Clinical Newswire December 6, 2009 (NEW ORLEANS, LOUISIANA USA)-
Adoptive immunotherapy with T regulatory cells (Tregs) prevented graft-versus-host disease (GvHD) in patients undergoing haploidentical stem cell transplant for hematologic malignancies, according to results presented at the 51st American Society of Hematology (ASH) conference.*
The prognosis for patients with high risk acute leukemia is poor when treated with conventional therapies. Hematopoietic stem cell transplantation has the potential to be curative “but many patients do not have a matched donor, so working with the Weizmann Institute of Science in Rehovot, Israel, we successfully pioneered transplantation from a partially incompatible family member to extend transplantation to almost all patients,” said Dr. Massimo F. Martelli, professor and head of Hematology and Clinical Immunology at Perugia University, Italy.
A total of 28 patients with high risk hematologic malignancies (22 AML, 5 ALL, 1 high-grade relapses NHL) received stem cell transplants from a mismatched family member. All the patients were treated with a high dose conditioning regimen consisting of total body irradiation (TBI), thiotepa, fludarabine, and cyclophosphamide. Three days later freshly isolated donor CD4+CD25+ Tregs were infused, followed by high doses of hematopoietic progenitor cells (CD34+) and mature donor T cells. The patients did not receive post-transplant immunosuppressive therapy for GvHD prophylaxis.
Of the 28 stem cell recipients, 26 achieved full donor-type engraftment. Immune recovery was rapid, with quick increases in CD4+ and CD8+ lymphocyte counts soon after transplant. Only 2 of the 26 patients developed GvHD. Cytomegalovirus activation was significantly reduced in the Treg-infused patients after 60 days (23%) compared to historic controls (52%).
For the first time, in the setting of mismatched transplantation for patients with high risk hematologic malignancies, infusion of freshly purified donor Tregs allows the administration of high doses of mature donor T cells with a low incidence of GvHD, concluded Dr. Martelli. The mature T cells promote rapid post-transplant immune recovery and reduced cytomegalovirus reactivation, while the Tregs prevent the mature T cells from causing GvHD.
According to Dr. Martelli, the hope is that studies with more patients and longer follow-up will show a reduction in transplant related mortality and better overall survival. Future applications of this technique could include the use of Tregs to reduce the incidence and severity of GvHD in conventional hematopoietic stem cell transplantation and to induce tolerance in organ transplantation.
*Di Ianni M, Falzetti F, Carotti A, et al. Adoptive Immunotherapy with Tregs prevents GvHD and favors immune reconstitution after HLA haploidentical transplants for hematological malignancies. ASH 2009. Abstract 4.
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