Myelodysplastic syndrome
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2008-06-28T16:56:16Z
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{{Infobox_Disease |
Name = {{PAGENAME}} |
Image = |
Caption = |
DiseasesDB = 8604|
ICD10 = {{ICD10|D|46||d|37}} |
ICD9 = {{ICD9|238.7}} |
ICDO = 9980/0-9989/3 |
OMIM = |
MedlinePlus = |
eMedicineSubj = med |
eMedicineTopic = 2695 |
eMedicine_mult = {{eMedicine2|ped|1527}} |
MeshID = D009190 |
}}
The '''myelodysplastic syndromes''' (MDS, formerly known as "preleukemia") are a diverse collection of [[hematology|hematological]] conditions united by ineffective production of blood cells and varying risks of transformation to [[acute myelogenous leukemia]] (AML). [[Anemia]] requiring chronic [[blood transfusion]] is frequently present.
Myelodysplastic syndromes (MDS) are bone marrow [[hematopoietic stem cell|stem cell]] disorders resulting in disorderly and ineffective [[hematopoiesis]] (blood production) manifested by irreversible quantitative and qualitative defects in hematopoietic (blood-forming) cells. In a majority of cases, the course of disease is chronic with gradually worsening [[cytopenia]]s due to progressive [[bone marrow]] failure. Approximately one-third of patients with MDS progress to AML within months to a few years.
== Signs and symptoms ==
The median age at diagnosis of a MDS is between 60 and 75 years; a few patients are less than 50; MDS are rare in children. Males are slightly more commonly affected than females. Signs and symptoms are nonspecific and generally related to the blood cytopenias:
* [[Anemia]]—chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain
* [[Neutropenia]] (low neutrophil count) —increased susceptibility to [[infection]]
* [[Thrombocytopenia]] (low platelet count) —increased susceptibility to [[bleeding]] and [[ecchymosis]] (bruising), as well as subcutaneous [[hemorrhage|hemorrhaging]] resulting in [[purpura]] or [[petechia]]<ref>Myelodysplastic Syndrome. The Leukemia & Lymphoma Society. White Plains, NY. 2001. p 24. Retrieved [[May 12|05-12]]-[[2008]].</ref>
Many individuals are asymptomatic, and blood cytopenia or other problems are identified as a part of a routine blood count:
* [[neutropenia]], [[anemia]] and [[thrombocytopenia]] (low cell counts of white and red blood cells, and platelets, respectively);
* [[splenomegaly]] or rarely [[hepatomegaly]];
* abnormal granules in cells, abnormal nuclear shape and size; and/or
* [[chromosome|chromosomal]] abnormalities, including [[chromosomal translocation]]s and abnormal chromosome number.
Although there is some risk for developing [[acute myelogenous leukemia]], about 50% of deaths occur as a result of bleeding or infection. Leukemia that occurs as a result of myelodysplasia is notoriously resistant to treatment.
==Diagnosis==
MDS must be [[differential diagnosis|differentiated]] from [[anemia]], [[thrombocytopenia]], and/or [[leukopenia]]. Usually, the elimination of other causes of these [[cytopenias]], along with a [[dysplastic]] bone marrow, is required to diagnose a myelodysplastic syndrome.
A typical investigation includes:
* [[Full blood count]] and examination of [[blood film]]. The [[blood film]] morphology can provide clues about [[hemolytic anemia]], clumping of the [[platelets]] leading to spurious [[thrombocytopenia]], or [[leukemia]].
* Blood tests to eliminate other common causes of [[cytopenias]], such as [[Lupus erythematosus|lupus]], [[hepatitis]], [[B12]], [[folate]], or other [[vitamin]] deficiencies, [[renal failure]] or [[heart failure]], [[HIV]], [[hemolytic anemia]], [[monoclonal gammopathy]]. [[Age-appropriate cancer screening]] should be considered for all [[anemic]] patients.
* [[Bone marrow examination]] by a [[hematopathologist]]. This is required to establish the diagnosis, since all hematopathologists consider dysplastic marrow the key feature of myelodysplasia.
