stem cell transplant.pptx

HEMATOPOETIC STEM CELL
TRANSPLANT

Outlines
• Introduction
• History of BMT
• Type of transplant
• Indication of HSCT
• Source and storage
• Transplant process
• Complication
• Management

Introduction
 Hematopoietic stem cells(HSCs)
 HSCs formation start during embryonic
development.
 Hemati= Greek prefix “blood’
Poiesis/Poietic= Greek suffix ‘formation”
 Express CD34
 Found in bone marrow and umbilical cord blood.

History of BM transplantation
• Early attempt was in 1891
• Oral administration of healthy BM to patient with
defective blood formation.
• It was not successful, but physicians had the right
idea: donor marrow cells----may find their way into
the BM cavity.
• Some unsuccessful BMT in 1930s and 1940s

• History of BM transplantation Hope within Tragedy:
After World War II
• Nuclear bomb Inspire the research into the effects of
the radiation on the bone marrow of survivors in
Hiroshima and Nagasaki.
• BM is very sensitive organ to radiation.
• This led to major breakthroughs for bone marrow
transplants in the 1950s

• 1956 – The First successful
Transplantation Between Identical Twins
with total body irradiation by E. Donnall
Thomas
• Performed total body irradiation followed
by infusion of bone marrow from an
identical twin that resulted in complete
remission of leukemia.
• Got the Nobel Prize in year 1990

• 1958 – an Important Discovery
• Allogeneic BMT was not performed on large scale until
Jean Dausset, a French medical researcher, made a critical
discovery about the human immune system : Human
histocompatibility antigens “HLA”
• Dausset describe HLA as “proteins on the surface of most
cells in the body. The immune system uses these proteins
to identify which cells belong in the body”
• The better the antigen match, less likely T cells of the donor
will react against the patient’s body.
• The Nobel Prize, 1980
• 1968 – First Bone Marrow Transplant Between HLA
matched Siblings

1956 – 1st marrow transplant (twin)
1968 – 1st marrow transplant (sibling)
1973 – 1st marrow transplant (unrelated)
1988 – 1ST Cord blood transplant in patient with Fanconi
anemia

Immune system
• HLA match
• T- cell

HLA
• Human leukocyte Antigen
• The genes for the HLA proteins are clustered in the
major histo-compatibility complex (MHC), located on the
short arm of chromosome 6.
• More polymorphic than red blood group
• ABO: 4 possible combinations (A,B,O,AB)
• HLA: >1 million combinations

2 class
Class I (HLA-A,HLA-B,HLA-C)- graft rejection
Class II (HLA-DR,HLA-DQ)- GVHD

• In reality, only 30% of patients actually find a
match within their family.
• The other 70% has to rely on organizations such
as the Bone Marrow Donor Program which has a
register of potential donors who are willing to
donate their stem cells.
• Globally, there are over 70 stem cell donor
registries and over 23 million donors waiting to
donate their stem cells.
The present scenario…

Donor registration and recruitment

Research Input
Access to hematopoietic stem-cell transplantation in India
U Kulkarni and B George
In India, there is still a vast difference between the patient needs
and the health-care delivery.
Aim- Study is done to investigate the use of HSCT as an
appropriate tool to cure Indian patients suffering from
hematological disorders.
Results-
• almost 71% patients with acute myeloid leukemia were
recently unable to undergo treatment with the standard of
care, mostly due to financial constraints.
• Addressing this problem needs a multipronged approach,
which includes increasing the number of transplant centers,
improving minimum standards for HSCT centers, reducing
overall costs associated with HSCT, and helping patients with
financial support for HSCT.

HSCT
• Hematopoietic stem cells are the stem cells that give
rise to other blood cells.
• Replacing the diseased / damaged bone marrow with
normal functioning.
• Def- Any procedure where hematopoietic stem cells of
any donor and any source are given to a recipient
with intention of repopulating/replacing the
hematopoietic system in total or in part.

Indication of HSCT
Malignant (cancerous)
• Acute myeloid leukemia (AML)
• Chronic myeloid leukemia (CML)
• Acute lymphoblastic
leukemia (ALL)
• Hodgkin lymphoma (HL)
(relapsed, refractory)
• Non-Hodgkin lymphoma (NHL)
(relapsed, refractory)
• Neuroblastoma
• Ewing sarcoma
• Multiple myeloma
• Myelodysplastic syndromes
• Gliomas, other solid tumors
Non-malignant (non
cancerous)
• Thalassemia
• Sickle cell anemia
• Aplastic anemia
• Fanconi anemia
• Malignant infantile
osteopetrosis
• Mucopolysaccharidosis
• Immune deficiency syndromes
• Autoimmune diseases

Source of stem cells
• Bone marrow (BM).
• Peripheral blood (PBSC)
• Umbilical cord blood (UCB)

Bone marrow (BM)
• Bone marrow is obtained through multiple marrow
aspiration from the bilateral posterior iliac crests
• 3x108 nucleated per kg of recipient weight(1 to 1.5 L
for an adult)
• The amount of bone marrow collected is
approximately 10 to 15 mL/kg and is based on the
recipient’s body weight.
• The bone marrow product is mixed with heparin to
prevent clotting.

