صفحه 1:
Bone Marrow
Transplantation
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صفحه 2:
Introduction
Hematopoieticstemcell transplantation (HSCT)/
thetransplantation of multipotent hematopoietic stem cell or boodusually derived
frombonemarrow peripheral blood stem cells, or umbilical cord blood
Stemcell transplantation isa medical procedurein the fields of iematologyand
oncoogy,most often performedfor people with diseases of the Hlood, bonemarrow,or
certaincancers,
The first Gonemarrow transplant-wasdonein 1959 on five Yugoslavian nuclear
workers whoseown marrow hadbeen damaged by irradiation, but all of these
transplantswere rejected.
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صفحه 3:
Indications
Itwasshown that bonemarrow ceflsinfusedintravenously couldrepopulate the bonemarrow and
produce new 6loodcelts.
Indications/
Many recipientsof HSCTsare multiple myeloma or leukemia patientswhowouldnot benefit from.
protongedtreatment with orare already resistant to, chemotherapy.
Other indications
inborn defect suchas severe combinedimmunodeficiency or congenital neutropenia withdefective
stemcel(s,aplasticanemia,sichle-celt disease, myeCodysplastic syndrome, neuroblastoma, lymphoma,
Ewing'sSarcoma,..and Hodgkin's diseas
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صفحه 4:
Graft Types
Autologous/
HSCT requires the extraction (apheresis) of iaematopoieticstemcelCs
] لمعه تله ها نالع اع خىه بصحمة علا دع وه جه كف هه اندع أ امه مرع ةع .دده ون
The patient isthen treatedwith high-dose chemotherapy withor without
radiotherapy with theintention of eradicating thepatient’smalignant
cell population at thecost of partial or complete bonemarrow ablation
(destruction of patient's bonemarrow function to grow new bloodcefCs).
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صفحه 5:
Graft Types
Autologous/
, body,
where they replace destroyedtissueandresume the patient's normal blood
cell production.
Autologous transplants have the advantage of Lower risk of infection
during the immune-compromisedportion of the treatment since the
recovery of immune functionisrapid.
Also, theincidence of patients experiencing rejection (
grvaft-versus-host disease) isvery rare due tothe donor andrecipient
being thesameindividual.
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صفحه 6:
Graft Types
Autologous/
Theseadvantages have establishedautologous HSCTas one of the
standardsecond-Cine treatments for suchdiseasesas lymphoma.
Allogeneic/
HSCTinvolves two people: the (healthy) donorandthe (patient)
recipient.
Allogeneic HSC donors must havea tissue (HLA) type that matches the
recipient.
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صفحه 7:
Graft Types
AlCogeneic/
Evenif thereisa goodmatchat thesecritical alleles, the recipient will
requireimmunosuppressivemedications tomitigate
graft-versus-host disease.
Allogeneic transplant donorsmay be related (usually a closely HLA
matched sibling), syngeneic (a monozygoticor identical twin of the
patient) or unrelated (donor whois not relatedandfoundtohavevery
close degree of HLA matching).
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صفحه 8:
Graft Types
AlCogeneic/
Allogeneic transplantsarealsoperformedusing umbilical cord blood
asthe source of stemcefCs.
Raceandethnicityareknown toplaya major rolein donor
recruitment drives,asmembers of the same ethnic grouparemore
Cikely tohavematching genes, including the genes for HLA.
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صفحه 9:
Sources of cells
Bonemarrow
Inthecaseofabonemarrow transplant, the HSCareremovedfroma large bone of the
donor, typically the pelvis, througha large needle that reaches the center of the bone.
The techniqueisreferredtoasa bonemarrow harvest andisperformedunder
generalanesthesia.
Peripheral bloodstemcells
Peripheral bloodstemcel(s are now the most common source of stem cel sfor altogeneic
HSCT. They are collectedfromthe blood througha process known as apheresis.
The donor's blood is withdrawn througha sterile needleinonearmandpassed through
amachine that removes white bloodcel(s, The red bloodcel(sarereturnedtothe donor.