* [[Cytogenetics]] or chromosomal studies. This is ideally performed on the bone marrow aspirate. These require a fresh specimen, since live cells are induced to enter [[metaphase]] to enhance [[chromosomal]] staining.
* [[Flow cytometry]] is helpful to establish the presence of any [[lymphoproliferative]] disorder in the marrow.
==Pathophysiology==
MDS is caused by environmental exposures such as radiation and benzene; other risk factors have been reported inconsistently. Secondary MDS occurs as a late toxicity of cancer treatment, usually with a combination of radiation and the radiomimetic alkylating agents such as busulfan, nitrosourea, or procarbazine (with a latent period of 5 to 7 years) or the DNA topoisomerase inhibitors (2 years). Both acquired aplastic anemia following immunosuppressive treatment and Fanconi's anemia can evolve into MDS.
MDS is thought to arise from [[mutation]]s in the [[hematopoietic stem cell|multi-potent bone marrow stem cell]], but the specific defects responsible for these diseases remain poorly understood. [[Cellular differentiation|Differentiation]] of blood precursor cells is impaired, and there is a significant increase in levels of [[apoptosis|apoptotic]] cell death in bone marrow cells. Clonal expansion of the abnormal cells results in the production of cells which have lost the ability to differentiate. If the overall percentage of bone marrow [[Myeloblasts|blasts]] rises over a particular cutoff (20% for [[Myelodysplastic#WHO classification|WHO]] and 30% for [[Myelodysplastic#French-American-British (FAB) classification|FAB]]) then transformation to [[acute myelogenous leukemia]] (AML) is said to have occurred. The progression of MDS to AML is a good example of the ''[[Knudson hypothesis|multi-step theory of carcinogenesis]]'' in which a series of mutations occur in an initially normal cell and transform it into a [[cancer]] cell.
While recognition of leukemic transformation was historically important (see [[Myelodysplastic#History|History]]), a significant proportion of the [[morbidity]] and [[death|mortality]] attributable to MDS results not from transformation to AML but rather from the cytopenias seen in all MDS patients. While anemia is the most common [[cytopenia]] in MDS patients, given the ready availability of [[blood transfusion]] MDS patients rarely suffer injury from severe anemia. However, if an MDS patient is fortunate enough to suffer nothing more than anemia over several years, they then risk [[iron overload#secondary iron overload|iron overload]]. The two most serious complications in MDS patients resulting from their [[cytopenia]]s are bleeding (due to lack of [[platelet]]s) or infection (due to lack of [[white blood cell]]s). Long-term, transfusion of [[packed red blood cells]] leads to iron overload.
The recognition of [[epigenetic]] changes in [[DNA]] structure in MDS has explained the success of two of three commercially available medications approved by the [[US FDA]] to treat MDS. Proper [[DNA methylation]] is critical in the regulation of proliferation genes, and the loss of DNA methylation control can lead to uncontrolled cell growth, and cytopenias. The recently approved [[DNA methyltransferase inhibitors]] take advantage of this mechanism by creating a more orderly DNA methylation profile in the [[hematopoietic stem cell]] [[nucleus]], and thereby restore normal blood counts and retard the progression of MDS to [[acute leukemia]].
Some authors have proposed that the loss of [[mitochondrial]] function over time leads to the accumulation of [[DNA mutations]] in hematopoietic stem cells, and this accounts for the increased incidence of MDS in older patients. Researchers point to the accumulation of mitochondrial [[iron]] deposits in the [[ringed sideroblast]] as evidence of [[mitochondrial]] dysfunction in MDS.<ref name="pmid12406866">{{cite journal |author=Cazzola M, Invernizzi R, Bergamaschi G, ''et al'' |title=Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia |journal=Blood |volume=101 |issue=5 |pages=1996–2000 |year=2003 |pmid=12406866 |doi=10.1182/blood-2002-07-2006}}</ref>
==Types and classification==
===French-American-British (FAB) classification===
In 1974 and 1975 a group of pathologists from France, the United States, and Britain met and deliberated and derived the first widely used classification of these diseases. This [[French-American-British classification| French-American-British (FAB) classification]] was published in 1976 and revised in 1982. Cases were classified into 5 categories: ([[ICD-O]] codes are provided where available)
* ({{ICDO|9980|3}}) '''Refractory [[anemia]]''' (RA) - characterized by less than 5% primitive blood cells ([[myeloblasts]]) in the bone marrow and pathological abnormalities primarily seen in red cell precursors;
* ({{ICDO|9982|3}}) '''Refractory anemia with ringed sideroblasts''' (RARS) - also characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called "ringed sideroblasts";
* ({{ICDO|9983|3}}) '''Refractory anemia with excess blasts''' (RAEB) - characterized by 5-19% myeloblasts in the marrow;
* ({{ICDO|9984|3}}) '''Refractory anemia with excess blasts in transformation''' (RAEB-T) - characterized by 20-29% myeloblasts in the marrow (30% blasts is defined as acute myeloid leukemia);
* ({{ICDO|9945|3}}) '''Chronic myelomonocytic leukemia''' (CMML) - not to be confused with [[chronic myelogenous leukemia]] or CML - characterized by less than 20% myeloblasts in the bone marrow and greater than 1000 * 10<sup>9</sup>/uL monocytes (a type of white blood cell) circulating in the peripheral blood.
