Stem cell transplantation Flashcards
What is stem cell transplantation
Eliminating an individuals heam and immune system by chemo or radiotherapy and replacing it with stem cells from another individual or with previously harvested stem cells
Non malignant haem dx
Aplastic anemia fanconi anemia Thallasemia SSD Congenital pure red cell aplasia Paraxosymal haemoglobinuria Severe combined immunodeficiency Wiskott aldrich syndrome Glanzmanns thrombastenia hereditary storage disorders osteoporosis Conenital leukocyte dysfunction syndromes
requirements of transplant donors
Good health
Have good performance status that will permit safe collection of cells from marrow or blood
Normal cardiac, pulmonary, hepatic, renal fxns
Sources of hematopoietic stem cells
Marrow,
Peripheral blood
Umbilical cord blood
Stem cell dose for stable long term engraftment
2*10^8 nuclear cells per kg of recipient body weight
Phenotype of stem cells should be
CD34+ AND CD38+
What is mobilisation
A process in which certain drugs are used to cause movement of stem cells from bone marrow into blood because hematopoietic stem cells circulate in the peripheral blood at extremely low levels
Drugs used in mobilisation
G-CSF
GM-CSF
IL3
Thrombopoietin
After mobilisation is
APheresis
where a technology seperates blood passed through where it takes out one particular component i.e stem cells and returns the rest to circulation
What can be used in combo with CSF
c-kit
What is conditioning
A process to eradicate underlying dx and to provide sufficient immunosuppression to allow for the administration of the graft without host rejection
Types of conditioning
Radiation based
non radiation based
Radiation based conditioning
use of radiation
Fractionated TBI+ CYCLOPHOSPHAMIDE
Fractionated TBI= ETOPOSIDE
Best result is Fractionated TBI+ CYCLOPHOSPHAMIDE=ETOPOSIDE
Non radiation based regimens
Oral busulphan 4 days, 16mg/kg cyclophosphamide 2days, 120mg/kg Etoposide+Busulphan SCarmusitine+Etoposide+Ara C +Melphanan Cisplatin+ Carboplatin;
Non radiation regimen with best result
Etoposide+ Busulphan
This non radiation regimen is used in lymphomas
Carmusitine+ Etoposide+ Ara C +Melphanan
Types of transplantation
Autologous
Allogenic
Syngernic
Allogeneic bone marrow transplant
Grafting of marrow from a donor into recipient of same sp
Examples of allogenic donors
HLA compatible siblings
Partially matched family members
Closely matched volunteer donors
What to do and expect immediately after post grafting
After high dose chemotheraoy- neausea and vomiting
Intravenous hyperalimentation must be administered to maintain caloric balance
How long does it take transplanted marrow to regenerate
3-4 wks
Precautions for patient after transplantation
Protected from infection by isolation or broad spectrum antibiotics till they have a have a platelet count of 0.5*10^9 or more granulocytes
Mean time for granulocyte count to return to 0.5*10^9/l
20 days
with platelet and RBC lagging a few steps behind
Post transplant supportive care
blood transfusion
red cells and platelets following aplasia after marrow grafting
Patients can develop these post transplant
oral mucositis
gastroenteritis
What happens secondary to chemotherapy and total body irradiation
decrease in caloric intake
decrease in intestinal absorption
How to manage the patient post chemo
parenteral nutrition
GM-csf
Complication of allogenic bone transplant
Patients are immunocompromised with breakdown of skin and mucosal barriers
Decreased immunoglobulin production
Bacterial, fungal, HSV can easily cause infection
Other complications of Allogeneic transplant
Neurological disorder
cataracts
endocrine disorders
recurrent dx and other malignancies
Treatment of Complications of allogeneic transplantation
Antibiotics for GI decontamination
Keep rooms with high efficiency particulate air filters
Give low dose amphotericin B to prevent fungal infection
Give broad spectrum antibiotics
What is acute graft vs host dx
Occurs 90 days after marrow transplant affecting skin, GIT, liver
How is skin affected in GVHD
Maculopapular rash
generalised erythrodema
bullae formation
Desquamation
How gut is affected in GVHD
Anorexia Nausea vomiting diarrhea abdominal crampa
pathophysiology GVHD
Donor T cells are activated by recognition of antigens on host tissues
The activated T cells proliferate and differentiate
They proliferate and produce cytokines that promote inflammatory response leading to tissue damage and necrosis
What is chronic GVHD
A major complication of allogenic BMT occurring in 30-40% of patients that suffer more than 100 days
Signs of chronic GVHD
Debilitating dx oral mucosistis dry eyes chronic liver dx weight loss neurologic disorders increasing succeptibility to bacteria severe obstruction liver dx
Treatment of chronic GVHD
Antithymocyte globulin Glucocorticoids Irradiation Cyclophosphamide Cyclosporine Azathioprine Thalidomide Prednisolone Prednisolone and azathioprine
Autologous marrow transplant
The patients own hematopoietic stem cells are used
No HLA matching, no GVHD, no immunosuppression
Four principal phases of autologous bone marrow transplantation
Stem cell collection, purge, storage
Autologous bone marrow transplant
Discharge
Recovery
Supportive care- autologous
blood components antibiotics parenteral nutrition protective isolation growth factors
How is autologous grafting done
AT time of grafting, the marrow or peripheral blood is rapidly thawed at patients bedside and infused via IV without further processing
Complications- Autologous process
nausea abdominal cramps coughing flushing hypertension
To prevent renal toxicity from cell lysis in BM
Adequate hydration
brisk diuresis
