Improvement of Supportive Care in Patients Undergoing Myeloablative Allogeneic Stem Cell Transplantation Not Only Reduces Transplant-Related Mortality but Also Increases Long-Term Survival
Authors: Bruno Benedicte , Seguy David , Maunoury Vincent , Coiteux Valerie , Magro Leonardo , Bauters Francis , Mazingue Francoise , Jouet Jean-Pierre , Yakoub-Agha Ibrahim 
Published: April 2020

Abstract
One of major hurdles to achieving good patient outcomes and survival rates in allogeneic stem cell transplantation (allo-SCT) after myeloablative conditioning is the high rate of transplant-related mortality (TRM). Much progress in supportive patient care has been accomplished over the last decade-notably the use of allelic HLA-matching (Yakoub-Agha, JCO 2006), the introduction of enteral nutrition (Seguy, Transplantation 2004), the development of wireless video-capsule endoscopy for the management of post-transplant diarrhea (Yakoub-Agha, Transplantation 2005), the availability of broad-spectrum antifungal prophylaxis, the use of busulfan IV instead of PO in the conditioning regimen, limitation of the use of ATG in graft-versus-host disease (GVHD) treatment and dose reduction when the latter drug is used in conditioning. Although all these various modifications have had a positive impact on short-term patient outcomes, their impact on long-term survival is still unclear. Hence, the main objective of the present study was to evaluate allo-CST outcomes as a function of the transplantation period. A total 445 patients have undergone post-myeloablation allo-CST in our department. The patient distribution over the time was as follows: prior to 1998 (first period): n=133; between 1998 and 2003 (second period): n=154; between 2003 and 2007 (third period): n=158. Only the first transplant for a given individual was taken into account. Kaplan-Meyer curves were plotted for 100-day survival, 180-day survival and 3-year survival for each time period. Setting aside the clear differences in supportive care methods, the three groups were well matched in terms of disease diagnosis, disease status at transplant and the main recipient and donor characteristics. It is noteworthy, however, that the median age of patients increased over time. Mean 100-day survival was 86 days (95% CI: 81–90), 93 days (95% CI: 90–96) and 96 days (95% CI: 94–98) for the first, second and third periods, respectively (p&lt;.0001). Mean 180-day survival was 137 days (95% CI: 126–147), 157 days (95% CI: 150–164) and 165 days (95% CI: 160–171) for the first, second and third periods, respectively (p&lt;.0001). The improvement in short-term survival has translated into an improvement in long-term survival, as the mean 3-year survival was 513 days (95% CI: 437–591), 705 days (95% CI: 635–775) and 782 days (95% CI: 715–850) for the first, second and third periods, respectively (p&lt;0.0001). Median survival was 339 days (95% CI: 145–533) for the first period but has not yet been reached for the two other periods. While we observed a significant reduction in TRM over the three periods, post-transplantation relapse is still a major complication which impacts negatively on long-term patient outcomes. In conclusion, this study highlights the positive impact of supportive care on both short-term patient outcomes and long-term survival after myeloablative allo-CST. The most recent data on myeloablative allo-CST must be taken into account before ruling out the latter as treatment option. Although supportive care will doubtless continue to progress, further research into reducing the post-transplantation relapse rate must now become a priority.