B and C.
• TSH
• PCR for parvovirus B19 in hypoplastic MDS.
• If suspicion of telomere-associated disease or other germline predisposition mutations, you may consider testing telomere length* and referral to a genetic counsellor, genetic testing
• Consider flow cytometry (FCM) to evaluate for large granular lymphocyte syndrome and PNH clone if clinically indicated

Morphology Diagnostic work-up requires evaluation of bone marrow aspirate and peripheral blood smears for the assessment of dysplasia and blast counts together with histological examination of a bone marrow biopsy, according to the WHO 2016 classification². Flow cytometry should be performed to aid with diagnosis (aberrant immunophenotype) and blast % enumeration but is not a substitute for histological diagnosis. Blast % enumeration (calculated out of all nucleated BM cells) by BM aspirate is the favored method.

Repeated bone marrow examinations within a few weeks or months may be necessary to establish the diagnosis of MDS and to identify cases with rapid disease progression.

Required elements:

• Significant dysplasia within at least one lineage (erythro-, granulo-, or megakaryopoiesis), and is defined as ≥ 10 % of cells with dysplastic features; a threshold of 30% is recommended for megakaryocytes.
• Blast count should be based on evaluation of at least 500 nucleated bone marrow cells (including erythroid) and 200 nucleated cells from peripheral blood.
• Marrow histology/immunohistochemistry: reporting should include cellularity, evidence of fibrosis, ring sideroblasts and marrow architecture including cell infiltrates or clustering. Immunohistochemistry for CD34 and p53 is recommended at diagnosis and at follow-up. The presence of cells with strong nuclear p53 staining may indicate an underlying TP53 mutation6
• The defining cytogenetic abnormalities in the appropriate clinical situation for a diagnosis of MDS unclassifiable are any of:
  • -7, del(7q), -5, del(5q), i(17q), t(17p), -13, del(13q), del(11q), del(12p) or t(12p), del(9q), idic(X)(q13), t(11;16)(q23;p13.3), t(3;21)(q26;q22.1), t(1;3)(p36.3;q21.2), t(2;11)(p21;q23), inv(3)(q21q26.2), t(6;9)(p23;q34)

Cytogenetics

• Standard metaphase karyotyping should be performed in all patients to allow correct classification and prognostic assessment.
• In cases of dry tap, peripheral blood testing for FISH of chromosome derangements including chromosomes 5, 7, 11 may be performed
• Next-generation sequencing (NGS): Mutational screening with NGS is recommended in all MDS categories to further refine risk stratification in lower risk patients and those being considered for allo transplant and strengthen the diagnosis in borderline cases^3-5. NGS may also help clarify diagnosis of MDS in patients with borderline dysplasia or ring sideroblasts such as the presence of Sf3B1 mutations. Common mutations and their frequency are summarized in table at end.

Differential diagnosis

The diagnosis of MDS may be difficult, in particular in patients with less than 5 % bone marrow blasts and only one cytopenia. No single morphologic finding is diagnostic for MDS and it is important to keep in mind that MDS sometimes remains a diagnosis of exclusion. Differential diagnoses to be considered:

• B12 / folate deficiency
• Recent cytotoxic therapy
• HIV/HCV/HBV/Parvovirus B19/CMV/EBV-infection
• Anemia of chronic disease
• Autoimmune cytopenia
• Chronic liver disease
• Excessive alcohol intake
• Exposure to heavy metals
• Drug-induced cytopenias
• Other stem cell disorders incl. acute leukemia (with dysplasia or megakaryoblastic leukemia), aplastic anemia, myelofibrosis (in case of MDS with marrow fibrosis) and paroxysmal nocturnal hemoglobinuria (PNH)
• Other cancers infiltrating the bone marrow
• Congenital cytopenias/bone marrow failure disorders

Prognosis

IPSS (International Prognostic Scoring System)⁶. The score excludes s/t-MDS and CMML with leukocyte count >12 x10⁹/l and is meant to be applied at diagnosis in untreated patients. Available in the appendix and online @ https://qxmd.com/calculate/calculator_123/mds-intnl-prognostic-scoring-sys-ipss

Revised IPSS (IPSS-R)⁷. Based on 7012 untreated patients excluded s/t-MDS and CMML with leukocyte count >12 x109 /l. Summarized in appendix and is available online. 

