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