Bone marrow and stem cell transplant

• Bone marrow


  Flexible tissue found in the hollow interior of bones
• Bone marrow


  • One of the largest organs in the body
  • Estimated to be 1600-3700g in the adult
  • Has a volume of about 20-50ml/kg body weight
  • Produces approximately 6 billion cells/kg of body weight per day
• Types of bone marrow

  • Red
  • Yellow
  • White
• Daily blood cell formation is 4 x 10¹¹ cells: 2 x 10¹¹ RBCs, 1 x 10¹¹ WBCs and 1 x 10¹¹ Platelets
• Embryology of bone marrow

  • Derived from mesenchyme
  • Starts haemopoiesis around the 5th month of intra-uterine life, fully functional by the 6th month
  • At birth all marrow is active (red marrow)
  • In adult, gradual fatty replacement confines red marrow to the bones of the central skeleton and proximal ends of long bones
• Anatomy of bone marrow

  • Bone is made up of compact[cortical] and cancellous[medullary] bone
  • The medullary area is where the bone marrow is located
  • The blood supply comes from two major sources: Nutrient and Periosteal artery
  • The nutrient artery penetrates the cortex through the nutrient canal and bifurcates into ascending and descending medullary arteries
  • Radial branches penetrate the endosteum and diminish in calibre to capillary size
  • They form sinusoidal network within the marrow cavity
• Bone marrow stroma


  • Consists of adipocytes, fibroblasts, endothelial cells, macrophages, osteoblast, osteoclast, extracellular matrix
  • Provides a supporting framework for the haemopoietic stem cell
• Haematopoietic microenvironment


  • Haematopoiesis takes place in the extravascular spaces between marrow sinuses
  • The marrow sinuses are lined by endothelial cells that cover the inner surface of the sinus
  • This trilaminer sinus is composed of endothelial cells, thin basement membrane and adventitial reticular cells
  • The endothelium and reticular cells are sources of haematopoietic cytokines
• Cellular organization of bone marrow

  • Haematopoietic cells lie in cords or wedge between vascular sinuses
  • Erythroblastic cells are arranged in clusters called erythroblastic islands
  • Megakaryocytes lie closely to the vascular wall
  • Granulocytes mature deeper in the haematopoietic cords away from the vascular sinuses
  • Stem cells and the granulocytic progenitor cells are concentrated in the subcortical region of the haematopoietic cords
  • Lymphocyte and macrophages concentrate around arterial vessels; near the center of the haematopoietic cords
• Proportion of major haematopoietic cells in bone marrow

  • Myeloblasts: 0-4%
  • Promylocytes: 0.5-5%
  • Myelocytes: 10-30%
  • Metamyelocytes: 10-30%
  • Mature granulocytes: 5-25%
  • Lymphiod cells: 5-20%
  • Plasma cells: 0-3%
  • Erythroid precursors: 5-30%
  • Megakaryocytes: 0-2%
• Functions of bone marrow

  • Haematopoietic function
  • Immunological function
  • Metabolic function
  • Lymphatic function
• Haematopoietic function


  • Bone marrow is a unique microenvironment that supports proliferation and differentiation of blood cells
  • It gives rise to red blood cells, white blood cells and platelets maintaining their normal peripheral pool
• Immunological function


  • Bone marrow is the ultimate source of all cells of the innate and adaptive immune system
  • It responds to infection or inflammation by increasing its output of granulocytes, T-cells, B-cells and NK cells
• Metabolic function


  • Osteoblast and Osteoclast originate in the bone marrow
  • They are concerned primarily with bone formation and resorption
  • Through specific growth factors, they contribute to body calcium levels
• Lymphatic function


  • Bone marrow helps prevent backflow of lymph in the body
• Organization of the bone marrow microenvironment is such that there is a complex interaction between stem cells, stromal cells and regulatory proteins
• The interaction gives rise to enormous number of cells having immunological, haematopoietic and metabolic role
• Stem Cell Transplantation (SCT)

  Also referred to as Haematopoietic Stem Cell Transplantation (HSCT), involves the intravenous infusion of hematopoietic stem cells to reestablish blood cell production in patients whose bone marrow or immune system is damaged or defective
• Over the past half century, this technique has been used with increasing frequency to treat numerous malignant and nonmalignant diseases
• Stem cell transplantation process

