Myelodysplastic Syndrome

Myelodysplastic Syndrome

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Myelodysplastic syndrome (MDS) refers to a heterogeneous group of closely related clonal hematopoietic disorders commonly found in the aging population. All are characterized by one or more peripheral blood cytopenias. Bone marrow is usually hypercellular, but rarely, a hypocellular marrow mimicking aplastic anemia may be seen. Bone marrow cells display aberrant morphology and maturation (dysmyelopoiesis), resulting in ineffective blood cell production.

MDS affects hematopoiesis at the stem cell level, as indicated by cytogenetic abnormalities, molecular mutations, and morphologic and physiologic abnormalities in maturation and differentiation of one or more of the hematopoietic cell lines. [1, 2, 3]  See the image below.

See Myelodysplastic Syndromes: Classification, Features, Diagnosis, and Treatment Options, a Critical Images slideshow, to help identify, classify, work up, and treat these disorders.

MDS may involve one, two, or all three myeloid hematopoiesis cell lineages—erythrocytic, granulocytic, megakaryocytic—depending on the subtype and stage of the disease. The heterogeneity of MDS reflects the fact that its course involves a series of cytogenetic events. In a subgroup of patients, the acquisition of additional genetic abnormalities results in the transformation of MDS into acute myeloid leukemia (AML). Thus, although  MDS is clonal, it is considered a premalignant condition.

Patients with MDS may present with clinical manifestations of anemia, thrombocytopenia, and/or neutropenia (see Presentation). The workup in patients with possible MDS includes a complete blood count with differential, peripheral blood smear, and bone marrow studies (see Workup).

Standard care for MDS is constantly changing, but it typically includes supportive therapy, including transfusions, and may include bone marrow stimulation and cytotoxic chemotherapy. Bone marrow transplantation has a limited role. (See Treatment.)

For discussion of MDS in children, see Pediatric Myelodysplastic Syndrome

MDS develops when a clonal mutation predominates in the bone marrow, suppressing healthy stem cells. The clonal mutation may result from genetic predisposition or from hematopoietic stem cell injury caused by exposure to any of the following:

MDS can be classified as primary (de novo) or secondary to aggressive treatment of other cancers, with exposure to radiation, alkylating agents, or topoisomerase II inhibitors; it also occurs in heavily pretreated patients with autologous bone marrow transplants.

In the early stages of MDS, the main cause of cytopenias is increased apoptosis (programmed cell death). As the disease progresses and converts into leukemia, further gene mutation occurs, and a proliferation of leukemic cells overwhelms the healthy marrow.

Cytogenetically, patients with MDS or AML fall into three groups:

Patients with complex karyotypes constitute 30% of primary MDS cases (only 20% of de novo AML) and up to 50% of therapy-related MDS and AML cases. These patients have a worse prognosis and response to treatment.

Balanced translocation abnormalities lead to the generation of fusion oncogenes such as Bcr-Abl in chronic myelogenous leukemia (CML) and PML-Rar alpha in acute promyelocytic leukemia (APL). Unbalanced recurrent aberrations, most commonly -5, 5q-,-7, 7q-, +8, 11q-, 13q-, and 20q-, suggest that genes within these regions have a role in the pathogenesis of MDS or myeloproliferative disorder (MPD), which is based on loss of tumor suppressor genes or haploinsufficiency of genes necessary for normal myelopoiesis.

Approximately 80% of patients with MDS do not have an obvious exposure or cause for MDS. In these cases, the disorder is classified as primary or idiopathic MDS.

The World Health Organiztion (WHO) classifies secondary MDS as MDS or acute leukemia that develops years after known exposure to sources of chromosomal damage. Patients who survive cancer treatment with alkylating agents, with or without radiotherapy, have a high risk of developing MDS or secondary acute leukemia 5-7 years after the exposure. These drugs are associated with a high prevalence of chromosomal abnormalities in bone marrow—in particular, the -5, del(5q), -7, del(q) and complex karyotype.