Peripheral blood (PBSC)
• The stem cell moves from the bone marrow into the
peripheral blood and is collected by apheresis.
• Following collection, the stem cells are cryopreserved,
frozen, and stored for future use.
• Common methods to mobilize stem cells include use of
CSFs such as granulocyte CSF (G-CSF) and
granulocyte-macrophage CSF (GM-CSF) or
chemotherapy plus CSFs
• Target dose: 1 to 5x 106 CD34 positive cells per Kg
• Engraft little faster than bone marrow, has similar
incidence of acute GVHD as BM, but higher occurrence
of chronic GVHD.

Umbilical cord blood (UCB)
• The use of UCB stem cells for transplantation continues
to evolve as an option for transplantation of autologous
or allogeneic stem cell transplantation.
• Collection and storage of autologous UCB may be done
for the purpose of saving the UCB stem cells for future
use if needed.
• Require less stringent HLA matching , resulting less
GVHD than BM and PBSC, but slower to engraftment

1. Autologous Transplant
• Requires the extraction (apheresis) and storage of the
harvested cells in a freezer
• The patient is then treated with high
dose chemotherapy with or without radiotherapy with the
intention of eradicating the patient's malignant cell
population at the cost of partial or complete bone
marrow ablation
• Transfused into bloodstream

Cont..
Advantage
• Lower risk of infection
since recovery is fast
• Incidence of
rejection(GVHD) is very
rare
Disadvantage
• Likelyhood of relapse and
related mortality(multiple
myeloma)
• There is no graft versus
tumor effect from the graft

2. Allogenic Transplant
• HLA tissue type matching for class I antigen(A, B, C) and
class II antigen(DR).
• Type
– Matched related sibling donor(MSD)
– Matched unrelated adult donor(MUD)
– Partially matched or haplo-identical related
donor(haplo)
– Unrelated cord blood cells(UCB)

Preferred hematopoietic stem cell transplantation
cell source

Matched related sibling donor(MSD)
• Sibling is the best donor with same HLA haplotypes as
both chromosome for HLA-A,HLA-B,HLA-C and HLA-DR
(8/8 match ).
• Identical twins(syngeneic) are the best donor
immunologically(no risk of GVHS), but have high risk of
relapse after transplant due to less GVT effect.

Matched unrelated adult donor(MUD)
• Chance of finding an appropriate unrelated donor
depends on the specific HLA typing and varies
significantly with different ethnic groups (about 90% for
caucasians, but only 60% in black )

Partially matched or haplo-identical related donor
(Haplo)
• Family members who are matched for only HLA
haplotype (4/8) can be used as donor
• Parents, children, or non-identical siblings
• Post transplant cyclophosphamide or graft manipulation
to limit GVHD and allow for effective engraftment
• The approach may also limit the HVT effect

Manipulation and graft engineering
Types of manipulation:
• Depletion of T lymphocytes and lymphocyte subset
• Enrichment of CD34 positive cell
• Stem cell expansion

Unrelated cord blood cells(UCB)
• Cord blood banks
• Useful in urgent need of transplant
• Cell require less stringent HLA compatibility , so 4 of 6
HLA matched unit(HLA-A,HLA-B,HLA-DR) can be used
• Slow engraftment and immune reconstitution
• Cell dose is limited and may need 2 cord blood unit
(double cord transplant) in adults

Advantage and disadvantage of HSCT
Advantage
• Product is free of tumor
or abnormal cell
• Can be used for replacing
deficient and defective
stem cell (aplastic anemia
and genetic disorders)
• Provide adaptive
immunity against the
tumor cells(GVT effcect)
Disadvantage
• Finding appropriate donor
• Risk of GVHD

Transplant process
1. Stem cells collection
2. Processing & Cryopreservation
3. Conditioning (Chemotherapy Regimen)
4. Stem cells infusion
5. Recovery

Stem cells collection
Bone marrow harvesting.
• General anaesthesia
• Marrow aspirated from pelvis.
Peripheral blood harvesting.
• Stem cells mobilised – G-CSF
• On day 5 : stem cells is collected (apheresis )
machine 3 hours session

collection of PBSCs
• Collection of PBSCs using comercially available cell
separators
• Remaining bld returned to pt
• Through a large bore double lumen catheter with flow
rate 50-70ml/mts (12 Fr)
• Mononuclear cell counts of 4-5x108/kg body
wt(population of cells express CD34 antigen)
• Stem cells cryo preserved with DMSO at -1960C

Investigations to be sent on harvest
• CD-34 count
• Viability testing
• Calculate the MNC count
• Bacterial culture
• Never irradiate the harvested stem cell

Complications
• Transient hypocalcemia
• Fatigue
• Anemia
• Thrombocytopenia
• Catheter related morbidity

Management
• Explain that it will take 3-4 hrs.
• To increase calcium intake.
• Inform apheresis technician in advance
• Take consent
• Check adequacy of veins for harvest
• Sent pt with all articles needed.

