Bone marrow Examination-检验医学专题网

Bone marrow (BM) is spongy tissue found inside some of your larger bones. Bone marrow has a fluid portion and a more solid portion. A bone marrow aspiration is usually done at the same time as a biopsy. In an aspiration, a sample of the liquid portion of your marrow is withdrawn. A bone marrow biopsy and aspiration are often called a bone marrow examination.

A bone marrow exam offers detailed information about the condition of your blood cells. Sometimes, collecting a blood sample through a vein in your arm provides enough information about your health. But if those results are abnormal or don't offer enough details, you may need further evaluation with an examination of your bone marrow. Because your bone marrow is essentially a blood cell factory, it's normally rich in young cells. Examining bone marrow gives a much more detailed picture of the types, amount and condition of these newly forming blood cells. The marrow can be studied to determine the cause of anemia, the presence of leukemia or other malignancy, or the presence of some “storage diseases” in which abnormal metabolic products are stored in certain bone marrow cells.

The basic indication for performing a bone marrow evaluation is to answer questions that a routine hematology examination of a blood sample does not answer. One need not take the additional effort to take a bone marrow aspirate and biopsy, if, for example, the blood already clearly indicated an immune mediated hemolytic anemia, a typical inflammatory response, or even a leukemia with clearly diagnostic features in EDTA blood is present. Most cases of anemia (low red blood cells) can be diagnosed by simple blood tests. When these tests are negative, examining the marrow can reveal problems with the red blood cells that are uncommon causes of anemia (sideroblastic anemia, aplastic anemia). The most common indications for bone marrow analysis are a deficiency of cells from one, two or all three cell lines. Cytopenias also suggest decreased bone marrow function so one should check for various bone marrow diseases. These would be a thrombocytopenia and/or leukopenia. Additionally, leukemia may be hidden in the marrow blast cells may be numerous in the bone marrow but few or no blast cells are seen in the blood (aleukemic leukemia). The more common indications are fever, hepatomegalia, splenomegalia, lymphadenectasis of unknown origin and juvenile cell in peripheral blood. Hypercalcemia may be caused by lymphosarcoma, which may be located in the bone marrow. Plasma cell myeloma may be suggested by hyperproteinemia or by lytic lesions in the spine.

The only absolute contraindication is hemophilia and other congenital hemorrhagic disorders.

The samples are preferably obtained from the posterior iliac crest (spina iliaca posterior superior)(Figure 2.2-1). In this location, a bone marrow aspiration is technically easy, less hazardous and less painful than a sternal aspiration. The anterior iliac crest can also be used as the site for bone marrow aspiration in order to avoid a repositioning of patient.

about 0.2 ml of marrow, is used for the preparation of several thin smears.The preparation and staining of these smears are same to peripheral blood smears.

It has been demonstrated that the blood cells are derived from the multipotential stem cell. The various blast cells which will be further differentiated have similar morphologic characteristic, a large cell with a nucleus and nucleoli. These structures are regularly changed as cells differentiate.

The transformation from an immature cell to a mature cell always involves changes in the cytoplasm, nucleus and cell size.

a. Size changes from large to small; nucleus disappears in matured red blood cell.

b. Color changes from dark blue to light blue in granulocyte, and to red in red cell. (Basophilic is proportional to the cytoplasmic content of ribonucleic acid-RNA as the cell matures, there is a gradual loss of cytoplasmic in general, the more basophilic the cytoplasm, the less mature the cell.)

In cells of myeloid series cytoplasmic differentiation is characterized by the appearance of granules. The granules are probably concerned with enzyme systems. When cytoplasmic granules first appear. They are few, coarse and wine red. The number gradually increases, and the granules differentiate into three types. These are eosinophilic, basophilic and neutrophilic granules. In erythroid cells, no granules are present during all stages of differentiation.

a. Proerythroblast (Pronormoblast) :Round or irregular, 15-22μm (2-3 times that of a mature red cell), the cytoplasm is deeply basophilic in appearance. No granules are present. Nucleus is oval or round in shape, exhibiting chromatin aggregation. Normally, 1 to 4 nucleoli are present.

b. Basophilic normoblast(Early normoblast): Similar to the pronormoblast but slightly smaller (12-20μm), cytoplasm is more abundant and less basophilic than that of pronormoblast. Nucleus reveals deeply stained chromatin bands. Nucleoli are sometimes present.

