Refractory anemia

< 1

< 5

10-40

Refractory anemia with ringed sideroblasts

< 1

< 5

10-35

Refractory anemia with excess blasts

< 5

5-20

25-30

Refractory anemia with excess blasts in transformation

> 5

21-29

10-30

Chronic myelomonocytic leukemia

< 5

< 20

10-20

• It introduces some modifications compared to FAB classification:
• ▪ it divides the categories RA and RARS into 2 subgroups, according to whether the diseases limited to red cell precursors or also involves granulocytic and/or platelet precursors;
• ▪ it considers separately MDS having the 5q [5q -].chromosomal deletion;
• ▪ it separates RAEB in RAEB-1 (5 to 10% of blasts medullar) and the RAEB-2 (11 to 20% of marrow blasts).

• It considers the following groups:
• ▪ pure refractory anemia (PRA);
• ▪ pure RA with ringed sideroblasts (PRARS);
• ▪ refractory cytopenias with multilineage dysplasia (RCMD);
• ▪ RCMD with ringed sideroblasts (RSMD);
• ▪ refractory anaemia with excess of blasts (RAEB):
• o RAEB-1 (> 5%; < 10% of marrow blasts)
• o RAEB-2 (> 10%; < 20% of marrow blasts)
• ▪ unclassifiable MDS;
• ▪ MDS associated with isolated 5q- (5q –syndrome).

% Moelle blaste

< 5 %

5-10 %

-

11-20 %

21-30 %

Caryotype^#

Fav

Interm

Défav

-

-

Cytopénie

0-1

2-3

-

-

^#Caryotype

Favorable

Intermédiaire

Défavorable

• Normal
• -Y
• del(5q)
• del(20q)

Autre

• Anomalies du 7
• Anomalies
• complexes
• (≥ 3 anomalies)

Risque bas :

Score = 0

Risque intermédiaire 1(INT-1) :

Score de 0,5 à 1

Risque intermédiaire 2 (INT-2) :

Score de 1,5 à 2

Haut risque :

Score ≥ à 2,5

Altering disease natural history

1. Complete remission (CR)

Bone marrow evaluation: repeat bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia.^* When erythroid precursors constitute less than 50% of bone marrow nucleated cells, the percentage of blasts is based on all nucleated cells; when there are 50% or more erythroid cells, the percentage blasts should be based on the nonerythroid cells.

Peripheral blood evaluation (absolute values must last at least 2 months)

Hemoglobin greater than 11 g/dL (untransfused, patient not on erythropoietin)

Neutrophils 1 500/mm³ or more (not on a myeloid growth factor)

Platelets 100 000/mm³ or more (not on a thrombopoetic agent)

Blasts, 0%

No dysplasia^*

Partial remission (PR) (absolute values must last at least 2 months):

All the CR criteria (if abnormal before treatment), except.

Bone marrow evaluation: Blasts decreased by 50% or more over pretreatment, or a less advanced MDS FAB classification than pretreatment. Cellularity and morphology are not relevant

3. Stable disease

Failure to achieve at least a PR, but with no evidence of progression for at least 2 months.

4. Failure

Death during treatment or disease progression characterized by worsening of cytopenias, increase in the percentage bone marrow blasts, or progression to an MDS FAB subtype more advanced than pretreatment.

5. Relapse after CR or PR one or more of the following:

a) Return to pretreatment bone marrow blast percentage.

b) Decrement of 50% or greater from maximum remission/response levels in granulocytes or platelets.

c) Reduction in hemoglobin concentration by at least 2 g/dL or transfusion dependence.^§

6. Disease progression

a) For patients with less than 5% blasts: a 50% or more increase in blasts to more than 5% blasts.

b) For patients with 5% to 10% blasts: a 50% or more increase to more than 10% blasts.

c) For patients with 10% to 20% blasts: a 50% or more increase to more than 20% blasts.

d) For patients with 20% to 30% blasts: a 50% or more increase to more than 30% blasts.

e) One or more of the following: 50% or greater decrement from maximum remission/response levels in granulocytes or platelets, reduction in hemoglobin concentration by at least 2 g/dL, or transfusion dependence.^§

7. Disease transformation

Transformation to AML (30% or more blasts).

8. Survival and progression-free survival

(See table 2)

Cytogenetic response

(Requires 20 analyzable metaphases using conventional cytogenetic techniques.)

Major: no detectable cytogenetic abnormality, if preexisting abnormality was present.

Minor: 50% or more reduction in abnormal metaphases.

Fluorescent in situ hybridization may be used as a supplement to follow a specifically defined cytogenetic abnormality.

Quality of life

Measured by an instrument such as the FACT Questionnaire.

Clinically useful improvement in specific domains: physical, functional, emotional, social, spiritual

Hematologic improvement (HI)

(Improvements must last at least 2 months in the absence of ongoing cytotoxic therapy.)

Hematologic improvement should be described by the number of individual, positively affected cell lines (e.g. HI-E; HI-E + HI-N; HI-E + HI-P + HI-N).

1. Erythroid response (HI-E)

Major response: for patients with pretreatment hemoglobin less than 11 g/dL, greater than 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, transfusion independence.

Minor response: for patients with pretreatment hemoglobin less than 11 g/dL, 1 to 2 g/dL increase in hemoglobin; for RBC transfusion-dependent patients, 50% decrease in transfusion requirements.

2. Platelet response (HI-P)

Major response: for patients with a pretreatment platelet count less than 100 000/mm³, an absolute increase of 30 000/mm³ or more; for platelet transfusion-dependent patients, stabilization of platelet counts and platelet transfusion independence.

Minor response: for patients with a pretreatment platelet count less than 100 000/mm³, a 50% or more increase in platelet count with a net increase greater than 10 000/mm³ but less than 30 000/mm³.

3. Neutrophil response (HI-N)

Major response: for absolute neutrophil count (ANC) less than 1500/mm³ before therapy, at least a 100% increase, or an absolute increase of more than 500/mm³, whichever is greater.

Minor response: for ANC less than 1500/mm³ before therapy, ANC increase of at least 100%, but absolute increase less than 500/mm³.

4. Progression/relapse after HI: one or more of the following: a 50% or greater decrement from maximum response levels in granulocytes or platelets, a reduction in hemoglobin concentration by at least 2 g/dL, or transfusion dependence.^§

For a designated response (CR, PR, HI), all relevant response criteria must be noted on at least 2 successive determinations at least 1 week apart after an appropriate period following therapy (e.g. 1 month or longer).

^* The presence of mild megaloblastoid changes may be permitted if they are thought to be consistent with treatment effect. However, persistence of pretreatment abnormalities (e.g. pseudo-Pelger-Hüet cells, ringed sideroblasts, dysplastic megakaryocytes) are not consistent with CR.

In some circumstances, protocol therapy may require the initiation of further treatment (e.g. consolidation, maintenance) before the 2-month period. Such patients can be included in the response category into which they fit at the time the therapy is started.

^§In the absence of another explanation such as acute infection, gastrointestinal bleeding, hemolysis, and so on.