Hematopoietic stem cell transplantation involves intravenous infusion of stem cells collected from bone marrow, peripheral blood, or umbilical cord blood to reestablish hematopoietic function in patients with damaged bone marrow or immune systems. It is potentially curative for various disorders. Stem cells are collected via bone marrow harvest or apheresis and may be manipulated before infusion. Complications can include mucositis, sinusoidal obstructive syndrome, and graft-versus-host disease.

1. Transfusion inTransfusion in
Hemotopoietic Stem CellHemotopoietic Stem Cell
Transplantation (HSCT)Transplantation (HSCT)
Rafiq Ahmad,Rafiq Ahmad,
MBBS, MTM, FASCPMBBS, MTM, FASCP

2. Stem CellsStem Cells
 PPopulaopulation oftion of
undifferentiated cellsundifferentiated cells
which are ablewhich are able
 To divideTo divide forfor
indefinite periodindefinite period
 ToTo self renewself renew
 To generate aTo generate a
functional progenyfunctional progeny
of highly specializedof highly specialized
cellscells

3. HierarchHierarchyy

4. Hematopoietic stem cell transplantationHematopoietic stem cell transplantation
 Definition:Definition:
 Intravenous infusion of autologous or allogeneic stem cellsIntravenous infusion of autologous or allogeneic stem cells
collected from bone marrow, peripheral blood or umbilicalcollected from bone marrow, peripheral blood or umbilical
cord bloodcord blood
 Re-establish hematopoietic function in patients withRe-establish hematopoietic function in patients with
damaged/defective bone marrow or immune systemsdamaged/defective bone marrow or immune systems
 Potentially curative for a widePotentially curative for a wide
variety of disordersvariety of disorders

5. BackgroundBackground
 First successful transplants—l959First successful transplants—l959
Noble prize forNoble prize for Donnall Thomas and JosephDonnall Thomas and Joseph
E. MurrayE. Murray
 50,000-60,000 transplants50,000-60,000 transplants performed yearlyperformed yearly
worldwideworldwide
 Number continues to increase by 10-20%Number continues to increase by 10-20%
each yeareach year
 >20,000 patients have survived >5 years>20,000 patients have survived >5 years

6. Hematopoietic stem cellsHematopoietic stem cells
Charakteristic:
• CD34+
• CD 133
•Lin-
•C-kit (CD117)
• BCRP

7. Graft SourcesGraft Sources
 Bone Marrow (HSC-M)Bone Marrow (HSC-M)
 Peripheral Blood Circulation (HSC-A)Peripheral Blood Circulation (HSC-A)
 Umbilical Cord Blood (HSC-C)Umbilical Cord Blood (HSC-C)
Types of HSCTTypes of HSCT
 Autologous: from the patientAutologous: from the patient
 Allogeneic: from another personAllogeneic: from another person
 Syngeneic: from an identical twinSyngeneic: from an identical twin
Choice of graft is based on disease type, patient condition,Choice of graft is based on disease type, patient condition,
donor compatibility and health.donor compatibility and health.

8. Autologous TransplantAutologous Transplant
 No evidence of disease in the blood or boneNo evidence of disease in the blood or bone
marrowmarrow
 Transplant related mortality (TRM) lowest withTransplant related mortality (TRM) lowest with
autos (<5%)autos (<5%)
 Relapse rates are higherRelapse rates are higher
depending on the diseasedepending on the disease
 Absence of graft versus tumorAbsence of graft versus tumor
effectseffects

9. Diseases treated by HSCTDiseases treated by HSCT
Malignant disordersMalignant disorders
 NHLNHL
 Hodgkin’s diseaseHodgkin’s disease
 AMLAML
 Multiple myeloma*Multiple myeloma*
 NeuroblastomaNeuroblastoma
 Ovarian cancerOvarian cancer
 Germ-cell tumorsGerm-cell tumors
Non-Malignant disordeNon-Malignant disordersrs
 Autoimmune disordersAutoimmune disorders
SLE, Systemic sclerosisSLE, Systemic sclerosis
 AmyloidosisAmyloidosis
Autologous TransplantAutologous Transplant

10. Allogenic TransplantsAllogenic Transplants
 Patients above 50 age - high TRM (30-50%)Patients above 50 age - high TRM (30-50%)
 Graft versus host effectsGraft versus host effects
 Lower relapse rates due to graft versus tumorLower relapse rates due to graft versus tumor
effectseffects