c. Polychromatic normoblast (Intermediate normoblast): It is up to twice the size of a mature red cell (10-15μm) round or irregular shape and polychromatic cytoplasm which is more abundant. Nucleus is reduced in size with deeply basophilic chromatin aggregation.

d. Orthochromic normoblast (Late normoblast): It is slightly larger than the mature red cell (7-12μm), with regular round shape. The cytoplasm is hemoglobinized and abundant in amount, the nucleus is pyknotic.

e. Reticulocyte: This cell stains as a mature red cell with the Wright’s dyes. It can be differentiated only supravital dye staining technique.

a. Myeloblast: It is 10-20μm, round and regular. Its cytoplasm stains basophilic by Wright’s stains. No granules are present. Nucleus is round in shape, no chromatin aggregations are normally present but 2-6 nucleoli are usually seen.

b. Promyelocyte: It is 12-25μm, regular in shape. Its cytoplasm is less basophilic than its precursor and is more abundant, often with purple granules. Nucleus may still be seen in the early cell.

c. Myelocyte: It is 10-18μm in diameter, regular and round. Its nucleus is smaller than that of the promyelocyte and some chromatin aggregates are seen in nucleus. Nucleoli are absent. The cytoplasm is light blue to pink and may contain azurophilic and specific granules which may be eosinophilic, basophilic or neutrophilic.

d. Metamyelocyte: It is 10-16μm in diameter. The nucleus is typically kidney shaped. The chromatin structure in the nucleus is more cyanotic than that of the myelocyte and is usually condensed into irregular thick and thin areas. The cytoplasm is abundant, pale or pink in color and contains specific granules.

e. Stab granulocyte (Band granulocyte): It is 10-13μm in diameter. The nucleus is elongated, sausage shaped or deeply indented. It is not segmented but may be slightly constricted at 1 to 2 points. The chromatin is continuous, thick and coarse. The cytoplasm is similar to that of metamyelocyte.

f. Segmented granulocyte: It is 10-13μm in diameter. The nucleus is central or eccentric, with heavy thick chromatin masses. It is divided into several lobes connected to each other by thin chromatin bridge. The cytoplasm is abundant, slightly eosinophilic or colorless, and contains specific granules. The basophilic and eosinophilic granules are large and overlie the nucleus. The neutrophilic granules are very fine.

a. Monoblast : 15-25μm in diameter, round or sometimes oval. The nucleus is round and sometimes indented with 2 to 6 nucleoli. The chromatin pattern may resemble that of a myeloblast showing delicate blue or purple stippling. The cytoplasm is often relatively large in amount, may contain a few azurophilic granules, and stains pale blue or gray. The cell border is irregular with pseudopods and indentations.

b. Promonocyte: 15-20μm in diameter. The nucleus is large, ovoid, and convoluted and indented. The chromatin forms a loose, open network. There may still be a nucleolus. The gray-blue cytoplasm contains fine azurophilic granules.

c. monocyte: 12-20μm in diameter. The nucleus is kidney shaped, horseshoe shaped or round and often lobulated. The chromatin is distributed in a linear arrangement of delicate strands. No nucleoli are seen. The cytoplasm is abundant with gray-blue “ground-glass” appearance. It contains azurophilic dust.

a. Lymphoblast : 10-18μm in diameter. The nucleus is round or oval and the chromatin has a stippled delicate pattern. 1 or 2 nucleoli are present, which are usually well outlined. The cytoplasm is no granular, stained deep blue.

b. Prolymphocytc : 10-20μm in diameter. The nucleus is oval but slightly indented and may contain nucleoli or nuclear remnants. The chromatin appears coarser than that of the lymphoblast. Cytoplasm stains basophilic and scantly azurophilic granules are occasionally present.

c. Large lymphocyte: 12-18μm in diameter. The dense, round, oval or slightly indented nucleus is centrally or eccentrically located. Its chromatin is dense and clumped. Cytoplasm is abundant and appears hyaline blue with the Wright’s stain. Small numbers of minute azurophilic granules may be present.

d. Small Lymphocyte : 6-8μm in diameter. Approximately that of a mature red cell nucleus is same as that of large lymphocyte. Scanty cytoplasm is seen which usually forms a narrow rim and often contains few azurophilic granules.