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صفحه 10:
Sources of cells
Peripheral bloodstemcel(s
The peripheral stemcell yieldis boosted with daily subcutaneousinjections
of Granwlocyte-colony stimulating factor, serving tomobilize stemcelCs
fromthe donor's bonemarrow into the peripheral circulation.
Amniotic fluid
It is also possible toextract hematopoieticstemcells fromamnioticfluidfor
GothautoCogous or heterologoususeat the time of childbirth.
Umbilical cord blood
]۱ mother donates fer infant's
umbilical cordandplacenta after birth.
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صفحه 11:
Sources of cells
‘Umbilical cord 6Cook
Cord bloodhasa higher concentration of HSC than isnormatly foundin adult blood. However, thesmatt
juantity of blood obtained froman umbilical cord typically about 50m£) makesit more suitablefor
ی ی و ¥ 7
Newer techiniquesusing ex-vivoexpansion of cord bloodunitsor theuse of twocord6loodunits from
different donorsareberngexploredtoatlow انم 2 یا تسج سس
‘Unlike other organs, bonemarrow cel(scan be frozen (cryopreserved) for protongedperiods,without
damaging tooman ells Thislsa necessity wishautalagors SCbecoue موي mits beharvestedfrom,
Rs
therecipient monthsinadvanceofthe transplant treatment.In the case of allogencictransplants,
fresh.aSCarepreferred inorder toavoidcett Coss that might occur during the freesingandthawing
process. Allogeneic cord bloodisstored frozen at a cord blood bank because it isonly obtainableat the
timeof chi(dbirth. Tocryopreserve HSC a preservative, DMSO,must be added,and the cel('smust be cooled
very slowly ina contro{ted-rate freezer toprevent osmoticceltular injury during icecrystal
formation. 1SCmay be storedfor yearsina cryofreezer,which typically utilizes liquidnitrogen.
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صفحه 12:
Storage of cells
‘Unlike other organs, bonemarrow cells can be frozen (cryopreserved) for
protonged periods, without damaging toomany cells.
Thisisa necessity withautologous HSC because thecells must beharvested
fromtherecipient monthsinadvance of thetransplant treatment.
Inthecase of allogeneic transplants freshHSCarepreferred inorder to
avoidcel( Coss that might occur during the freezingandthawing process.
Allogeneic cord bloodisstoredfrozenatacordbloodbank becauseit isonly
obtainableat the time of childbirth. Tocryopreserve HSC, a preservative,
Dimethyl sulfoxide (DMSO), must beadded.
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صفحه 13:
Conditioning regimens
Myeloablativetransplants
The chemotherapy or irradiation givenimmediately prior toa
transplant iscalledthe conditioning or preparative regimen, the
purpose of whichis tohelperadicatethepatient s disease prior tothe
infusion of HSCandtosuppressimmune reactions.
The bonemarrow can beablatedwith dose-Cevels that causeminimal
injury to other tissues. This treatment alsohasanimmunosuppressive
effect that prevents rejection of the HSC by the recipient's immune system.
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صفحه 14:
Conditioning regimens
Non-myeloablativetransplants
Thisisa newer treatment approachusing lower doses of chemotherapyand
rvadiation,whichare toolow toeradicateall the bonemarrow cells ofa
recipient.
Instead, non-myeloablative transplants run lower risks of serious
infectionsandtransplant-relatedmortatity.
Because of their gentler conditioning regimens, these transplantsare
associatedwitha lower risk of transplant-relatedmortalityand
therefore allow patients whoare considered too high-risk for conventional
allogeneic HSCT toundergopotentially curative therapy for their disease.
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صفحه 15:
Complications
HSCTisassociatedwitha high troatment-relatedmortalityintherecipient (10%0r
Aigher), which limits itsuse toconditions that ave themselves life-threatening.
Infection
Bonemarrow transplantationusually requires that the recipient'sown bonemarrow
bedestroyed( myeloablation andpatientsmay gofor several weeks without
appreciable numbers of white bloodce((s tohelpfight infection.
