Myeloablative Conditioning Followed by T-Cell Depletion Is Associated with Low Treatment Related Mortality.

Introduction: Classically the conditioning for transplantation in haematological malignancies has been with myeloablative doses of radiation or chemotherapy, and was followed by variable immunosuppression for the prevention of GvHD. This strategy has been associated with substantial transplant related mortality from regimen toxicity and GvHD, which were most pronounced in older patients. Reduced intensity conditioning programs that are mainly immunosuppressive allow engraftment and predisposed to donor chimerism and appear to have lower TRM, but seem associated to higher rates of GvHD and disease recurrence. To better apportion conditioning strategies for patients undergoing allogeneic stem cell transplantation, we studied the outcome of 81 patients who received similar GvHD prophylaxis with T-cell depletion and immunosuppression, after myeloablative conditioning.

Patients & methods: Patients with haematological malignancies, in remission or still responsive to chemotherapy who had an HLA identical sibling were offered T-cell depleted stem cell grafts. Conditioning was with ablative doses of either chemotherapy or total body radiotherapy. Stem cells were mobilised into the blood (PBPC) with G-CSF (5–10ug/kg × 5) and grafts were harvested by large volume (30 litres) apheresis. GvHD prophylaxis was by ex vivo depletion of lymphocytes from the graft with CAMPATH-1 H antibodies followed by therapeutic doses of cyclosporin until day 90. End points were TRM, disease recurrence rate and overall survival time.

Results: 90 consecutive patients with median age of 45 (17–62) years were studied. The diagnosis included acute leukaemia (ALL in 7) in CR in 38, myeloproliferative disorders in 16, lymphoproliferative diseases in 26 and multiple myeloma in 10. Post transplantation, patients with CML received, in addition, escalating doses of lymphocytes at 6 months (maximum 1 × 10⁷/kg CD3) or imatinib for 12 months. Median CD34+ cell number was 2.7 (1–12.3) and the median dose of campath-1H was 10 (range 7.5–45) mg. Median time to engraftment was 11 days. Overall, 20 (22%) individuals died while treatment related mortality occurred in 17% (n= 15; VOD 3, infections in 8, pneumonitis in 1, EBV lymphoma in 1 and GvHD in 2). GvHD (> grade1) occurred in 7 patients, was controlled with further immunosuppression but lead to death from infections in 6. Disease recurrence was seen in 12, but 7 with CML or myeloma responded to DLI. At a median follow up of 688 days, 77 survive; 75% in unsustained remission.

Conclusions: Myeloablative conditioning is well tolerated in patients receiving T-cell depleted grafts, and treatment related mortality of <20% can be expected consistently with this strategy. This information is useful to more precisely select patients who would benefit most from reduced intensity conditioning schedules.