New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): Characteristics of refined MDS types

Accepted Manuscript Title: New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): characteristics of refined MDS types Authors: Corinna Strupp, Kathrin Nachtkamp, Barbara Hildebrandt, Aristoteles Giagounidis, Rainer Haas, Norbert Gattermann, John M. Bennett, Carlo Aul, Ulrich Germing PII: DOI: Reference:

S0145-2126(17)30064-4 http://dx.doi.org/doi:10.1016/j.leukres.2017.02.008 LR 5736

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Leukemia Research

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9-11-2016 17-1-2017 26-2-2017

Please cite this article as: Strupp Corinna, Nachtkamp Kathrin, Hildebrandt Barbara, Giagounidis Aristoteles, Haas Rainer, Gattermann Norbert, Bennett John M, Aul Carlo, Germing Ulrich.New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): characteristics of refined MDS types.Leukemia Research http://dx.doi.org/10.1016/j.leukres.2017.02.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

New proposals of the WHO working group (2016) for the diagnosis of myelodysplastic syndromes (MDS): characteristics of refined MDS types

Running title: WHO 2016 proposals for the diagnosis of MDS

Corinna Strupp, Kathrin Nachtkamp, Barbara Hildebrandt1, Aristoteles Giagounidis2, Rainer Haas, Norbert Gattermann, John M Bennett3, Carlo Aul4, Ulrich Germing

Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany 1

Department of Human Genetics, Heinrich-Heine-University, Düsseldorf, Germany

2

Marienhospital, Department of Oncology and Hematology, Düsseldorf, Germany

3

James P. Wilmot Cancer Institute, Department of Pathology, University of Rochester Medical Center, Rochester, New York, USA 4

Department of Hematology, Oncology and Clinical Immunology, St. Johannes Hospital, Duisburg, Germany

Corresponding author: Corinna Strupp, MD Department of Hematology, Oncology and Clinical Immunology Heinrich-Heine-University Moorenstr. 5 40225 Düsseldorf, Germany Tel.:++49-211-8117720 Fax: ++49-211-8118853 E-mail: [email protected]

Highlights 1. 2. 3. 4.

The new nomenclature describes the MDS types more detailed. The new definition of MDS RS MLD and MDS del(5q) lead to a shift of 16.7% patients. There were no shifts with regard to the blastic MDS types. A new definition of 3 MDS unclassified categories is useful for rare scenarios.

Abstract Based on centrally diagnosed 3528 patients in the Düsseldorf registry, we validated the new proposals for the classification of the MDS by the WHO working group: 256 patients were diagnosed as MDSSLD (7,3%), 978 MDSMLD (27,7%), 227 MDS RS SLD (6,4%); 321 MDS RS MLD (9,1%), 159 MDS del(5q) (4,5%), 481 MDSEB 1 (13,6%), 620 MDSEB 2 (17,6%), and 148 MDS-U (4,2%). 352 patients (16,9 % of the non blastic types) changed the category, mainly moving from RCMD to MDS RS MLD, RCUD and RCMD to MDS del(5q). Median survival times of the refined groups differed from more than 60 months in the MDSSLD (RS) groups, 37 months in the MDSMLD (RS) groups, 79 months of the MDS del(5q) group and 21 and 11 months in the MDSEB 1 and 2 groups, respectively. The difference between the groups with regard to the risk of AML evolution was also impressing. No major changes were made with regard to the MDS-U categories. In summary, the proposals of the WHO group for the classification of MDS are thoughtful, taking into account biologic parameters of the diseases, a more precise wording, to some extend pragmatic and feasible.

Key words: Myelodysplastic syndromes, classification, prognosis, subtypes

Introduction Myelodysplastic syndromes (MDS) have been classified according to the FAB proposals [1] since 1982. Subsequently two proposals of WHO [2,3] working groups have been developed including more and more parameters describing the biology of the disease such as cell counts, dysplastic lineages, and chromosomal findings. All classifications are aiming at a better definition of MDS types associated with a certain prognosis and course of the disease. The latest proposal for an even more refined classification became necessary as molecular findings became evident in the last five years and new information on the course of the disease became available. The major changes proposed by the WHO working group were 1) refined definition of the ring sideroblastic MDS types including molecular characteristics and including the reintroduction of a group of MDS with multilineage dysplasia and ring sideroblasts, 2) refinement of the definition of MDS del(5q), 3) refinement of CMML

