Current Pharmaceutical Design - Volume 14, Issue 20, 2008

Hematopoietic stem cell transplantation (HSCT) has been established as a curative procedure for malignant diseases such as leukemia and non-malignant diseases such as severe combined immunodeficiency. Because HSCT carries significant risk of morbidity and mortality, it has up to now been reserved for patients with very high-risk diseases, where the chance of mortality is unacceptable without doing a transplant. The Read More

Hematopoietic stem cell transplantation is an established treatment modality for malignant and non-malignant diseases. Prior to the infusion of allogeneic or autologous cells, patients usually receive radiation or chemotherapy. This “preparative” or ‘conditioning’ regimen provides treatment for the underlying disease and is expected to impair the recipient's immune system and allow engraftment. The last decade witnessed a Read More

Busulfan is the only agent used in myeloablative regimens for hematopoietic stem cell transplantation for which therapeutic drug monitoring (TDM) has been widely used. Studies of oral busulfan (Bu) indicate wide intrapatient and interpatient variations in pharmacokinetic (PK) behavior, particularly in children. Dose adjustments of oral Bu based on TDM to bring exposures within established therapeutic ranges have been s Read More

Mobilized, peripheral blood stem cells (PBSC) are increasingly used for both autologous and allogeneic transplants. Granulocyte- colony-stimulating factor is the most widely used cytokine for mobilization. Several different mechanisms of stem cell mobilization have been proposed including protease-dependent and non-protease- dependent mechanisms. In autologous transplants, the addition of chemotherapy to mobilizatio Read More

Acute graft-vs.-host disease (GVHD) remains one of the most significant barriers to successful allogeneic stem cell transplantation, accounting for a substantial portion of early transplant-related morbidity and mortality. Acute GVHD results from the complex interaction of donor T cells and host tissues that involves recognition of major and minor histocompatibility antigens in an inflammatory milieu. The current view of the patho Read More

Chronic graft-versus-host disease is the most common late, non-relapse complication of transplantation yet it is also one of the least studied. It is the primary cause of morbidity and mortality of long-term survivors of allogeneic bone marrow transplants. Like acute graft-versus-host disease, it does have a strong antitumor effect. The recent National Institutes of Health sponsored Chronic Graft-versus- Host Disease Consensus C Read More

Allogeneic hematopoietic stem cell transplantation (HSCT) may be performed to treat a variety of malignant and nonmalignant disorders by eradicating tumor, replacing a non-functioning with a normal immune system, or replenishing a deficient enzyme. While HSCT may provide cure for many patients, barriers such as acute and chronic graft-versus-host disease (a/cGVHD) and graft failure continue to challenge clinicians Read More

Viral infections are important causes of morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Some viruses, such as the respiratory and gastrointestinal viruses, are acquired from the healthcare or community in the midst of or after HSCT. Other viruses, such as the herpes-virus family, establish latency after resolution of primary infection but then may reactivate during the immunosuppression that o Read More

Invasive fungal infections are major complications of stem cell transplantation associated with significant morbidity and mortality. Allogeneic stem cell transplant recipients are at a significantly greater risk for fungal infection than recipients of autologous transplantation. Although with the wide use of fluconazole prophylaxis the incidence and associated mortality of invasive candidiasis has been minimized, mold diseases remain Read More