Secondary MDS after treatment with a topoisomerase II inhibitors such as an anthracycline or etoposide occurs 1-3 years after exposure to these agents. The chromosomal abnormalities commonly involve the MLL gene (11q23).

MDS may also develop after exposure to certain chemicals (eg, benzene). Insecticides, weed killers, and fungicides are also possible causes of MDS and secondary leukemia. [4] Viral infections have also been implicated. Less evidence supports genetic predisposition, but familial incidences have been described. Some of the congenital platelet disorders with RUNX1 and GATA2 mutations can predispose to MDS.

Although familial cases of myelodysplastic syndromes are rare, they are immensely valuable for the investigation of the molecular pathogenesis of myelodysplasia in general. The best-characterized familial MDS is familial platelet disorder with propensity to myeloid malignancy, which is caused by heterozygous germline RUNX1 mutations. The incidence of MDS/AML in affected pedigrees is over 40%, with a median age of onset of 33 years. Familial monosomy 7; unusually short telomeres in dyskeratosis congenita; and four pedigrees with inherited MDS caused by heterozygous mutations in GATA2 have been reported. [5] These familial forms may occasionally be found in the course of screening family members of a patient with MDS as bone marrow transplant donors.

A study by Kristinsson et al found that chronic immune stimulation is a trigger for acute leukemia and MDS development. The underlying mechanisms may also be caused by a genetic predisposition or treatment for infections or autoimmune conditions. [6]

The actual incidence of MDS in the United States is unknown. MDS was first considered a separate disease in 1976, and its occurrence was estimated at 1500 new cases every year. At that time, only patients with less than 5% blasts were considered to have this disorder. MDS was not classified as neoplastic and included in cancer registries until 2001. [7] Current estimates of the incidence of MDS in the United States vary widely, from 10,000 to 30,000-55,000 new cases each year. [7, 8, 9, 10] The higher figures have been questioned as possible overestimates resulting from inclusion of other hematopoietic conditions. [11]

The incidence of MDS has appeared to be increasing. The apparent rise is believed to reflect the increase in the elderly population, but may also reflect improvements in recognition and criteria for the diagnosis. [8]

Although MDS may occur in persons of any age, including children, MDS primarily affects elderly people, with the median onset in the seventh decade of life. Data from 2001 through 2003 of the first National Cancer Institute’s Surveillance, Epidemiology & End Reports (SEER) indicate 86% of MDS cases were diagnosed in individuals who were 60 years of age or older (median age: 76y).

Other data from SEER also show that the estimated incidence of MDS increases significantly with age, ranging from 0.7 per 100,000 population during the fourth decade of life to 20.8-36.3/100,000 after age 70 years. There is a fivefold difference in risk between age 60 and ≥80 years.

At all ages, MDS is more common in males than in females. In SEER data from 2001-2003, the incidence rate was significantly higher in men than in women (4.5 vs 2.7 per 100,000 population). [12]

MDS is found worldwide and is similar in characteristics throughout the world. Data based mainly on European numbers from Germany and Sweden were very similar to the US numbers. [10]

A review of United Kingdom population-based data from September 2004 to August 2013 found marked variations in MDS incidence, depending on the standard population used to calculate rates. For example, using the 1996 world standard, the population with the greatest weighting towards younger groups, the incidence rate was 1.67 per 100,000 population; using the 2013 European Standard Population, which has the greatest weighting towards older ages, the rate was 4.4 per 100,000 population. [13]

In some patients, MDS is an indolent disease. Other patients develop significant cytopenias; the resulting complications (eg, bleeding and infections) account for almost all the mortality related to MDS. In the remainder of cases the disease follows an aggressive course and converts into an acute form of leukemia.

Risk classification systems to estimate prognosis in patients with MDS have been developed by the French-American-British (FAB) Cooperative Group, the World Health Organization (WHO), and the MDS Risk Analysis Workshop.

The FAB system classifies MDS into the following five subgroups, differentiating them from acute myeloid leukemia [14] :

Refractory anemia (RA)

RA with ringed sideroblasts (RARS)

RA with excess blasts (RAEB; 6-20% myeloblasts)

RAEB in transition to AML (RAEB-T; 21-30% myeloblasts)

Chronic myelomonocytic leukemia (CMML)

An underlying trilineage dysplastic change in the bone marrow cells is found in all subtypes.