2-Processing & Cryopreservation
Processing
• BM /PBSC processed and stem cells concentrated
and purify and prepared for freezing process.
Cryopreservation
• Stem cells are preserved by freezing to keep stem
cells alive until day of infusion into the patient.

Storage
• Bone marrow cells can be frozen (cryopreserved) for
prolonged periods without damaging too many cells.
• To cryopreserve HSCs, a preservative, DMSO (Dimethyl
sulfoxide) , must be added, and the cells must be cooled very
slowly in a controlled-rate freezer to prevent osmotic cellular
injury during ice crystal formation. HSC may be stored for
years in a cryofreezer, which typically uses liquid nitrogen.
• This is a necessity with Autologous HSC because the cells
must be harvested from the recipient months in advance of
the transplant treatment.
• Allogeneic cord blood is stored frozen at a cord blood
bank because it is only obtainable at the time of childbirth.

Storage
• For autologous BMT
– Mix with hep solution
– Filtration
– Purging
– Mixed with DMSO
– Cryopreserved
• For allogeneic marrow
– T-cell depletion
– Removal of RBC
– Immediate transfusion

3.Conditioning therapy
• High dose of CT/RT prior to the transplant
• Vital functions:
 Obliterate malignant disease
 Destroy pts preexisting immunity
 Create space in BM cavity
• Types:
– Myeloablative conditioning(MAC)
– Reduced intensity conditioning(RIC)
– Non myeloablative conditioning(NMC)

Myeloablative conditioning(MAC)
• Maximum tolerated dose with or without RT
• Typical doses:
Cyclophosphamide 200mg/kg
+
Busulfan 16 mg/kg or total body irradiation(TBI)
10Gy.
• Other agents: Melphalan, Thiotepa, Or Etoposide
can be combined
• Maximum tumor killing but also have substantial non-
hematologic toxicity which may not tolerated in pt.
with co-morbidities or older age

Reduced intensity conditioning(RIC)
• Uses lower doses of conditioning that still may be
myeloablative and allow for donor hematologic and
immunologic engraftment.
• Most common regimen:
Fludarabine + reduced dose of (busulfan, cyclo,
melphalan, or thiotepa or with TBI (5 to 8 Gy).
• Some increased risk of relapse compared to MAC
regimens
• Advantage : decreased nonrelapse mortality so transplant
can be consider in pt. with co-morbidities or older age

Non myeloablative conditioning(NMC)
• Further reduction of doses with minimal
cytopenia and toxicities and could allow for
autologous cell recovery without the need for
donor stem cells.
• Example: TBI (1-2 Gy), total lymphoid irradiation,
combination of fludarabine(90mg) and
cyclophosphamide(1-2 G/m2).
• Primarily been used in low grade lymphoma.

4. Stem cell infusion
• Infusion - 20 minutes to an hour, varies depending on
the volume infused.
• Infused through a central venous line CVL, much like a
blood transfusion.
• Premedication with acetaminophen and
diphenhydramine to prevent reaction.

Autologous
 Frozen BM bag brought to pts room
 Bag thawed in a N/S bath
 Drawn up in large syringes
 Given through rapid push via CVC
 Can be hanged & transfused
 Takes 20-30mts
 SOB, nausea, vomiting occurs sometime

–The marrow or stem cells are infused on the same day
as they are collected
–Resembles blood transfusion
–Unfiltered tube must be used, DO NOT IRRADIATE
–1-5 hours
• S/E
–Shortness of breath,Chills,Fever,rash,chest pain,
Hypotension
 Rx
Diphenhydramine
Hydrocortisone
Epinephrine
O2 therapy

Pre transplant Check list
• Recipient
 Hx & P/E
 BM Bx & aspiration with cytogenetics
 Blood chemistry profile
 CBC,platelets, reticulocyte count
 ABO & Rh typing, coagulation profile
 Serum immunoelectrophoresis
 Hepatitis screen,CMV,HIV,HSV markers

