Stem cell transplantation

stem cell transplantation

1. STEM CELL TRANSPLANTATION

2. STEM CELLS All blood cells are derived from pluripotent haematopoietic stem cells. These comprise only 0.01% of the total marrow cells, but they can self-renew (i.e. make more stem cells) or differentiate to produce a hierarchy of lineage-committed progenitor cells. The resulting primitive progenitor cells cannot be identified morphologically, so they are named according to the types of cell (or colony) they form during cell culture experiments.

3. Bone marrow transplantation, was the original term used to describe the collection and transplantation of hematopoietic stem cells.  Hematopoietic stem cell transplantation , is preferred term, because the peripheral blood and umbilical cord  blood are also used as source of stem cells. Transplantation of haematopoietic stem cells (HSCT) has offered the only hope of ‘cure ’ in a variety of haematological and non- haematological disorders.

4. Definition.: Hematopoietic stem cell transplantation is defined as the process of collecting and infusing hematopoietic stem cells obtained from bone marrow (bone marrow transplantation) and peripheral blood (peripheral stem cell transplantation). 

5. Stem cell transplantation is a procedure that can restore marrow function for patients who have had severe marrow injury or abnormalities of the immune system. Marrow injury can occur because of primary marrow failure, destruction or replacement of marrow by disease, or intensive chemical or radiation exposure.

6. TYPE OF HSCT Allogeneic (from different genes) HSCT, the stem cells come from a donor – either a related donor (usually an HLA-identical sibling) or a closely HLA-matched volunteer unrelated donor (VUD). Autologous (from self) transplant, the stem cells are harvested from the patient and stored in the vapour phase of liquid nitrogen until required. Stem cells can be harvested from the bone marrow or from the blood. Syngeneic ( from same genes)-HSC are obtained from an identical twin.

7. Types of Stem Cell Transplants Autologous Allogeneic stem cells obtained from the patient Stem cells from a donor • Stem cells frozen in lab before conditioning chemotherapy • Donor must ‘match’ (what do we mean by a match • Rejection is never a problem • Rejection can occur in both directions • Fast recovery • Takes longer for immune system to recover • For Myeloma and Lymphoma • For other blood cancers like AML, ALL, MDS, etc

8. Indications for allogeneic Haematopoietic stem cell transplantation Red blood disorders Severe aplastic anaemia Thalassemia major Fanconi anemia Sickle cell disease Pure red cell aplasia WBC disorders Leukemia –ALL.,CML.,AML. Myelodysplastic syndrome , myelofibrosis Lymphomas: Hodgkin & non-Hodgkin Multiple myeloma

9. Immunological disorders Severe autoimmune disorders:- scleroderma ,lupus erythematosus Immune deficiency syndromes Solid tumors Germ cell tumors Neuroblastoma

10. Purpose of HSC transplantation : To repopulate or replace totally or partly recipient's hematopoietic system. HSC are self renewing cells which can repopulate all the cell lineages in the blood. 

11. Major sources of hematopoietic stem cells: ‌Bone marrow- obtained directly from bone marrow by multiple aspirations from the pelvic bones.  ‌Peripheral blood (peripheral blood stem cells).  ‌Umbilical cord blood. 

12. Origin of hematopoietic stem cell used for transplantation.  Origin of hematopoietic stem cell -Autologous -Syngeneic  -Allogeneic - Genotypically HLA-identical siblings -Phenotypically HLA-identical or HLA-mismatched family members -Unrelated volunteer donors

13. Bone marrow: marrow is the original source of stem cell. They are removed  by bone marrow puncture.  Peripheral blood : this has become a preferred alternative to marrow to obtain stem cells. Stem cells have to mobilized into peripheral blood by injecting granulocyte-macrophage colony -stimulating factor (GM-CSF)  . Placental blood : T lymphocytes in placental blood appear to be less alloreactive than T cells from adults and hence less likely to produce GVHD. Placental blood is obtained from the umbilical cord after birth.