Additional Prognostic Factors

• Performance status, frailty and comorbidity
• Fibrosis (grade 2-3)
• LDH
• Red cell transfusion dependence
• Serum ferritin
• Beta-2 microglobulin
• Mutations associated with poor prognosis: TP53, EZH2, ETV6, RUNX1, NRAS and ASXL but their relevance varies according to risk score^4,8
• Several mutated genes are linked to specific clinical risk factors like thrombocytopenia and higher bone marrow blasts and the presence of ring sideroblasts.

Recommendation for diagnosis and prognosis

• All patients should be classified according to WHO 2016 classification.
• All patients should be risk stratified according to IPSS and IPSS-R.
• Additional prognostic features, such as bone marrow fibrosis, co-morbidity and molecular genetics may also be useful, as well as TP53 analysis by immunohistochemistry or sequencing.

Simplified definition of risk

• Low risk: Patients with IPSS Low and Int-1 risk disease or those with IPSS-R of Very Low, Low and Intermediate risk disease, although one study defined an IPSS-R score of <5 as lower risk⁹
• High risk: IPSS Int-2 and High or IPSS-R risk score of High and Very High (or > score of 3.5)

General principles for treatment low risk (individually detailed below)

1. Consider potentially curative treatment (allogeneic stem cell transplantation) for patients with IPSS-R intermediate, in particular in the case of additional risk factors (high-risk genetic features, bone marrow fibrosis, significant transfusion need, mutated TP53 etc.).
2. For patients with symptomatic anemia, consider ESA ± G-CSF to patients with predictive score 0 or 1 according to the Nordic predictive model.
3. For patients with ring sideroblasts not candidates for ESA, or having relapsed or been refractory to ESA, use luspatercept (NOC expected Feb 2021)
4. High-quality transfusion- and chelation therapy, when indicated.
5. Evaluate patients without excess blasts for immunosuppressive treatment.
6. Lenalidomide treatment for patients with IPSS-R low and intermediate risk MDS with isolated del(5q), who have failed growth factor treatment or are not eligible for this treatment according to the predictive model, and who are not TP53 positive by immunohistochemistry.
7. Patients with severe cytopenia and/or transfusion dependency who have failed other relevant therapies should be considered for experimental treatment within a clinical trial.

Red Cell Transfusions

• Transfuse for symptoms of anemia at an individualized threshold although this is rarely < 80 g/L. Transfuse with Rh and K prophylactically phenotype matched blood if possible. Ensure at time of first group & screen to notify Blood Bank.

Platelet Transfusions

• In general should not be used routinely in patients with thrombocytopenia in the absence of bleeding.
• Transfuse prophylactically for symptomatic grade 3-4 bleeding or recurrent grade 2 bleeds despite tranexamic acid
• Transfuse therapeutically for occasional symptomatic grade 1-2 bleeds
• There is no universal transfusion trigger but for patients being treated prophylactically, a plt count of 10 x 10⁹/L seems sensible but should be individuated
• Tranexamic acid 500 mg-1.5 grams po BID-TID may mitigate mucosal bleeding and reduce the need for allogeneic platelet transfusions

Iron Chelation Therapy

• Iron chelation prolongs event free survival in lower risk, transfusion dependent MDS patients with evidence of transfusional iron overload (TELESTO study)¹⁰
• Iron chelation is recommended in patients for whom long term transfusion therapy is likely, generally meaning patients with low and INT-1 IPSS-score (Very Low, Low and Intermediate risk in IPSSR). Start treatment when S-Ferritin > 1000-2500 mg/l, or after approximately 25 units red cell transfusions. Follow ferritin and TIBC every 3 months.
• For transfusion-dependent patients (including high risk) that may be candidates for a future allogeneic transplant, iron chelation should be initiated at an earlier stage.
• The target ferritin level is <1000 mg/l.