• Urinalysis,creatinine clearance
• Chest & sinus Xray film
• ECG,echo,radionucleotide ventriculogram
• PFT,allergy testing
• Audiology,psychology,ophthalmology,surgery
consult
• Physical therapy consult
• Dental & dietary consultation
• HLA matching
• Financial screening and evaluation
• Insertion of a multilumen catheter

Donor
• Hx & P/E
• Chemistry profile
• CBC,platelet
• ABO & Rh typing
• Hepatitis screen,HIV, CMV & HSV tests
• Chest X ray
• ECG

5-Recovery
Neutropenic phase
• (2-4 wk), during this period the patient essentially has no
effective immune system
• Supportive care and antibiotic therapy are the mainstays of
successful passage through this phase.
Engraftment phase
• Recovery of normal levels cells is called engraftment
• Bone Marrow (2-6 weeks)
• PBSC ( 8-10 days for neutrophil & 10-12 days for platelets )
• Cord blood (Neutrophil is 4 weeks)
• Neutrophil engraftment is important (may give G-CSF)
• Platelets are the next to return with red cells last (Commonly
patients require transfusion of red cells and platelets).

Neutropenic phase
• During this period, the patient essentially has no
effective immune response.
• Healing is poor, the patient is susceptible to infection.
• Supportive care and antibiotic therapy are the mainstays
of successful passage through this phase.

Engraftment phase
• Transfused cells will migrate & regenerate
• Takes typically 2-3 wks
• Allogenic take 5-16 days
• Cord blood around 26-42 days
• Experiences severe pancytopenia & immuno-
suppression
• Immediate complications: infection & bleeding
• Hematopoietic growth factors are given.

Signs of engraftment
• Return of WBCs to a sufficient level defined as
Absolute neutrophil count (ANC) > 500/mm for 3
consecutive days
• Is achieved after 7-14 days of transplant
• Increased platelet levels , achieved 2-3 weeks
following the transplant

Post engraftment phase
• A 2 to 4 weeks waiting period follows the transfusion
before its success is begin to be judged.
• Patient is kept in isolation to minimize potential
infections.
• Patient receives chemo, anti viral, anti fungal, antibiotic,
blood and platelets transfusion to help fight off infection
and prevent excessive bleeding
• Blood test are performed
• ANC,KFT,LFT levels are checked
• Daily monitoring of nutritional status is done.

Research Input
HIV
• In 2007, a team of doctors in Berlin, Germany, including Gero
Hütter, performed a stem cell transplant
for leukemia patient Timothy Ray Brown, who was also HIV-
positive. From 60 matching donors, they selected a [CCR5]-
Δ32 homozygous individual with two genetic copies of a rare
variant of a cell surface receptor. This genetic trait confers
resistance to HIV infection by blocking attachment of HIV to
the cell. Roughly one in 1000 people of European ancestry
have this inherited mutation, but it is rarer in other
populations.
• In 2019, a British man became the second to be cleared of
HIV after receiving a bone marrow transplant from a virus-
resistant (Δ32) donor. This patient is being called "the London
patient" (a reference to the famous Berlin patient).

Supportive care
• Blood product
• Specific measures
• Protective isolation and prophylaxis
• Prevention and suppression of GVHD

Blood product
• All blood product(except HSC )should be irradiated with
1.5Gy (to prevent transfusional GVHD) as soon as
conditioning regimen is initiated.
• RBC transfusion: to maintain hematocrit at 27% or
higher if clinically indicated
• Platelet transfusion: prophylactic platelet
transfusion(>10,000/ml), but higher level needed if pt.
are febrile and bleeding symptoms.

Blood product
RBC
 Packed RBCs
 Hb <8.0gms
 Pt symptomatic
 Active bleeding present
 Filtered, irradiated, leucodepleted blood
Platelet concentrates
 Platelet count <20000
 Active bleeding
 Prior to surgery/minor procedure

Specific supportive care measures
• Adequate hydration and antiemetic therapy throughout the
preparative regimen.
• Allopurinol for all pt. with bulky tumor and stopped on day
minus 1 or sooner depending on tumor burden and pt.
response.
• Weekly Vit. K replacement with antibiotic therapy(because
of poor oral intake)
• Menstruating females started on anovulatory agent prior to
conditioning regimen, Norethinodrone 5-10 mg PO daily
and maintain until platelet count recover to > 50,000/ml
• GCSF given at day plus 2 following transplant.