e. Plasmacyte: Up to twice the size of a mature red cell (8-9μm ) oval shape. The nucleus is eccentrically placed. The condensed chromatin forms clumps that may be concentrated in the periphery of the nucleus showing typical “cartwheel’’ pattern. No nucleoli are seen. The cytoplasm is dark blue and there is usually a clear zone close to the nuclear membrane. The cytoplasm is no granular but may contain vacuoles.

a. Megakaryoblast : 20-30μm diameter. Nucleus is large, indented and irregular in shape with a fine reticulum chromatin network. Occasionally 1 or 2 small indistinct nucleoli are present. Cytoplasm appears moderately basophilic and the periphery shows pseudopodia like structure. No granules are present.

b. Promegakaryocytc: 30-50μm in diameter. It is much larger than the megakaryoblast. The nucleus is large, indented and poly lobulated, rarely multinucleated. The chromatin appears coarse and may show some clumping. Nucleoli may be still present. Cytoplasm is abundant and appears basophilic with early azurophilic granules.

c. Megakaryocyte: 40-100μm in diameter. It is the largest cell found in the normal bone marrow. The nucleus is lobulated and irregular in shape. The chromatin is heavy clump, and nucleoli are not seen.The cytoplasm is abundant, appearing slightly basophilic or polychromatic with numerous azurophilic granules. The cytoplasm of the platelet-producing (active) megakaryocyte produces pseudopod-like projection and contains aggregates of azurophilic granules surrounded by pale halos. This structure gives rise to platelets at the periphery of the megakaryocytes.

The cytoplasm of non-platelet-producing (inactive) megakaryocyte is free from azurophilic granules and aggregates.

d. Platelet: 2-3μm in diameter, non nucleated each platelet consists of a central group of azurophilic granules, granulomere, and a surrounding light blue hyalomere.

a. Observe the quality of the stains smear under the low power and evaluate whether it is fit for study. Thin and well-stained areas were selected for cell count. Observe the ratio between erythrocytes and nucleated cells and determine the degree of hyperplasia.

c. Examine the whole smear particularly its tail portion for special cells such as tumor cells or other large pathologic cells.

d. A minimum of 200 nucleated cells should be counted under the oil immersion and the relative positive proportions of various cells are enumerated.

According to the ratio between erythrocytes and nucleated cells, five grades can be enumerated (table 2.5-1).

b. Obvious hyperplasia: leukemia, hyperplastic anemia, idiopathic thrombocyto- penic purpura, et al.

Normally about 2-4: 1, the M: E Ratio is increased in acute and chronic infection, leukemoid reactions (e.g, chronic inflammation, metastatic tumor), acute and chronic myeloid leukemia, myelodysplastic disorders and pure red cell aplasia. Decreased in agranulocytosis, anemias with erythroid hyperplasia (megaloblastic, iron-deficiency, thalassemia, hemorrhage, hemolysis, sideroblastic), and erythocytosis (excessive RBC production). Normal in aplastic anemia (though marrow hypocellular), myelofibrosis(marrow hypocellular), multiple myeloma, lymphoma, anemia of chronic disease.

Cytochemical technics allow further differentiation of hematopoietic cells. According to the chemical characteristics of the different elements of the cells, certain cytochemical stain may expose some of them, such as enzymes, ribonucleic acid, iron granules, etc. The reaction can be visualized based on the precipitation of an added dye.

The cytochemical reactions of blood cells are sometimes helpful in the diagnosis of some disorders or in the identification of the cell line to which certain cells belong.

Cytochemical reactions are most useful in:①distinguishing certain types of leukemias,②distinguishing a leukemoid reaction from leukemia,③distinguishing benign from malignant lymphocytic proliferations,④identifying the ringed sideroblasts in the sideroblastic anemia.

The enzyme peroxidase is present in the granules of myeloid cells. It may act on hydrogen peroxide with liberation of oxygen, which oxidizes benzdine into a brownish compound.

The peroxidase reaction is positive in cells of the neutrophilic, eosinophilic and monocytic series.

It can be used to differentiate cells of these types from lymphoid or erythroid cells, which are peroxidase negative.

The enzyme is only present in the cytoplasm of granulocytes. The Alkaline phosphatase stain usually using α-naphthyl phosphate as substrates is positive in the granulocytes. The positive reaction shows that blackish-brown precipitates are diffusely scattered throughout the cytoplasm of cells.

