1. MYELODYSPLASTIC SYNDROMES
Presented by
Marwa Ahmed Gamal Eldin

2. MYELODYSPLASTIC SYNDROMES
The myelodysplastic syndromes (MDS) are a group of diseases characterized by increasing BM failure with quantitative and qualitative (functional and morphological) abnormalities of all three myeloid cell lineages.

3. MDS
In contrast to leukaemia, in which one specific type of blood cell (the white cell) is produced in excessively large numbers, the production of any, and sometimes of all, types of blood cells is affected.

4. MDS
The myelodysplastic syndromes were formerly referred to by many names including preleukaemia.
The term preleukaemia is no longer used because it is very misleading.
Although a minority of patients with MDS develop acute leukaemia, most do not.
When leukaemic transformation does occur, it is to acute myeloid leukaemia (AML).

5. MDS
Two features:
Ineffective hemopoiesis; the combination of a hyperactive marrow with low blood cell counts is the hallmark of the disease.
Abnormality in the appearance of the bone marrow and blood cells. These abnormalities (e.g. white cells lacking normal granules) are characteristic of the condition.

6. Pathophysiology of MDS
MDS is thought to arise from mutations in the multi-potent bone marrow stem cell.
Differentiation of blood precursor cells is impaired, and
there is a significant increase in levels of cell death apoptosis in bone marrow cells.
If the overall percentage of bone marrow blasts rises over a particular cutoff (20% for WHO and 30% forFAB) then transformation to leukemia (specifically acute myelogenous leukemia or AML) is said to have occurred.

7. While recognition of leukemic transformation is important, a significant proportion of the morbidity and mortality attributable to MDS results not from transformation to AML but rather from the cytopenias seen in all MDS patients.

8. Causes of myelodysplasia
Primary myelodysplastic syndrome is of no known cause but several risk factors are established.
Therapy-related (secondary) myelodysplastic syndrome occurs following treatment with either chemotherapy (eg. Alkylating agents) or radiotherapy for another neoplasm as Hodgkin's disease or ovarian carcinoma.

9. Classification
FAB classification of MDS
WHO classification of MDS

10. FAB classification of MDS
Bone marrow
Peripheral blood
Blasts < 5%
Blasts < 1%
Refractory anemia (RA)
Ring sideroblasts >15% of total erythrocytes
Refractory anemia with ringed sideroblasts (RARS)
Blasts 5-20%
RA with excess blasts (RAEB)
Blasts 20-30% or Auer rods present
Blasts > 5%
RAEB in transformation (RAEB-t)
As any of the above with
As any of the above with >1000/cmm monocytes
Chronic myelomonocytic leukemia (CMML)

11. WHO classification of MDS

12. Anemia No or rare blasts No Auer rods < 1 x 109/L monocytes
Bone Marrow Findings
Blood Findings
Disease subtype
Erythroid dysplasia only-ie, < 10% grans or megas dysplasia < 5% blasts < 15% ringed sideroblasts
Anemia No or rare blasts
No Auer rods < 1 x 109/L monocytes
Refractory anemia (RA)
15% ringed sideroblasts < 5% blasts
Anemia No blasts
Refractory anemia with ringed sideroblasts (RARS)
10% of cells in two or more myeloid cell lines < 5% blasts in marrow No Auer rods < 15% ringed sideroblasts
Cytopenias (bicytopenia or pancytopenia) No or rare blasts No Auer rods < 1 x 109/L monocytes
Refractory cytopenia with multilineage dysplasia (RCMD)
15% ringed sideroblasts < 5% blasts No Auer rods
Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)
Unilineage or multilineage dysplasia 5%–9% blasts No Auer rods
Cytopenias < 5% blasts No Auer rods < 1 x 109/L monocytes
Refractory anemia with excess blasts – 1 (RAEB-1)
Unilineage or multilineage dysplasia 10%–19% blasts Auer rods +/–
Cytopenias 5%–19% blasts Auer rods +/– < 1 x 109/L monocytes
Refractory anemia with excess blasts – 2 (RAEB-2)
Unilineage gran or mega dysplasia < 5% blasts No Auer rods
Cytopenias No or rare blasts No Auer rods
Myelodysplastic syndrome, unclassified (MDS-U)
Normal to increased megakaryocytes with hypolobulated nuclei < 5% blasts No Auer rods Isolated del (5q)
Anemia < 5% blasts Platelets normal or increased
MDS associated with isolated del (5q)
10% of cells in two or more myeloid cell lines
Dysplasia in
Dysplasia in
Erythroid dysplasia only

