Bone Marrow Transplantation

The term bone marrow transplantation, although still commonly used, is actually a misnomer. The term refers to a process in which a patient is treated with such intensity of chemotherapy and total body irradiation that the ability of the bone marrow to create blood cells is destroyed. This treatment is referred to as conditioning (Mori et al. 2008). The patient is then "rescued" with an infusion of hematopoietic (blood-making) cells. The infusion is done using an intravenous drip; no surgery or "transplantation" is done. The infused cells may be the patient's own bone marrow cells (autologous transplant), cells removed from a related or unrelated donor's bone marrow (allogeneic transplant), peripheral blood stem cells, or stem cells from umbilical cord blood (Bunin et al. 2008). Each method has advantages and disadvantages (Ka-ranes et al. 2008; MacMillan et al. 2008).

The principal advantage of using the patient's cells is that they will be histocompatible with (biologically match) those of the body. This method avoids having the immunologically active white cells made by the transplanted hematopoietic cells attempt to reject the rest of the patient's body. This phenomenon, called graft-versus-host disease, is functionally like an autoimmune disease, in which the immune system attacks the other organs. The closer the match between the human leukocyte antigens (HLAs) of the transplanted blood cells and the recipient's cells, the less likely is graft-versus-host disease (Krance 2008). Recent studies have found that cryopreserved (frozen) umbilical cord blood from matched unrelated donors contains sufficient numbers of hematopoietic stem cells for pediatric patients, and even for some adults (Barker 2007). Because cord blood does not require as close a match or the harvesting of marrow from a living donor, the use of umbilical cord blood is becoming increasingly common (Sauter and Barker 2008). However, use of related family donors does appear to offer some benefits in terms of reduction of graft-versus-host disease (Fagioli et al. 2008).

Bone marrow transplantation is used for hemato-logical malignancies that originate in the hemato-poietic cells, such as leukemia and lymphoma, in which eradication of the disease requires ablation of the bone marrow (Woods 2006). However, bone marrow transplantation may also be used as a rescue when the intensity of chemotherapy or radiation required to eliminate aggressive or metastatic disease destroys the bone marrow. This procedure is sometimes referred to as "salvage" (Woods 2006). Non-malignant diseases of the bone marrow may also require ablation of the marrow, as well as rescue.

During the time between the destruction of the native bone marrow and the engraftment of the transplanted hematopoietic cells, the patient is unable to produce red cells, white cells, or platelets. The resulting immunosuppression requires protective isolation from environmental microbes, because normally benign bacteria, viruses, and fungi could prove fatal, even with use of antimicrobial agents. Food, toys, books, and clothes must be kept as sterile as possible, and rooms are usually ventilated so as to reduce introduction of microbes from the air outside the room. Visitors are limited, sick visitors are prohibited, and everybody must carefully wash their hands before entering the child's hospital room. Use of medications, such as granulocyte colony-stimulating factor, that enhance production of white cells has substantially decreased the amount of time patients are severely immuno-suppressed (Mori et al. 2008; Smith et al. 2006). Precautions such as gowns, masks, and gloves are now rarely used, and low microbial diets and laminar airflow or high-efficiency particulate air-filtered rooms are used selectively (Dadd et al. 2003). Although these changes have greatly reduced the medical and psychological risks of prolonged immuno-suppression and isolation, this is still a frightening and lonely time for both child and family (Phipps et al. 2005; Rini et al. 2004).

Children undergoing bone marrow transplantation are exposed to high levels of chemotherapy and radiation and are thus at high risk for many of the physical sequelae, including neurocognitive impact (Wilkins et al. 2007). Typical problems encountered by over 25% of survivors in the first 10 years after transplant include infections, cataracts, bone and joint complications, hypothyroidism, learning disabilities, and psychological problems (Ferry et al.

2007). Although cognitive status may be stable for up to 2 years posttransplant (Barrera and Atenafu

2008), neurocognitive impairment appears progressive over the first 5 years posttransplant and is chronic. It appears to be associated with radiation to the brain and affects memory, visual perception, and verbal learning (Shah et al. 2008).

Studies suggest that HRQOL is impaired prior to the transplant, becomes worse during conditioning, and improves in 4-12 months posttransplant. By 6 months to 8 years posttransplant, the pediatric recipients had HRQOL comparable to or better than population norms (Lof et al. 2009). Meta-analyses have shown that pretransplant family functioning and social skills are significant predictors of HRQOL (Clarke et al. 2008).

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