Long-Term Complications (LTC) and Quality of Life (QOL) After Reduced-Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT),
Authors: Clavert Aline , Zina Peric , Cahu Xavier , Chevallier Patrice , Brissot Eolia , Malard Florent , Guillaume Thierry , Delaunay Jacques , Ayari Sameh , Dubruille Viviane , Mahe Beatrice , Blin Nicolas , Gastinne Thomas , Roland Virginie , Le Gouill Steven , Harousseau Jean-Luc , Moreau Philippe , Milpied Noel , Mohty Mohamad 
Published: October 2019

Abstract
Abstract 4100

Background.
RIC allo-SCT is increasingly used in elderly or frail patients not eligible for myeloablative conditioning. While the natural history of LTC and QOL are rather well described in the myeloablative allo-SCT setting, data is still sparse in the RIC setting. This single centre survey analyzed the outcome and features of LTC and QOL in 110 RIC allo-SCT pts who survived for a minimum of 2 years after allo-SCT. QOL was assessed in a cross-sectional study using the EORTC QLQ-C30 questionnaire and the FACT-BMT questionnaire.

Results.
The median age of recipients was 55 (range, 20–68) y. In all, 74 pts (67%) had a lymphoid malignancy, while 34 pts (31%) were diagnosed with myeloid malignancies. Two pts (2%) were treated for severe aplastic anemia. In total, 94 pts (86%) received G-CSF-mobilized PBSCs, while 9 pts (8%) received unmanipulated bone marrow and 7 pts (6%) received unrelated cord blood. Sixty seven grafts (61%) were obtained from HLA identical siblings, 35 (32%) from HLA matched unrelated donors and 8 (7%) from 1 Ag HLA mismatched unrelated donors. Eighty pts received a fludarabine, busulfan and ATG-based RIC (73%), 11 pts (10%) received fludarabine and low-dose TBI, while the remaining 17 pts (15%) received different chemotherapy-based RIC regimens.
The K-M estimate of overall survival (OS) was 93% (95%CI, 88–99%) and 81% (95%CI, 71–94%) at 5 and 10 years, respectively. The primary cause of death was the reccurence of the primary malignancy, found in 4 (4%) pts. A total of 6 pts (5%) died of non-relapse-related causes at a median of 3.2 y. (range, 2.4–5.1) post allo-SCT. The non-relapse causes of death were secondary malignancies (n=3), chronic GVHD (cGVHD; n=2) and infection (n=1).
With a median follow-up of 4.6 y. (range, 2–12.1), cGVHD was the most prevalent LTC with a cumulative incidence (CInc) of 66% (95%CI, 57–74) at 10 y. The CInc of cardiovascular complications was 47% (95%CI, 35–58) with heart failure occurring in 15 pts (14%). Pulmonary complications were mostly related to cGVHD for a CInc of 46% (95%CI, 19–70). The CInc of renal impairment was 35% (95%CI, 26–44). Endocrine disorders had a CInc of 13% (95%CI, 7–22) involving thyroid dysfunction in 6 pts (5%). The observed incidence of psychological disorders (mostly depression) was 11% (95%CI, 5–20). A secondary malignancy occured in 9 pts for a CInc of 11% (95%CI, 5–20). Three pts were diagnosed with two malignancies. The main encountered malignancies were skin (n=4), colon (n=3), prostate (n=2), lungs (n=1), urinary bladder (n=1) and neuroendocrine tumor (n=1). In multivariate analysis, a mismatched unrelated donor allo-SCT was the strongest independent risk factor associated with the development of LTC (RR=4.06, 95%CI 1.81–9.10, p=0.002).
In this series, 61 pts (55%) accepted to participate to the the QOL survey and responded to the different questionnaires. Among these 61 pts, 46 (75%) had developed cGVHD. Overall, in the EORTC QLQ-C30 questionnaire 70% of patients from the whole group, reported a good to very good QOL, with a mean global QOL group score of 71.7 (SD, 20.8). Compared to the group without cGVHD, pts with cGVHD had significantly lower QOL in terms of physical, role, emotional, cognitive and social functioning. They also reported significantly more fatigue, pain and diarrhea (p<0.05 for all comparisons). Similarly, in the FACT-BMT questionnaire the scores in all subscales indicated good QOL. However, when comparing the groups of patients with and without cGVHD, statistically significant differences were found between average QOL scores in the physical and functional well-being and BMT subscales, as well as for the FACT-G, FACT-TOI and FACT-BMT total composite scores. Moreover, the QOL survey revealed that 29% of working age-patients could return to full-time work. Finally, 2 childbearing age women (18%) were reported to have had pregnancies.

Conclusion.
In summary, pts who are alive beyond 2 years after RIC allo-SCT have a high probability of cure with excellent OS and good QOL. However, cGVHD remains an issue requiring long-term appropriate psychological support. Also, the natural history of LTC after RIC appears to be different from that described in the standard myeloablative setting, warranting more research in this field and lifelong surveillance through a close partnership between the transplant center and organ-specific specialities. (This study was supported by a grant from the „Agence de Biomedecine“, France).

Disclosures:
Moreau: Janssen: Advisory board, Honoraria; Millennium Pharmaceuticals, Inc.: Advisory board, Honoraria.