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Transcript of 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
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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.
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• "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 $"&.
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• 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.
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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
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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
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MDS: Clinical
• Symptoms of Cytopenia
• $nemia 9 5eutropenia :2* Thrombocytopenia
• /rganomegaly -infre;uent
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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 $"&.
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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$@7*t
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Morphologicalcharacteristics of MDS
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!" classification
• The WA/ proposed changes including
reclassification of R$@7*t to $"& and
adding a subgroup called refractory
cytopenias !ith dysplasia -RCD
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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
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#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.
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%&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.
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• 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.
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• 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.
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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.
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• "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
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• &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.
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• 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.
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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 $
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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.
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• @%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.
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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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