Protective isolation and prophylaxis
Protective isolation
• Begin when absolute neutophils count is <500/ml
• Room should be equipped with air filtration units.
• Must perform good hand washing or gloving prior to
entering the pt. area.
• Pt. wash daily with a microbial cleaning solution
• Antifungal, antibacterial, antiviral prophylaxis can be
initiated prior to conditioning regimen

Prophylaxis
1. Pnemocystis prophylaxis:
• Who have had extensive corticosteroid exposure should
receive Pnemocystis prophylaxis.
• Start trimethoprim-sulfamethoxazole (Bactrim DS, one
tab. PO every 8 hrs) at onset of conditioning therapy and
stop at day minus 1 before transplant.
• Restarted after sustained neutrophil engraftment(Bactrim
DS, one tab. PO TID twice a week with folinic acid 5mg
twice a week) and continued until day 100 after
transplant or longer.
• Dapsone (50 -100mg PO daily), atovaquone (1,500 mg
once daily), or pentamidine (aerosolized 300mg or
4mg/kg IV) monthly can be used as an alternative for the
patients with allergic to sulfa.

2. Cytomegalovirus (CMV)prophylaxis/ Prevention:
• Pt who are CMV seronegative prior to transplant should
receive only blood products that are CMV seronegative
or leukoreduced.
• CMV seropositive pt. undergoing an allogeneic
transplant can receive gancyclovir (6 mg/kg IV/d)
starting at the onset of conditioning therapy and
stopping at day minus 1 prior to the transplant.
• After allogeneic transplant gancyclovir (6mg/kg IVPB/d,
5 d/wk) restarted after sustained neutrophils
engraftment and continued to day 100 for prophylaxis.
• Alternatively, after engraftment monitored for viremia
weekly with evaluation of blood CMV DNA to determine
when pre-emptive treatment is needed.

Prevention and suppression of GVHD
Allogeneic HSC transplant: immunosuppressant treatment.
Calcineurin inhibitors:
• Cyclosporine(3mg/kg/d) or tacrolimus (0.03 mg/d),
starting on day minus 2 and doses are adjusted to
maintain therapeutic serum level and to prevent renal
failure
Post-transplant cyclophosphamide:
• Haplo transplant: Unmodified haplo donor cells are
infused on day 0, initially allowing alloreactive T cell to
proliferate, cyclophosphamide 50mg/kg/d is then given
on day plus 3 and plus 4 post transplant for in vivo T-cell
depletion.

Cont..
Other agents:
• Corticosteroid, antithymocyte globulin (ATG,
thymoglobulin), mycophenolate, serolimus, or
methotrexate can be used depending on the GVHD risk
of the transplant and patient status.
T-cell and subset depletion:
• Programs using partial T cell depletion or adding back of
lymphocyte subpopulations at various times may be
helpful.

Complications associated with HSCT
• Graft failure
• Infection
• Mucositis
• Nausea vomiting
• Pulmonary complications
• Veno-occlusive disease
• Graft versus host diseases
• Recurrence

Complications
Early
Before day +100
• Hemorrhage
• Veno-occlusive disease of liver
• Pulmonary complications
• Nutritional complications
• Infection
• Acute graft vs. host disease
Late
After day +100
• Cataract
• Neurological conditions
• Endocrine dysfunction
• Osteoporosis
• Chronic graft vs host disease
• Relapse of malignancy

Graft Failure
Failure of marrow recovery to return/loss of marrow
function after an initial period of recovery.
• Occurs in 1-4 wks
Symptoms :
Absent /Prolonged Neutropenia,
Hypoplasia
Hemolysis
Rx:
Administer blood component therapy
Consider re-transplantation

Veno-occulsive disease
 In 1-3 wks,early
 A complication of conditioning regimen
 Occlusion of central veins of liver
 s/s:
wt gain> 5%,hepatomegaly,RUQ pain,total serum
Bil.>2mg/dl
 R/F :
Hx of hepatitis,mismatched /unrelated transplant,use of
methotrexate as GVHD prophylaxis

Management- veno-occulsive disease
 Maintain IV volume
 Vital sign monitoring
 Weight record daily
 Abdominal girth daily
 Low dose heparin and anticoagulants
 Ursodiol to reduce bile

GVHD
• Graft versus host disease (GvHD) is a condition that
might occur after an allogeneic transplant. In GvHD, the
donated bone marrow or peripheral blood stem cells
view the recipient’s body as foreign, and the donated
cells/bone marrow attack the body.
• There are two forms of GvHD:
– Acute graft versus host disease (AGvHD).
– Chronic graft versus host disease (CGvHD).

Incidence
1. AGvHD (Grade II to IV) :
• <30% of matched sibling
• 60-90% with mismatched unrelated transplant.
2. AGvHD (Grade III to IV) : about 35% for 7 of 8 HLA
mismatched adult donor transplants but only 10% for
mismatched UCB donor transplant
3. CGvHD:
• 25-60% of pt. surviving >4 month post allogenic
transplant.
• 2/3rd pt. who develop CGvHD had preceding AGvHD .

Acute GvHD
• The skin, liver, and gastrointestinal tract are the principal
target organs in patients with acute GVHD.
• Grading of AGVHD depending on the severity of organ
involved.

