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Hematopoietic Cell Transplantation

Hematopoietic Cell Transplantation. Definition. Hematopoietic cell transplantation (HCT) is a potentially curative treatment for malignant and nonmalignant diseases, including leukemia, lymphoma, multiple myeloma, aplastic anemia, hemoglobinopathies, and congenital immune deficiencies.

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Hematopoietic Cell Transplantation

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  1. Hematopoietic Cell Transplantation l.yekehfallah.-phd student of nursing education-2012

  2. Definition • Hematopoietic cell transplantation (HCT)is a potentially curative treatment for malignant and nonmalignant diseases, including leukemia, lymphoma, multiple myeloma, aplastic anemia, hemoglobinopathies, and congenital immune deficiencies. • HCT may have a role in the treatment of certain solid tumors such as renal cell carcinoma, and breast cancer. High-dose chemoradiation is typically used to eradicate the underlying disease and is followed by intravenous infusion of the stem cell graft l.yekehfallah.-phd student of nursing education-2012

  3. History of Bone Marrow Transplantation • First successful human bone marrow transplantation procedure (1968). l.yekehfallah.-phd student of nursing education-2012

  4. Stem cells • Stem cells are ‘generic’cells that develop into particular types of cells. So they may become nerve cells, muscle cells, blood cells… in fact, any cell in the body! Stem cells divide over and over to produce new cells.

  5. Stem cells, bone marrow and blood cells One of the main places you find stem cells is in bone marrow. Stem cells in bone marrow produce new blood cells to replace those that have died. When the cells are mature they are released into the bloodstream. A ‘bone marrow’ donation is really a donation of stem cells. Bone marrow is found in the cavities inside the long and flat bones of the body. l.yekehfallah.-phd student of nursing education-2012

  6. Leukocytes White blood cells Defend body through: the inflammatory process phagocytosis removal of cell debris immune reactions 6 l.yekehfallah.-phd student of nursing education-2012

  7. White Blood Cell Types:Granulocytes and Agranulocytes Granulocytes–visible granules in the cytoplasm. Granules contain: Enzymes Other biochemicals that serve as signals and mediators of the inflammatory response 7 l.yekehfallah.-phd student of nursing education-2012

  8. Granulocyte cell types: Neutrophils– phagocytes Eosinophils– red granules, associated with allergic response and parasitic worms Basophils– deep blue granules - Release heparin, histamine and serotonin 8 l.yekehfallah.-phd student of nursing education-2012

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  12. Agranulocytes Granules too small to be visible Monocytes– become macrophages Lymphocytes– B cells and T cells = immune functions 12 l.yekehfallah.-phd student of nursing education-2012

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  15. WBC’s originate in red bone marrow from stem cells. Granulocytes mature in the marrow and have a lifespan of hours to days Agranulocytes finishmaturing in blood, or in other locations. Monocytes live about 2 - 3 months, lymphocytes for years. l.yekehfallah.-phd student of nursing education-2012

  16. Production of WBC’s increases in response to : Infection Presence of steroids Decreased reserve of leukocyte pool in bone marrow 16 l.yekehfallah.-phd student of nursing education-2012

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  20. Diseases Treated with Bone Marrow Transplantation • Acute leukemia (ALL, AML) • Chronic myelogenous leukemia • Aplastic Anemia • Myeloproliferative Disorders • Multiple Myeloma • Non-Hodgkin’s lymphoma • Hodgkin’s Disease • Chronic lymphocytic leukemia • Genetic Disorders (Thalassemia, others) • Solid tumors (neuroblastoma, germ cell tumors) • Congenital immunodeficiency diseases • Lymphomas • Metabolic disease of childhood l.yekehfallah.-phd student of nursing education-2012

  21. Transplants save lives Bone marrow transplants not only save the lives of leukaemia patients. They can also save the lives of those suffering from: • illnesses where the immune system does not function properly such as aplastic anaemia (where the bone marrow stops making enough blood cells) • all kinds of cancers(where healthy stem cells have been damaged during treatments to destroy cancer cells)

  22. GENERAL PRINCIPLES • Classification:HCT can be categorized according to the source of stem cells, the type of donor, and the intensity of the preparative regimen. Determining the type of HCT to be used in an individual patient is a complex decision based on patient's age, diagnosis, donor availability, and presence of comorbidities l.yekehfallah.-phd student of nursing education-2012