RA and RARS are characterized by 5% or less myeloblasts in bone marrow. RARS is defined morphologically as having 15% erythroid cells with abnormal ringed sideroblasts (see the image below), reflecting an abnormal accumulation of iron in the mitochondria. Both RA and RARS have a prolonged clinical course and a low prevalence of progression to acute leukemia. In a review of United Kingdom population-based data, with followup of 2 to 11 years, progression to acute leukemia occurred in 5% of RARS cases, compared with 25% of RAEB cases. [13]

RAEB and RAEB-T (see the image below) are characterized by greater than 5% myeloblasts. The higher the percentage of myeloblasts present, the shorter the clinical course and the closer the disease is to acute myelogenous leukemia.

Transition from early to more advanced stages may occur, which indicates that these subtypes are merely stages of disease rather than distinct entities. Elderly patients with MDS who progress to acute leukemia are often considered to have a poor prognosis because their disease response to chemotherapy is worse than that of de novo acute myeloid leukemia patients.

The 1999 WHO classification proposed including all cases of RAEB-T in the category of acute leukemia because these patients have similar prognostic outcomes. [15] However, the response to therapy is worse than in patients with de novo or more typical AML or acute nonlymphocytic leukemia.

The fifth type of MDS, CMML, is the most difficult to classify. This subtype can have any percentage of myeloblasts but manifests as a monocytosis of 1000/μL or more, a total white blood cell (WBC) count of less than 13,000/μL, and trilineage dysplasia.

CMML may be associated with splenomegaly. This subtype overlaps with myeloproliferative disease (MPD) and may have an intermediate clinical course. CMML must be differentiated from classic chronic myelocytic leukemia, which is characterized by a negative Ph chromosome.

The 2008 WHO classification proposed that juvenile myelomonocytic leukemia and CMML be listed as separate entities within a group of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) overlap syndromes. WHO criteria for these forms of CMML include splenomegaly and a WBC count greater than 13,000/μL.

The WHO classification scheme for MDS was published in 1999. Updates to the scheme were published in 2008 and 2016. The 2016 WHO classification of MDS is as follows [16] :

MDS with single-lineage dysplasia (MDS-SLD) – 1 or 2 blood cytopenias; in bone marrow, dysplasia in ≥ 10% of one cell line, < 5% blasts

MDS with multilineage dysplasia (MDS-MLD) – 1-3 blood cytopenias, < 1 × 109/L monocytes; in bone marrow, dysplasia in ≥ 10% of cells in ≥ 2 hematopoietic lineages < 15% ring sideroblasts (or < 5% ring sideroblasts if SF3B1 mutation present) < 5% blasts 

MDS with ring sideroblasts (MDS-RS) –  Anemia, no blasts;  in bone marrow, ≥ 15% of erythroid precursors with ring sideroblasts or ≥ 5% ring sideroblasts if SF3B1 mutation is present

MDS with isolated del(5q) –  Anemia, platelets normal or decreased; in bone marrow, unilineage erythroid dysplasia, isolated del(5q), < 5% blasts ± one other abnormality except -7/del(7q)

MDS with excess blasts (MDS-EB) – 1-3 blood cytopenias, 0-3 dysplastic bone marrow lineages, and 5-9% blasts in bone marrow or 2-4% blasts in blood (MDS-EB1) or 10-19% blasts in bone marrow or 5-19% blasts in blood (MDS-EB2)

Unclassifiable MDS – Cytopenias, ±1% blasts on at least 2 occcasions; in bone marrow, single-lineage dysplasia or no dysplasia but characteristic MDS cytogenetics, < 5% blasts

The WHO classification also includes provisional category of refractory cytopenia of childhood, with cytopenias and < 2% blasts in peripheral blood and, in bone marrow, dysplasia in 1–3 lineages and < 5% blasts.