types, and 4) the recognition of RARS-T as a separate entity within the MDS/MPN group. We reported earlier on these entities [4, 5, 6, 7, 8]. In addition new names for different MDS types better describing the characteristics of the types were introduced. The WHO also proposed cut-off values of cytopenias (defined as haemoglobin <10g/dl, platelet count <100.000/ µl, and absolute neutrophil count <1800/µl) as prerequisites for the diagnosis of MDS, taking into account that there might be some patients with higher cell counts. Finally, the WHO group proposed to numerate the medullary blast count based on all nucleated cells in the marrow, neglecting the amount of erythroid cells. This topic was validated by the Düsseldorf MDS registry recently [9]. The Düsseldorf MDS registry allows to easily validate the other proposals on a large data set with high quality diagnostic procedures as well as follow up of the patients. Herein we report on the newly defined MDS types as proposed by the WHO working groups [3].

Materials and Methods Between 1970 and 2015, 3528 patients with primary myelodysplastic syndromes were diagnosed at our hospital and included in our MDS Registry. All bone marrow smears were examined by the same investigator(s) (CA and/or UG). Morphological diagnosis was made according to the FAB, WHO 2001, WHO 2008 and WHO2016 classification [1, 2, 3, 10]. Patients with the former MDS type of RAEB-T were also analyzed. Patients were followed for survival and leukemic progression through July 31st, 2015. The median time of follow up was 19 months (1-36). As the initial karyotype at the time of diagnosis was available in only 1584 patients of the entire cohort, the IPSS [11] and IPSS-R [12] could be described in a subset of 1466 (IPSS and IPSSR) of the cohort, respectively. In order to better compare the real frequency of the subtypes, we also report on patients within the registry that lived in the city of Düsseldorf at the time of diagnosis, as due to clinical trial and research activities at our institution, MDS del(5q) and ringsideroblastic phenotypes might be overrepresented in the entire cohort. As reported earlier, we are able to catch virtually all patients with MDS living in the city of Düsseldorf by close collaboration with other hematologists [13]. Outcome and leukemic evolution were calculated in months from date of diagnosis to date of the respective event. Categorical variables were analysed by frequency tables, continuous variables were described via median (range). Time-to-event-curves were calculated by the Kaplan-Meier method. Log-rank test was used for univariate comparisons. 2-test was employed for univariate comparison cross tabulation. A p value <.05 was considered as statistically significant.

Results In all, 3190 patients were diagnosed as MDS. 256 patients were diagnosed as MDS SLD (8.0%), 978 MDS MLD (30.7%), 227 MDS RS SLD (7.1%); 321 MDS RS MLD (10.1%), 159 MDS del(5q) (5.0%), 481 MDS EB 1 (15.1%), 620 MDS EB 2 (19.4%), and 148 MDS-U

(4.6%). In addition, 338 patients were diagnosed as RAEB-T. Table 1 shows the shift of patients from the WHO 2008 classification into categories of the WHO 2016 classification. There were no shifts with regard to the RAEB groups, but due to MDS RS MLD category and the new definition of MDS del(5q), 350 patients (16.7% of the non-RAEB types) changed the category, leading to a larger group of MDS del(5q). Looking on only those patients living in the city of Düsseldorf there were 6.3% MDS SLD, 28.9% MDS MLD, 6.6% MDS RS SLD, 11.6% MDS RS MLD, 1.8% MDS del(5q), 10.3 % MDS EB1, 18.7% MDS EB2, and 5.3% MDS-U. These data show that there is no major difference between the entire cohort and those patients living in the city of Düsseldorf, besides the fact that MDS del(5q) was slightly less frequent. Table 2 presents important clinical, hematological, cytogenetic, and prognostic information of the WHO 2016 types. A part of these characteristics was influenced per definition. The degree and number of cytopenias as well as the frequency of clonal aberrations, in parallel to the number of dysplastic lineages and the blast percentages differed between the groups. In detail, pancytopenia rises and median cell counts for platelets and neutrophils drop with increasing multilineage dyplasia and medullary blasts, whereas the median hemoglobin values were comparable between all groups. Interestingly, there are patients primarily within all the non-blastic MDS types without cytopenias according to the WHO definitions who present with mild cytopenia only. The distribution of patients to IPSS and IPSS-R as shown in table 3 also differs significantly between the MDS types, allocating the most patients to the high and very high risk groups within the MDS EB types. The percentage of patients with aberrant karyotype differs significantly as shown in table 2 with the lowest percentage of 29% of abnormal karyotypes within the MDS SLD RS-group in contrast to 54% and 55% in the MDS EB 1 and MDS EB 2 group. Surprisingly, the highest percentage of abnormal karyotypes was found in the MDS-U Pan group with 64%. Patients with very high or high risk cytogenetics were seen more often in the more advances types of MDS, namely MDS EB 1 and 2, vice versa very low risk karyotypes were more frequent in MDS SLD and MDS MLD types. Table 4 presents prognostic characteristics of the WHO 2016 types. The median survival of MDS SLD groups was better as compared to MDS MLD, and MDS EB types. The newly defined MDS del(5q) group had a similar survival time and progression rate as the former group. In addition, we analysed, if the IPSS-R was able to identify risk groups within the WHO subtypes. In general, the IPSS worked fine for the description of the natural course of the disease and the risk of AML progression. In a last step, we analysed, if the allocation to WHO types, i.e. the description if a patient presents with uni- or multilineage dysplasia has prognostic impact besides the IPSS-R. Table 5 a and 5 b presents the result of multivariate analyses. The most important prognostic parameter was the karyotype risk group according to the IPSS-R, followed by the medullary blast count category according to the IPSS-R. In addition to the cell counts according to IPSS-R, the presence of multilineage dysplasia was identified as an independent prognostic