A table comparing these is available from the Cleveland Clinic.<ref name="urlTable 1: French-American-British (FAB) Classification of MDS">{{cite web |url=http://www.clevelandclinicmeded.com/diseasemanagement/hematology/myelo/table1.htm |title=Table 1: French-American-British (FAB) Classification of MDS |format= |work= |accessdate=}}</ref>
The best prognosis is seen with refractory anemia with ringed sideroblasts and refractory anemia, where some non-transplant patients live more than a decade (the average is on the order of three to five years, although long-term remission is possible if a bone marrow transplant is successful). The worst outlook is with RAEB-T, where the mean life expectancy is less than 1 year. About one quarter of patients develop overt leukemia. The others die of complications of low blood count or unrelated disease. The ''International Prognostic Scoring System'' is another tool for determining the prognosis of MDS, published in ''Blood'' in 1997.<ref>{{cite journal | author=Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J | title=International scoring system for evaluating prognosis in myelodysplastic syndromes | journal=Blood | year=1997 | pages=2079–88 | volume=89 | issue=6 | pmid=9058730}}</ref> This system takes into account the percentage of blasts in the marrow, cytogenetics, and number of cytopenias.
The FAB classification was used by pathologists and clinicians for almost 20 years.
===WHO classification===
In the late 1990s a group of pathologists and clinicians working under the [[World Health Organization]] (WHO) modified this classification, introducing several new disease categories and eliminating others.
One new category was refractory cytopenia with multilineage dysplasia (RCMD), which includes patients with pathological changes not restricted to red cells (i.e., prominent white cell precursor and platelet precursor (megakaryocyte) dysplasia. See below for morphologic definitions of dysplasia.
The list of dysplastic syndromes under the new WHO system includes:
# Refractory anemia (RA)
# Refractory anemia with ringed sideroblasts (RARS)
# Refractory cytopenia with multilineage dysplasia (RCMD)
# Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)
# Refractory anemia with excess blasts I and II
# [[5q- syndrome]]
# Myelodysplasia unclassifiable (seen in those cases of megakaryocyte dysplasia with fibrosis and others)
RAEB was divided into *RAEB-I (5-10% blasts) and RAEB-II (11-19%) blasts, which has a poorer prognosis than RAEB-I. Auer rods may be seen in RAEB-II which may be difficult to distinguish from acute myeloid leukemia.
The category of RAEB-T was eliminated; such patients are now considered to have acute leukemia. 5q- syndrome, typically seen in older women with normal or high platelet counts and isolated deletions of the long arm of chromosome 5 in bone marrow cells, was added to the classification.
CMML was removed from the myelodysplastic syndromes and put in a new category of myelodysplastic-myeloproliferative overlap syndromes. 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.