Acute GvHD
• 3-14 wks
• Maculo papular rash,nausea,vomiting, diarrhea,
jaundice,hepatomegaly,elevated LFT
• Skin,GI tract & liver are target organs.
• Prolongs immune deficiency

Chronic GvHD
• Characterized by chronic inflammatory process leading
to fibrosis and collagen vascular disease-like syndrome.
• A systemic multi organ syndrome, can involve the skin,
eyes, mouth, lungs, GI tract, liver, genitourinary tract,
and musculoskeletal, immune, and hematopoietic
systems.
• It mimicking autoimmune process such as arthritis,
immune cytopenias, polymyositis, and sclerodermatous
skin, GI, and lung changes.

Chronic GvHD
 Skin
Hypo/hyper pigmentation, patchy eryrthematous
scaling,fibrosis,hair loss
 Mouth
White striae,erythema on mucosa,dryness,dec.salivary flow
 Eyes
Itching,burning,dryness,redness,corneal thickening
 Sinuses
Chronic sinusitis,infections

Treatment
AGvHD (Grade II to IV):
• Calcineurin inhibitors when diagnosed
• T-cell suppression: corticosteroid, mycophenolate, and
sirolimus
• Treatment with ATG, alemtuzumab, anti-interleukin-2-
inhibitor(daclizumab) or anti-TNF inhibitors(etanercept)
• Organ specific: topical skin t/t, topical enteric coated
steroid (budesonide), antiperistalsis (loperamide),
antisecretary(octereotide) and bile acid(ursodiol) agents.

Treatment- CGvHD
• Steroids and other treatment, extracorporeal photo
chemotherapy, mesenchymal stem cells, pentostatin,
elemtuzumab(anti CD52 antibody), or rituximab(anti CD 20
antibody).
• Extracorporeal photo chemotherapy is a photopheresis with
exposure of blood mononuclear cells to the photosensitizing
compound PUVA-psoralen plus UV-A, prior to reinfusion.
• Infusion of intravenous IgG (IVIG) in pt. with significant
hypoglobulinemia.
• Supportive care: topical steroids, skin lubricants, eye drops,
artificial saliva, acyclovir
• Physical therapy: sclerodermatous GvHD and restricted
range of motion
• Sunscreen and avoid sun exposure

Infections
Conditioning regimen:
• Prophylactically broad spectrum antibiotics or therapeutic at early sign of
fever or infection
Viral infection and reactivation:
• Herpes viral infection (following UCB transplant)
• CMV infection (after allogenic transplant engraftment): ganciclovir
(5mg/kg IV every 12 hrs for 3 wks)
• CMV pneumonia: additional IVIG (500mg/kg every other day for 10
doses)
• Other: infection with varicella zoster, adenovirus, resp. syncytial virus,
influenza can be quite severe.
Pneumocystis jirovecii:
• Therapeutic dose of trimethoprim-sulphamethoxazole (15 to 20 mg/kg/d)
IV administered in 3-4 divided doses
Infection with encapsulated bacteria: pneumococus, Meningococus,
Haemophilus
• Can be seen late in course (sometime a yearsor more)
• IVIG should be given if immunoglobulin levels are low

Nursing management- Infections
• Barrier nursing
• No visitors
• Aseptic techniques whenever needed
• Care of the central line
• Personel hygiene
• Frequent oral care
• Proper room cleaning
• Proper hand washing
• Use of hand rubs
• Autoclaved dress and linen for patients
• Monitoring temperature of pt and reporting if fever
• Antibiotics and antipyretics as ordered

Bleeding
• Platelets engraftment lags behind neutrophil
engraftment, but spontaneous count of >20,000/ml are
attained by most pt. by:
– Day 21(autologous transplant)
– Day 28(allogeneic transplant), but
– > 40 days(UCB transplant)

Non-marrow organ toxicity
• Due to high dose of CT/RT for conditioning therapy
• Toxicity of lungs, kidney, heart, liver, GI tract, endocrine
glands, and CNS can seen post transplant
• Infection, sepsis, tumor lysis.
• Venooclusive disease of the liver also Known as hepatic
sinusoidal obstruction syndrome(VOD/SOS): result from
injury to the sinusoidal endothelial cells and hepatocytes
from high dose conditioning therapy
– Seen within 1-2 months post transplant
– Characterised by hepatomegaly with right upper
quadrant pain, unexplained fluid retention, and jaundice,
– Mild VOD occur in 60% of pt. and can be reversible
without t/t
– When severe, associated with multiorgan failure and is
frequently fatal.