marker for the entire group. Focusing on the non-RAEB types only was the second most important prognostic parameter after chromosomal findings. Discussion Based on data of 3528 patients with primary MDS the Düsseldorf registry we were able to demonstrate the usefulness of the recent WHO proposals for the classification of MDS with regard to clinical characteristics as well as from the prognostic point of view. Although there still are no minimal diagnostic criteria for MDS and probably there will never be such, and although there is no single cell dysplasia [14] that allow the diagnosis of MDS, a well-defined description of different MDS types as proposed by the WHO group allows to clearly distinct MDS types with different biological features, with different risk of progression and with different prognosis. The majority of the patients belong to the non-blastic MDS types (59,2%), the most frequent being the MDSMLD type with 27,7 % whereas MDSEB1 and MDSEB2 account for only 31,2. Only 4.2% of the patients are allocated to the MDS-U categories. Taking into account the assessment of lineage involvement of dysplasia in the marrow, as established [15, 16, 17] was kept as the most important classifying item in the non-blastic MDS by the new WHO proposals. In addition, by considering the strong phenotypegenotype correlation of ring sideroblasts and mutation of SF3B1 this mutation was the first to be introduced as a classifier in MDS. The resulting 4 groups are very similar to the RA, RCMD, RARS and RCMD-RS groups from the WHO 2001 classification [18, 19], now realizing the good risk of single lineage dysplasia and SF3B1 mutation. Having in mind promising data of Luspatercept in patients with SF3B1 mutation the recognition of this mutation might be helpful as well [20]. It is unlikely that many patients with >5% but < 15% ring sideroblasts will be included in the "RARS" category on the basis of an SF3B1 mutation. In a series of 47 patients with MDS RS SLD or MDS RS MLD, we found only two such cases (4.2%), with 6% and 10% ring sideroblasts, respectively. As the correlation of the dysplastic lineage in the marrow with the cytopenic lineage in blood is low [21], the terms RA, RN, and RT were disposed. New definitions of cytopenias as proposed by the WHO draw the physicians´ attention on the fact, that 87,3% of our patients present with at least one significant cytopenia at the time of diagnosis and a mild anemia very rarely is indicating the presence of MDS. The note of the new WHO proposal that there are differences in normal ranges of cell counts between races [22] indicates that potentially typical degrees of cytopenia may vary. However, there might be differences in the frequency of WHO types between far east and western countries was well described by Matsuda et al [23], but it is not possible to address these differences in the classification. Of interest, the number of patients who present with mild cytopenia not fulfilling the defintions of the WHO proposals cannot be neglected. The relatively high number of patients with mild cytopenia, primarily mild anemia may be explained by very early MDS diagnoses, as the majority of those patients drop with the cell counts during the course of the disease.

