Outcomes of older adults undergoing allogeneic stem cell transplant with post-transplant cyclophosphamide.
Authors: Bhatia Ishan Iyengar , Patel Shyam Ajay , Suzuki Sakiko , Pearson Laurie , Bindal Poorva , Gillis-Smith Andrew J. , Ramanathan Muthalagu , Gerber Jonathan Michael , Nath Rajneesh , Cerny Jan 
Published: June 2024

6559

Background: The two most common disease indications for stem cell transplants (SCTs) are AML and MDS, with average age of diagnoses of 71 and 68, respectively. However, SCTs historically were not offered to older adults because of the associated risks, such as graft-vs-host disease (GVHD). The use of post-transplant cyclophosphamide as an immunosuppressant has been shown to help prevent GVHD. We aimed to compare the effectiveness of GVHD prophylaxis regimens with (post-Cy) and without (non-Cy) cyclophosphamide and to identify characteristics that make patients more likely to be long-term survivors. To our knowledge, studies focusing specifically on patients aged 70+ remain very limited. Methods: This was a retrospective, single-institution study assessing all patients aged 70+ who received an allogeneic SCT between 2009-2023. Our main outcome was GVHD-free, relapse-free survival (GRFS) at endpoints of 1 and 5 years. We also assessed risks of developing clinically significant acute (grade III-IV) and chronic (extensive) GVHD, relapse rate, overall survival (OS), and non-relapse mortality (NRM) at one and five-year endpoints. Results: We evaluated 61 patients aged 70+ (median 75, IQR 5), 23 of whom were female (38%). 42 patients received GVHD prophylaxis with post-Cy and 19 patients received non-Cy regimens (18 ATG-based). Myeloid malignancies were the primary indication for transplant (85%). We stratified patients based on Disease Risk Index, with 64% of patients as intermediate risk and 33% high risk. Unrelated donors contributed 80% of allografts, and 100% of non-Cy patients had a 10/10 HLA-matched donor compared to post-Cy patients having 64% 10/10, 29% haploidentical, and 7% mismatched unrelated donors. Acute GVHD developed in 19% of post-Cy patients, compared to 26% in non-Cy ( p = ns). At one year, the probability of having chronic GVHD was 12% vs 26% in post-Cy vs non-Cy patients ( p = ns). Post-Cy patients had a one-year relapse rate, NRM, and OS of 2%, 52%, and 45%, respectively, whereas non-Cy patients had 5%, 26%, and 68% ( p = ns). Notably, patients treated with both regimens had a similar one-year GRFS (33% post-Cy, 37% non-Cy; p = ns). At five years, OS was 19% vs 32% and GRFS was 14% vs 16% for post-Cy and non-Cy patients, respectively ( p = ns). Conclusions: We observed similar outcomes among patients aged 70+ receiving GVHD prophylaxis with post-Cy compared to non-Cy regimens. Importantly, non-Cy patients had HLA-matched donors, whereas mismatched donors were possible for the post-Cy group. In this way, post-Cy seems to have equalized the outcomes for fully matched and non-matched SCTs by yielding a similar one and five-year GRFS. Patients without a full match would otherwise have a poor outcome. We also found no significant difference in relapse rate, NRM, OS, and five-year GRFS between patients aged 70-74 and ages 75+, showing that numerical age should not be a contraindication to SCT with post-Cy.