Bone Marrow Transplantation
Definition Bone marrow transplantation was the original term used to “describe the collection & transplant.
of haematopoietic stem cells (HSCs),” but w. the demonstration that peripheral blood and
umbilical cord blood are also useful sources of stem cells – HSC transplantation has become the
preferred generic term.
Properties
of HSCs
• High regenerative capacity
• Ability to home to the marrow space after IV injection
• Feasible for cryopreservation
Types of HSC
transplant
• Autologous
• Allogenic (twin x genetically-different individual)
o Pz. need to be HLA matched to reduce the risk of adverse events (esp. graft-versushost
disease aka GVHD.)
Indications • Immunodeficiency disorders
• Aplastic anaemia
• Haemoglobinopathies
• Acute leukaemia
• Chronic leukaemia
• Myelodysplasia
• Lymphoma
• Myeloma
• Some solid tumours
Sources of HSC
(About 1.5 to
5.0 x 108
cells
are req. per
transplant.)
• Posterior/Anterior Iliac Crests
• Peripheral blood (req. administration of haematopoietic growth factors before collection.
Haematopoietic growth factors incl. G-CSF, GM-CSF, etc.)
o Donor are typically treated w. 4 or 5 days of haematopoietic growth factors,
following which stem cells are collected in one or two pheresis sessions.
• Umbilical cord blood
Transplant
preparative
regimen for
recipients
• The Tx. regimen administered to Pz. immediately preceding transplantation is designed to
eradicate the patient’s underlying disease and, in the setting of allogenic transplantation,
immunosuppress the Pz. adequately to prevent rejection.
o Aplastic anaemia
▪ Use high-dose cyclophosphamide + antithymocyte globulin
o Thalassemia & Sickle-cell anaemia
▪ High-dose busulfan ± cyclophosphamide
o Malignant diseases
▪ Regimens typically incl. busulfan, cyclophosphamide, melphalan, carmustine,
etoposide and total body irradiation (TBI) in various combinations.
Transplant
procedure
• About 10 – 15 ml/kg of marrow is aspirated from the donors and placed in heparinized media
or, alternatively, HSC may be collected from peripheral blood by lekapheresis.
• The collected marrow undergoes further processing (removal of bone spicules, RBCs,
removal of donor T-cells, etc.)
• Stem cells for transplantation are usually infused through a large-bore central venous
catheter.
Complications • Early direct chemoradiotoxicities
o The preparative regimen may cause a spectrum of acute toxicities, but frequently
results in nausea, vomiting and mild skin erythema.
o There may be oral mucositis, hepatotoxicity (may lead to ascites, jaundice, etc. May
culminate in hepatorenal syndrome.)
o Regimens that incl. high-dose cyclophosphamide can cause haemorrhagic cystitis.
Prevent w. bladder irrigation or MESNA (antidote.)
• Late direct chemoradiotoxicities
o Late complications of the preparative regimen incl. decreased growth velocity in
children and delayed dev. of secondary sex characteristics.
o Most men become azoospermic and most post-pubertal women will dev. ovarian
failure.
o Thyroid dysfunction & cataracts are common in Pz. treated w. TBI.
o Aseptic necrosis of the femoral head is common in Pz. receiving GC therapy.
• GVHD
o Is the result of allogenic T-cells that are transferred w. the donor’s stem cell
inoculum reacting w. antigenic targets on host cells.
• Graft Failure
o While complete and sustained engraftment (functioning HSCs indicative of a
successful transplant) is usually seen post-transplant, occasionally marrow function
either does not return or, after a brief period of engraftment, is lost.