High alkaline phosphatase activity of granulocytes is found in infections, aplastic anemia, leukemoid reaction, acute lymphocytic leukemia.

Periodic acid (HIO₄) is an oxidizing agent that converts hydroxyls groups of adjacent carbon atoms to aldehydes. The resulting dialdehydes are combined with Schiff’s reagent to give a red-colored product. A positive reaction is therefore seen with polysaccharides, mucopolysaccharides, and glycoproteins.

Cells of neutrophilic or eosinophilic series all react with positive results, being mostly marked in the mature stage; monocytes have a faint staining reaction. Lymphocytes may contain a few small or large granules. Normoblasts are normally PAS negative.

In erythroleukemia and in thalassemia, some of the erythroid precursors are positive. In iron deficiency anemia, the positive PAS reactions usually appear. In malignant lympho-proliferative diseases, the lymphocytes may have increased numbers of PAS-positive granules.

The non-specific esterase reaction usually using α-naphthyl acetate as substrates is strongly positive in monocyte but weak or negative in granulocytes. The positive reaction shows that redish-brown precipitates are diffusely scattered throughout the cytoplasm of cells.

NSE reaction can be used to differentiate the leukemic cells originated from monocytic or granulocytic series. The more specific esterases that react positively in monocytes are inhibited by the presence of sodium fluoride.

Siderocytes are red cells containing non-hemoglobin iron granules, which stain with a potassium ferrocyanide acid mixture. A sideroblast is a nucleated red cell containing iron granules. The iron granules stain blue.

Marrow iron is representative of body iron store. In normal bone marrow, sideroblasts are ranged from 19% to 44%. The number of sideroblasts depends on the serum iron level. With iron deficiency, the sideroblasts disappear. Their absence is a reliable criterion of iron-deficiency anemia. The sideroblasts are increased in hemolytic anemias, hemochromatosis. In “ringed sideroblast” the stained iron particles surround the nucleus. These cells are found in lead poisoning and sideroblastic anemia.

Acute leukemias are diagnosed according to morphological criteria on peripheral blood and bone marrow smears. The additional use of cytochemical staining techniques greatly facilitates the differentiation and classification into the following major subgroups:

-acute myeloid leukemias (AML), synonymous with the term acute non-lymphocytic leukemias (ANLL). Based on the widely accepted French-American-British(FAB) classification, acute leukemias are further subdivided into eight myeloid and three lymphocytic leukemias.

The diagnosis criteria of acute leukemias have been established: At least 30% of all nucleated cells in the bone marrow are blasts(FAB).

Acute myeloid leukemia (AML) is a clonal malignancy of myeloid bone marrow precursors in which poorly differentiated cells accumulate in the bone marrow and circulation. Signs and symptoms occur because of the absence of mature cells normally produced by the bone marrow, including granulocytes (susceptibility to infection) and platelets (susceptibility to bleeding). In addition, if large numbers of immature malignant myeloblasts circulate, they may invade organs and rarely produce dysfunction. Distinct morphologic subtypes exist that have largely overlapping clinical features. AML accounts for about 80% of acute leukemias in adults. Etiology is unknown for the vast majority. Certain genetic abnormalities are associated with particular morphologic variants: t(15;17) with acute promyelocytic leukemia (APL), inv(16) with eosinophilic leukemia; others occur in a number of types. Chromosome 11q23 abnormalities are often seen in leukemias developing after exposure to topoisomerase Ⅱinhibitors. Chromosome 5 or 7 deletions are seen in leukemias following radiation plus chemotherapy. The particular genetic abnormality has a strong influence on treatment outcome.

Initial symptoms of acute leukemia have usually been present for less than 3 months, a preleukemic syndrome may be present in some 25% of patients with AML. Signs of anemia, fatigue, pallor, weakness, palpitations, and dyspnea on exertion are most common. WBC may be markedly elevated, normal, or low, circulating blast cells may or may not be present. Minor pyogenic infections of the skin are common. Thrombocytopenia leads to spontaneous bleeding, fever may be present. Bacterial and fungal infection are common; infections may be clinically occult in presence of severe leukopenia, and prompt recognition requires a high degree of clinical suspicion. Hepato-splenomegaly occurs in about one-third of patients, leukemic meningitis may present with headache, nausea, seizures.