==5q- syndrome==
Since at least 1974, the loss of the long arm of [[chromosome 5]] has been associated with dysplastic abnormalities of hematopoietic stem cells.<ref name="pmid3552346">{{cite journal |author=Bunn HF |title=5q- and disordered haematopoiesis |journal=Clinics in haematology |volume=15 |issue=4 |pages=1023–35 |year=1986 |pmid=3552346 |doi=}}</ref><ref name="pmid4421285">{{cite journal |author=Van den Berghe H, Cassiman JJ, David G, Fryns JP, Michaux JL, Sokal G |title=Distinct haematological disorder with deletion of long arm of no. 5 chromosome |journal=Nature |volume=251 |issue=5474 |pages=437–8 |year=1974 |pmid=4421285 |doi=10.1038/251437a0}}</ref> By 2005, it was recognized that [[Revlimid]] was effective in MDS patients with the [[5q- syndrome]],<ref name="pmid15703420">{{cite journal |author=List A, Kurtin S, Roe DJ, ''et al'' |title=Efficacy of lenalidomide in myelodysplastic syndromes |journal=N. Engl. J. Med. |volume=352 |issue=6 |pages=549–57 |year=2005 |pmid=15703420 |doi=10.1056/NEJMoa041668}}</ref> and in December 2005, the [[US FDA]] approved the drug for this indication.
==Diagnosis==
Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness, dyspnea, and pallor, but at least half the patients are asymptomatic and their MDS is discovered only incidentally on routine blood counts. Previous chemotherapy or radiation exposure is an important historic fact. Fever and weight loss should point to a myeloproliferative rather than myelodysplastic process. Children with [[Down syndrome]] are susceptible to MDS, and a family history may indicate a hereditary form of [[sideroblastic anemia]] or [[Fanconi anemia]].
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 [[melphalan]], mustard, [[cyclophosphamide]], [[busulfan]], and [[chlorambucil]]) or [[radiation]] (therapeutic or accidental), or both (e.g., at the time of stem cell transplantation for another disease). Workers in some industries with heavy exposure to hydrocarbons such as the petroleum industry have a slightly higher risk of contracting the disease than the general population. Males are slightly more frequently affected than females. Xylene and benzene exposure has been associated with myelodysplasia. Vietnam Veterans that were exposed to Agent Orange are at risk of developing MDS.
The features generally used to define a MDS are: Blood cytopenias; ineffective hematopoiesis; dyserythropoiesis; dysgranulopoiesis ;dysmegakaropoiesis and increased myeloblast.
Dysplasia can affect all three lineages seen in the bone marrow. The best way to diagnose dysplasia is by morphology and special stains (PAS) used on the bone marrow aspirate and peripheral blood smear. Dysplasia in the myeloid series is defined by:
*Granulocytic series
*# 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
* Erythroid series
*# Binucleated erythroid percursors and karyorrhexis
*# Erythroid nuclear budding
*# Erythroid nuclear strings or internuclear bridging (also seen in congenital dyserythropoietic anemias)
*# PAS (globular in vacuoles or diffuse cytoplasmic staining) within erythroid precursors in the bone marrow aspirate (has no bearing on paraffin fixed bone marrow biopsy). Note: One can see PAS vacuolar positivity in L1 and L2 blasts (AFB classification; the L1 and L2 nomenclature is not used in the WHO classification)
*# 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)
* Megakaryocytic series (can be the most subjective)
*# Hyposegmented nuclear features in platelet producing megakaryocytes (lack of lobation)
*# Hypersegmented (osteoclastic appearing) megakaryocytes
*# Ballooning of the platelets (seen with interference contrast microscopy)
Other stains can help in special cases (PAS and napthol ASD chloroacetate esterase positivity) in eosinophils is a marker of abnormality seen in chronic eosinophilic leukemia and is a sign of aberrancy.
On the bone marrow biopsy high grade dysplasia (RAEB-I and RAEB-II) may show atypical localization of immature precursors (ALIPs) which are islands of immature cells clustering together. This morphology can be difficult to recognize from treated leukemia and recovering immature normal marrow elements. Also topographic alteration of the nucleated erythroid cells can be seen in early myelodysplasia (RA and RARS), where normoblasts are seen next to bony trabeculae instead of forming normal interstitially placed erythroid islands.
Myelodysplasia is a diagnosis of exclusion and must be made after proper determination of iron stores, [[vitamin]] deficiencies, and nutrient deficiencies are ruled out. Also congenital diseases such as [[congenital dyserthropoietic anemia]] (CDA I through IV) has been recognized, [[Sideroblastic anemia|Pearson's syndrome (sideroblastic anemia)]], [[Jacobson's syndrome]], ALA (aminolevulinic acid) enzyme deficiency, and other more esoteric enzyme deficiencies 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.