11. Diseases treated by HSCTDiseases treated by HSCT
Malignant disordersMalignant disorders
 AMLAML
 NHLNHL
 Hodgkin’s DiseaseHodgkin’s Disease
 ALLALL
 CMLCML
 CLLCLL
 MPDMPD
 MDSMDS
 Multiple Myloma*Multiple Myloma*
Non-Malignant disorderNon-Malignant disorderss
 Aplastic anemiaAplastic anemia
 ThalassemiaThalassemia
 Sickle Cell DiseaseSickle Cell Disease
 SCIDSCID
 Fanconi’s anemiaFanconi’s anemia
 Blackfan-DiamondBlackfan-Diamond
 Wiskott-AldrichWiskott-Aldrich
 Inborn errors ofInborn errors of
metabolismmetabolism
 Auto immune disordresAuto immune disordres
Allogenic Transplant

12. Donor SourcesDonor Sources
 Matched Related Donor (siblings)Matched Related Donor (siblings)
 25% chance a sibling will be a match25% chance a sibling will be a match
 The more siblings a patient has the better chance for aThe more siblings a patient has the better chance for a
matchmatch

13. Donor SourcesDonor Sources
 Alternative DonorsAlternative Donors
 Matched Unrelated Donors (MUD)Matched Unrelated Donors (MUD)
 NMDPNMDP
 WMDAWMDA
 Severe GVHDSevere GVHD
 Higher TRMHigher TRM
 Haploidentical DonorsHaploidentical Donors
 From parent, child or siblingFrom parent, child or sibling
 Must have many stem cells to overcome risk of graft rejectionMust have many stem cells to overcome risk of graft rejection
 Increased risk of GVHDIncreased risk of GVHD

14. Donor selection for HSCT
 Qualifies as blood donor
 Routine studies:
- History/Physical exam.
- CBC
- Electrolytes, RFT, LFT
- Viral studies/VDRL
- HLA, ABO
- XRC, ECG

15. HLA TypingHLA Typing
 HLA typing became feasible in 1960sHLA typing became feasible in 1960s
 Linked on chromosome 6Linked on chromosome 6
 Inherited as haplotypesInherited as haplotypes
 1 in 4 chance a sibling will be identical1 in 4 chance a sibling will be identical

16. HLA MatchingHLA Matching
 6/6, 8/8, or 10/106/6, 8/8, or 10/10
 HLA loci on chromosome 6HLA loci on chromosome 6
 HLA-A, HLA-B, HLA-C(Cw), HLA-DR (DRB1), HLA-HLA-A, HLA-B, HLA-C(Cw), HLA-DR (DRB1), HLA-
DQ alleles (‘’10 of 10 match”), HLA-DPDQ alleles (‘’10 of 10 match”), HLA-DP
IDENTIFICATION OF A RELATED ALLOGENEIC DONORIDENTIFICATION OF A RELATED ALLOGENEIC DONOR
 Identical TwinIdentical Twin < 1%< 1%
 HLA-matched SiblingHLA-matched Sibling
6 antigen6 antigen 25 - 30%25 - 30%
5 antigen5 antigen 10 - 20%10 - 20%
4 antigen4 antigen 50 - 60%50 - 60%
3 antigen3 antigen > 90%> 90%
 ABO incompatibility is not an exclusionABO incompatibility is not an exclusion

17. Patient EligibilityPatient Eligibility
 Age < 65Age < 65
 Autologous, mini-alloAutologous, mini-allo
 Age < 55Age < 55
 Myeloablative allogeneicMyeloablative allogeneic
 ExclusionsExclusions
 CHF, uncontrolled diabetes mellitus, activeCHF, uncontrolled diabetes mellitus, active
infections, renal insufficiencyinfections, renal insufficiency

18. Preparative RegimensPreparative Regimens
 MyeloablativeMyeloablative
 High doses of chemotherapy +/- radiationHigh doses of chemotherapy +/- radiation
 3 goals3 goals
 Eliminate malignancyEliminate malignancy
 Immunosuppression to allow engraftmentImmunosuppression to allow engraftment
 Decrease graft versus host effectsDecrease graft versus host effects

19. Preparative RegimenPreparative Regimen
 Non-Myeloablative (Reduced inductionNon-Myeloablative (Reduced induction
conditioning - mini transplant)conditioning - mini transplant)
 Reduction in mortalityReduction in mortality
 Reduction in non-relapse mortalityReduction in non-relapse mortality
 Reduced PRBC and platelet transfusionsReduced PRBC and platelet transfusions
 Duration of neutropenia reducedDuration of neutropenia reduced
 Reduced numbers of bacteremiasReduced numbers of bacteremias
 Able to give to heavily pretreated patientsAble to give to heavily pretreated patients
 Reduced GVHD compared to myloablative therapyReduced GVHD compared to myloablative therapy
 Late onset acute GVHD occuring beyond day 100Late onset acute GVHD occuring beyond day 100

