REDUCED-INTENSITY CONDITIONING USING ALEMTUZUMAB IN ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION.

Abstract

Purpose Allogeneic hematopoietic transplantation after a myeloablative conditioning regimen has been shown to be an effective and potentially curative treatment for many hematologic malignancies due to the graft-versus-malignancy (GVM) effect. However, significant toxicities of such regimens have limited their use to younger, otherwise healthy patients. Reduced-intensity conditioning (RIC) transplantation has broadened eligibility to include older patients and those with comorbid conditions. RIC regimens using fludarabine and melphalan have been associated with a high risk of graft-versus-host disease (GVHD). Our institution adopted a RIC protocol that added alemtuzumab, an anti-CD52 monoclonal antibody that decreases T cells in the transplant recipient, to melphalan and fludarabine in an attempt to reduce the risk of GVHD while maintaining the GVM effect. Methods From January 2005 to June 2006, 19 patients with hematologic malignancies received an allogeneic transplant using the RIC protocol. Median patient age was 52 years (34-66). Results Acute and chronic GVHD occurred in 6 of 19 (31%) and 5 of 19 (26%), respectively, with only 17% of each being > grade II. Cytomegalovirus (CMV) reactivation occurred in 13 of 19 (68%). Seven of 19 (37%) patients experienced disease relapse or progression. One hundred-day survival was 79%. Ten of 19 (53%) have died at the time of this report. CMV infection was the probable cause of death in 3 of 10 (30%) deaths, or 16% of patients overall. Only one death was attributable to GVHD. Conclusions RIC allogeneic transplant represents a reasonable treatment option for a variety of hematologic malignancies. There was a low incidence of severe GVHD and a 100-day survival of 79%. However, the mortality rate due to toxicity of this regimen was high at 37%. CMV infection represents a large proportion of this toxicity and provides an area to be improved upon in future RIC protocols, perhaps by using lower doses of alemtuzumab.