All of these conditions are characterized by abnormalities in the production of one or more of the cellular components of blood ([[red blood cell|red cell]]s, [[white blood cell|white cell]]s other than [[lymphocyte]]s and [[platelets]] or their progenitor cells, [[megakaryocyte]]s).
== Myelodysplastic syndrome unclassified ==
WHO proposed criteria for diagnosis and classification of MDS apply to most cases. However, occasional cases are difficult to classify into defined categories because of one or more atypical or unusual features:
I- Rare cases with less than 5% blast will present with auer rods. These cases usually have the features of RAMD.
II- Occasionally cases of MDS present with isolated neutropenia or thrombocytopenia without anemia and with dysplastic changes confined to the single lineage. The term refractory neutropenia and refractory thrombocytopenia have sometimes used to describe these cases. A dignosis of MDS in patients with neutropenia or thromobocytopenia without anaemia should be made with caution.
III- Patients with RA or RAEB occasionally present with leukocytosis or thrombocytosis instead of usual cytopenia.
==Epidemiology==
The exact number of people with MDS is not known because it can go undiagnosed and there is no mandated tracking of the syndrome. Some estimates are on the order of 10,000 to 20,000 new cases each year in the [[United States]] alone. The incidence is probably increasing as the age of the population increases, and some authors propose that the incidence in patients over 70 may be as high as 15 cases per 100,000 per year.<ref name="pmid11503953">{{cite journal |author=Aul C, Giagounidis A, Germing U |title=Epidemiological features of myelodysplastic syndromes: results from regional cancer surveys and hospital-based statistics |journal=Int. J. Hematol. |volume=73 |issue=4 |pages=405–10 |year=2001 |pmid=11503953 |doi=}}</ref>
== Prognosis and prognostic indicator in MDS ==
'''Indicators of a good prognosis in MDS'''
Younger age; normal or moderately reduced neutrophil or platelet counts; low blast counts in the bone marrow(<20%) and no blasts in the blood; no Auer rods; ringed sideroblasts; normal karyotypes of mixed karyotypes without complex chromosome abnormalities and in vitro marrow culture- non leukemic growth pattern.
'''Indicators of a poor prognosis in MDS'''
Advanced age; Severe neutropenia or thrombocytopenia ; high blast count in the bone marrow (20-29%) or blasts in the blood;
Auer rods; absence of ringed sideroblasts; abnormal localization or immature granulocyte precursors in bone marrow section
all or mostly abnormal karyotypes or complex marrow chromosome abnormalities and in vitro bone emarrow culture-leukemic growth pattern.
'''Prognosis and karyotype'''
Good: Normal,-Y,del(5q); Intermaediate: All other abnormalities Poor; Complex(>3 abnormalities); chromosome 7 anomalies
The International Prognostic Scoring System (IPSS) is the most commonly used tool in MDS to predict long-term outcome. <ref>Greenberg et al. International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes. Blood 1997;89:2079-2088.</ref>
==Therapy==
The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to [[acute myelogenous leukemia]].