Iron chelation therapy treatment options

Desferrioxamine (DFO) treatment

• 40 mg/kg (20-50 mg) by subcutaneous infusion over 8-12 hours 5-7 days per week.
• Continuous (uninterrupted) 24 hour DFO should be considered in patients at high risk, e.g. with Ferritin persistently > 2500 mg/l and significant cardiac disease.
• All patients should have baseline and yearly audiometry and ophthalmology assessments
• Discontinue if creatinine clearance < 40 ml/min

Deferasirox treatment

• Available as dispersible formulation (Exjade) and as tablets (Jadenu)
• Jadenu has less GI side effects
• Dosing of Exjade is 20-40 mg/kg and for Jadenu (14-28 mg/kg) and depends on baseline iron burden and transfusion frequency
• Serum creatinine, bilirubin and ALT should be measured weekly the first four weeks of treatment, and then monthly.
• Dose limiting toxicities are renal and GI (lower with Jadenu)
• In case of elevated S-creatinine > 2 ULN, deferasirox should be interrupted and then restarted at lower dose. If rise in creatinine is excessive, drug may need to be discontinued if creatinine clearance < 40 ml/min
• All patients should have baseline and yearly audiometry and ophthalmology assessments

Deferiprone treatment

• May be available compassionately from APOTEX for patients unable to tolerate deferoxamine or deferasirox
• 75 mg/kg in three divided doses
• Can be combined with DFO to improve the efficiency of iron chelation
• Check blood counts weekly to rule out deferiprone-induced neutropenia/agranulocytosis, although the reported incidence is probably low

Thrombopoietin (TPO) receptor agonists

• Thrombopoietin (TPO) receptor agonists romiplostim (Nplate) and eltrombopag (Revolade) are approved for the treatment of immunological thrombocytopenic purpura (ITP). They have also been tested in several clinical studies for thrombocytopenic MDS patients, both as monotherapy^11,12 and in combination with myelosuppressive drugs (review¹³) and have been shown to increase platelet counts, reduce clinically significant bleeding events and reduce platelet transfusions but primarily in patients with lower risk disease and plt counts of > 20.
• Because of their potential to stimulate leukemia blasts, they are considered experimental in MDS and ideally administered in either the context of clinical trials or as bridging for seriously thrombocytopenic patients who need surgery or are refractory to platelets.
• They are not recommended for patients with lower risk disease but excess blasts (blasts > 5%)

Treatment and prevention of infections

• Infections should be treated promptly and with follow up of outcome.
• Routine use of prophylactic antibiotic treatment cannot be recommended, but may be considered in patients with repeated infections
• Consider antifungal prophylaxis (e.g. voriconazaole in neutropenic patients with high risk MDS receiving induction chemotherapy, as well as acyclovir.
• G-CSF treatment G-CSF injections can be considered as prophylaxis for severely neutropenic patients with recurring, serious infections or during infectious episodes.
• Long-acting G-CSF has not been evaluated in MDS and cannot be recommended.

Erythropoietin Stimulating Agents (ESAs)

Treatment with EPO may improve hemoglobin levels and abrogate transfusion need in low-risk MDS. Addition of G-CSF has a synergistic effect on erythroid progenitor cells, and may induce responses in EPO refractory patients.¹⁴

EPO improves quality of life, and significantly prolongs time to transfusion requirement. Retrospective studies indicate a survival benefit in responding patients, with no impact on AML transformation.

Darbepoetin (DAR) has longer half-life than EPO but a comparable efficacy.

Indication for treatment

• Low risk MDS (IPSS low or intermediate 1, IPSS-R very low, low or intermediate).
• Symptomatic anemia, individual assessment, rarely reasonable to start treatment if hemoglobin level >100 g/l
• Nordic predictive score for response 0 or 1 point (https://qxmd.com/calculate/calculator_142/mds-anemia-epo-gcsf-response)
• Endogenous EPO level of < 500 mU/L

Dosing of erythropoiesis stimulating agents

• Target hemoglobin level 110-120 g/L
• Starting dose Eprex 40,000 IU SC weekly, escalate to 60,000 IU weekly if no response by 8 weeks and 80,000 units/week if no response by 12 weeks
• Starting dose of darbepoetin (DAR) is 500 ug SC q 3 weeks and increase to q 2 weeks and q 1 week as clinically indicated.
• Maximal trial period of ESA alone 16-20 weeks
• Dosing may be to be adjusted (lower dose, longer intervals) if hemoglobin overshoots

Dosing of G-CSF:

• Add if no response to 8 weeks of full dose EPO or DAR.
• Start with 300 µg (or equivalent) once weekly, alternatively 100 µg 2-3 times a week. Aim for a clear rise in neutrophil count (6-10 x 10⁹ /l). Maximum dose 300 µg x 3 times a week.
• Long-acting G-CSF has not been evaluated in MDS and cannot be recommended

Inadequate or lost response:

• Evaluate for iron and vitamin deficiencies.
• Increase the dose of EPO or DAR.
• If no response at maximum dose, then add G-CSF and evaluate after maximum of another 8 weeks
• Bone marrow examination is recommended if response cannot be rescued or in case of clinical signs of disease progression (18-28 % of patients show signs of disease progression at time of lost response).

Immunosuppressive therapy with ATG and or cyclosporine

Option for patients with MDS and ULD or MLD and lower risk disease who have significant symptomatic bicytopenia and have failed conventional therapy

Response rates average 43-49% with CR rate of 12% and RBC TI rates of 30-33%^15,16.

• Patients with higher probabilities of response have been reported to be the following, although these have not consistently been found to be predictive on multivariate analysis:
• Trisomy 8
• PNH phenotype
• Hypocellular (predictive of achieving RBC TI)¹⁶
• Shorter history of RBC transfusion dependence
• LGL by flow cytometry
• Age < 70
• Short time from diagnosis (< 2 years)
• HLA DR15+
• ATG is dosed at aplastic anemia dosing (insert)
• Cyclosporine is dosed at 3-6 mg/kg in q12 hour dosing with a target trough cyclosporine levels of 200-400 ng/ml. Close monitoring of BP, renal function and electrolytes needed
• Responding patients should be treated for 6 months and then dose of CsA titrated down gradually to the lowest possible dose that maintains response.

Lenalidomide and del5q MDS^17,18

• In transfusion dependent patients with lower risk MDS with del(5q) 43-56% achieve transfusion-independence and 23-57% show cytogenetic response.
• The response rates are higher with 10 mg/day 21/28 days compared to 5 mg continuous dosing, without added toxicity and the median time until erythroid response is 4.2 weeks.
• The median OS among patients achieving RBC TI is 5.7 years
• Grade IIII/IV neutropenia and thrombocytopenia is seen in around 50% of patients.
• The response duration is around 2 years.
• The 5-year cumulative incidence of AML in treated patients is approximately 35%.
• Presence of TP53 mutation or marrow progenitors with strong TP53 staining is associated with increased risk of progression

Lenalidomide and nondel5q MDS¹⁹

• Lenalidomide 10 mg x 21 d/28 associated with RBC-TI of 27% lasting median of 31 weeks
• Associated with high rate of neutropenia (62%) and thrombocytopenia (36%)
• Slightly higher response rates are seen in patients who are female, with lower rates of RBC-TD and EPO levels of < 500
• While not funded by MOH, it may be considered as second line therapy in patients with lower risk MDS who are not responding to ESAs if private insurance permits
• Lenalidomide may restore sensitivity of MDS erythroid precursors based on higher response rates when combined with EPREX (ORR 39% versus 23%) versus Len alone.
• Drug may be discontinued if no response is seen after 16 weeks.

Decision-making and treatment considerations

• Eligible patients are lower risk MDS with isolated del(5q) that have failed EPO or are not considered candidates according to the predictive model
• No TP53 alteration (TP53 mutation by deep sequencing of presence of >2% of marrow cells with strong TP53 staining); such patients should be evaluated for alternative treatments due to their adverse prognosis and lenalidomide should only be considered in frail patients where no suitable alternative is available
• Non-eligible patients are candidates for allo SCT; if lenalidomide is given in selected transplant candidates it should only be in the absence ofTP53 alterations, with careful monitoring for signs of disease progressions of disease progression.
• Dosing: Repeated courses of 10 mg daily for 21 days followed by a 7-day break.
• In elderly frail patients or patients with renal impairment consider 5 mg 21 of 28 days.
• Prior to lenalidomide treatment, patients should be informed about the increased risk of other malignancies observed in multiple myeloma patients
• Lenalidomide may be considered for non del(5q) lower risk MDS but with a durable expected red blood cell transfusion rate of < 20% and a high rate myelosuppression.
• Sexually active, fertile patients must use effective contraception

