PF773 LOWER SERUM LEVELS OF ZINC AND MAGNESIUM ARE ASSOCIATED WITH WORSE ORAL CGVHD AND DYSGEUSIA IN CGVHD PATIENTS
Authors: M. Mravak-Stipetic, M. Radman, L. Desnica, I. Sabol, R. Serventi-Seiwerth, Z. Perić, N. Durakovic, D. Ljubas Kelecic, E. Bilic, R. Ceovic, I. Karas, T. Vukic, A. Samardzic, A. Kerep Zelic, M. Katić, R. Vrhovac, S.Z. Pavletic, D. Pulanic
Journal: HemaSphere (2019)

Background: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are hematological malignancies predominantly occurring in elderly patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the curative therapy for refractory AML or high risk MDS, but old age had been a limitation to access the eligibility for allo-HSCT. Seldom studies investigate the outcomes associated pre-transplant risk evaluations for elderly patients undergoing allo-HSCT. Aims: We conducted a retrospective study to research the practical pre-transplant risk stratification and identify the prognostic factors predicting outcomes of elderly patients with allo-HSCT for acute leukemia and MDS. Methods: By reviewing Taiwan Bone Marrow Transplantation registry data, we collected the clinical features of patients diagnosed with AML or MDS, who underwent allo-HSCT at age older than 50 years old from April 2011 to January 2018. Clinical characteristics including age, gender, type of allogeneic transplant, underlying disease, conditioning regimens, Charlson comorbidity index (CCI), donors’ age and presence of acute graft-versus-host disease (aGVHD) or chronic GVHD (cGVHD) were collected and analyzed. Cox proportional hazard model was adopted to explore the independent prognostic factors for overall survival (OS), and non-relapse mortality (NRM). Results: A total of 255 elderly patients were included during study period and the median age at allo-HSCT was 57 years old. There were 203 (80%) patients receiving allo-HSCT for AML, and 143 (56%) recipients’ stem cell source were unrelated donors. 175 (69%) patients underwent non-myeloablative conditioning regimens and CCI ≥ 3 was noted in 97 (38%) patients. 40 (16%) cases developed grade III-IV aGVHD, while 44 (17%) had moderate to severe cGVHD. The significant prognostic factors associated with worse OS were CCI ≥ 3 (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.25–2.52; P = 0.001), and grade III-IV aGVHD (HR 3.23, 95% CI 2.16–4.83; P < 0.001). Similar finding in NRM analysis: CCI ≥ 3 (HR 1.78, 95% CI 1.09–2.90; P = 0.02), and grade III-IV aGVHD (HR 4.93, 95% CI 2.96–8.12; P < 0.001) were associated with higher NRM. To investigate the cGVHD effects on outcomes, we performed the OS analysis for elderly patients with survival after allo-HSCT > 100 days. The CCI ≥ 3 (HR 1.88, 95% CI 1.22–2.90; P = 0.004) and grade III-IV aGVHD (HR 2.73, 95% CI 1.62–4.62; P < 0.001) remained poor prognostic factors for OS, while mild cGVHD (HR 0.43, 95% CI 0.24–0.76; P = 0.004) was associated with better OS. Kaplan-Meier curve of OS according to CCI ≥ 3 were illustrated in Figure 1.Summary/Conclusion: We identify CCI ≥ 3 and grade III-IV aGVHD as poor prognostic factors for OS and NRM in elderly patients underwent allo-HSCT. Development of mild cGVHD may allow elderly patients to have better OS. Graft-versus-leukemia may have important influences on survival and disease control for elderly patients experiencing allo-HSCT. Carefully to evaluate elderly patients’ comorbidities before allo-HSCT is necessary and this cohort study suggests that CCI ≥ 3 predicts poor outcomes, mainly resulted from higher risk for NRM. Indicated patients determined by CCI before transplantation and careful management of GVHD after transplantation may help elderly patients with AML or MDS get better survival after allo-HSCT.