13. WHO classification of MDS
The major changes include:
Lowering the threshold for defining acute myeloid leukemia (AML) .
RCMD includes RA and RARS with 2 or 3 dysplastic cell lines.
Subdividing RAEB into two categories depending on the number of blasts in the blood and marrow.
Removing chronic myelomonocytic leukemia (CMML) from the MDS category into a new group of diseases; the MDS/MPD overlap diseases. .
Addition of 5 q-syndrome that affects the elderly females and is characterized by macrocytic anemia, thrombocytosis, erythroid dysplasia, hypolobated micromegakaryocytic hyperplasia and the 5 q- chromosome deletion (band q13 to q33). It is associated with good prognosis.

14. WHO classification of MDS
Not all physicians concur with this reclassification.
This is because the underlying pathology of the diseases is not well understood.
It is difficult to classify things that are not well understood.

15. Problems in classification of MDS
Still, other categories of MDS are not addressed by this classification, such as hypocellular MDS and MDS with fibrosis. These latter entities remain problematic, and their recognition as well as their place among the other subcategories await further clarification.

16. Signs and symptoms of MDS
The average age at diagnosis for MDS is about 65 years, but pediatric cases have been reported.
Some patients have a history of exposure to chemotherapy (especially alkylating agents such as) or radiation (therapeutic or accidental), or both (e.g., at the time of stem cell transplantation for another disease).
Males are slightly more frequently affected than females.
About one-fifth of MDS patients have no signs or symptoms and are diagnosed by chance as a result of a routine blood test.
Those patients who do have symptoms present with clinical features due to bone marrow failure.
In about 80% of patients this is simple (transfusion-dependent ) anaemia.
whilst about 20% present with infections or bleeding as the major clinical problem.
Because neutrophils, monocytes and platelets are often functionally impaired, spontaneous infections in some cases, or bruising or bleeding in others, may occur out of proportion to the severity of the cytopenia.

17. Laboratory diagnosis
There are no definitive tests for MDS. It is a diagnosis of exclusion and is made when a patient has typical features of MDS with no obvious underlying cause.
Under the microscope, affected cells show characteristic abnormalities both in the circulating blood and in the bone marrow. This is the defining feature of the disease.

18. Peripheral blood Pancytopenia is a frequent finding. Red cells
Anemia-macrocytic or dimorphic
-hypochromic
Normoblasts may be present.
The reticulocyte count is low.
Granulocytes
Often reduced in number.
Hypogranularity.
Nuclear hyposegmentation (pseudo-Pelger-Huet anomaly (single or bilobed nucleus).
Platelets
Thrombocytopenia.
Large platelets.
Micromegakaryocytes.
When a patient is found to have cells on the blood film suggestive of MDS a full clinical history will be taken to rule out other causes and a bone marrow sample will be obtained.

19. Bone marrow
The most important findings in the BM are the dysplastic changes and, in some cases, increased myeloblasts.
In the majority of cases the bone marrow will be more active than normal (hyperplastic) and this feature, combined with the characteristic dysplasia in appearance of the cells and the low blood cell numbers will make the diagnosis straightforward. These dysplastic changes are the defining features of the disease.
Cells that are difficult to identify as either agranular myelocytes, monocytes or promonocytes are frequent.
In about 10% the BM is hypocellular and may resemble aplastic anemia.
Myelofibrosis is occasionally present, particularly with therapy-related MDS.
Iron stores are often increased.

20. MDS Dysplasia can affect all three lineages seen in the bone marrow.
The best way to diagnose dysplasia is by morphology and special stains used on the bone marrow aspirate and peripheral blood smear.
Dysplasia in the myeloid series is defined by:
Erythroid series
Binucleated erythroid percursors and karyorrhexis
N-C asychrony and megaloblastoid chromatin.
Erythroid nuclear budding
Erythroid nuclear strings or internuclear bridging (also seen in congenital dyserythropoietic anemias)
PAS-positive erythroblasts. (globular in vacuoles or diffuse cytoplasmic staining within erythroid precursors in the bone marrow aspirate). Note: One can see PAS vacuolar positivity in L1 and L2 blasts.
Ringed sideroblasts seen on Prussian blue iron stain (10 or more iron granules encircling 1/3 or more of the nucleus and >15% ringed sideroblasts when counted amongst red cell precursors).