The IPSS scoring system can help triage patients for more aggressive treatment (i.e. [[bone marrow transplant]]) as well as help determine the best timing of this therapy.<ref>{{cite journal | author=Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, Bolwell BJ, Cairo MS, Gale RP, Klein JP, Lazarus HM, Liesveld JL, McCarthy PL, Milone GA, Rizzo JD, Schultz KR, Trigg ME, Keating A, Weisdorf DJ, Antin JH, Horowitz MM | title=A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. | journal=Blood | year=2004 | pages=579–85 | volume=104 | issue=2 | pmid=15039286 | doi=10.1182/blood-2004-01-0338}}</ref> Supportive care with blood product support and hematopoeitic growth factors (e.g. [[erythropoietin]]) is the mainstay of therapy. The regulatory environment for the use of [[erythropoietins]] is evolving, according to a recent [[Medicare (United States)|US Medicare]] [[National Coverage Determination]]. No comment on the use of hematopoeitic growth factors for MDS was made in that document.<ref>{{cite web |url=http://www.cms.hhs.gov/mcd/viewdecisionmemo.asp?id=203 |title=Centers for Medicare & Medicaid Services |accessdate=2007-10-29 |format= |work=}}</ref>
Three agents have been approved by the US [[FDA]] for the treatment of MDS:
{| class="wikitable"
|-
! Name
! Comment
! References
|-
| [[5-azacytidine]]
| 21 month median survival similar to that of [[decitabine]]
|<ref name="pmid10694544">{{cite journal |author=Wijermans P, Lübbert M, Verhoef G, ''et al'' |title=Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients |journal=J. Clin. Oncol. |volume=18 |issue=5 |pages=956–62 |year=2000 |pmid=10694544 |doi=}}</ref><ref name="pmid11529854">{{cite journal |author=Lübbert M, Wijermans P, Kunzmann R, ''et al'' |title=Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine |journal=Br. J. Haematol. |volume=114 |issue=2 |pages=349–57 |year=2001 |pmid=11529854|doi=10.1046/j.1365-2141.2001.02933.x}}</ref><ref name="pmid12011120">{{cite journal |author=Silverman LR, Demakos EP, Peterson BL, ''et al'' |title=Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B |journal=J. Clin. Oncol. |volume=20 |issue=10 |pages=2429–40 |year=2002 |pmid=12011120|doi=10.1200/JCO.2002.04.117}}</ref><ref name="pmid16921040">{{cite journal |author=Silverman LR, McKenzie DR, Peterson BL, ''et al'' |title=Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B |journal=J. Clin. Oncol. |volume=24 |issue=24 |pages=3895–903 |year=2006 |pmid=16921040 |doi=10.1200/JCO.2005.05.4346}}</ref>
|-
| [[Decitabine]]
| Complete response rate reported as high as 43%. A phase I study has shown efficacy in AML when decitabine is combined with [[valproic acid]].
|<ref name="pmid17133405">{{cite journal |author=Kantarjian HM, O'Brien S, Shan J, ''et al'' |title=Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome |journal=Cancer |volume=109 |issue=2 |pages=265–73 |year=2007 |pmid=17133405 |doi=10.1002/cncr.22376}}</ref><ref name="pmid16532500">{{cite journal |author=Kantarjian H, Issa JP, Rosenfeld CS, ''et al'' |title=Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study |journal=Cancer |volume=106 |issue=8 |pages=1794–803 |year=2006 |pmid=16532500 |doi=10.1002/cncr.21792}}</ref><ref name="pmid16882708">{{cite journal |author=Kantarjian H, Oki Y, Garcia-Manero G, ''et al'' |title=Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia |journal=Blood |volume=109 |issue=1 |pages=52–7 |year=2007 |pmid=16882708 |doi=10.1182/blood-2006-05-021162}}</ref><ref name="pmid17679729">{{cite journal |author=Blum W, Klisovic RB, Hackanson B, ''et al'' |title=Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia |journal=J. Clin. Oncol. |volume=25 |issue=25 |pages=3884–91 |year=2007 |pmid=17679729 |doi=10.1200/JCO.2006.09.4169}}</ref>
|-
| [[Lenalidomide]]
| Most effective in reducing red cell transfusion requirement
|<ref name="pmid17021321">{{cite journal |author=List A, Dewald G, Bennett J, ''et al'' |title=Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion |journal=N. Engl. J. Med. |volume=355 |issue=14 |pages=1456–65 |year=2006 |pmid=17021321 |doi=10.1056/NEJMoa061292}}</ref>
|}
