Download MBBS Transfusion Medicine and Blood Bank Presentations 12 Stem Cell Transplantation Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st Year, 2nd Year, 3rd Year and Final year Transfusion Medicine and Blood Bank 12 Stem Cell Transplantation PPT-Powerpoint Presentations and lecture notes








Stem cell transplantation

Contents

History

Types

Stem cell procurement

Indications

Procedure

Complications








History of HSCT

?

Human patients
? 1959?1963 : first

Mouse

Dog

al ogeneic HSCT in

humans

First successful bone marrow
transplant

1956
Dr E Donnal Thomas in

New York

Patient- leukaemia
Donor-identical twin




The Nobel Prize, 1990

E. Donnall Thomas

first succsessful HSCT in treatment of acute leukemias

Thomas ED, Lochte HL, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients

receiving radiation and chemotherapy. N. Engl. J. Med. 1957; 257: 491.

1958

Dr Georges Math?
Defined the
`graft versus host'
disease




1968

Major landmark year for BMT in

immunodeficiency disorders

Children with X-linked lymphopenic immune

deficiency

Wiskott-Aldrich syndrome
Aplastic anemia

Stem cells

undifferentiated cells which are able
?

to divide for indefinite period

?

to self renew

?

to generate a functional progeny of highly specialised cells




HSCT

Allogeneic HSCT

Syngeneic-identical twin
from sibling/related donor
from unrelated donor

Autologous HSCT

Sources of stem cells

Bone

Peripheral

Umbilical

marrow

blood

cord blood






Bone marrow

Peripheral blood


Umbilical Cord

Indications for HSCT

Neoplastic disorders

Hematological malignancies

Lymphomas

Leukemias

Multiple myeloma

Solid tumors

Non-neoplastic disorders

Aplastic anemia
Autoimmune diseases
Immunodeficiency
Inborn errors of metabolism


Indications -Autologous HSCT

Multiple myeloma
Non-Hodgkin lymphoma

Hodgkin disease, Acute myeloid
leukemia

Neuroblastoma, Germ cel

tumors

Autoimmune disorders (systemic

lupus erythematosus [SLE],
systemic sclerosis), Amyloidosis

Indications - Allogeneic HSCT

Acute myeloid

Hodgkin disease

metabolism

leukemia

Aplastic anemia

Epidermolysis bul osa

Acute lymphoblastic Pure red-cel aplasia

Severe congenital

leukemia

Paroxysmal nocturnal

neutropenia

Chronic myeloid

hemoglobinuria

Shwachman-

leukemia

Fanconi anemia

Diamond syndrome

Chronic lymphocytic Thalassemia major

Diamond-Blackfan

leukemia

Sickle cel anemia

anemia

Myeloproliferative

Severe combined

Leukocyte adhesion

disorders

immunodeficiency

deficiency

Myelodysplastic

Wiskott-Aldrich

HSCT-related

syndromes

syndrome

morbidity and

Multiple myeloma

Hemophagocytic

mortality

Non-Hodgkin

lymphohistiocytosis

lymphoma

Inborn errors of






Major steps

Selection of donor

Based on tissue typing -HLA antigens

Harvest of stem cells from donor

Bone marrow harvest or pheresis of peripheral blood

Preparative regimen

Chemo-radiation for ablation and immune suppression

Stem cell infusion

Post-transplant supportive care

Autologous 100 days

Allogeneic 180 days or longer

Stem cell donors

Identical twins
Matched related or unrelated donors
Mismatched related donors
Haploidentical donors
Umbilical cord blood donors


Donor selection

History and physical examination
Investigations

Serum creatinine, electrolyte, and liver function

studies.

Serologic studies

cytomegalovirus (CMV), herpes virus, HIV RNA, anti-HIV

antibodies, hepatitis B and C viruses, syphilis (VDRL)

ABO blood typing
Human leukocyte antigen (HLA) typing
Chest radiography
Electrocardiography (ECG)

Mobilization of stem cells

Mobilization of peripheral

blood stem cells (PBSC) in
healthy volunteers with
granulocyte colony-
stimulating factor (G-CSF)





Stem cell procurement

Amount of stem cel s collected is based on

recipients body weight

Minimal number

2 x 108/kg nucleated cel s
2 x 106/kg CD 34 + cel s

Procedure

Recipient undergoes myeloablative

conditioning

high-dose radiotherapy and immunosuppressive

agents




Recipient preparation

Cyclophosphamide 60 mg/kg/day
During two days and Toal body irradiation

Busulfan 4mg/kg/day for four days and

Cyclophosphamide without irradiation

Etoposide ,Cytarabine as a maximizer antitumor

properties,myeloblation,immunosuppression

Procedure

? Donor stem cel s are

infused

? Migrate to the bone

marrow to repopulate the
immune system

? "Home" to micro-

environment niches in
marrow and spleen




Hematopoietic stem cell infusion


Special Blood Requirement

? Irradiated
? CMV Negative
? Leukocyte-Reduced
? Saline-washed or volume reduced

