Second allogeneic stem cell transplantation for acute leukemia using a chemotherapy only cytoreduction with clofarabine melphalan and thiotepa

摘要

Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains one of the leading causes of mortality in patients with leukemia. Treatment options in this population remain limited, with concern for both increased toxicity and further relapse. We treated 18 patients with acute leukemia for marrow +/- extramedullary relapse after a prior alloHSCT, with a myeloablative cytoreductive regimen including clofarabine, melphalan, and thiotepa, followed by a second or third transplant (HSCT2/3) from the same or different donor. All patients were in remission at the time of HSCT2/3. All evaluable patients engrafted. The most common toxicity was reversible transaminitis associated with clofarabine. Two patients died from transplant-related causes. Seven patients relapsed post-HSCT2/3 and died of disease. Nine of 18 patients are alive and disease-free, with a three-year 49% probability of overall survival. Patients whose remission duration after initial alloHSCT was >6 months achieved superior outcomes (3-year OS 74%, 95% CI: 53-100%), compared with those relapsing within 6 months (0%), (p<0.001). This new cytoreductive regimen has yielded promising results with acceptable toxicity for second transplants in patients with high-risk ALL and AML who relapsed after a prior transplant, using various graft and donor options,. This approach merits further evaluation in collaborative group studies.