Research Input
Pre-transplantation Risks and Transplant-Techniques in Haematopoietic
Stem Cell Transplantation for Acute Leukaemia
Rafael Duarte et al , Eclinicalmedicine2019
Background
The role of conditioning intensity and stem cell source on modifying
pre-transplantation risk in allogeneic haematopoietic stem cell
transplantation (HSCT) is a matter of debate, but crucial when
benchmarking centres.
Method
Retrospective, multicenter exploratory-validation analysis of 9103
patients, (55.5% male, median age 50 years; 1–75 years range) with
an allogeneic HSCT between 2010 and 2016 from a matched sibling
(N = 8641; 95%) or matched unrelated donor (N = 462; 5%) for acute
myeloid (N = 6432; 71%) or acute lymphoblastic (N = 2671; 29%)
leukaemia in first complete remission, and reported by 240 centres in
30 countries. searched for factors associated with use of transplant
techniques (standard N = 6375;70% or reduced intensity conditioning
N = 2728;30%, respectively bone marrow N = 1945;21% or peripheral
blood N = 7158;79% as stem cell source), and their impact on
outcome.

Research Input
Findings
• Treatment groups differed significantly from baseline population
(p < 0.001), and within groups regarding patient-, disease-, donor-,
and centre-related pre-transplantation risk factors (p < 0.001);
choice of technique did depend on pre-transplantation risk factors
and centre (p < 0.001). Probability of overall survival at 5 years
decreased systematically and significantly with increasing pre-
transplantation risk score (score 2 vs 0/1 HR: 1·2, 95% c.i. [1·1–
1·.3], p = 0.002; score 3 vs 0/1 HR: 1·5, 95% c.i. [1·3–1·7],
p < 0.001; score 4/5/6 vs 0/1 HR: 1·9, 95% c.i. [1·6–2·2], p < 0.001)
with no significant differences between treatment groups (likelihood
ratio test on interaction: p = 0.40). Overall survival was significantly
associated with selection steps and completeness of information
(p < 0.001).
Interpretation
• Patients' pre-transplantation risk factors determine survival,
independent of transplant techniques.

Nursing responsibilities
• Before the procedure
• During the procedure
• After the procedure

Before the procedure
• Provide Isolation to the patient
• Counsel the patient and family member about the
procedure
• Explain the measures which should be take care
during the hospital stay.
• Explain duration of procedure(3-4hrs)
• Increase calcium intake
• Inform apheresis technician in advance
• Take informed written consent
• Check all tests and departmental clearance
• Arrange for funds and blood donation cards
• Asses catheter site for infection
• Arrange all articles needed

Role of Nurse -Pre-procedure
Hickman catheter
• Book O.T
• PAC to be done
• Informed written consent
• Part preparation and savlon bath
• Check availability of articles needed
• Dressing and check X-ray

Role of Nurse -Pre-procedure
Care of catheter
• Alternate day dressing
• Change the three-way daily
• Daily inspection of exit site
• Heplock after each use
• Weekly X-ray to check catheter tip

During the procedure
Take care of following things:
• Performed procedure under strict asepsis
• Continuous monitoring of vital signs
• Monitoring lab values
• Strict intake/output monitoring
• Ask patient for any discomfort
• Remain with patient
• Observe closely
• Report if any signs of reaction or bleeding appears

During the procedure
• During transplant, patient may get adverse reactions
due to cytoprotactant DMSO, so ongoing support and
teaching is needed.
• Assess for shortness of breath,Chills,fever,rash,chest
pain, hypotension
• Provide O2 therapy, diphenhydramine,
hydrocortisone, epinephrine if SOB, chills ,fever
occurs.
• Premedicate with diphenhydramine/ hydrocortisone
• Keep emergency articles ready
• Teach the family the possible reactions

After the procedure
• Patient stay in a special bone marrow transplant unit in
the center. This is to limit the chances of getting an
infection.
• Monitor the patient's kidney and liver function, as well as
nutritional status
• Ask for any fever,loose stools, pain anywhere, cough,
nausea, vomiting,bleeding
• Any skin changes,about apetite, mucositis etc..
• Daily haemogram, biochemistry
• Maintaining comfort & mobility
• Taking care of the dressing
• Prevent from developing complications
• Monitoring vitals
• Monitoring blood counts
• Psychological support
• Monitor the patient during first 30 days post-transplant, as
they are at risk of reactivation of infections.