21. MDS DYSERYTHROPOIESIS
Multinucleate polychromatic erythroblasts

22. MDS DYSERYTHROPOIESIS
Ring sideroblasts

23. MDS DYSERYTHROPOIESIS
Perl’s stain showing iron overload in macrophages of a bone marrow fragment, i.e., increased iron stores.

24. MDS DYSERYTHROPOIESIS
Macrocytosis, biphenotypic population

26. MDS Granulocytic series dysplasia
Hypersegmented neutrophils (also seen in Vit B12/Folate deficiency)
Hyposegmented neutrophils (Pseudo-Pelger Huet)
Hypogranular neutrophils or pseudo Chediak Higashi large granules
Dimorphic granules (basophilic and eosinophilic granules) within eosinophils
MPO – deficient neutrophils.

27. MDS DYSGRANULOPOIESIS
Monocytoid cells and an agranular neutrophil.

28. MDS DYSGRANULOPOIESIS
White cells showing pseudo-Pelger cells, agranular myelocytes and neutrophils.

29. MDS DYSGRANULOPOIESIS
Hypogranulation, nuclear-cytoplasmic asynchrony

30. MDS DYSGRANULOPOIESIS
Pseudo-Pelerg-Huet anomaly

31. MDS DYSGRANULOPOIESIS
Hypersegmented , hypogranulation

32. MDS DYSGRANULOPOIESIS
Aberrant granulation

34. MDS Megakaryocytic series dysplasia (can be the most subjective)
Hyposegmented nuclear features in megakaryocytes (hypolobation or monolobation)
Hypersegmented (osteoclastic appearing) megakaryocytes
Micromegakaryocytes.
Hypogranulation.

35. MDS DYSMEGAKARYOPOIESIS
Hypogranular platelets

36. MDS DYSMEGAKARYOPOIESIS
Circulating micromegakaryocyte

37. MDS DYSMEGAKARYOPOIESIS
Abnormal megakaryocyte

38. MDS DYSMEGAKARYOPOIESIS
Mononuclear megakaryocyte

39. MDS Atypical localization of immature precursors (ALIPs)
It refers to the distribution of developing granulocytes on BM trephine biopsy sections.
Normally, the most immature granulocytic precursors are located in groups along the BM trabeculae or adjacent to blood vessels. As they mature, they extend towards more central areas between bone trabeculae.
In an MDS, the most mature granulocytic precursors may be found in clusters remote from the usual paratrabecular location.
This morphology can be difficult to recognize from treated leukemia and recovering immature normal marrow elements.

40. MDS
Despite active investigations, morphology remains the cornerstone for diagnosis.

41. Morphologic problems
One of the most difficult diagnostic challenges in MDS is that morphologic dysplasia is not specific for MDS but can be seen in other conditions, including:
megaloblastic anemia.
congenital dyserythropoietic anemia.
sideroblastic anemia.
exposure to toxins such as arsenic and alcohol.
after cytotoxic and growth-factor therapy.
HIV or parvovirus B19 infections.
Modest dyserythropoiesis is also not uncommon when there is brisk erythroid hyperplasia or regeneration, i.e., "stress erythropoiesis.
These are known to give a pseudomyelodysplastic picture in one of the cell lines, however, all three cell lines are never morphologically dysplastic in these entities with the exception of chloramphenicol, arsenic toxicity and other poisons.

42. MDS
Myelodysplasia is a diagnosis of exclusion and must be made after proper determination of iron stores, vitamin deficiencies, and nutrient deficiencies.
Causes of secondary dysplasia must be considered and excluded by appropriate clinical and laboratory studies prior to rendering a diagnosis of MDS.
Furthermore, a small number of dysplastic erythroid, granulocytic or megakaryocytic cells can be seen in marrow specimens from normal individuals. Hence, the guideline that 10% of the cells in a lineage should be dysplastic to consider the lineage as dysplastic and as evidence for MDS is a reasonable rule.

