P1321: incidence and impact of graft-versus-host disease (gvhd) in patients over 60 years of age undergoing hematopoietic stem cell transplantation (hsct). retrospective experience of two spanish centers

Background: Acute and chronic GVHD are of the main complications of HSCT and their frequency and impact in patients over 60 years is not fully understood. Aims: To describe their incidence and to analyze the influence of age and modalities of HSCT on their appearance, as well their impact on survival. Methods: Retrospective study of 142 patients over 60 years with hematological neoplasms undergoing allogeneic HSCT Results: Patient characteristics and survival curves are shown in Image 1. Acute GVHD was the most common complication (incidence of 72.5%) although only 10.5% were severe cases (Grades 3-4). It was an early complication (median onset 28 days). A higher incidence was observed in unrelated donor transplant recipients (82%/100% if mismatch) compared to related (62%) and haploidentical (66%) (p-value 0.28). There were no differences with the intensity of conditioning (Myeloblative 78.5% and reduced intensity 72%) although the highest severe cases was observed of myeloablative unrelated transplant (66.5%; p-value 0.03). The incidence was higher with older age (91% in >70 years; 74% in 65-69 and 69% in <65; p-value 0.15) and in CMV serological discrepancy (88.5% in recipient+/donor-; p-value 0.19). In relation to immunosuppression, there was a higher incidence with Tacrolimus/Sirolimus (82%) and less with Cyclosporine/ Mycophenolate of Mofetil (MMF) (40%): p-value 0.2; however they were the regimen most and least used, respectively. Severe aGVHD had an unfavorable impact on survival: median Progression-Free Survival (PFS) of 5 months vs 25 and 27 if not aGVHD or if mild (p-value 0.008/HR 2.3 (CI 1.2-4.6)); and median overall survival (OS) of 7 months vs 40 and 45 if not aGVHD or if mild (p-value 0.002/HR 2.6 (CI 1.3-5.4)). Severe aGVHD was associated with a higher frequency of infectious complications: more CMV reactivation (73.5% vs 37.5% if mild and 25.5% if not aGVHD; p-value 0.005), CMV disease (40% vs 4.5% if mild or 0% if not aGVHD; p-value <0.001), bacterial sepsis (60% vs 13.5% if mild or 18% if not aGVHD; p-value <0.001) and invasive fungal infection (26.5% vs 1 and 5% if mild or not aGVHD; p-value 0.001). And, these complications were associated with worse survival (median OS of 6 months vs 34 at the global serie). Together (aGVHD and related infections) caused 15% of deaths and were the first cause of mortality related to treatment. Chronic GVHD was less frequent (31%), only 13.5% were severe cases, and it occurred later (median onset of 7.5 months). A higher incidence was in unrelated-mismatch donor recipients (60%; p-value 0.04) and lower in haploidentical (15%) and no differences were observed with the intensity of conditioning (mieloablatyve 35,5% and reduced intensity 30.5%). There was a higher incidence with older age (36.5% in >70 years; 33.5% in 65-69 and 28.5% in <65; p-value 0.61) and if serological CMV discrepancy recipient -/donor+ (50%; p-value 0.83). The incidence was again higher with Tacrolimus / Sirolimus regimen and the lowest with Tacrolimus/MMF/Ciclofosfamide-post-transplant (p-value 0.09). Mild-moderate cGVHD had a protective effect on survival: median PFS of 38 months vs 8 if not cGVHD (p-value 0.03/HR 0.55 (CI 0.32-0.94)); and median OS of 19 months vs 11 if not cGVHD (p-value 0.001/HR 0.47 (CI 0.27-0.84)). Image:Summary/Conclusion: GVHD is a very relevant complication: the aGVHD due to its high incidence and impact on survival and appearance of infectious complications; and the protective effect of the cGVHD. Although a higher incidence is observed with older age, longer series and comparative studies are needed to confirm these results.