After the procedure
• Pay close attention to hygiene: Patient may shower or bathe
normally, as long as he don’t submerge his central venous
catheter under water
• To help minimize infection and gum bleeding, daily oral (mouth)
care is necessary
• Prevent infections transmitted by direct contact: Wash hands
with antimicrobial(antibacterial) soap and warm water before
and after any central venous catheter care or intravenous
infusions, before taking oral medicines, after touching soiled
linens or clothes.
• Prevent respiratory infections:Avoid close contact with people
who have respiratory illnesses (cough, cold, etc.), Avoid
crowded areas, Avoid tobacco and marijuana use. The use of
these substances increases risk for bacterial, viral, and fungal
infections, Avoid the use of a room humidifier due to the water-
harboring bacteria

After the procedure
Caring for recipients:
• Ongoing nursing assessment in follow-up visits is to
detect late effects of therapy after BMT which occurs days
or more after the procedure
• Sterility often results due to total body irradiation as of the
ablative regimen
• Psychological assessments must be ongoing
Caring for donors:
• Donors also need nursing care. They commonly
experiences mood alterations, decreased self-esteem, &
guilt from feelings of failure if the transplantation fails
• Family members must be educated & supported to reduce
anxiety & promote coping during this difficult time

Nursing diagnosis
1. Risk for infection related to potential bone marrow
depression due to chemotherapy
2. Risk for bleeding related to thrombocytopenia
3. Pain related to mucositis as evidence by the patient’s
verbal reports
4. Fatigue related to effects of cancer, chemotherapy, and
radiation therapy
5. Imbalance nutrition les then body requirement related
to difficulty in swallowing
6. Anxiety related to the diagnosis of disease and effects
of treatment

Risk for infection related to potential bone marrow
depression due to chemotherapy
• Assess the vital level of the patients
• Monitor /inspect entry ports for pathogens/ I.V site, oral cavity
and urinary catheter.
• Frequently clean the catheter port sites and change daily.
• Avoid contact with people who have known or recent infection
.
• Give steam inhalations, Mouthwashes and Sitz bath to
prevent infection from suspected sites.
• Teach family members about Hand hygiene before and after
touching the patient.
• Advice not to eat raw fruits and vegetables
• Do not keep fresh flowers or plants near the patient.
• Provide antibiotics

Risk for bleeding related to thrombocytopenia
• Avoid giving IM injections
• Tell the patient to use soft brushes
• Avoid using razor blades use electric one
• give syp looz to prevent constipations
• tell patient not blow nose forcefully.
• Avoid invasive procedure as much as can be.

Pain related to mucositis as evidence by the patient’s
verbal reports
• Assess the pain level of the patient
• Apply xylocaine gelly some time before eating.
• Give ice chips to the patient
• Tell him to avoid taking spicy food which can increase
the pain
• Analgesics are given to the patient

Fatigue related to effects of cancer and
chemotherapy
• Assess the ability of patient to perform the ADLs
• Encourage the patient to perform some activities
• High calorie diet provided to the patient
• Tell him to take small and frequent naps.

Imbalance nutrition less then body requirement related to
difficulty in swallowing
• Assess the amount of intake by the patient
• Provide xylocaine jelly before eating .
• Provide high calorie diet.
• Provide more liquid diet

Anxiety related to the diagnosis of disease and
effects of treatment
• Assess the anxiety level of the patient by talking to her
• Answer the question asked by the patient
• Clarify the doubt of the patient regarding therapy as per
the understanding level of the patient.

Psychosocial- Individual and Family
• Provide opportunities for patient and family to
communicate with each other.
• Reinforce successful coping skills.
• Establish trust and congruence in goals and
objectives.
• Provide information in a timely and specific
manner.
• Demonstrate caring, respect and concern for
patient and family.
• Use positive reinforcement.

Patient teaching before discharge
The precautions that the patient must take care are:
• How to care for central venous catheter
• Exerted activities should be avoided.
• About personal hygiene
• About diet
• Importance of follow up
• What medications and how to be taken
• To avoid crowds and contact with pets

Discharge Criteria
• Patient is stable condition
• Absolute Neutrophil count of 500/mm
• Hematocrit 25% or greater
• Off antibiotics for at least 48 hours
• Afebrile for at least 48 hours
• Adequate oral nutritional intake
• If present, GVHD under good control

Prognosis
• Prognosis in HSCT varies widely dependent upon
disease type, stage, stem cell source, HLA-matched
status and conditioning regimen.
• A transplant offers a chance for cure or long-term
remission if the inherent complications of graft versus
host disease, immuno-suppressive treatments and the
spectrum of opportunistic infections can be survived.

Conclusion
• HSCT is a unique effective treatment modality providing
normal stem cells production for many malignancies and
genetic disorders
• HLA matching is critical in allogeneic transplant.
• HLA Allele level matching is associated with lower risks
of graft failure, GVHD and transplant related mortality.

References
• https://en.wikipedia.org/wiki/Hematopoietic_
stem_cell_transplantation#cite_note-
pmid3558716-42
• https://bethematch.org/transplant-
basics/matching-patients-with-donors/how-
donors-and-patients-are-matched/hla-basics/
• https://www.bbmt.org/article/S1083-
8791(18)31328-4/fulltext

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