Hypomethylating agents

• While there is no clear evidence that HMA’s alter the natural history of lower risk MDS, they may reduce or reverse rbc transfusion dependence in 30-50% and raise platelet counts 28-36%^20,21.
• While not funded in Ontario for this indication, they are often available compassionately and may be considered in selected patients with excessive transfusion dependence who are not candidates for allogeneic stem cell transplant
• Both AZA 75 mg/m² SC and Decitabine 20 mg/m² IV have been evaluated in shorter treatment schedules of 3-5 days
• An oral formulation of decitabine (ASTX-727) has recently been granted health Canada approval for patients with intermediate and high risk MDS.

Management of higher risk disease

(IPSS INT-2 or high, IPSS-R high and very high, or IPSS-R > 3.5, or lower risk with unfavourable mutations)

• Clinical Trial
• Hypomethylating agent (Azacitidine or Decitabine)
• Induction chemotherapy
• Allogeneic stem cell transplant

Allogeneic stem cell transplantation in MDS

• Allogeneic stem cell transplantation is the only known curative treatment option in patients with MDS
• The outcome after allogeneic transplantation is very heterogeneous and the prognosis has been related to several different prognostic factors
• Relapse is the most significant cause of death with an overall relapse rate about 30 %. The overall transplant related mortality (TRM) has been reported to be 5-20 %, higher with myeloablative, lower with reduced intensity.
• Predictive factors for NRM: age, advanced stage, therapy related MDS, incomplete match, high comorbidity index, poor performance status
• Predictive factors for relapse: age, advanced stage, complex karyotype, mutated TP53, severe marrow fibrosis, blast % > 10%.

Indications:

• All fit patients without comorbidities should be considered for allogeneic SCT. There is no specific age limit, but age should be taken into consideration and is usually < age 75.
• The indication should be assessed in association with donor availability, eventual co-morbid conditions and functional status (see comorbidity index) and cytogenetic and molecular mutational status.
• IPSS-R high and very high risk.
• For intermediate risk and for some patients with low risk additional poor risk factors such as life-threatening cytopenias, high transfusion burden, poor risk cytogenetics/molecular characteristics and blast increase may indicate a need for an early SCT.

Decision making:

• At diagnosis always consider if the patient is a candidate for allogeneic stem cell transplantation. It is not recommended to wait for significant disease progression before a decision about allogeneic transplantation is taken.
• In patients < 50 years of age consider the possibility of underlying rare familial syndromes (Fanconi, telomere-associated disorders) that may have implications for the choice of conditioning regimen and donor.
• Prior to decision-making regarding allogeneic transplantation, the patient should be thoroughly informed by his/her physician about benefits and risks with transplantation. Any patient must be individually evaluated and should be discussed by the caretaking physician and the transplant unit.
• In case of decision to transplant – proceed immediately with HLA typing and family work-up.
• Patients with a high transfusion burden should when possible receive appropriate iron chelation before transplantation, but the ferritin level should not postpone the transplantation

AML-like chemotherapy

• In younger MDS patients and excess blasts (> 10%) being considered for allogeneic stem cell transplant, cytoreduction with AML-Like chemotherapy may be appropriate and are guided by our AML treatment guidelines f
• CR rates average 43% (range 18-74%) and OS ranges from 6-21 months.
• CR durations are generally short without consolidative allogeneic stem cell transplant.