  1. Harvest haemopoietic stem cells from donor

  2. Infuse into matched recipient after eliminating unhealthy cells and stem cells of recipient

  3. Healthy stem cells repopulate marrow and peripheral blood of recipient
• Bone marrow transplant


  When the source of the stem cells are from bone marrow and transplanted into a patient
• Peripheral blood stem cell transplant


  When the transplanted stem cells came from the peripheral bloodstream
• Sources of stem cells for HSCT

  • Patient (autologous transplant)
  • Another person, such as a sibling or unrelated donor (allogeneic transplant)
  • Identical twin (syngeneic transplant)
  • Bone marrow
  • Peripheral blood
  • Umbilical cord blood
  • Fetal liver
• Haematopoietic stem cell transplantation

  • Dangerous procedure with many possible complications
  • Initially reserved for patients with life-threatening diseases
  • As survival increased, use expanded beyond cancer to haemoglobinopathies, autoimmune diseases, and hereditary skeletal dysplasias
• Diseases that can be treated with HSCT

  • More than 70
• More than half of autologous transplantations are performed for multiple myeloma and non-Hodgkin lymphoma, and a vast majority of allogeneic transplants are performed for hematologic and lymphoid cancers
• Worldwide, approximately 90,000 first HSCTs—53% autologous and 47% allogeneic—are performed every year, according to the World Wide Network of Blood and Marrow Transplantation
• The number of HSCTs continues to increase by 10-20% annually, and reductions in organ damage, infection, and severe, acute graft versus host disease (GVHD) seem to be contributing to improved outcomes
• Phases of stem cell transplant

  1. Conditioning (7-14 days)

  2. Stem cell infusion

  3. Neutropenic phase (2-4 weeks)

  4. Engraftment phase (several weeks)

  5. Postengraftment period (months to years)
• Report describing a patient who received 18ml of bone marrow intravenously from his brother as treatment of aplastic anemia

  1939
• Georges Mathé


  French oncologist who performed the first European bone marrow transplant in November 1958
• Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s
• Robert A. Good


  First physician to perform a successful human bone marrow transplant on a disease other than cancer, at the University of Minnesota in 1968
• Malignant indications for HSCT

  • Acute myeloid leukemia (AML)
  • Chronic myeloid leukemia (CML)
  • Acute lymphoblastic leukemia (ALL)
  • Hodgkin lymphoma (HL) (relapsed, refractory)
  • Non-Hodgkin lymphoma (NHL) (relapsed, refractory)
  • Neuroblastoma
  • Ewing sarcoma
  • Multiple myeloma
  • Myelodysplastic syndromes
  • Gliomas, other solid tumors
• Non-malignant indications for HSCT

  • Thalassemia
  • Sickle cell anemia
  • Aplastic anemia
  • Fanconi anemia
  • Malignant infantile osteopetrosis
  • Mucopolysaccharidosis
  • Immune deficiency syndromes
  • Autoimmune diseases
• Haematological indications for non-malignant HSCT

  • Disorders of HSC number - aplastic anaemia, fanconi anaemia
  • Red cell disorders - thalassaemia, sickle cell anaemia, Diamond Blackfan Anaemia
  • White cell disorders - congenital neutropenia, Shwachmann Diamond
  • Lymphocyte disorders - immunodeficiency (SCID), Haemophagocytic syndromes
  • Platelet disorders - Glanzmann's
• Non-haematological indications for non-malignant HSCT

  • Enzyme deficiency
  • Mucopolysaccharide disorders (MPS)
  • Adrenoleucodystrophy
  • Disorders of Osteoclast function
  • Osteopetrosis
  • Osteogenesis imperfecta
  • Autoimmune disorders - Systemic sclerosis
• Autologous SCT


  Stem cells are extracted (apheresis) from the patient and stored, then the patient is treated with high-dose chemotherapy and/or radiotherapy to eradicate malignant cells, followed by infusion of the patient's own stored stem cells
• Autologous SCT


  • Lower risk of infection during immune-compromised portion
  • Very rare incidence of rejection and graft-versus-host disease
• Allogeneic HSCT


  Involves a donor and a recipient, the donor must have a tissue (HLA) type that matches the recipient