43. Cytogenetics of MDS
No cytogenetic abnormality is specific for MDS. However, some unique cytogenetic/morphologic correlations exist, the most common of which is the "5q- syndrome," described in the classification section.
Cytogenetic studies play a major role in confirmation of diagnosis and prediction of clinical outcome in MDS.
Clonal chromosomal abnormalities are detected in 40%–70% of cases of de novo MDS, and 95% of cases of therapy-related MDS (t-MDS).
In t-MDS, deletion of part or all of chromosomes 5 and/or 7 or trisomy 8 can be detected.

44. Cytogenetics of MDS Deletion 5q Monosomy 7 Trisomy 8
Loss of Y chromosome
Deletion 20q
3q rearrangements
Various abnormalities of chromosome 11
Various abnormalities of chromosome 17p
Other complex chromosomal defects

45. International Prognostic Scoring System
Presence of the following abnormalities: Good = normal or –Y only, 5q- only or 20q- only Intermediate = Complex (3+ abnormalities), or abnormal chromosome 7 Poor = All other abnormalities
Count 1 each for: Hemoglobin level below 10g/dl, Absolute neutrophil count (ANC) below 1.8 x 109/l Platelet count below 100 x 109/l
IPSS Score
Value
Indicators
5% or less
Blasts
0.5
5 to 10%
1.5
11 to 20%
2.0
21 to 30%
Good
Cytogenetics
Intermediate
1.0
Poor
0/1
Blood cytopaenias
2/3

46. International Prognostic Scoring System
The individual scores for bone marrow blast percentage, karyotype and cytopaenias are added together to give the IPSS score. The scores for the risk groups are as follows:
Low
INT-1
INT-2
>2.5
High

47. MDS
Although a bone marrow biopsy specimen is not always necessary to establish a diagnosis of MDS, it offers valuable diagnostic and prognostic information:
Dysplasia, particularly of megakaryocytes, can be appreciated in well-prepared biopsies.
Evidence of disruption of the normal marrow architecture, such as abnormal localization of immature precursors (ALIP), lends further support for the diagnosis of MDS.
An underappreciated role of the biopsy is that it may provide evidence for another disease that can mimic MDS clinically, such as lymphoma or metastatic tumor.
In cases of MDS that are hypocellular or associated with fibrosis, the biopsy is essential for diagnosis.

48. Myelodysplastic/ Myeloproliferative Diseases

49. MDS/MPD
The myelodysplastic/myeloproliferative diseases (MDS/MPD) are clonal myeloid disorders that possess both dysplastic and proliferative features but are not properly classified as either myelodysplastic syndromes (MDS) or chronic myeloproliferative disorders (CMPD).

50. MDS/MPD This category is composed of 3 major myeloid disorders:
Chronic myelomonocytic leukemia (CMML).
Juvenile myelomonocytic leukemia (JMML).
Atypical chronic myeloid leukemia (aCML).
Myeloid disease that shows features of both MDS and CMPD but does not meet the criteria for any of the 3 major MDS/MPD entities is designated as myelodysplastic/myeloproliferative disease, unclassifiable (MDS/MPD-U).

51. MDS/MPD
Patients with MDS/MPD do not have a Philadelphia chromosome or BCR/ABL fusion gene.
In general, the treatment of these diseases is tailored to the manifestations, myeloproliferative or myelodysplastic, that predominate in the individual patient.

52. Chronic Myelomonocytic Leukemia
Chronic myelomonocytic leukemia (CMML) was classified as a myelodysplastic syndrome (MDS) under the French-American-British scheme. The World Health Organization classification removed CMML from MDS, placing it in the new category MDS/MPD.

53. CMML CMML is characterized by the following:
Persistent monocytosis >1 x 109/L in the peripheral blood.
No Philadelphia chromosome or BCR/ABL fusion gene.
<20% blasts in the blood or bone marrow.
Dysplasia involving one or more myeloid lineages or, if myelodysplasia is absent or minimal, either an acquired clonal cytogenetic bone marrow abnormality or at least 3 months of persistent peripheral blood monocytosis, if all other causes are ruled out.

54. CMML Clinical features of CMML include the following:
The median age at diagnosis of CMML is 65 to 75.
Fever, fatigue, night sweats, and weight loss.
Infection.
Bleeding caused by thrombocytopenia.
Hepatomegaly (in some patients).
Splenomegaly (in some patients).
In patients with normal or slightly decreased white blood cell count, clinical features may be identical to MDS.
In patients with elevated white blood cell count, features are more like chronic myeloproliferative disorders (CMPD), including more frequent splenomegaly and hepatomegaly.