Another classifying item is the presence of blasts in peripheral blood. As soon as 1% blasts have been described by 2 independent examinations the patients are allocated to the MDS unclassified (MDS-U) group (MDS SLD or MDS MLD with 1% blasts). Still the data published by Knipp et al [24] hold true a poor prognosis of these patients. This has now been commented more precisely by the WHO2016 proposals. The second group of MDS-U includes patients with MDS SLD or MDS MLD with pancytopenia reflecting their poorer prognosis, as compared to uni- or bicytopenic patients [21]. The contribution of our data with regard to the third MDS-U category, namely the patients with minimal signs of dysplasia but with a clonal marker is low, as we saw less than 5 cases with that condition. The WHO advice to regard the presence of a least 15% ring sideroblasts as a sign of dysplasia is helpful in some cases. Another refinement is dealing with MDS del(5q), as patients with one additional nonchromosome 7 abnormality now are allocated to the MDS del(5q) group. Our data show, that it affects only a small number of patients and that the prognosis of these patients is similar to patients with isolated del(5q). As morphology, clinical course and response to treatment are also not different [25, 26, 27, 28], the new WHO proposal is justified. A very small number of patients who present with pancytopenia now are allocated into the MDS unclassified cases. One could argue, if pancytopenia or a distinct chromosomal aberration is a more important classifier, but there were only 4.2% of the del(5q) group to be reclassified. The blastic MDS types remain unchanged but received new names (MDS EB1 und 2). As the prognostic difference between these types is well established since decades, there was no need for changes [29, 30, 31]. However patients formerly classified as AML M6 will be allocated to the MDS EB groups according to their medullary blast percentage counted on the basis of all nucleated cells. We have no sufficient data at hand to validate that proposal. There are two major topics with regard to classification that still are not addressed sufficiently due to lack of data: The first one is the definition of what is called dysplastic lineage, a topic that is discussed controversially. Matsuda et al [32] proposed to refine the definition of the percentage of dysplastic cells of the megakaryocytes to 40% and no more of 10%. A similar proposal from our group [33] aimed at the same direction but needs to be confirmed in an independent data set. Goasguen et al [34] published helpful recommendations for the correct evaluation of dysmegakaryocytes. The second one is the vague situation with regard to CHIP, IDUS, and ICUS [35, 36, 37]. At least a part of those entities has MDS or at least is at risk to develop MDS, whereas another part of the patients has secondary cytopenia only. Another refinement of these conditions and reports on clinical data in detail, this topic is waiting to be addressed in the future. The introduction of new terms (MDS SLD, MDS MLD, and MDS EB) drive the pathologists and hematologists to get used to these terms, but is aiming at a better description of the diseases focusing on the major characteristic of the MDS type. Again the low correlation of dysplastic lineage in the marrow and the cytopenic lineage in the blood ended up in describing the more important feature, i.e. single- versus multilineage dysplasia. The same is

true for the introduction of the term MDS EB, as “refractory anemia” in these patients is not the main problem; “MDS EB” explains the character of these types of MDS as real preleucemic status. With regard to prognosis, we could show that the IPSS-R was able to stratify patients with in all newly defined MDS types. In addition, the identification of multilineage dysplasia as an independent prognostic parameter besides the parameters used in the IPSS-R underlines the necessity of a well performed marrow assessment not only from a diagnostic but also from a prognostic point of view. In summary, the proposals of the WHO group for the classification of MDS are thoughtful, taking into account biologic parameters of the diseases, a more precise wording, to some extend pragmatic and feasible, which we herein can demonstrate clearly.

Acknowlegdements: None 

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cum. survival

Figure 1a: Survival according to WHO-classification 2016 for non-blastic MDS

MDS SLD MDS del(5q) MDS MLD MDS RS SLD MDS RS MLD

0      3      6       9     12    15    18    21    24   27    30    33    36    39   42

years

Figure 1b: Survival according to WHO-classification 2016 for blastic MDS

cum. survival

 

MDS EB 1

MDS EB 2

MDS RAEB‐T

0          2           4          6           8          10        12        14         16        18 

years

Fig. 2a: Cumulative risk of AML-evolution according to WHO classification 2016 in the low-risk types

cum. AML‐risk

 

MDS MLD MDS SLD MDS del(5q) MDS RS MLD MDS RS SLD

0       3      6       9     12    15     18    21    24    27     30    33    36     39    42

years

Fig. 2b: Cumulative risk of AML-evolution according to WHO classification 2016 in the high-risk types   MDS  RAEB‐T

cum. AML‐risk

MDS EB 2

MDS EB 1

0                  3                 6                  9                12               15               18

years

Table 1: New distribution of patients to categories (+ percentages) and shift of cases WHO 2008

WHO 2016

n=3190

n=3190

Shift of cases of the entire patient population n= 350 (11%)

RCUD, 8,1%, n=258 (RA, RT, RN) RARS, 7,2%, n= 229

MDS SLD, 8%, n= 256 ->MDS del(5q) MDS RS SLD, 7,1%, n= 227 ->MDS del(5q)

