Work

Optimizing results of non-myeloablative allogeneic transplantation (NMAT): identification of patients at high risk of treatment failure based upon pre-transplant variables

Year: 2004

Type: article

Abstract: 47 consecutive patients (27–68 y; median 51) with hematologic malignancies were studied to develop a scoring system to identify those at high (HR) and low (LR) risk of transplant-related mortality (TRM) and relapse (REL) based on pretransplant factors. The conditioning regimen was 100 mg/m2 melphalan on day-1 (+50 mg/kg cyclophosphamide on day-2 if no prior autograft), cyclosporine (HLA-matched sibling; n = 32) or tacrolimus (1-locus mismatched sibling; n = 3, or unrelated; n = 12), and mycophenolate mofetil. The 2-y cumulative incidences of TRM and REL were 20% and 50%, with 2-y actuarial disease-free (DFS) and overall (OS) survival probabilties of 30% and 40% respectively. TRM was higher with creatinine >1.5 mg/dL (2 points), HLA mismatch (2 points), poor performance status (0–3 points), and age 60 (1 point). The 11 patients with a total score of >2 points (HR-TRM) had significantly higher TRM than the 36 with a score of 0–2 (LR-TRM) (64% vs 7%; P = 0.0005). REL was higher with non-chemosensitive disease (2 points), platelets <100 x 109/L (1 point), and prior autograft (1 point). The 15 patients with a total score of >2 points (HR-REL) had significantly higher REL than the 21 with a score of 0–2 (LR-REL) (83% vs 21%; P = 0.003) after eliminating HR-TRM patients from the analysis. Overall, the outcome of the 21 LR patients was significantly better than the 26 HR patients (11 HR-TRM, 15 HR-REL) in terms of OS (92% vs 19% at 1.5 y; P < 0.0001) and DFS (70% vs 6% at 1.5 y; P < 0.0001). The model will be tested in the next 50 patients treated similarly. If it is validated, the regimen intensity will be lowered for HR-TRM patients to reduce TRM. From the remaining patients, HR-REL patients will be identified and their regimen intensified to decrease REL. For both the groups with modified conditioning, GVHD prophylaxis will be changed (e.g. omission of mycophenolate) to augment graft-vs-tumor. Patients who are LR for both TRM and REL will continue to receive the current therapy in view of their excellent outcome. We conclude that the outcome of LR patients undergoing NMAT is excellent. In such patients, this mode of transplantation should be considered standard therapy rather than investigational. Confirmation of our observations may justify using NMAT as a safer alternative procedure for patients who fulfill the LR criteria specified here but who would normally undergo conventional allogeneic transplantation. Modified treatment may improve the outcome of HR patients.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2003.12.141