55. CMML Morphologically, the disease is characterized by:
Persistent peripheral blood monocytosis (always >1 x 109/L) that may exceed 80 x 109/L with monocytes typically accounting for >10% of the white blood cells.
Fewer than 20% blasts are seen in the blood or bone marrow.
Neutrophilia occurs in nearly 50% of patients with neutrophil precursors (e.g., promyelocytes and myelocytes) accounting for >10% of the white blood cells.
Mild normocytic anemia is common.
Moderate thrombocytopenia is often present.

56. CMML Bone marrow findings include the following:
Hypercellularity (75% of cases).
Blast count <20%.
Granulocytic proliferation (with dysgranulopoiesis).
Monocytic proliferation, dyserythropoiesis (e.g., megaloblastic changes, abnormal nuclear contours, ringed sideroblasts, etc.).
Micromegakaryocytes and/or megakaryocytes with abnormally lobated nuclei (as many as 80% of the cases).
Fibrosis (30% of the cases).

57. CMML CMML with eosinophilia
A subtype of CMML associated with severe tissue damage secondary to eosinophil degranulation.
All criteria for CMML are present, and the eosinophil count in the peripheral blood is >1.5 x 109.

58. CMML
Although clonal cytogenetic abnormalities are found in 20% to 40% of patients with CMML, none is specific.
Prognostic factors associated with shorter survival include the following:
Low hemoglobin level.
Low platelet count; high white blood cell, monocyte, and lymphocyte counts.
Presence of circulating immature myeloid cells.
High percentage of marrow blasts.
Low percentage of marrow erythroid cells.
Abnormal cytogenetics.
High levels of serum LDH and ß2-microglobulin.
Progression to acute leukemia occurs in approximately 15% to 20% of cases.

59. Juvenile Myelomonocytic Leukemia
JMML (also known as juvenile chronic myelomonocytic leukemia) is a rare hematopoietic malignancy of childhood accounting for about 2% of all childhood leukemias.
A definitive diagnosis requires the following:
Major criteria (all 3 required)
No Philadelphia chromosome or BCR/ABL fusion gene.
Peripheral blood monocytosis >1 x 109/L.
<20% blasts (including promonocytes) in the blood and bone marrow.
Minor criteria (2 or more required)
Fetal Hemoglobin (Hb F) increased for age.
Immature granulocytes in the peripheral blood.
White blood cell count >10 x 109/L.
Clonal chromosomal abnormality (e.g., monosomy 7).

60. JMML Clinical features:
Constitutional symptoms (e.g., malaise, pallor, and fever) or evidence of an infection.
Symptoms of bronchitis or tonsillitis (in approximately 50% of cases).
Bleeding diathesis.
Maculopapular skin rashes (in 40%-50% of cases).
Lymphadenopathy (in approximately 75% of cases).
Hepatosplenomegaly (in most cases).

61. JMML
The clinical and laboratory features of JMML can closely mimic a variety of infectious diseases, including those caused by:
Epstein-Barr virus.
cytomegalovirus.
human herpesvirus 6.
histoplasma.
mycobacteria.
toxoplasma.

62. JMML
Morphologically, the peripheral blood picture in this disease shows:
leukocytosis, anemia, and frequently, thrombocytopenia.
The median reported white blood cell count varies from 25 x 109/L to 35 x 109/L.
The leukocytosis is comprised of neutrophils, promyelocytes, myelocytes, and monocytes.
Blasts, including promonocytes, usually account for <5% of the white blood cells and always for <20%.
Nucleated red blood cells are seen frequently.
Thrombocytopenia is typical and may be severe.

63. JMML Bone marrow findings include the following:
Hypercellularity with granulocytic proliferation.
Hypercellularity with erythroid precursors (in some patients).
Monocytes comprising 5% to 10% of marrow cells (30% or more in some patients).
Minimal dysplasia.
Reduced numbers of megakaryocytes.

64. JMML
Prognosis
Prognosis is related to age at the time of diagnosis. The prognosis is better in children younger than 1 year at the time of diagnosis. Children older than 2 years at the time of diagnosis have a much worse prognosis.
A low platelet count and a high Hb F level have been associated with a worse prognosis.
Approximately 10% to 20% of cases may evolve to acute leukemia.

