Bone marrow transplantation

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Bone Marrow Transplantation 01/01/25 

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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. 01/01/25 2 

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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 01/01/25 3 

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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). 01/01/25 

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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. 01/01/25 5 

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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. 01/01/25 6 

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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). 01/01/25 7 

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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. 01/01/25 

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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. 01/01/25 9 

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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. 01/01/25 10 

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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. 01/01/25 11 

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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. 01/01/25 12 

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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. 01/01/25 13 

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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. 01/01/25 14 

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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. 01/01/25 15 

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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. 01/01/25 16 

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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. 01/01/25 17 

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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. 01/01/25 18 

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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. 01/01/25 19 

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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. 01/01/25 20 

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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. 01/01/25 21 

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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. 01/01/25 22