[Effect of the Degree of Myelofibrosis on the Therapeutic Efficacy and Survival in Patients with Myelodysplastic Syndromes].

[OBJECTIVE] To investigate the effect of the degree of myelofibrosis (MF) on clinical characteristics, therapeutic efficacy of hypomethylating agents (HMA) and survival in patients with myelodysplastic syndromes (MDS).

[METHODS] The clinical data of 103 patients with newly diagnosed MDS who received HMA treatment in the Department of Hematology of the Second Hospital of Shanxi Medical University from January 1, 2016 to July 15, 2021 were retrospectively analyzed. The patients were divided into three groups according to the degree of fibrosis in bone marrow biopsy: MDS-MF0, MDS-MF1, and MDS-MF2/3. The clinical characteristics, efficacy and survival were compared among three groups. Logistic regression and Cox regression analyses were employed to identify factors affecting the efficacy and prognosis.

[RESULTS] Among 103 MDS patients, 60 cases (58.2%) had no myelofibrosis (MDS-MF0), 28 cases (27.2%) had mild myelofibrosis (MDS-MF1), and 15 cases (14.6%) had moderate to severe myelofibrosis (MDS-MF2/3). The median hemoglobin (Hb) of patients in the MDS-MF0, MDS-MF1, and MDS-MF2/3 groups showed statistical differences (=0.016), and the proportion of patients with -5/del(5q) also showed statistical differences among the three groups (=0.046). A total of 97 patients were included in the efficacy analysis, with an overall response rate (ORR) of 62.9%. The ORRs of the MDS-MF0, MDS-MF1, and MDS-MF2/3 groups were 72.2%, 53.6% and 46.7%, respectively, with no statistically significant difference (=0.093). The ORR in MDS patients combined with MF was 51.2%, which was statistically significantly different from that in MDS-MF0 patients (=0.033). Multivariate analysis showed that more than 4 cycles of treatment was an independent favorable factor affecting the overall response to HMA therapy (=7.532, 95%: 2.031-27.938, =0.003), while the degree of myelofibrosis did not affect the efficacy (>0.05). By the end of follow-up, among 101 patients included in the survival analysis, 27 cases (26.7%) transformed into leukemia, a total of 75 cases (74.3%) died, 19 cases (18.8%) remained alive, and 7 cases (6.9%) were lost to fllow-up. The median overall survival (OS) was 21.4 months, the median progression-free survival (PFS) was 10.3 months, and the median leukemia-free survival (LFS) was 18.1 months. In the MDS-MF0, MDS-MF1, and MDS-MF2/3 groups, the median OS was 27.9, 12.2 and 11 months (=0.017), respectively; the median PFS was 13.5, 9.1 and 6.4 months (=0.025), respectively; and the median LFS was 24.5, 11 and 11 months (=0.020), respectively. For MDS patients with low blast (MDS-LB), there were statistically significant differences in OS and LFS between those with and without MF (OS: =0.024, LFS: =0.026), while no significant difference was observed in PFS (=0.057). Multivariate analysis showed that an increased proportion of bone marrow blasts and complex karyotype were independent risk factors for OS, while more than 4 cycles of treatment was an independent protective factor for OS. The degree of myelofibrosis did not have independent prognostic significance.

[CONCLUSION] MDS patients with moderate to severe myelofibrosis have more severe anemia and more common -5/del(5q) chromosome abnormalities. MDS patients with myelofibrosis had a lower ORR to HMA therapy, but there was no significant difference in ORR among MDS patients with different degrees of myelofibrosis. In the context of HMA treatment, the myelofibrosis has an adverse effect on the survival of MDS patients, though it did not show independent prognostic significance.