Thisputsa patient at highriskofinfections, sepsisandseptic shock, despite
prophylacticantibiotics. However, antiviral medications suchasacyclovirand
valacyclovir,ave quiteeffectivein prevention of HSCT-relatedoutbreak of herpetic
infection in seropositivepatients.
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صفحه 16:
Complications
Infection
The immunosuppressive agents employedin altogencic transplants for theprevention
or treatment of graft-versus-host diseasefurther increase theriskof
opportunisticinfection.
Immunosuppressive drugsare given for a minimum of 6-monthsaftera
transplantation, or muchlonger if requiredfor the treatment of graft-versus-host
disease,
Transplant patients (ose their acquiredimmunity,for exampleimmunity to childhood
diseases suchasmeas(esor polio. For this reason transplant patientsmust bere-
vaccinatedwithchildhoodvaccines once they are offimmunosuppressivemedications.
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صفحه 17:
Complications
‘Veno-occlusive disease
Severe liver injury can result fromfepatic veno-occlusive disease (VOD).
EevatedCevels of bilirubin, hepatomegalyandftuidretentionareclinical halfmarks of this
condition.
Thereisnow agreater appreciation ofthegeneratizedcelCulay injuryandabstructionin
hiepaticvein sinuses andhepatic VOD hastately been referred toas sinusoidal obstruction
syndrome (SOS).
Anticoagulants or defibrotide may be effectivein reducing the severity of VOD but may also
increase bleeding complications. Ursodiol has been shown to helpprevent VOD, presumably by
facilitating theflow of hile.
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صفحه 18:
Complications
Mucositis
Theinjury of themucosal lining of themouthandthroatisacommon
regimen-related toxicity following ablative HSCT regimens.
Itisusuatly not life-threatening butisverypainful,andprevents
eatinganddrinking.
Mucositisistreatedwithpain medications plus intravenous infusions
toprevent dehydrationandmalnutrition.
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صفحه 19:
Complications
Graft-versus-host disease
Graft-versus-host disease (GVHD) isaninflammatory disease thatis
unique toallogeneictransplantation.
Itisanattackof the new’ bonemarrow simmunecel(sagainst the
recipient's tissues. This can occur evenif the donorand recipient are
HLA-identical because theimmune systemcan still recognize other
differences between their tissues.
Itisaptly named graft-versus-host disease because bonemarrow
transplantation is the only transplant procedurein whichthe
transplantedcells must accept the body rather than the body accepting
thenew celCs.
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صفحه 20:
Complications
Graft-versus-host disease
Acute graft -versus-host disease typically occurs in thefirst 2monthsafter
transplantationandmay involve the skin,intestine,or theliver.
High-dose corticosteroids suchas prednisoneareastandardtreatment !
however thisimmunosuppressive treatment often leads to deadly infections.
Chronic graft-versus-host diseasemay also develop after allogeneic
transplant.It is themajor source of (ate treatment-relatedcomplications,
althoughit less often resultsin death.
Inaddition toinflammation, chronic graft-versus-host diseasemayleadto
the development of fibrosis, or scar tissue, similar to scleroderma tit may cause
functional disability and require profongedimmunosuppressive therapy.
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صفحه 21:
Complications
Graft-versus-tumor effect
Graft-versus-tumor effect (GVT) or graft versus leukemia’ effect is the
beneficial aspect of the Graft-versus-Host phenomenon. For example,
HSCTpatients witheither acuteandinparticular chronicgraft-
versus-host disease after an allogeneic transplant tendtohavealower
risk of cancer relapse.
This is due toa therapeuticimmune reaction of the اس
Cymphocytes against the diseased bone marrow of the recipient.
This Cower rate of reCapse accounts for the increased success rate o}
allogeneictransplants,comparedtotransplantsfromidentical twins,
andindicatesthat allogeneic HSCTis a form of immunotherapy. GVTis
themajor benefit of transplants that do not employ the highest immuno-
suppressive regimens.
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صفحه 22:
Complications
Oral carcinoma
Patientsafter HSCTareata higher riskfor oral carcinoma. Post-HSCT
oral cancer may have more aggressive behavior with poorer prognosis,
when comparedtooral cancerin non-HSCTpatients.
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