ABO compatibility

Is not a MUST!!
major or minor ABO incompatibility?

patient's /donor's antibody titers




Post HSCT

Infection prophylaxis is essential

Care in HEPA-filtered, positive-air-pressure

accomodation, with strict hand hygiene

Antibacterial and antifungal prophylaxis

Bone marrow transplantation unit


Outcome is influenced by:

Stage of disease

Patient - related factors: age, comorbidity

Donor - related factors: Histocompatibility (HLA)

Peri-transplant factors:Conditioning

Post-transplant factors:GVHD

Complications

Early

Infection, aGVHD, bleeding, toxicity, graft failure

Late

chGVHD, infection, relapse, gonadal failure, secondary

malignancy, toxicity


Cord Blood

Less prone to rejection than

either bone marrow or

peripheral blood stem cells.

Limitations of Allogeneic HSCT

Scarcity of suitable donors

Graft versus Host Disease

Infections


HLA Typing

Human Leukocyte Antigen

HLA are proteins found on short arm of chromosome 6

3-antigens important in HSCT- one set of 3 from each

parent

HLA-A
HLA-B
HLA-DR


Brings to a total of six antigens to match

A full match is "6/6" or "perfect" match

HLA or Tissue Typing

Rate of GVHD

Donor

Incidence

6/6

40%

5/6

50%

4/6

80%

3/6

90%




Graft-versus-host disease

Donor immune cel s attack recipient tissues,

often skin, gut and liver.

It can be very debilitating or even fatal.

Acute GVHD

Within the first 100 days after

the procedure

It starts as an erythematous,

macular skin rash, blistering,
abdominal pain, profound
diarrhea, and
hyperbilirubinemia.


Acute GVHD: Skin

Acute GVHD

Stage I disease is confined to the skin and is

mild

Stage II-IV have systemic involvement

Stage III and IV acute GVHD carry a grave

prognosis


Acute GVHD

Risk factors for acute GVHD

HLA-mismatched grafts
MUD grafts (Matched unrelated donor)
grafts from a parous female donor
advanced patient age

Acute GVHD

Prophylaxis

imunosuppressive agents

Treatment

high-dose steroids and antithymocyte globulin

(ATG)


Chronic GVHD

? Risk factors

peripheral blood stem cel transplants
mismatched or unrelated donors
second transplant
donor leukocyte infusions (DLIs)
acute GVHD

Chronic GVHD

? approximately 40-80% of long-term survivors
? 2-12 months after HSCT
? almost any organ in the body

? Treatment- Immunosuppression


Graft-versus-leukaemia (GvL)- is essential to

prevent relapse when treating malignant
disease.

Graft failure -failure to establish hematologic

engraftment

Graft failure is associated with increased risk of

infection and peritransplant mortality.

Cost of BMT

Variable due to several factors:

Complications: hospital days, blood products
Stem cel source: PBSC<Marrow (faster

engraftment)

Preparative regimen: TBI expensive
Unrelated>>Al ogeneic>Autologous


Outcome

Nonmalignant disease- more favorable

70-90% if the donor is a matched sibling
36-65% if the donor is unrelated.

Transplants for acute leukemias (eg- ALL,

AML) in remission

55-68% if the donor is related
26-50% if the donor is unrelated.

Donor registries- datri




Developing Applications II

Damaged Heart muscle

Injection of stem cel s into area of dead heart

muscle regenerates viable muscle

Promotes formation of new blood vessels in

injured heart muscle




Gene therapy

Deficiency in a patient's own hematopoietic

stem cel is rectified by gene correction or
addition and is reinfused

similar to autologous HSCT

HIV infection
Beta-thalassemia
Sickle cel disease

iPS- induced pluripotent stem cells

Dedifferentiation of cells into induced pluripotent stem cells

Correction of gene mutation in vitro

Subsequently stimulation to differentiate into hematopoietic stem cells

Transplantation


Conclusions

Stem cel s can be derived from adult, cord blood

and embryonic stem cel s

Bone marrow transplantation (BMT) is rapidly

expanding as a therapeutic modality with the

advancements in techniques, indications, and

supportive therapy

This post was last modified on 08 April 2022