Non-Relapse Mortality Associated with Autologous Stem Cell Transplant (ASCT).

Advances in supportive care have reduced early treatment related mortality with ASCT to approximately 1%. Registry data has shown that relapse is the cause of treatment failure in approximately 80% of patients. However, non-relapse mortality (NRM), over time, affects 20% of transplant recipients. Delayed NRM is poorly studied. To characterize the factors associated with NRM, we reviewed 1573 consecutive autologous transplants performed at the Cleveland Clinic from 1/1992 through 12/2005. This analysis included only adult patients (pts) receiving peripheral stem cells, busulfan based preparative regimens, single transplants, and diagnoses of NHL, HD and MM (n = 856). The median age was 49, 62% were male, and 30% received prior radiation therapy. The most common number of prior chemotherapy regimens was 2 (48%); the primary diagnosis was NHL (67%), HD (18%), MM (15%); and 90% had sensitive disease at the time of transplant. 471 (55%) are alive and 385 (45%) have died. Relapse was the most common cause of death, occurring in 303 (79%) patients. Non-relapse mortality occurred in 82 patients (21% of deaths). The most common cause of NRM was pulmonary toxicity, occurring in 26 patients, followed by secondary malignancy in 19 pts, infection (12 pts), cardiac toxicity (7 pts), other organ failure (7 pts), and other causes (11 pts). Patients who died from secondary malignancy were significantly more likely to have received prior radiation therapy (p = 0.004), to require more days of pheresis to collect stem cells (p<0.001) and had a longer time to platelet engraftment than did other patients (p<0.001). 16/19 deaths due to secondary malignancy were from hematologic malignancies. Causes of death in the “other” category included accidents (n=3), homicide (n=1) and suicide (n=1). Liver toxicity was the most common organ affected in the “other organ failure” category. 46% of patients with NRM due to pulmonary toxicity had a prior exposure to radiation therapy, as did 43% of those with cardiac toxicity. The time to development of NRM is shown below:

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The substantial majority of NRM due to pulmonary toxicity, other organ failure or infection occurs within one year post-transplant. This suggests a need for more intensive surveillance of recipients of autologous transplantation for 12 months, possibly with regular visits to the transplanting institution. We have adopted more stringent follow up with promising early results at reducing 1 year NRM. The median time of NRM from secondary malignancy is 3.5 years, which suggests that surveillance of blood counts should continue well beyond one year post-transplant. Whether more aggressive surveillance will reduce NRM associated with ASCT requires further study.