Bone marrow reveals extreme or obvious hyperplasia. The predominant cells are leukemic cells which are morphologically same as blast cells. The presence of Auer’s body is characteristic of myeloid or monocytic leukemia. Cells of erythroid and megakaryoctic series are markedly decreased in number.

AML subtype which cannot be further differentiated based on morphological and cytochemical findings. The blasts are mostly of moderate size and have an ungranulated cytoplasm. The perxidase is positive in <3% whereas the esterase reaction is negative. The final classification depends on the immunocytochemical findings.

Mid-sized to large blasts without or only with faint azurophilic granulation predominate. Auer rods are very rare. Isolated (<3%) promyelocytes may be present. At least 3% but less than 10% of the blasts are weakly MPO-positive. The NSE is negative. Cytochemical examinations are mandatory for the diagnosis of AML-M1.

This subtype is characterized by the presence of more than 30% of type I and type II blasts with the percentage of monocytic precursors not exceeding 20%. The cytoplasm of the blasts frequently displays ample azurophilic granulation. Isolate Auer rods are easily found. The MPO strongly positive. The NSE is in most case weakly positive and cannot be inhibited by NaF.

AML-M3: acute promyelocytic leukemia (hepergranular promyelocytic leukemia)

Blast with atypical promyelocytic granulation are the predominant cell type. The cytoplasm is filled with coarse azurophilic granulation which may even obscure the nucleus. Auer rods are frequently present and may occur in bundles. The cells vary greatly in size and shape. The nuclei are variable and even monocytoid. A microgranular variant(AML-M3V) must be differentiated which is associated with very fine, dust-like granulation that is still detectable in the mature granulocytes. The microgranules are less than 250 nm and therefore are below the resolution threshold of light-microscopy. The nuclei are kidney-shaped and lobulated. As in the case of typical M3, the specific translocation t(15;17) is encountered. The patients often have a high WBC and blast cell count. Morphologically, this variant can be confused with monocytic leukemia and therefore requires a thorough immunocytochemical and cytogenetic investigation. In both types, cytochemical examinations yield marked MPO positivity in more than 30% of the blasts, usually 100%. The NSE is weakly to moderately positive and cannot be inhibited by NaF.

In this subtype, two different blast populations are present, i.e. one with myeloid(MPO-positive) and the other one with monocytic (NSE- positive) differentiation. The granulocytic cells must range from 20-80% of the non-erythroblastic nucleated cells. The same range applies to the percentage of monocytic cells. According to this distribution of cells, blasts with marked MPO positivity(>20%) are found on the one hand and blasts with pronounced NSE activity(>20%) on the other. The eosinophil variant AML-M4 Eo is defined by the simultaneous presence of≥3% of abnormal, heterogeneous eosinophil granulocytes. In addition to eosinophilic granules, these cells also have coarse, immature, dark purplish to black-blue granules.

This disease may occur in an immature or a mature form. Granulopoietic precursor cells are <20% of the nucleated cells. Confirmation of the diagnosis requires cytochemical staining, especially by NSE staining. More than 50% of the blasts are strongly NSE-positive. The MPO is positive in only <20% of the blasts. This subtype is divided by two form, one is acute monocytic leukemia, poorly differentiated(AML-M5a, blast are predominant, ≥80% of monocytic cells);The other is acute monocytic leukemia, differentiated (AML-M5b, differentiated monocytic cells predominate, ≥20% of monocytic cells).

Besides >50% of abnormal, megaloblastic appearing, immature erythroid cells, myeloid typeⅠand type Ⅱ blasts(≥30% in the group of nonerythroid cells) are found as well. The abnormal erythroblasts are often bizarre in appearance including, for example, lobulated nuclei, nuclear fragments, giant forms with megaloblastic changes, and cytoplasmic vacuoles. Auer rods in myeloid blasts and an abnormal megakaryopoiesis are common findings. Cytochemically, PAS positive in the form of coarse drops is characteristic.

For this rare form, aspiration only rarely yields the megakaryocyte percentage of 30% which is required for establishing the diagnosis. The performance of a biopsy is therefore mandatory. Cytologically, round to polymorphic undifferentiated blasts predominate, some of these cells display prominent nucleoli and deeply basophilic, ungranulated cytoplasm. Cytochemical technics are of minor importance.