To improve prognostic classification, the MDS Risk Analysis Workshop developed the Myelodysplastic Syndrome International Prognostic Scoring System (IPSS). The IPSS was published in 1997 and updated in 2012. [17, 18] The revised IPPS (IPSS-R)  score is calculated on the basis of five variables:

Hemoglobin level

Absolute neutrophil count

Platelet count

Percentage of bone marrow blasts

Cytogenetic category

With the IPSS, patients were stratified tinofour risk groups: low, intermediate 1 and 2, and high. The IPSS-R score is used to stratify patients into five risk groups, as shown in Table 1, below:

Table 1. Revised International Prognostic Scoring System risk groups and prognosis [18] (Open Table in a new window)

Risk Group

Time to Development of AML (y)

Median Survival (y)

Very low

NR

8.8

Low

10.8

5.3

Intermediate

3.2

3.0

High

1.4

1.6

Very High

0.7

0.8

AML – Acute myelogenous leukemia

Mean survival is 18-24 months or longer in patients with the following features:

Single or mild cytopenias

Normal chromosomes or a single chromosomal abnormality (except those involving chromosome 7)

Fewer than 10% myeloblasts in the bone marrow

Mean survival is 6-12 months in patients with the following features:

Pancytopenia requiring red blood cell or platelet transfusions

Chromosome 7 abnormalities or multiple chromosomal abnormalities

Greater than 10% myeloblasts

Besa EC. Myelodysplastic syndromes (refractory anemia). A perspective of the biologic, clinical, and therapeutic issues. Med Clin North Am. 1992 May. 76(3):599-617. [Medline].

Germing U, Kobbe G, Haas R, Gattermann N. Myelodysplastic syndromes: diagnosis, prognosis, and treatment. Dtsch Arztebl Int. 2013 Nov 15. 110(46):783-90. [Medline].

Dao KT. Myelodysplastic Syndromes: Updates and Nuances. Med Clin North Am. 2017 Mar. 101 (2):333-350. [Medline].

Goldberg H, Lusk E, Moore J, Nowell PC, Besa EC. Survey of exposure to genotoxic agents in primary myelodysplastic syndrome: correlation with chromosome patterns and data on patients without hematological disease. Cancer Res. 1990 Nov 1. 50(21):6876-81. [Medline]. [Full Text].

Sperling AS, Gibson CJ, Ebert BL. The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia. Nat Rev Cancer. 2017 Jan. 17 (1):5-19. [Medline]. [Full Text].

Kristinsson SY, Bjorkholm M, Hultcrantz M, et al. Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes. J Clin Oncol. 2011 Jul 20. 29(21):2897-903. [Medline]. [Full Text].

Bejar R, Steensma DP. Recent developments in myelodysplastic syndromes. Blood. 2014 Oct 30. 124 (18):2793-803. [Medline]. [Full Text].

What are the key statistics about myelodysplastic syndromes?. American Cancer Society. Available at http://www.cancer.org/cancer/myelodysplasticsyndrome/detailedguide/myelodysplastic-syndromes-key-statistics. January 22, 2018; Accessed: February 28, 2018.

Rollison DE, Hayat M, Smith M, et al. First report of national estimates of the incidence of myelodysplastic syndromes and chronic myeloproliferative disorders from the U.S. SEER program [abstract 247]. Blood. 2006. 108:77a. [Full Text].

Rollison DE, Howlader N, Smith MT, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008 Jul 1. 112(1):45-52. [Medline]. [Full Text].

Ma X. Epidemiology of myelodysplastic syndromes. Am J Med. 2012 Jul. 125 (7 Suppl):S2-5. [Medline].

Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007 Apr 15. 109(8):1536-42. [Medline]. [Full Text].

Roman E, Smith A, Appleton S, Crouch S, Kelly R, Kinsey S, et al. Myeloid malignancies in the real-world: Occurrence, progression and survival in the UK’s population-based Haematological Malignancy Research Network 2004-15. Cancer Epidemiol. 2016 Apr 15. [Medline]. [Full Text].

Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985 Oct. 103(4):620-5. [Medline].

Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol. 1999 Dec. 17(12):3835-49. [Medline]. [Full Text].