65. Atypical Chronic Myelogenous Leukemia
aCML is characterized pathologically by the following:
Peripheral blood leukocytosis with increased numbers of mature and immature neutrophils.
Prominent dysgranulopoiesis.
No Philadelphia chromosome or BCR/ABL fusion gene.
Neutrophil precursors (e.g., promyelocytes, myelocytes, and metamyelocytes) >10% of white blood cells.
Minimal absolute basophilia with basophils <2% of white blood cells.
Absolute monocytosis with monocytes typically <10% of white blood cells.
Hypercellular bone marrow with granulocytic proliferation and granulocytic dysplasia.
<20% blasts in the blood or bone marrow.
Thrombocytopenia.

66. aCML Clinical features: Anemia. Thrombocytopenia.
Splenomegaly (in 75% of cases).

67. aCML
Morphologically
The white blood cell count in the peripheral blood is variable. Median values range from 35 x 109/L to 96 x 109/L, and some patients may have white blood cell counts >300 x 109/L.
Blasts in the peripheral blood typically account for <5% of the white blood cells. I
Immature neutrophils usually total 10% to 20% or more.
The percentage of monocytes is rarely >10%.
Minimal basophilia may be present.
Nuclear abnormalities, such as acquired Pelger-Huët anomaly, may be seen in the neutrophils.
Moderate anemia (often showing changes indicative of dyserythropoiesis) and thrombocytopenia are common.

68. aCML Bone marrow findings: Granulocytic hypercellularity.
Blast count <20%.
Dysgranulopoiesis
Megakaryocytic dysplasia.
Erythroid precursors >30% of marrow cells with dyserythropoiesis present (in some cases).

69. aCML Thrombocytopenia and marked anemia are poor prognostic factors.
Atypical CML evolves to acute leukemia in approximately 25% to 40% of patients.
In the remainder, fatal complications include resistant leukocytosis, anemia, thrombocytopenia, hepatosplenomegaly, cerebral bleeding associated with thrombocytopenia, and infection.

70. Myelodysplastic/Myeloproliferative Disease, Unclassifiable
Myelodysplastic/Myeloproliferative Disease, Unclassifiable (MDS/MPD-U) (also known as mixed myeloproliferative/myelodysplastic syndrome, unclassifiable and overlap syndrome, unclassifiable) shows features of both myeloproliferative disease and myelodysplastic disease but does not meet the criteria for any of the other MDS/MPD entities.

71. Myelodysplastic/Myeloproliferative Disease, Unclassifiable
Diagnostic criteria for MDS/MPD-U can be either:
The combination of all 4 sets of criteria :
Clinical, laboratory, and morphologic features of myelodysplastic syndrome with <20% blasts in the blood and bone marrow.
Prominent myeloproliferative features, e.g. platelet count >600 x 109/L associated with megakaryocytic proliferation, or white blood cell count >13.0 x 109/L with or without splenomegaly.
No history of an underlying chronic myeloproliferative disorder (CMPD), MDS, or recent cytotoxic or growth factor therapy that could cause the myelodysplastic or myeloproliferative features.
No Philadelphia chromosome or BCR/ABL fusion gene, del(5q), t(3;3)(q21;q26), or inv(3)(q21q26).
Mixed myeloproliferative and myelodysplastic features that cannot be assigned to any other category of MDS, CMPD, or MDS/MPD.

72. MDS/MPD-U Clinical characteristics: Features of both MDS and CMPD.
Hepatomegaly.
Splenomegaly.

73. MDS/MPD-U Laboratory features:
Anemia and dimorphic erythrocytes on the peripheral blood smear.
Thrombocytosis (platelet count >600 x 109/L) or leukocytosis (white blood cell count >13 x 109/L) are present.
Neutrophils may exhibit dysplastic features.
Giant or hypogranular platelets may be present.
Blasts make up <20% of the white blood cells and of the nucleated cells of the bone marrow.
The bone marrow is hypercellular and may exhibit proliferation in any or all of the myeloid lineages. Dysplastic features are present in at least one cell line.
No cytogenetic or molecular findings are available that are specific for MDS/MPD-U. Because of its rare occurrence, the prognosis and predictive factors are unknown.

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