According to the FAB group, Acute lymphocytic leukemia (ALL) is subdivided into the morphological subtypes L1, L2, L3. The cytological differentiation between L1 and L2-blast is clinically, however, of little significance because no clear relationships exist with the immunocytological classification. The most important differences between the three subtypes are: cell size, nucleus-cytoplasm ratio, presence of nucleoli, regularity of the nuclear and cellular shape. Cytochemically, the POX reaction must be negative and the esterase reaction is negative to weakly positive.

Chronic Myeloid Leukemia(CML) is a clonal malignancy usually characterized by splenomegaly and production of increased numbers of granulocytes, course is initially indolent but eventuates in leukemic phase (blast crisis) that has a poorer prognosis than denovo AML, rate of progression to blast crisis is variable, overall survival averages 4 years from diagnosis. Over 90% of cases have a reciprocal translocation between chromosomes 9 and 22, creating the Philadelphia (Ph) chromosome abnormality appears in all bone marrow-derived cells expect T cells. The protein made by the chimeric gene is 210kDa in chronic phase and 190kDa in acute blast transformation. In some patient, the chronic phase is clinically silent and patients present with acute leukemia with the Ph chromosome.

Symptoms develop gradually, easy fatigability, malaise, anorexia, abdominal discomfort, excessive sweating. Occasional patients are found incidentally based upon elevated leukocyte count. WBC count is usually (100-250)×10⁹/L with the increase accounted for by granulocytes and their precursors back to the myelocyte stage, bands and mature forms predominate. Basophils may account for 10%-15% of the cells in blood. Platelet count is normal or increased. Anemia is often present. Neutrophil alkaline phosphatase score is low.

Bone marrow reveals extreme hyperplasia with granulocytic hyperplasia. Marrow blast cell count is normal or slightly elevated. Immature myeloid cells (Myelocyte and Metamyelocyte) are predominant. Eosinophilic granulocytes and basophilic granulocytes are easily seen. Erythroid maturation is normal and megakaryocytes are usually present in normal or increased number unless blast crisis sets in during the later stage. Serum levels of vitamin B12, B12-binging protein, and LDH are elevated in proportion to the WBC.

Chronic phase lasts 2-4 years. Accelerated phase is marked by anemia disproportionate to the disease activity or treatment. Platelet counts fall. Additional cytogenetic abnormalities appear. Blast cell counts increase. Usually within 6-8 months, overt blast crisis develops in which maturation ceases and blasts predominate. The clinical picture is that of acute leukemia. Half of the cases become AML, one-third have morphologic features of acute lymphoid leukemia, 10% are erythroleukemia, and the rest are undifferentiated. Survival in blast crisis is often <4 months.

In the peripheral blood, myelodysplastic syndromes(MDS) are characterized by refractory cytopenias；in the bone marrow, by typical morphological, cytogenetic, and molecular-biological changes. In 1982, the FAB group presented a morphological classification of MDS based on the quantitative and qualitative evaluation of peripheral blood and bone marrow smears. It has since been supplemented by the detection of characteristic cytochemical, cytogenetic, immunocytological, and molecular biological findings.

The peripheral blood smear reveals remarkable quantitative and qualitative changes in MDS. Even the occurrence of circulating normoblasts, partly with megaloblastic changes is noted. The mature granulocytes show hardly any or no granules at all, may display a MPO defect as well as hypo and hypersegmentation with bizarre forms. The platelets also show anomalies including the presence of giant forms. Even micromegakaryocytes can also be observed.

The FAB classification is based on smears of the peripheral blood and the bone marrow. Only the blast and ringed sideroblast proportions are used as differential criteria for the classification into the five subtypes: ①Refractory anemia(RA);②Refractory anemia with ringed sideroblasts(RARS);③Refractory anemia with an excess of blasts(RAEB);④Refractory anemia with excess of blasts in transformation(RAEB-T);⑤Chronic myelomonocytic leukemia (CMML). It is currently the only classification with widespread acceptance. The FAB classification of MDS according to FAB group is presented in Table 2.8-1

FAB subtye Blasts Blasts Ringed Monocytes extent of

in the blood in the BM sideroblasts dyserythropoiesis

RA ≤1% <5% <15% Rare +

RARS ≤1% <5% ≥15% Rare +++

RAEB <5% 5-20 Variable Rare ++

RAEB-T ≤10% 21-30% Variable variable ++

CMML <5% 1-20 Variable increased ++