RCMD, 41,3%, n=1316

MDS del(5q), 4,5%, n= 142

n=2, (0.8 %)

n=2, (0.9 %)

MDS MLD, 30,6%, n=976 ->MDS RS MLD

n=321 (24.4%)

->MDS del(5q)

n=19 (1.4%)

MDS del(5q), 5%, n= 159 ->MDS U Pan

(+ 23) n=6 (4.2%)

MDS U Pan, 0,7%, n= 23

MDS U Pan, 0,9%, n= 29

(+ 6)

MDS U PB, 3,7%, n=118

MDS U PB, 3,7%, n= 118

-

MDS U clonal, 0,001%, n=3

MDS U clonal, 0,001%, n= 3

-

RAEB I, 15,1%, n=481

MDS EB 1, 15,1%, n=481

-

RAEB II, 19,4%, n= 620

MDS EB 2, 19,4%, n=620

-

Legend to Table 1: Abbreviations WHO 2008:

RCUD: Refractory cytopenia with unilineage dysplasia, RA: Refractory anemia, RT: Refractory thrombocytopenia, RN: Refractory neutropenia, RARS: Refractory anemia with ring sideroblasts , RCMD: Refractory cytopenia with multilineage dysplasia, MDS del(5q): Myelodysplastic syndrome associated with isolated del(5q), MDS U Pan: Myelodysplastic syndrome unclassifiable with single lineage dysplasia and pancytopenia, MDS U pB: Myelodysplastic syndrome unclassifiable with 1% blood blasts, MDS U clonal: Myelodysplastic syndrome unclassifiable only based on defining cytogenetic abnormality, RAEB I: Refractory cytopenia with excess blasts-1, RAEB II: Refractory cytopenia with excess blasts-2

Abbreviations WHO 2016:

MDS SLD: Myelodysplastic syndrome with single lineage dysplasia, MDS RS SLD: Myelodysplastic syndrome with ring sideroblasts and single lineage dysplasia, MDS MLD: Myelodysplastic syndrome with multilineage dysplasia, MDS RS MLD: Myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia, MDS del(5q): Myelodysplastic syndrome with isolated or with 1 additional abnormality except -7 or del(7q), MDS EB 1: Myelodysplastic syndrome with excess blasts 1, MDS EB 2: Myelodysplastic syndrome with excess blasts 2

   

Table 2: Haematological and morphological characteristics, cytogenetic parameters MDS SLD

MDS SLD

RS MDS MLD

RS MDS 5q

del MDS MLD

MDS EB1

MDS EB2 RAEB-T

MDS-U pB

MDS-U PAN

MDS-U noDys

male

50,8

51,1

55,1

29,6

58,3

61,5

58,2

54,4

53,4

44,4

66,7

female

49,2

48,9

44,9

70,4

41,7

38,5

41,8

45,6

46,6

55,6

33,3

Median

72

72

73

67

71

69

70

69

71

69

77

Range

18-91

18-91

25-92

32-89

18-93

20-104

18-94

18-96

18-88

19-90

72-81

9,7

9,6

8,9

9,3

9,6

9,4

9,1

8,8

9,3

8,6

9,4

3,4

3,6

2,2

3

4

3,6

3,7

3,2

5,3

4,6

7,4

15,9

13,7

13,1

13,2

16,6

17,5

15,9

15,2

16,9

9,8

10,4

Median

139

260,5

202

270,5

117

97,5

81

76

146

51

111

Minimum

2

36

5

14

1

0

2

2

9

3

36

Maximum

850

581

450

1540

1140

238

809

4426

1012

160

322

Median

2393

3024

2312

2121,5

2000

1359

1080

822

2100

1050

800

Minimum

125

64

46,9

200

50

12

6

0

133

375

504

Maximum

18144

14450

18518

13500

32830

87305

88960

38056

11703

5950

4543

1

1

2

2

2

8

14

25

1

1

2

0-4

0-4

0-4

0-4

0-4

1-9

1-20

2-29

0-4

0-4

0-4

0

0

0

0

0

0

0

1

1

0

0

0-0

0-0

0-0

0-0

0-1

0-4

0-19

0-29

1-1

0-0

0-0

37

33

0

0

0

0

0

0

0

0

15-97

15-94

0-90

0-14

0-96

0-85

0-69

0-97

0-5

0-0

0

0

0

0

0

9

16

0

0

0

Gender (%)

Age (years)