Azacitidine

• In the pivotal AZA-001 study²², Azacitidine demonstrated a significant improvement in overall survival with azacitidine (24 vs 15 months, p=0.0001) and time to AML transformation (24 vs 12 months, p=0.004) although in ‘real world’ data, median survival ranges from 13-18 months²³.
• The benefit of azacitidine compared to BSC has also been proven in sub group analyses of patients >75 years of age, and for AML with 20-30 % marrow blasts (former RAEB-t)
• Azacitidine 75 mg/m² SC daily x 7 days (consecutive or 5-2-2 schedule) q 28 days is approved for treatment of IPSS INT-2 and HR MDS and MDS/AML with 20-30 % blasts in patients not eligible for hematopoietic stem cell transplantation or as a bridge for patients with planned allogeneic stem cell transplant who cannot tolerate induction chemotherapy.
• The expected response rate (CR, PR and hematological improvement = HI with or without marrow CR) is 35-40% to azacitidine-treatment and first response is seen in 91% of the responders within 6 cycles and best response is seen in 48% of the responders within 12 cycles, underscoring the importance of continuing treatment even if no response can be observed after a few courses
• Myelosuppression is maximal within the first 2 cycles but it is important to adhere to dose and schedule if possible to maximize probability of response.
• BM should be repeated after 6 months to assess for response (or earlier, if suspected progression due to excessive toxicity or myelosuppression)
• BM should be performed after 3 cycles in patients being considered for allogeneic stem cell transplant.
• Combination therapy with azacitidine has not demonstrated a higher survival than monotherapy but there are a number of clinical trials (with Pevonedistat, APR246 for TP53 mutated MDS, venetoclax) that are currently underway with promising phase 2 results.
• Azacitidine should be considered in patients with a life expectancy of > 3 months but be balanced by consideration of comorbidities and frailty
• The minimum # of treatment courses prior to considering the treatment a failure should be 6
• Azacitidine should be continued until clear signs of loss of response, progression or intolerable toxicity. In patients benefitting but experiencing significant cytopenias after the first 3 cycles, dose reduction or a cycle length of 5 weeks may be considered.

Second line treatment when HMAs fail in higher risk MDS

• Median OS is short (3-6 months)
• There is no approved agent
• Clinical trials are strongly recommended
• In selected cases, the addition of venetoclax may be considered or induction chemotherapy if an allogeneic stem cell transplant is an option

Key website sources that influenced these guidelines:

• Guidelines for the diagnosis and treatment of Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia
• National Comprehensive Cancer Network

2016 Revision to the WHO classification of MDS

Entity name	Number of dysplastic lineages	Number of cytopenias	Ring sideroblasts as percentage of marrow erythroid elements	Bone marrow (BM) and peripheral blood (PB) blasts	Cytogenetics by conventional karyotype analysis
MDS-SLD	1	1-2	<15% / <5%b	BM <5%, PB <1%, no Auer rods	Any, unless fulfils all criteria for MDS with isolated del(5q)
MDS-MLD	2-3	1-3	<15% / <5%b	BM <5%, PB <1%, no Auer rods	Any, unless fulfils all criteria for MDS with isolated del(5q)
MDS-RS MDS-RS-SLD MDS-RS-MLD	1 2-3	1-2 1-3	≥15% / ≥5%b	BM <5%, PB <1%, no Auer rods	Any, unless fulfils all criteria for MDS with isolated del(5q)
MDS with isolated del(5q)	1-3	1-2	None or any.	BM <5%, PB <1%, no Auer rods	del(5q) alone or with 1 additional abnormality, except loss of chromosome 7 or del(7q)
MDS-EB MDS-EB-1 MDS-EB-2	0-3	1-3	None or any.	BM 5–9% or PB 2–4%, no Auer rods BM 10–19% or PB 5–19% or Auer rods	Any.
MDS-U with 1% blood blasts with SLD and pancytopenia based on defining cytogenetic abnormality	1-3 1 0	1-3 3 1-3	None or any. None or any. <15%d	BM < 5%, PB = 1%c, no Auer rods BM < 5%, PB < 1%, no Auer rods BM < 5%, PB < 1%, no Auer rods	Any. Any. MDS-defining abnormality

 

 

 

 ° Good: normal, -Y, del(5q), del(20q). Poor: complex (≥ 3 abnormalities) or chromosome 7 anomalies. Intermediate: other abnormalities. * Hemoglobin <100 g/l, ANC <1.8 x 109/l, platelets <100 x 109/l.

 

Prognostic variable	Score
	0	0.5	1	1.5	2	4	5
Cytogenetics	Very good	-	Good	-	Intermediate	Poor	Very poor
BM blasts (%)	≤2%	-	>2%-<5%	-	5%-10%	>10%	21-30
Hemoglobin	≥100	-	80-<100	<80
Plateles	≥100	50-<100	<50
ANC	≥0.8	<0.8

 

 

 

Predicted response: 0 point 74%, 1 point 23%, 2 points 7%

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