Mucositis associated with stem cell transplantation: current status and innovative approaches to management.
Treatment-related morbidity, and in some cases, mortality, associated with autologous and allogeneic bone marrow transplantation has decreased in the past decade largely due to the use of blood stem cells combined with hematopoietic growth factors. However, these procedures remain morbid, with several series documenting regimen-related injury to the oral mucous membranes, the worst form of toxicity from a patient perspective. The pathophysiology of transplant-related mucositis is related to two major events: direct mucosal basal cell injury leading to atrophy and ulcerations, and local infections that can become systemic, the latter of which are exacerbated by the severe neutropenia accompanying high-dose chemotherapy. Recent investigational agents designed to interfere with these two aspects of mucositis have been developed and are showing promise in early clinical trials. In particular, keratinocyte growth factor (KGF) and interleukin-11 appear active. They increase basal cell proliferation, prevent apoptosis due to the preparative regimen, and appear to ameliorate the mucositis seen with high-dose chemotherapy regimens. Oral, nonabsorbable anti-infective agents are also being tested in an attempt to prevent both local and systemic infections. Devoid of significant side-effects, KGF is now in large phase 2 trials that, if positive, will be a significant advance in promoting less morbid transplants by reducing pain and the risk of secondary infections and thus may reduce supportive care costs.
Stiff
P
P
Loyola University Medical Center, 2160 South First Avenue, Maywood, IL 60153, USA.
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology; D016207:Cytokines / Q000008:administration & dosage / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D009061:Mouth Mucosa / Q000473:pathology; D015995:Prevalence; D013280:Stomatitis / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology*
D000890:Anti-Infective Agents; D016207:Cytokines