Myeloablative Conditioning Is Well Tolerated by Older Patients Receiving T-Cell Depleted Grafts.

Introduction: Older age is associated with increased transplant related mortality from GvHD and organ dysfunction. Depletion of T-cells from stem cell grafts prevents GvHD and could allow more older patients to receive standard forms of myeloablative conditioning.

Patients and Methods: Adult patients with haematological malignancies received allogeneic grafts from HLA identical siblings. Conditioning was with radiation or chemotherapy based myeloablative schedules. PBPC grafts were incubated ex vivo with CAMPATH-1H (anti CD52) antibody and infused into patients. Patients were given therapeutic doses of cyclosporin until day 90 post transplantation. The survival of patients younger or older than the population median age was analysed to determine if age was a risk factor for outcome.

Results: 72 unselected patients aged from 15 to 59 years (median 44) received myeloablative conditioning followed by median of 2.64 (range 1.14–12.3) CD34+ cells exposed “ex vivo” to a median dose of 10 mg (range 7.5–50) CAMPATH-1H. There was one early death from sepsis and all the other patients engrafted. GvHD occurred in 11%. Death was procedure related in 12 (17%) and from relapse in 3. The median follow up is 539 (7–2316) days and 79% survive disease free. The diagnosis of acute leukemia and lymphoma was more common among younger and older individuals (p< 0.01) respectively. 75% of 33 younger individuals and 79% (p= 0.4) in the older cohort survive disease free, at a median follow up of 911 and 475 days (p= 0.4) respectively. Furthermore, when outcome of patients younger than 40 years, aged between 40 and 49 and older than 49 years were compared, there was again no difference. Cox analysis showed that survival was not associated with diagnosis of disease and that developing GvHD was the only adverse factor for survival (p< 0.04).

Conclusions: In patients receiving T-cell depleted grafts, as GvHD rates are low, myeloablative conditioning is well tolerated supporting the use of this transplantation modality up to the age of 59. This information is useful to select patients who would benefit most from reduced intensity conditioning schedules.