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19. 127 (20):2391-405. [Medline]. [Full Text].

Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15. 89(6):2079-88. [Medline]. [Full Text].

Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012 Sep 20. 120 (12):2454-65. [Medline]. [Full Text].

Adema V, Bejar R. What lies beyond del(5q) in myelodysplastic syndrome?. Haematologica. 2013 Dec. 98(12):1819-21. [Medline].

Molldrem JJ, Leifer E, Bahceci E, et al. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med. 2002 Aug 6. 137(3):156-63. [Medline]. [Full Text].

Angelucci E, Urru SA, Pilo F, Piperno A. Myelodysplastic Syndromes and Iron Chelation Therapy. Mediterr J Hematol Infect Dis. 2017. 9 (1):e2017021. [Medline]. [Full Text].

[Guideline] Bennett JM, MDS Foundation’s Working Group on Transfusional Iron Overload. Consensus statement on iron overload in myelodysplastic syndromes. Am J Hematol. 2008 Nov. 83 (11):858-61. [Medline]. [Full Text].

Musto P, Lanza F, Balleari E, et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol. 2005 Jan. 128(2):204-9. [Medline].

[Guideline] NCCN Clinical Practice Guidelines in Oncology. Myelodysplastic Syndromes. National Comprehensive Cancer Network. Available at http://www.nccn.org/professionals/physician_gls/pdf/mds.pdf. Version 1.2019 — July 16, 2018; Accessed: July 23, 20018.

Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood. 2005 Aug 1. 106(3):803-11. [Medline]. [Full Text].

Clark RE, Jacobs A, Lush CJ, Smith SA. Effect of 13-cis-retinoic acid on survival of patients with myelodysplastic syndrome. Lancet. 1987 Apr 4. 1 (8536):763-5. [Medline].

Crisà E, Foli C, Passera R, Darbesio A, Garvey KB, Boccadoro M, et al. Long-term follow-up of myelodysplastic syndrome patients with moderate/severe anaemia receiving human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3: independent positive impact of erythroid response on survival. Br J Haematol. 2012 Jul. 158 (1):99-107. [Medline].

List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5. 355 (14):1456-65. [Medline]. [Full Text].

List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10. 352(6):549-57. [Medline]. [Full Text].

Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002 May 15. 20(10):2429-40. [Medline]. [Full Text].

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar. 10(3):223-32. [Medline].

Bejar R, Lord A, Stevenson K, Bar-Natan M, Pérez-Ladaga A, Zaneveld J, et al. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014 Oct 23. 124 (17):2705-12. [Medline]. [Full Text].

Parikh AR, Olnes MJ, Barrett AJ. Immunomodulatory treatment of myelodysplastic syndromes: antithymocyte globulin, cyclosporine, and alemtuzumab. Semin Hematol. 2012 Oct. 49 (4):304-11. [Medline]. [Full Text].

Platzbecker U. Who benefits from allogeneic transplantation for myelodysplastic syndromes?: new insights. Hematology Am Soc Hematol Educ Program. 2013. 2013:522-8. [Medline].

Sandhu KS, Brunstein C, DeFor T, Bejanyan N, Arora M, Warlick E, et al. Umbilical Cord Blood Transplantation Outcomes in Acute Myelogenous Leukemia/Myelodysplastic Syndrome Patients Aged ≥70 Years. Biol Blood Marrow Transplant. 2015 Sep 28. [Medline].

Shaffer BC, Ahn KW, Hu ZH, Nishihori T, Malone AK, et al. Scoring System Prognostic of Outcome in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelodysplastic Syndrome. J Clin Oncol. 2016 Apr 4. [Medline].

Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation. N Engl J Med. 2017 Feb 9. 376 (6):536-547. [Medline]. [Full Text].

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19. 127 (20):2391-405. [Medline]. [Full Text].

[Guideline] Fenaux P, Haase D, Sanz GF, Santini V, Buske C, ESMO Guidelines Working Group. Myelodysplastic syndromes: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep. 25 Suppl 3:iii57-69. [Medline]. [Full Text].

