Reduced-Intensity Conditioning Is Associated with Shorter Duration of Chronic GVHD Than Myeloablative Conditioning and Provides Very Good Quality of Life for Long-Term Survivors after Allogeneic Stem Cell Transplantation.
Authors: Shimoni Avichai , Hardan Izhar , Shem-Tov Noga , Rand Avital , Ribakovsky Elena , Yerushalmi Ronit , Nagler Arnon 
Published: April 2020

Abstract
Reduced-intensity conditioning (RIC) has been increasingly used over the last decade as a curative approach for patients (pts) not eligible for myeloablative (MA) conditioning. It is now established that RIC can allow consistent engraftment and reduce toxicity of allogeneic stem-cell transplantation (SCT). However, the long-term effects, and in particular the duration of immunosuppressive therapy (IST) needed and quality of life of long-term survivors are less defined. To explore these issues we analyzed the results of 48 pts given SCT with RIC from 1/2000 to 8/2002, such that survivors have at least 5 year follow-up, and compared them to results of 41 SCT with MA conditioning given during the same period. The RIC group included older pts than the MA group, median age 49 (range, 20–65) and 37 (range, 20–65), respectively (p=0.01). The MA group included more pts with acute leukemia/MDS (68% vs 33%, p=0.001) while pts with myeloma were only given RIC (31% of the RIC group, p&lt; 0.001). 48% of pts in the RIC group had a prior autologous SCT compared with none in the MA group (p&lt; 0.001). There was no difference in donor type, 26% of all pts were given SCT from unrelated donors. After a median follow-up of 6.1 years (range, 5.1–7.6) 40 pts are alive, 20 after RIC and 20 after MA conditioning with estimated survival of 42% (95ci, 28–56) and 47% (95ci, 31–63), respectively (p=NS). Long-term survival with RIC was achieved across all diagnoses including 6 of 16 pts with acute leukemia/MDS, 6 of 6 pts with CML, 3 of 11 pts with lymphoid malignancies and 5 of 15 pts with myeloma. The corresponding rates for acute leukemia/MDS, CML and lymphoid malignancies in the MA group were 13 of 28, 3 of 4 and 4 of 9, respectively. Chronic GVHD occurred in 22 pts after RIC and in 26 pts after MA conditioning with a cumulative incidence of 48% (35–65) and 66% (53–83), respectively (p=0.07). 12 of 22 pts with chronic GVHD after RIC were eventually able to stop IST, 9 died on IST (relapse-5, non-relapse mortality (NRM)-4) and only 1 of 20 long-term survivors was still on IST at last follow-up. The median duration of IST was 17 months and the cumulative probability of stopping IST after 5 years (with relapse been competing risk) was 79%. In the MA group 10 of 26 pts with chronic GVHD were able to stop IST, 8 died on IST (relapse-6, NRM-2) and 8 of 20 long-term survivors were still on IST at last follow-up. The median duration of IST was 41 months (p=0.05) and the cumulative probability of stopping IST after 5 years was 48% (p=0.001). Two women gave birth in the RIC group while 2 men in the MA group fathered children spontaneously. There was one secondary malignancy in the MA group and none in the RIC group. Two pts in the MA group sustained myocardial infarction (one fatal) compared to none of the RIC group. One pt in the RIC group had reversible nephrotic syndrome. In summary long term(&gt;5y) survival is similar for both RIC and MA SCT, however IST is significantly shorter after RIC and quality of life seems better. Overall, all 20 pts surviving more than 5 years after RIC SCT sustained excellent quality of life and only one still required IST. The more rapid achievement of transplantation tolerance with RIC may relate to better preservation of thymic function, but this requires further investigation. These observations require further confirmation in larger registry studies.