Académie royale de Médecine de Belgique


Résumé de Frédéric Baron

(Séance du 29 janvier 2011)



par F. BARON (U.Lg.), invité.      

Allogeneic hematopoietic cell transplantation (HCT) following myeloablative (conventional) conditioning regimen is associated with a high incidence of transplant-related morbidity and mortality, limiting its use to younger patients without medical co-morbidities. Unfortunately, median patient age at the time of diagnosis of leukemia, multiple myeloma or non-hodgkin lymphoma ranges from 60 to 70 years. Over the past few years, it has become more and more evident that alloreactivity of donor immunocompetent cells present in the graft against the host tumor plays a major role in eradicating malignancies after allogeneic HCT (graft-versus-tumor effects). Based on these observations, several groups of investigators have developed nonmyeloablative conditioning regimens allowing the use of allogeneic HCT in older patients, and those with co-morbidities. These approaches rely nearly exclusively on graft-versus-tumor effects for tumor eradication. The Seattle team has developed an original nonmyeloablative regimen consisting of low-dose total body irradiation (TBI, 2 Gy), preceded in some patients by fludarabine (90 mg/m²), and followed by immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP) or tacrolimus. This approach has been used in patients who were deemed too old or sick to tolerate conventional high-dose HCT regimens, and who had a HLA-matched related or a 9/10 or 10/10 HLA-allele-matched unrelated donor. Toxicities were relatively mild, and a majority of patients could be transplanted in the ambulatory care setting. Further, complete responses have been achieved in 40-50% of patients with measurable disease at HCT.