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__NOTOC__
__NOTOC__
{{Myelodysplastic syndrome}}
{{Myelodysplastic syndrome}}
{{CMG}}
{{CMG}};{{AE}}{{NM}}
 
==Overview==
==Overview==
 
[[Chemotherapy]] is recommended among all patients who develop myelodysplastic syndrome.<ref name=cancerca>Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015</ref>
==Medical therapy==
==Medical Therapy==
The goals of therapy are to control symptoms, improve quality of life, improve overall survival, and decrease progression to [[acute myelogenous leukemia]].
*Treatment is based on the type of myelodysplastic syndrome and the person's age and general health. The goal of treatment for myelodysplastic syndrome is to:<ref name=cancerca>Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015</ref>
 
**Relieve symptoms
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=Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyshiki K, Toyama K, Aul C, Hufti G, Bennett J | volume=89 | issue=6 | id=PMID 9058730}}</ref> <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  | id=PMID 15039286}}</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 [[erythropoietin]]s 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>
**Slow or prevent progression of the disease
 
**Improve quality of life
The IPSS uses 3 criteria; cytogenetic abnormalities, proportion of bone marrow myeloblasts and number of cytopenias.  Points are assigned to these variables and are added to create 4 risk groups; low, intermediate 1, intermediate 2 and high risk.  If patients have >10% blasts in their bone marrow by morphology they are automatically classified as having higher risk MDS.  Patients with chromosome 7 abnormalities, loss of chromosome 7 or complex cytogenetics typically have high-risk MDS.  A major limitation of the IPSS is that it does not distinguish  between patients with severe and modest degrees of cytopenias; this may influence outcome. 
===Chemotherapy===
 
*The most common chemotherapy drug used to treat myelodysplastic syndrome is cytarabine. Cytarabine may be combined with other pharmacological agents such as:<ref name=cancerca>Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015</ref>
Survival and AML evolution score
**[[Idarubicin]]
{|  class="wikitable"
**[[Topotecan]]
|-
**[[Fludarabine]]
! Prognostic Variable
* Other chemotherapeutic agents that may be used to treat myelodysplastic syndrome include:<ref name=cancerca>Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015</ref>
! 0
**[[Daunorubucin]]
! 0.5
**[[Mitoxantrone]]
! 1
===Supportive Therapy===
! 1.5
*Supportive therapy is given to relieve symptoms and lessen the problems caused by abnormal blood cell counts or treatment for myelodysplastic syndrome.<ref name=cancerca>Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015</ref>
! 2     
====Transfusions====
|-               
*Patients with anemia may receive blood transfusions to correct the red blood cell counts.
| Bone marrow blasts (%)     
*Frequent blood transfusions can be complicated by a buildup of extra iron in the body, which is treated with drug therapy.
| <5                 
*Patients with bleeding problems due to low platelet counts may be given platelet transfusions.
| 5-10                 
====Growth Factors====
| X                   
*[[Epoetin]] (erythropoietin)
| 11-20                 
:*Helps improve production of red blood cells
| 21-30
*[[Filgrastim]]
|-
:*Also called granulocyte colony-stimulating factor (G-CSF)
| Karyotype *                
:*Helps improve production of white blood cells
| good               
*[[Pegfilgrastim]]
| intermediate         
:*A long-acting G-CSF
| poor               
====Supportive Therapy====
| X                     
*Other drugs that may be used to treat symptoms or side effects of therapy include:<ref name=cancerca>Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015</ref>
| X
*[[Deferoxamine]]
|-
:*treats excess iron in the blood
| Cytopenias **             
:*sometimes given with Vitamin C.
| 0 or 1             
*[[Lenalidomide]]
| 2 or 3               
:*decreases the need for transfusions in people with a specific chromosome change
| X                   
*[[Antithymocyte globulin]]
| X                     
:*decreases the need for transfusions in certain types of myelodysplastic syndrome
| X
*Antibiotics
|}
:*help to prevent or treat infections
 
*Hypomethylating agents, such as [[5-azacytidine]] or [[decitabine]]
*Good = normal or any 1 of the following; deletion Y, deletion 5q, deletion 20q.
:*stop cancer cells from producing DNA or RNA so the cells die
Intermediate = other abnormalities.
Poor = complex (>/= 3 abnormalities) or chromosome 7 abnormalities.
** Hemoglobin < 10 g/dl, ANC<1800 /uL, Platelets <100,000. 
 
