Bone Marrow Transplantation The transfer of living cells, tissues, or organs from a donor to a recipient, with the intention of maintaining the functional integrity of the transplanted material in the recipient

Indications Acute and chronic leukemias Aplastic anemia Congenital immunodeficiency diseases Lymphomas Metabolic disease of childhood Myelodisplasia Thalassemia

Donor Limitations 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)

Recipient preparation Cyclophosphamide 60 mg/kg/day During two days and Toal body irradiation Busulfan 4mg/kg/day for fur days and Cyclophosphamide without irradiation Etoposide,Cyarabine as a maximizer antitumor properties,myeloblation,immunosuppression

Transplantation Procedure

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.

Nota Bene Nitrouse Oxide should be avoided as an inactivator of Vit B12 wich is an essential coenzyme for methionine synthetase.This enzyme facilitate the conversion of homocystine and methyltetehydrofolate to methionine are essential for deoxyribonucleic acid (DNA) synthesis.

Complications Rejection by hte host of the marow graft Acute graft-vs,-host disease (GVHD) Infections Chronic GVHD Prolonged immunodeficiency Disease recurrence

Bone Marrow Transplantation HLA antigens matched optimally – Autologous (marrow cancer free); Allogeneic – Peripheral Blood Stem Cell Transplantation Hi-dose CTX +/- total body irradiation – ablate diseased marrow / cells (  risk rejection) – Infused healthy cells repopulate marrow – Immune function returns within 1 – 2 years if successful

Bone Marrow Transplantation - Toxicity GVHD – Graft Versus Host Disease ~50% risk in allogeneic Transplant – Donor T-cells attack normal host cells Acute GVHD rash  slough; mucositis; bronchiolitis – Intestinal: cramping, diarrhea, anorexia, ileus – Rare: Guillain-Barre Syndrome; Polymyositis Chronic GVHD: 3 Months – 3 Years inflammation / fibrosis: skin; lung; GI – contractures; neuropathy; respiratory insuff

Bone Marrow Transplantation - Toxicity Chemotherapy –pancytopenia (during induction) –Peripheral Polyneuropathy: Cisplatin; MTX; 5FU; Vincristine; Paclitaxel; Docetaxel; Interferon –Cardiomyopathy (arrhythmia / pump failure): Doxorubicin; paclitaxel; cyclophos; (Herceptin) –Renal: electrolyte abnormality  MSΔ Immunosuppressants (cyclo, MTX, FK506) –Renal Failure

Bone Marrow Transplantation - Toxicity hi-dose Steroids ( Anti-inflammatory; Immunosuppression ) –Myopathy; Osteoporotic compression Fx; AVN Nutritional Insufficiency / Muscle Wasting – skin ulcers; mucositis; immobility-related weakness; loss of functional reserve Graft Failure / Rejection – extremely poor prognosis

Bone Marrow Transplantation Rehabilitation Induction/Acute Post-Transplant: Prophylaxis Nutritional Counseling and Supplementation Skin: specialized pressure relief – bed and Pancytopenia – Hold Therapy if: Hgb< ~8g (Arrhythmia; Exertional Intolerance;  SaO2) Plt (<50K - No PRE; <20K - bedside; <10K – no Tx) ANC < 1500 – High Risk Infection: reverse isolation until day 100 (mask/gloves) – Public / Hospital – Remain Mobile / Maintain ADLs ROM / limb & resp muscle PRE / Endurance Exercise

Bone Marrow Transplantation Rehabilitation Post-Acute Transplant – Home Exercise Program; Community Re-entry – Energy Conservation: Day 100 – 80% pts fatigued – “Incremental Treadmill walking after hi-dose CTX and PBSCT   maximal physical performance and  HR / report of fatigue & somatic complaints” GVHD – As above; splinting / casting (protect joints & skin) – Aggressive daily stretching (pec, IP, Ham, gastroc)