[[Chemotherapy]] with the [[DNA methylation|hypomethylating agents]] [[5-azacytidine]] and [[decitabine]] has been shown to decrease blood transfusion requirements and to retard the progression of MDS to [[AML]]. [[Lenalidomide]] was approved by the [[FDA]] in December [[2005]] only for use in the [[5q- syndrome]]. It was approved in July, 2006 for use in [[multiple myeloma]]. The retail price of [[lenalidomide]] is estimated at $7,000 per month.<ref name="pmid16625140">{{cite journal |author= |title=Lenalidomide (Revlimid) for anemia of myelodysplastic syndrome |journal=The Medical letter on drugs and therapeutics |volume=48 |issue=1232 |pages=31–2 |year=2006 |pmid=16625140 |doi=}}</ref>
[[Stem cell transplantation]], particularly in younger patients (ie less than 40 years of age), more severely affected patients, offers the potential for curative therapy. Success of bone marrow transplantation has been found to correlate with severity of MDS as determined by the IPSS score, with patients having a more favorable IPSS score tending to have a more favorable outcome with transplantation.<ref>{{cite journal |author=Oosterveld M, Wittebol S, Lemmens W, Kiemeney B, Catik A, Muus P, Schattenberg A, de Witte T |title=The impact of intensive antileukaemic treatment strategies on prognosis of myelodysplastic syndrome patients aged less than 61 years according to International Prognostic Scoring System risk groups |journal=Br J Haematol |volume=123 |issue=1 |pages=81–9 |year=2003 |pmid=14510946 |doi=10.1046/j.1365-2141.2003.04544.x}}</ref>
==History==
Since the early 20th century it began to be recognized that some people with [[acute myelogenous leukemia]] had a preceding period of [[anemia]] and abnormal [[blood cell]] production. These conditions were lumped with other diseases under the term "refractory anemia". The first description of "preleukemia" as a specific entity was published in 1953 by Block ''et al''.<ref>Block M, Jacobson LO, Bethard WF. ''Preleukemic acute human leukemia.'' [[Journal of the American Medical Association|JAMA]] 1953;152:1018-28. PMID 13052490</ref> The early identification, characterization and classification of this disorder were problematical, and the syndrome went by many names until the 1976 FAB classification was published and popularized the term MDS.
==References==
{{reflist|2}}
==Further reading==
* {{cite journal |author=Bennett JM, Catovsky D, Daniel MT, ''et al'' |title=Proposals for the classification of the myelodysplastic syndromes |journal=Br. J. Haematol. |volume=51 |issue=2 |pages=189–99 |year=1982 |month=June |pmid=6952920 |doi= |url=}}
* {{cite journal |author=Harris NL, Jaffe ES, Diebold J, ''et al'' |title=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 |journal=J. Clin. Oncol. |volume=17 |issue=12 |pages=3835–49 |year=1999 |month=December |pmid=10577857 |doi= |url=http://www.jco.org/cgi/pmidlookup?view=long&pmid=10577857}}
==External links==
* ''[http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?rid=cmed.chapter.32804 Cancer Medicine]''. Online textbook. Chapter by Lewis R. Silverman on Myelodysplastic Syndrome.
* [http://www.mayoclinic.com/print/myelodysplastic-syndromes/DS00596/DSECTION=all&METHOD=print Myelodysplastic syndromes]. Comprehensive article at [[Mayo Clinic]]
* [http://www.aplastic.org/aplastic/disease_information/about_the_diseases/meylodsyplastic_synd.php Aplastic Anemia & MDS International Foundation] information about MDS
* [http://www.virtualcancercentre.com/diseases.asp?did=68 Myelodysplastic syndrome (MDS)].
* [http://www.qxmd.com/hematology/Myelodysplastic-Syndrome-International-Prognostic-Scoring-System.php Online calculator] for the International Prognostic Scoring System (IPSS).
* [http://www.mds-foundation.org MDS-Foundation]
* [http://www.ewog-mds.org European Working Group of MDS in Childhood]
==See also==
*[[Myeloproliferative syndrome]]
*[[Acute myeloid leukemia]]
*[[Chloroma]]
{{Hematology}}
{{Hematological malignancy histology}}
[[Category:Hematology]]
[[Category:Syndromes]]
[[ar:متلازمة خلل التنسج النقوي]]
[[de:Myelodysplastisches Syndrom]]
[[es:Síndrome mielodisplásico]]
[[fr:Syndrome myélodysplasique]]
[[it:Sindrome mielodisplasica]]
[[ja:骨髄異形成症候群]]
[[pl:Zespoły mielodysplastyczne]]
[[pt:Síndrome mielodisplásica]]
[[sv:Myelodysplastiskt syndrom]]