 
{|  class="wikitable"
|-
! IPSS Risk Category
! Low                 
! Intermediate 1                   
! Intermediate 2                     
! High
|-
| Combined score             
| 0                   
| 0.5-1                           
| 1.5-2                             
| >/=2.5
|-
| AML evolution             
| 19%                 
| 30%                             
| 33%                               
| 45%
|-
| Median time to AML (years) 
| 9.4                 
| 3.3                             
| 1.1                               
| 0.2
|-
| Median survival (years)   
| 5.7                 
| 3.5                             
| 1.2                               
| 0.4
|}
 
Lower risk disease includes those classified as low or intermediate 1 with a combined IPSS score of 1 or lower.  For these patients observation and supportive care only has been advocated.  (However, once blood transfusions are required then some form of treatment should be considered.) 
 
Since 2004 3 medications have been approved for MDS; 5-azacytidine and decitabine are hypomethylating agents, lenalidomide is immunomodulatory.  Lenalidomide is especially useful in the treatment of 5q minus syndrome; for these patients the medication not only improves counts but it also has a high complete response rate in the bone marrow and a high remission rate for the chromosome.  For non-5q deletion, low-risk MDS patients treatment options include lenalidomide and demethylating agents. 
 
DNA-methyltransferase inhibitors; normally methylation of cytosine in gene promoters causes them to become silent; they would otherwise cause terminal differentiation.  There is survival benefit with the hypomethylating agents (Decitabine & Azacitadine)in higher-risk disease (intermediate-2 or high risk disease).Azacitidine and Decitabine are different chemically and patients whose disease doesn't respond or becomes refractory to one may respond to the other.  The recommendation is to proceed until progression; sometimes stopping allows the disease to relapse or it relapses as it is resistant disease.  The major toxicities are nausea, vomiting, diarrhea, cytopenias and fatigue. 
<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=}}</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=}}</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>
<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>
 
IMiDS, such as Lenalidomide are for erythroid failure such as in transfusion-dependent del(5q).  The response rate (~67%)is independent of the karyoptype.  Treatment can give a positive cytopgenetic response, the patient becomes transfusion-free and would no longer require Erythropoietin.  With treatment there is a transient decrease in the leukocytes and platelets. It has been known to be useful in paients without the 5q deletion with ~25% of patients experiencing a significant response in hemoglobin levels.
<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>
<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>.
 
====Contraindicated medications====
 
{{MedCondContrAbs
 
|MedCond = High-risk myelodysplastic syndromes|Deferasirox}}
 
==References==
==References==
{{reflist|2}}
{{reflist|1}}


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Latest revision as of 02:49, 27 November 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Nawal Muazam M.D.[2]

Overview

Chemotherapy is recommended among all patients who develop myelodysplastic syndrome.[1]

Medical Therapy

  • Treatment is based on the type of myelodysplastic syndrome and the person's age and general health. The goal of treatment for myelodysplastic syndrome is to:[1]
    • Relieve symptoms
    • Slow or prevent progression of the disease
    • Improve quality of life

Chemotherapy

  • The most common chemotherapy drug used to treat myelodysplastic syndrome is cytarabine. Cytarabine may be combined with other pharmacological agents such as:[1]
  • Other chemotherapeutic agents that may be used to treat myelodysplastic syndrome include:[1]

Supportive Therapy

  • Supportive therapy is given to relieve symptoms and lessen the problems caused by abnormal blood cell counts or treatment for myelodysplastic syndrome.[1]

Transfusions

  • Patients with anemia may receive blood transfusions to correct the red blood cell counts.
  • Frequent blood transfusions can be complicated by a buildup of extra iron in the body, which is treated with drug therapy.
  • Patients with bleeding problems due to low platelet counts may be given platelet transfusions.

Growth Factors

  • Helps improve production of red blood cells
  • Also called granulocyte colony-stimulating factor (G-CSF)
  • Helps improve production of white blood cells
  • A long-acting G-CSF

Supportive Therapy

  • Other drugs that may be used to treat symptoms or side effects of therapy include:[1]
  • Deferoxamine
  • treats excess iron in the blood
  • sometimes given with Vitamin C.
  • decreases the need for transfusions in people with a specific chromosome change
  • decreases the need for transfusions in certain types of myelodysplastic syndrome
  • Antibiotics
  • help to prevent or treat infections
  • stop cancer cells from producing DNA or RNA so the cells die

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Treatment of myelodysplastic syndrome. National Cancer Institute (2015). http://www.cancer.ca/en/cancer-information/cancer-type/leukemia/leukemia/myelodysplastic-syndromes/?region=on. Accessed on December 15, 2015


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