  23. Donor Types • Autologous - self to self .Using one's own stem cells. • Syngeneic - from genetically identical twin (no genetic disparity between donor and recipient). • Allogeneic: Donor with similar human leukocyte antigen (HLA) type. • (1) Sibling donor. The statistical likelihood that a sibling is fully HLA-matched with the patient is 25%. The likelihood of identifying an HLA-matched sibling increases with the number of available siblings. • (2) Unrelated donor. HLA-matched volunteer donor who was identified through a database search. • Matched sibling • Matched family member • Matched unrelated • Partially matched and haploidentical

  24. Stem cell (“bone marrow”) donation There are three ways to collect stem cells from a donor: • Bone marrowA donor has a small operation under general anesthetic. Marrow is harvested from the iliac crest under general anesthesia

  25. Stem cell (“bone marrow”) donation • Circulating bloodA donor’s circulating stem cells are boosted with a special drug. Then they are connected to a cell separator machine, which collects the stem cells and returns the rest of the blood to the donor. • Cord bloodSelected hospitals offer new mothers the chance to donate the blood that remains in the placenta and umbilical cord after their baby’s birth. Collected from the umbilical cord after delivery of a baby. Engraftment takes longer compared with other sources of stem cells. l.yekehfallah.-phd student of nursing education-2012

  26. Advantages / disadvantages for patients • Advantages: • Cord blood: • hasn’t been exposed to environment so less likely to contain viral infection; • requires less stringent matching; • once collected is banked and can be readily available at short notice. • Bone marrow and circulating blood: • tend to have a greater number of stem cells in the donation, so tend to be accepted into the patient’s body more quickly. l.yekehfallah.-phd student of nursing education-2012

  27. Advantages / disadvantages for patients • Disadvantages • Cord blood: • tends to have less stem cells in the donation. • Bone marrow and circulating blood: • finding a match and arranging a donation can take weeks, or months (this is time the patient may not have). l.yekehfallah.-phd student of nursing education-2012

  28. Bone Marrow “Mobilized” peripheral blood stem cells Umbilical cord blood Cryopreserved Fresh SOURCE OF STEM CELLS l.yekehfallah.-phd student of nursing education-2012

  29. Potential Donors • Self • HLA-matched sibling • HLA-mismatched sibling • Matched unrelated • Cord blood l.yekehfallah.-phd student of nursing education-2012

  30. DonorLimitations • 25 – 30% of patients have an HLA-identical sibling. • Marrow procured from unrelated living donor • Marrow procured from related HLA-identical or HLA non –identical living donor • Autologous transolantation(marroe procured during remession) l.yekehfallah.-phd student of nursing education-2012

  31. Stages of Allogeneic Transplantation Preparation Transplantation Recovery Immune suppression Disease treatment IV Infusion GVHD Prevention Infection control Nutrition Hematopoietic recovery l.yekehfallah.-phd student of nursing education-2012

  32. RISKS OF BONE MARROW TRANSPLANT • Short term (TRM) • Sepsis,AGVHD, multi-organ failure or toxic death • Longer term • Chronic graft-versus-host disease (lung,liver, skin) • Relapse • Infection • Endocrine l.yekehfallah.-phd student of nursing education-2012

  33. Factors influencing survival • Disease factors • Remission, relapse, refractory • Transplant related mortality • Donor factors • Age, sex, conditioning • Recipient factors • Age, CMV status, performance status • Risk of graft-versus-host disease • Donor factors • PBSC, matching, age, parity • Recipient factors • Age l.yekehfallah.-phd student of nursing education-2012

  34. GENERAL PRINCIPLES • Epidemiology. Current estimates of annual numbers of HCT are 45,000 to 50,000 worldwide. Approximately two thirds of patients have autologous HCT and one third have allogeneic HCT l.yekehfallah.-phd student of nursing education-2012

  35. Risk factors • The likelihood of developing transplant-related complications depends on: 1/patient age 2/intensity of the preparative regimen 3/type and stage of the underlying disease 4/presence of comorbidities.

  36. Risk factors • The likelihood of developing transplant-related complications depends on: 5/allogeneic HCT recipients have a greater risk of transplant-related morbidity and mortality than autologous HCT recipients 6/HLA disparity between donor and recipient further increases the risk owing to the greater likelihood of developing GVHD and graft rejection

  37. Prognosis Prognosis after HCT is highly variable and is influenced by numerous factors that predict for mortality related to the transplant procedure itself and to recurrent malignancy after surviving the transplant: - Patients with chronic myelogenous leukemia (CML) in chronic phase who have HCT from an HLA-identical sibling, for example, have a greater than 80% to 90% chance of long-term survival -In contrast, less than 50% of patients with more advanced leukemia at the time of HCT will be cured l.yekehfallah.-phd student of nursing education-2012

