Myelodysplastic Syndrome Overview.23111DEFANGED-Ppt

8/9/2019 Myelodysplastic Syndrome Overview.23111DEFANGED-Ppt

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Myelodysplastic syndrome

Dr. Tjatur Winarsanto SpPD

RS CiremaiCirebon



Myelodysplastic syndrome

(MDS)• It is a term for a heterogeneous collection of

haemopoietic stem cell disorders affecting

older adults.

• There is underlying ineffectieness of

haemopoiesis that results in dysplasia of

bone marro! precursors and peripheralcytopenias.



• "oderate anaemia is the most common

clinical problem in "DS patients# but

complete myeloid bone marro! failure also

occurs leading to death from bleeding or

infection.

• $ppro%imately half of the patientstransform to $"&.



• Prognosis depends on the indiidual’s ris' factors#

!ith median surial ranging from (.) years in

lo!er*ris' group to +., years or less in those !ithhigher*ris' "DS.

• "DS is e%tremely difficult to treat. "ost cases are

resistant to current therapies# and the most potent

anti*"DS treatments -transplantation and dose

intensie chemotherapy are often too to%ic for the

majority of patients.



MDS: Epidemiology

• /lder adults -median age0 )1 years

• Primary s. Secondary "DS -S2P chemotherapy

• Incidence0 32+11#111 non*age corrected,12+11#111 oer age )1



MDS: Etiology

• Primary

4 5o 'no!n history of to%ic e%posure

4 Possible etiologies0 6irus# 7en8ene# cigarette -,

fold ris'.

• Therapy*related

4 Chemotherapy -al'ylating agents

4 Radiation Therapy



MDS: Clinical

• Symptoms of Cytopenia

• $nemia 9 5eutropenia :2* Thrombocytopenia

• /rganomegaly -infre;uent



MDS background

• Pathobiology

4 The cardinal features of "DS are

• Increased marro! proliferation• <ailure of stem cells to differentiate

• $nd increased marro! apoptosis.

4 The disease is of clonal origin

4 Chromosomal abnormalities are detectable in 31*)1=of patients. The no. of chromosomal abn. may correlate

!ith the ris' of progression to $"&.





FAB classification

• In +>?, The <$7 group classified "DS accordingto "orphology and the = of myeloblasts in the 7"

and P7.• These included 4 Refractory anaemia -R$

4 Refractory anaemia !ith ringed sideroblasts -R$RS

4 Refractory anaemia !ith e%cess blast in marro! -R$@7 4 C""&

4 Refractory anaemia !ith e%cess blast in transformation

-R$@7*t



Morphologicalcharacteristics of MDS





!" classification

• The WA/ proposed changes including

reclassification of R$@7*t to $"& and

adding a subgroup called refractory

cytopenias !ith dysplasia -RCD



Myelodysplastic Syndromes

• <$7 Classification

4 R$

4 R$RS

4 R$@7

4 R$@7*T

4 C""&

• WA/ classification 4 "yelodysplastic Syndromes

• R$

• R$RS

• RC"D B RC"D*RS• R$@7*+ B R$@7*,

• "DS nclassified

• "DS del-(;

4 "yelodysplastic2"yeloproliferatie

Diseases• C""&

• $typical C"&

• uenile C""&

• "DS2"PD# unclassified



#nternational $rognostic Scoring

System (#$SS)• The most practical and alidated "DS

classification system currently aailable to

clinicians is the IPSS !hich predicts both

surial and ris' of transformation to $"&

based on0

4 "arro! blast = 4 Cytogenetics

4 $nd number of cytopenias.





%&e scope of MDS

• "DS is primarily a disease of the elderly#!ith a median age at diagnosis of bet!een

E1*?1 years.• The incidence is appro%imately double that

of $"&.

• The recent increase in "DS incidence may be related to gro!ing a!areness# betterdiagnosis# and an aging population.



• Prognosis for most patients is poor.

• If not cured by 7"T# the disease is inariably

fatal.

• The common symptoms at presentation# fatigue or

!ea'ness# are attributable to cytopenia.

• @asy bruising# ecchymosis# epista%is# gingial bleeding# and bacterial infections may also be

encountered.



• Transformation to acute leu'aemia occurs

in up to F1= of patients.

• $lthough progression to fran' $"& is a

primary concern# ,1*F1 = or more of

patients die of infections and2or

haemorrhagic complications.



Con'entional t&erapies

• Supportie care including blood products

!ith defero%amine# haemopoietic gro!th

factors and antibiotics. @P/ increases red blood cells in some patients# G"*CS< may

limit infections.

• Aormone suppressie therapy !ith dana8olhas been used to help resole anaemia and

reduce transfusion re;uirements.



• "ost attempts to induce haemopoietic celldifferentiation hae failed. <or e%ample# interferonalfa*, transiently improes platelet counts in some"DS patients. Ao!eer progression is also possible.

• Clinical studies !ith differentiation promoters suchas retinoids# 6it D3# butyrates hae beendisappointing.

• In contrast# the hypomethylating agent (*a8acytidinehas produced significant clinical benefit in patients!ith "DS



• &o! intensity chemotherapy !ith cytarabine

induces response in appro%imately 31= of "DS

patients. Ao!eer # the relapse rate is high# andthere is no improement in oerall surial.

• Recent studies sho! that using lo! dose

cytarabine in conjunction !ith "*CS<# G"*CS<#

or $TR$ may improe oerall response and

surial.



• 7one marro! transplantation is currently the only potentially curatie therapy for "DS patients.

• /erall disease*free surial at 3 years !ithallogenic procedures ranges appro%imately from3(*E1= depending on IPSS score and other patient’s ris' factor especially age.

• Ao!eer# the procedure related mortality amongthese pt is significant# !ith patients older than (1years haing an appro%imately (1= chance ofdying from the transplant itself.



AntiMDS agents in de'elopment

• $TR$

• $mifostine 4cytoprotectie agent

• "elphalan

• $8acytidine* bloc's D5$ methylation and may

initiate transcription and differentiation.

• Thalidomide*antiangiogenic# anti*T5< alpha andimmunosuppressie.

• Immunosuppressie therapy*$TG# cyclosporine $





Conclusion

• In the majority of patients !ith "DS !ho

are not eligible for allogenic

transplantation# the disease is fatal.

• $ppro%imately ,23 of patients die !ithin 3*

F years of diagnosis.

• Patients !ith high ris' "DS generally

surie appro%imately one year.



• @%cept for a recent trial of a8acytidine# none of the

other currently aailable drugs for "DS e%tends

surial# and many are highly to%ic.• The <TIs are an e%ample of targeted therapy !ith

potential clinical applicability in "DS*modulating

an array of tumour signaling cascades ia

inhibition of farnesyitransferase.



Current treatment options for

MDS • 5o "DS*specific therapies are aailable .

• Clinicians typically choose the therapy on the basis

of ris' factors# such as patient age# "DS subtype#IPSS score# and performance status.

• <or e%ample# lo!er ris' patients generally receiesupportie care and perhaps lo! intensity

chemotherapy or differentiating agents.• While those !ith higher ris' may be candidates for

dose intensie chemotherapy or in younger patients# bone marro! transplantation.



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Myelodysplastic Syndrome Overview.23111DEFANGED-Ppt