[Guideline] Malcovati L, Hellström-Lindberg E, Bowen D, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013 Oct 24. 122 (17):2943-64. [Medline]. [Full Text].

Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005 Oct 20. 23 (30):7594-603. [Medline]. [Full Text].

Malcovati L, Della Porta MG, Strupp C, Ambaglio I, Kuendgen A, Nachtkamp K, et al. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS). Haematologica. 2011 Oct. 96 (10):1433-40. [Medline]. [Full Text].

Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008 Mar. 22 (3):538-43. [Medline]. [Full Text].

Myelodysplastic Syndromes Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Available at http://www.cancer.gov/cancertopics/pdq/treatment/myelodysplastic/HealthProfessional/page1#Reference1.9. April 2, 2015; Accessed: November 20, 2017.

Saunthararajah Y. Key clinical observations after 5-azacytidine and decitabine treatment of myelodysplastic syndromes suggest practical solutions for better outcomes. Hematology Am Soc Hematol Educ Program. 2013. 2013:511-21. [Medline].

Visor MT, et.al. Revised International Prognostic Scoring System (IPSS) Predicts survival and Leukemia Evaluation of Myelodysplastic Syndromes Significantly Better than IPSS and WHO Prognostic System: Validation by the Gruppo Romano Mielodisplasie Italian Regional Database. Journal of Clinical Oncology. 2013. 31:2671-2677.

Liew E, and Owen C. Familial myelodysplastic syndromes: a review of literature. Haematologica. 2011. 10:1536-1542.

Risk Group

Time to Development of AML (y)

Median Survival (y)

Very low

NR

8.8

Low

10.8

5.3

Intermediate

3.2

3.0

High

1.4

1.6

Very High

0.7

0.8

AML – Acute myelogenous leukemia

Cytogenetic prognostic subgroups

Cytogenetic abnormalities 

Very good

-Y, del(11q)

Good

Normal, del(5q), del(12p), del(20q), double

including del(5q)

Intermediate

Del(7q), +8, +19, t(17q), any other single or

double independent clones

Poor

-7, inv(3)/t(3q)/del(3q), double including

-7,/del(7q), complex: 3 abnormalities

Very poor

Complex: >3 abnormalities

Points Assigned

0

0.5

1

1.5

2

3

4

 

 

 

Variable

Cytogenetic subgroup

Very Good

Good

Intermediate

Poor

Very Poor

Bone marrow blasts (%)

≤2

>2-

< 5

5-10

>10

Hemoglobin (g/dL)

≥10

8-9.9

< 8

Platelet count (x 109/L)

≥100

50-99.9

< 50

Absolute neutrophil count (x 109/L)

≥0.8

< 0.8

Risk Score

Risk Category

≤1.5

Very Low

>1.5-3

Low

>3-4.5

Intermediate

>4.5-6

 High

>6

Very High

IPSS-R Risk Category

Very Low

Low

Intermediate

High

Very High

Clinical Outcome

Median survival (years)

8.8

5.3

3.0

1.6

0.8

Median time to 25% acute myelogenous leukemia evolution (years)

NR

10.8

3.2

1.4

0.7

FAB

Classification

WHO–2004

Classification

WHO–2008

Classification

RA

RA RCMD 5q-

RCUD RCMD 5q-

RARS

RARS RCMD-RS

RARS RCMD-RS RARS-T

RAEB

RAEB-1 RAEB-2

RAEB-1 RAEB-2

CMML

CMML-1 CMML-2

CMML-1 CMML-2

RAEB-T

AML

AML

MDS with ring sideroblasts (MDS-RS)

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Srikanth Nagalla, MBBS, MS, FACP Associate Professor of Medicine, Division of Hematology and Oncology, UT Southwestern Medical Center

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Koyamangalath Krishnan, MD, FRCP, FACP Dishner Endowed Chair of Excellence in Medicine, Professor of Medicine, James H Quillen College of Medicine at East Tennessee State University

Koyamangalath Krishnan, MD, FRCP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society of Hematology, Royal College of Physicians

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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