14. Characteristic Bone marrow Peripheral blood Cord blood Stem cell content Adequate Good Low Risk of tumor cell contamination High N/A N/A HLA matching Close matching Close matching Less restrictive Engraftment Medium Fastest Slowest Risk of aute graft-versus-host disease High High Lowest Risk of chornic GVHD Medium Highest Lowest

15. Transplantation Stem cell transplantation is a procedure that can restore marrow function for  patients who have had severe marrow injury or abnormalities of the immune  system . Marrow injury can occur because of primary marrow failure, destruction or  replacement of marrow by disease, or intensive chemical or radiation exposure .

16. TRANSPLANT PROCESS Donor evaluation Stem cell collection Processing and cryopreservation Conditioning of patient Chemotherapy Stem cell transfusion Recovery

17. Transplant Eligibility Before receiving an SCT, patients must have a checkup to make sure that they are healthy enough for the procedure. In order to find out if a patient is a good candidate for SCT, the patient’s doctor will consider.

18. The patient’s general health Results of the physical checkup and medical tests The type and stage of cancer or disease Previous medical treatments The likelihood that the disease will respond to the transplant The ability to use the patient’s own stem cells, or the availability of a suitable donor Some patients may not be eligible for standard SCT due to advanced age or other major health problems such as heart, lung or kidney disease

19. Side Effects of Conditioning Treatment for Stem Cell Transplantation The conditioning treatment given prior to allogeneic or autologous transplantation can affect any body system that depends on replacement by stem cells or that may be directly affected by chemotherapy or radiation. Some of these effects manifest quickly; others may not appear for years

20. Side Effects Cataracts Loss of blood cell formation Congestive heart failure Mucositis Diarrhea Nausea and vomiting Growth retardation Occlusion (blockage) of veins in liver Hair loss Pneumonitis (pneumonia) Infertility Premature menopause

21. POST TRANSPLANTATION Post transplantation Autologous or allogeneic stem cell transplantation, or a portion of an either type, may be done in an outpatient or inpatient setting. The patients who are treated on an inpatient basis recover sufficiently to leave the hospital in three to five weeks post transplant. The recovery rate of blood cell counts and the severity of other associated complications, especially graft-versus-host disease (GVHD), vary from patient to patient.

22. A patient is ready for discharge when., The patient’s marrow is producing a sufficient number of healthy red cells, white cells and platelets There are no severe treatment complications The patient has a sense of well-being (as a result of restored blood cell counts) Mouth sores and diarrhea lessen or disappear Appetite improves; it is important that patients be able to eat and drink to get sufficient fluid and nourishment before they are discharged from the hospital The patient does not have fever and is not vomiting.

23. Complications of hematopoietic cell transplantation Vascular access complications: Graft failure Blood group incompatibilities&hemolytic complications: Acute GVHD Chronic GVHD Infectious complications Bacterial infections, Fungal infection, Cytomegalovirus infection, Herpes simplex virus, Varicella-zoster virus , Epstein barr virus, Adenovirus.

24. Gastrointestinal complications Mucosal ulceration/bleeding Nutritional support Hepatic complications Sinusoidal obstructive syndrome Hepatitis Cardiac toxicity Structural ( valvular abnormalities or CAD) Functional (cardiomyopathies) Lung injury Interstitial pneumonitis, Diffuse alveolar hemorrhage, Bronchiolitis. Renal –Nephrotoxicity. Bladder –Hemorrhagic cystitis. Endocrine – Drug-drug interactions , Thyroid dysfunction

25. Infections during recovery from haematopoietic stem cell transplantation (HSCT) Infection Time after HSCT Management Herpes simplex 0–4 weeks (aplastic phase) Acyclovir prophylaxis and therapy Bacterial, fungal 0–4 weeks (aplastic phase) As for acute leukaemia – antibiotic and antifungal prophylaxis and therapy Cytomegalovirus 5–21 weeks (cell-mediated immune deficiency) Antigen screening in blood (PCR) and pre-emptive therapy (e.g. ganciclovir) Varicella zoster After 13 weeks Acyclovir prophylaxis and therapy Pneumocystis jirovecii 8–26 weeks Co- trimoxazole Encapsulated bacteria 8 weeks to years (immunoglobulin deficiency, prolonged with GVHD Prophylaxis and revaccination

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