20. Principals of ConditioningPrincipals of Conditioning
 Donor Lymphocyte Infusions (DLI)Donor Lymphocyte Infusions (DLI)
 T cells and NK cellsT cells and NK cells
 Additional anticancer effectsAdditional anticancer effects
 Preventing relapse or eliminating active diseasePreventing relapse or eliminating active disease
 CML and multiple myelomaCML and multiple myeloma

21. Collection of Stem CellsCollection of Stem Cells
 Bone Marrow HarvestBone Marrow Harvest
 General anesthesiaGeneral anesthesia
 Equivalent of 50-100 bone marrow biopsiesEquivalent of 50-100 bone marrow biopsies
 Used much less oftenUsed much less often

22. Collection of Stem CellsCollection of Stem Cells
 ApheresisApheresis
Stem Cell Collection (mobilization)Stem Cell Collection (mobilization)
 Stem cells circulate in the bloodStem cells circulate in the blood
 Identified by CD34+ by flow cytometryIdentified by CD34+ by flow cytometry
 Filgrastim, Sargramostim, AMD 3100Filgrastim, Sargramostim, AMD 3100
 Stem cells are collected through an apheresis catheterStem cells are collected through an apheresis catheter
 More cells are collectedMore cells are collected
 Higher chronic GVHD than bone marrow harvestHigher chronic GVHD than bone marrow harvest
 More rapid marrow recoveryMore rapid marrow recovery

23. Umbilical Cord BloodUmbilical Cord Blood
 11stst
UCB transplant 26 years agoUCB transplant 26 years ago
 Child with FanconiChild with Fanconi’’s anemias anemia
 Cell dose is given per recipient weightCell dose is given per recipient weight
 Lower patient weights the high the cell doseLower patient weights the high the cell dose
 2 x 102 x 1077
nucleated cells/kgnucleated cells/kg
 1.7 x 101.7 x 1077
CD 34+ cells/kgCD 34+ cells/kg
 4/6 match UCB with sufficient cells has a similar4/6 match UCB with sufficient cells has a similar
outcome to a matched or one antigen mismatchedoutcome to a matched or one antigen mismatched
MUDMUD

24. Umbilical Cord BloodUmbilical Cord Blood
 Umbilical Cord BloodUmbilical Cord Blood
 CryopreservedCryopreserved
 Small number of stem cellsSmall number of stem cells
 Higher incidence of engraftment failureHigher incidence of engraftment failure
 Using more than one unit in adultsUsing more than one unit in adults
 Lower risk of GVHDLower risk of GVHD
 Degree of matching not as stringentDegree of matching not as stringent
 TRM not different than MUDTRM not different than MUD
 Can be used with myeloablative or nonmyeloablativeCan be used with myeloablative or nonmyeloablative
conditioning (on a clinical trial)conditioning (on a clinical trial)

25. HarvestingHarvesting
 Depends upon collection methodsDepends upon collection methods
 TargetTarget
2-4x102-4x1088
nucleated cells/Kg of recipient weightnucleated cells/Kg of recipient weight
or 2-10x10or 2-10x1066
CD 34+ cells/Kg of recipientCD 34+ cells/Kg of recipient
weightweight
 Umbilical cord blood is obtained from one ofUmbilical cord blood is obtained from one of
the umbilical cord veins and frozen with anthe umbilical cord veins and frozen with an
anticoagulant and nutrient mediaanticoagulant and nutrient media

26. Stem Cell ManipulationStem Cell Manipulation
 ABO incompatibleABO incompatible
 Removal of Isoagglutinins or RBCsRemoval of Isoagglutinins or RBCs
 T-cell depletionT-cell depletion
 Reduce incidence of GVHDReduce incidence of GVHD
 Increased graft failureIncreased graft failure
 Increased relapse ratesIncreased relapse rates
 In vitro purgingIn vitro purging
 Removal of tumor cellsRemoval of tumor cells
 Positive selection of CD34+ cellsPositive selection of CD34+ cells

27. Units that may result from post-collectionUnits that may result from post-collection
processingprocessing
 HPC, (RBC reduced)HPC, (RBC reduced)
 HPC, (Plasma reduced)HPC, (Plasma reduced)
 HPC, (CD34 enriched)HPC, (CD34 enriched)
 HPC, (Buffy coat enriched)HPC, (Buffy coat enriched)
 HPC, (Mononuclear cell enriched)HPC, (Mononuclear cell enriched)
 Cryopreserved HPCCryopreserved HPC

28. Infusion of Stem CellsInfusion of Stem Cells
 Stem cells may be infused fresh within a fewStem cells may be infused fresh within a few
hours of collectionhours of collection
 May be frozen using DMSOMay be frozen using DMSO
 Creamed corn or garlic smellCreamed corn or garlic smell