Haemoglobin (g/dl) Median Minimum Maximum

Platelets (/µl)

ANC (/µl)

Bone marrow blasts (%) Median range Peripheral (%)

Blasts

Median range Ring Sideroblasts (%) Median

0 0-13

Range Auer rods (%)

0

Cytopenias defined by WHO (1) 2016 None

17,1

30

16,6

16,8

14,2

6,3

4,1

3

13,4

-

40

Unicytopenia

49

54

42,5

54,0

39,6

32,7

24,5

21,6

42,0

-

20

Bicytopenia

33,9

16

32,3

29,2

30,5

38,8

43,4

38,7

32,8

-

20

Pancytopenia

-

-

8,6

-

15,8

22,1

28,0

36,6

11,8

100

20

Abnormal karyotypes (%)

40

29

46

100

41

55

54

55

55

64

100

6.9

6.1

7.1

0

5.0

1.1

1.9

1.1

2.2

0

-

70.3

77.3

58.7

100

65.5

55.3

53.5

49.7

53.3

78,6

-

12.9

12.1

17.5

0

16.8

18.7

16.4

16.6

22.2

21,4

75.0

4.0

3.0

11.1

0

6.9

9.9

9.2

11.4

15.6

0

25.0

5.9

1.5

5.6

0

5.8

15.0

18.9

21.1

6.7

0

-

Chromosomal risk groups % Very low Low Intermediate high Very high

1 Cytopenia defined as haemoglobin <10g/dl, platelet count <100.000/ µl, and absolute neutrophil count <1800/µl

 

Table 3: Distribution of IPSS-R and IPSS risk groups for the different WHO types

MDS SLD

MDS RS SLD

MDS RS MLD

MDS del5q

MDS MLD

Very low

34,3

33,9

25,5

15,5

Low

42,5

57,6

56,4

Intermediate

18,3

8,5

High

4,9

Very high

MDS EB1

MDS EB2

RAEB-T

MDS-U pB

MDS-U Pan

MDS-U noDys

17,2

-

-

-

27,5

-

-

76,0

48,1

12,3

3,7

-

30,0

42,9

-

13,8

8,5

27,8

37,3

22,8

11,4

27,5

50,0

50,0

-

4,3

-

5,0

29,5

34,2

39,6

10,0

7,1

50,0

-

-

-

-

1,9

19,9

39,3

49.0

5,0

-

-

Low

54,9

65,1

44,7

67,4

34,9

-

-

-

35,0

100,0

-

Intermediate I

41,5

34,9

48,9

32,6

58,5

66,1

12,4

-

55,0

-

50,0

Intermediate II

3,6

-

6,4

-

6,6

33,9

56,7

15,7

10,0

-

50,0

high

-

-

-

-

-

-

30,9

84,3

-

-

-

IPSS-R (%)

IPSS (%)

 

Table 4: WHO2016 types by median survival, survival after 2 and 5 years, percentage of AML progression, and AML progression rate after 2 and 5 years from first diagnosis

Median WHOsurvival classification 2016 (months)

AML Survival Survival after 2 after 5 progression years (%) years (%) rate (%)

MDS SLD

62

71

51

8,2

6

12

MDS RS SLD

61

79

51

3,1

2

3

MDS RS MLD

37

64

33

9,3

8

14

MDS del 5q

79

89

64

13,2

5

14

MDS MLD

38

63

36

10,6

9

15

MDS EB1

21

48

21

21,4

25

41

MDS EB2

11

34

15

34,4

47

59

RAEB-T

5

23

11

61,2

76

82

MDS-U pB

35

60

35

11,0

11

16

MDS-U PAN

32

77

42

14,8

4

20

MDS-U NoDys

36

53

53

0

-

-

 

AML -evolution after 2 (%)

5 years (%)

Table 5 a: Multivariate Analysis of prognostic parameters for survival (all patients)

Karyotype (IPSS-R)

160.384

0.00005

Medullary blasts (IPSS-R)

45.44

0.00005

Hemoglobin (IPSS-R)

17.35

0.00005

Platelets (IPSS-R)

14.21

0.00005

ANC (IPSS-R)

11.23

0.001

Presence of dysplasia

10.1

0.002

 

Table 5 b: Multivariate Analysis of prognostic parameters for survival (only non-RAEB types)

Karyotype (IPSS-R)

71.35

0.00005

Presence of dysplasia

11.52

0.001

Hemoglobin (IPSS-R)

8.64

0.003

Platelets (IPSS-R)

5.09

0.024