Non-Relapse Mortality (NRM) after Autologous Stem Cell Transplant (ASCT) Is Reduced with Stringent Follow-up Post-Transplant.
Authors: Stotler Christy , Rybicki Lisa , Kalaycio Matt , Dean Robert , Copelan Edward A. , Sobecks Ronald , Pohlman Brad , Andresen Steven , Sweetenham John , Cherni Kelly , Chan Josephine , Bolwell Brian J. 
Published: April 2020

Abstract
Advances in supportive care have reduced early treatment related mortality with ASCT to approximately 1%. ASCT is so well tolerated that it is commonly thought that patients (pts) either relapse or are cured from their disease. However, registry data continues to show that NRM accounts for 25% of treatment failures following ASCT. NRM in this setting is poorly studied and represents a possible area of intervention. We previously reported on NRM at the Cleveland Clinic (ASH 2007: Abstract 1671) in which we reviewed 1573 consecutive autologous transplants performed between 1/92 and 12/05. This analysis included only adult pts receiving peripheral stem cells, single transplants, busulfan based preparative regimens, diagnoses of HL, NHL and MM (n=856). Relapse was the most common cause of death in 303 (79%) pts with NRM occurring in 82 pts (21% of deaths). The most common cause of NRM was pulmonary toxicity in 26 pts, followed by secondary malignancy (19 pts), infection (12 pts), cardiac toxicity (7 pts), other organ failure (7pts) and other causes (11 pts). The majority of NRM from pulmonary toxicity, other organ failure and infection occurred within one year of transplant. Forty-seven patients died within 100 days of transplant – 30 from relapse and 17 from NRM. In an effort to reduce NRM, we targeted pulmonary toxicity as a point of intervention. To identify pts at higher risk for pulmonary toxicity we prospectively followed 137 consecutive pts from 4/05 to 4/06 with monthly phone calls from the BMT nurses using a questionnaire focused to identify pts with symptoms of pulmonary toxicity, and obtained PFTs 1 and 6 months post-ASCT. 12/137 pts had a decrease in DLCO with 7 (58%) of events occurring within one month of transplant, an additional 4 (33%) events within 6 months and one event (9%) at 11 months. HL was the underlying diagnosis in 41% of pts, and prior radiation therapy (XRT) was also identified as a risk factor. Based on this analysis high risk pts were then defined as pts with a decline in DLCO &gt;25% at one month post-ASCT, pts with HL and those with history of prior XRT. High risk pts received 4 and 8 months post-ASCT PFTs. Increased vigilance for the low risk group included phone calls at 3, 6 and 12 months to check for symptoms of pulmonary dysfunction. Patients experiencing a drop in DLCO of &gt;25% at any point in time received a course of steroids and repeat PFT testing. The patient’s local oncologist also received a letter which included a copy of CDC vaccination guidelines with recommendations for re-immunization at one year post-ASCT, and a list of signs and symptoms of delayed pulmonary toxicity. To evaluate if changes made to our follow-up protocol impacted on rates of NRM, we identified 149 pts undergoing ASCT from 5/06 to 12/07 (using the same inclusion criteria as the original cohort). Data regarding the original 856 patients was also updated. For the 5/06 to 12/07 study group 127 pts (85%) are alive and 22 pts (15%) have died. Twenty pts (90.9 %) died from relapse and 2 pts (9.1%) died from NRM, both due to pulmonary toxicity. Only two patients died within 100 days of transplant, both due to relapse. There was no NRM within 100 days of transplant. On multivariable analysis of risk factors for NRM for all patients, year of transplant (1/92 to 12/05) emerged as a risk factor for NRM (HR 5.24, P=0.026). Age at transplant (HR 1.26, P=.013), number of prior chemotherapy regimens (HR 1.24, P=.019), prior radiation (HR 1.81, P=.006) and time to platelet engraftment (HR 0.24, P=.001) also emerged as risk factors for NRM. We have adopted more stringent post-ASCT surveillance protocols and while follow-up is short, results suggest that it may be possible to reduce NRM after ASCT.