  38. TransplantationProcedure l.yekehfallah.-phd student of nursing education-2012

  39. Anesthesic Management • Intravenouse anesthesia sould be procured. • Intravenouse, Thiopental, Fentanyl ,Vecuronium can be used in common doses • Maintanance can be provide with Propofol and Isoflurane. l.yekehfallah.-phd student of nursing education-2012

  40. Step 1: Bone marrow transplant with less toxic recipient treatment that includes antibodies.Donor marrow is T cell depleted Blood cells are a mixture of donor and host: Mixed chimerism is achieved without GVHR Wait 1-2 months. Inflammation from preparative treatment subsides. Step 2: Infuse donor T cells. Donor T cells interact with “presenting cells” of mixed chimera to maximize GVHR Donor T cells are armed to kill tumor cells that express recipient antigens. They stay inside the blood and lymph, where tumor is. T cells don’t go to skin/gut/liver. There is no GVHD. Tumor is killed

  41. TRANSPLANT RELATED COMPLICATIONS l.yekehfallah.-phd student of nursing education-2012

  42. The problems after HCT that typically cause procedure-related morbidity and mortality can broadly be categorized into five groups: hemolysis, toxicity of the preparative regimen, infection, bleeding, and GVHD l.yekehfallah.-phd student of nursing education-2012

  43. Hemolysis • General principles. The inheritance of blood group antigens (e.g., ABO, Rh, Jk) is independent of that of the HLA antigens. ABO incompatibility between donor and recipient, however, is not a barrier to successful allogeneic HCT. Acute or delayed immunohemolytic complications due to ABO incompatibility should be distinguished from anaphylactic reactions precipitated by infusion of foreign proteins l.yekehfallah.-phd student of nursing education-2012

  44. Hemolysis • Etiology/pathophysiology: 1/ Acute (at the time of infusion) or delayed (5 to 15 days after HCT) immunohemolyticcomplications due to ABO incompatibility occur in patients with minor ABO-incompatibility (donor-derived isohemagglutinins directed against recipient red blood cells [RBCs]). 2/ Immediate hemolysisoccurs if the graft contains preexisting isohemagglutinins that lyse recipient RBCs. l.yekehfallah.-phd student of nursing education-2012

  45. Hemolysis • Etiology/pathophysiology: 3/ Delayed hemolysisis due to generation of new isohemagglutinins by passenger lymphocytes in the graft. 4/Delayed hemolysisdue to minor ABO incompatibility is a rare complication but can be dramatic and life-threatening. 5/ Major ABO incompatibility(recipient-derived isohemagglutinins directed against donor RBCs) may lead to chronic hemolysis and pure red cell anemia (PRCA). l.yekehfallah.-phd student of nursing education-2012

  46. Hemolysis • Diagnosis 1/Clinical presentation: a/ Mild hemolysis due to major ABO incompatibility may be associated with prolonged RBC transfusion requirements b/Delayed hemolysis due to minor ABO incompatibility may cause rapid lysis of all recipient RBCs over a few days. This may lead to acute renal failure or pulmonary edema and may be fatal. Plasma exchange in the recipient and plasma removal or RBC removal from the graft are standard procedures that minimize the risk of preventable hemolytic complication after ABO-mismatched HCT.

  47. Hemolysis • Diagnosis 2/Laboratory and radiologic studies: a/Emergence of donor-derived RBC and isohemagglutinin titers should be monitored after allogeneic HCT b/Serum levels of (indirect) bilirubin and lactate dehydrogenase (LDH), reticulocyte counts, and the direct agglutinin test (DAT) are useful markers of hemolysis l.yekehfallah.-phd student of nursing education-2012

  48. Hemolysis Treatment: 1/ Chronic hemolysis due to major ABO incompatibility is usually self-limited. 2/ Patients with refractory or more acute immune hemolysis may require interventions aimed at suppressing ongoing donor-directed isohemagglutinin production (corticosteroids, donor lymphocyte infusion, rituximab) or removal of the offending antibody (plasma exchange). 3/Supportive care measures to maintain renal function are critical l.yekehfallah.-phd student of nursing education-2012

  49. Toxicity of the preparative regimen • Cytotoxic chemotherapy with or without total body irradiation (TBI) may compromise the function of the lungs, heart, kidneys, nervous system, and gastrointestinal tract including the liver. This type of toxicity occurs predominantly within the first 3 to 4 weeks after HCT. l.yekehfallah.-phd student of nursing education-2012

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