29. RecoveryRecovery
 For Autologous & AllogenicFor Autologous & Allogenic
 Bone Marrow (2-6 weeks)Bone Marrow (2-6 weeks)
 PBSC ( 8-10 days for neutrophil & 10-12 daysPBSC ( 8-10 days for neutrophil & 10-12 days
for platelets )for platelets )
 for cord blood (Neutrophil is 4 weeks)for cord blood (Neutrophil is 4 weeks)

30. ComplicationsComplications
 EarlyEarly
 MucositisMucositis
 Sinusoidal obstructive syndrome (VOD)Sinusoidal obstructive syndrome (VOD)
 Fluid retention, jaundice, hepatomegalyFluid retention, jaundice, hepatomegaly
 Transplant related infectionsTransplant related infections
 Damage to mouth, gut and skin, hemorrhagic cystitisDamage to mouth, gut and skin, hemorrhagic cystitis
 Prolonged neutropeniaProlonged neutropenia
 PancytopeniaPancytopenia
 PRBC and platelet transfusionsPRBC and platelet transfusions
 Broad spectrum antimicrobialsBroad spectrum antimicrobials
 Antifungals if prolonged fevers 3-5 daysAntifungals if prolonged fevers 3-5 days

31. ComplicationsComplications
 EarlyEarly
 Graft Versus Host DiseaseGraft Versus Host Disease
 Acute GVHD to day 100Acute GVHD to day 100
 Skin, GI tract, liverSkin, GI tract, liver
 Graft RejectionGraft Rejection
 Host versus graftHost versus graft
 Drug injury to marrowDrug injury to marrow
 Viral infections: CMV, HHV-6 & 8Viral infections: CMV, HHV-6 & 8
 Interstitial PneumonitisInterstitial Pneumonitis
 Diffuse alveolar hemorrhageDiffuse alveolar hemorrhage
 Too few donor stem cellsToo few donor stem cells
 ARDS often caused by CMVARDS often caused by CMV

32. ComplicationsComplications
 DelayedDelayed
 Chronic GVHDChronic GVHD
 Scleroderma or Sjogrens syndromeScleroderma or Sjogrens syndrome
 BronchiolitisBronchiolitis
 KeratoconjunctivitisKeratoconjunctivitis
 MalabsorptionMalabsorption
 CholestasisCholestasis
 Esophageal strictureEsophageal stricture

33. Late ComplicationsLate Complications
 Secondary TumorsSecondary Tumors
 Acute leukemias, solid tumors, MDSAcute leukemias, solid tumors, MDS
 Months to years after transplantMonths to years after transplant
 Increased incidence with TBIIncreased incidence with TBI
 Late InfectionsLate Infections
 Bacterial, viral, fungalBacterial, viral, fungal
 Months after transplantMonths after transplant
 Associated with GVHDAssociated with GVHD
 Need repeat vaccinationsNeed repeat vaccinations
 Pneumovax, Hep B, Hemophilus influenza b, poliovirus,Pneumovax, Hep B, Hemophilus influenza b, poliovirus,
diphtheria/tetanus, fludiphtheria/tetanus, flu

34. Transfusion in HSCTTransfusion in HSCT
3 phases3 phases
 Pre-transplantPre-transplant
 Peri-transplantPeri-transplant
 Post-transplantPost-transplant
 Pre-transplantPre-transplant
 Leukocyte reduced and irradiated bloodLeukocyte reduced and irradiated blood
productsproducts
 Avoid family member transfusionAvoid family member transfusion

35. Transfusion in HSCTTransfusion in HSCT
OO
Recipient Type Donor Type Mismatch RBC type FFP type
O A Major O A, AB
O B Major O B, AB
O AB Major O AB
A AB Major A AB
B AB Major B AB
A O Minor O A, AB
B O Minor O B,AB
AB O Minor O AB
AB A Minor A AB
AB B Minor B AB
A B Bidirectional O AB
B A Bidirectional O AB

36. Transfusion in HSCTTransfusion in HSCT
 Peri-transplantPeri-transplant
 Continue support as aboveContinue support as above
 Follow the chartFollow the chart

37. Transfusion in HSCTTransfusion in HSCT
 Post-transplantPost-transplant
 Irradiated products give for 1 yearIrradiated products give for 1 year
 Continue CMV vigilanceContinue CMV vigilance
 ABO mismatchABO mismatch
 After engraftment (original ABO antibodiesAfter engraftment (original ABO antibodies
disappear after several months), transfuse ABOdisappear after several months), transfuse ABO
identical blood , but after proper compatibilityidentical blood , but after proper compatibility
test.test.
 In case of incompatibility use tableIn case of incompatibility use table

38. The EndThe End!!
Thank youThank you