Myelodysplastic Syndrome with Fibrosis: Experience of a Single-Institution with 139 Patients.
Authors: Santos Fabio P.S. , Schlette Ellen , Kantarjian Hagop , Sargent Rachel , Garcia-Manero Guillermo , Verstovsek Srdan , Kadia Tapan , Jabbour Elias , Pierce Sherry , Borthakur Gautam 
Published: October 2019

Abstract
Abstract 2775
Poster Board II-751

Background:
A fraction of patients with MDS present with bone marrow fibrosis in addition to dysplastic hematopoiesis. It is believed that MDS patients who present with fibrotic features in the bone marrow constitute a group with worse survival.

Aims:
To describe clinical features and survival outcomes of patients with a diagnosis of MDS with myelofibrosis treated at the M.D. Anderson Cancer Center.

Methods:
We carried out a retrospective review of patients who had a diagnosis of MDS in the presence of grade 2+ or greater fibrosis. Relevant clinical data at presentation was reviewed. Survival was estimated by Kaplan-Meier method.

Results:
From 1997 until 2008, 129 patients with a diagnosis of MDS with myelofibrosis and 10 patients with chronic myelomonocytic leukemia (CMML) and myelofibrosis were seen at our institution. Median age was 64 years (range 27–85). Subclassification by the World Health Organization criteria included refractory anemia (N=16, 12%), refractory anemia with ringed sideroblasts (N=4, 3%), refractory cytopenias with multilineage dysplasia (N=16, 12%), refractory anemia with excess blasts (RAEB; N=62, 45%), 5q- syndrome (N=2, 1%) and therapy-related MDS (t-MDS; N=29, 21%). Marrow reticulin fibrosis was graded in 115 patients, being grade 2 in 34 patients (30%), grade 3 in 40 patients (35%) and grade 4 in 41 patients (35%). Splenomegaly was present in 16 patients (12%), being more common in patients with a morphological diagnosis of CMML (9% vs 50%, p=0.001), and the median spleen size below the left costal margin was 8 cm (range 2–10). The median white blood cell count at diagnosis was 3.6×109/L (0.6–60.7), hemoglobin 9.6 g/dL (5.1–14.4) and platelet count 53×109/L (6–1195). Median lactate dehydrogenase level was 621 IU/L (range 263–4037). The median bone marrow blasts percentage was 4% (0–19%). Cytogenetic analysis was available in 127 (91%) cases, and was abnormal in 63 (50%) patients. The most common abnormalities were: complex karyotype in 35 patients (28%), −7/del(7q) in 7 patients (6%), del(20q) in 6 patients (5%), −5/del(5q) and trisomy 8 in 4 patients (3%) each. Analysis of the JAK2V617F mutation was done in 30 patients, being positive in 6 (20%; RAEB=3, t-MDS, CMML and 5q− syndrome in one each). One additional patient with RAEB was positive for the MPLW515K mutation. After excluding patients with CMML and t-MDS, the International Prognostic Scoring System (IPSS) score was available in 92 patients. IPSS scores were distributed as follows: low (N=15; 16%); intermediate-1 (N=47; 51%); intermediate-2 (N=25; 27%) and high (N=5; 6%). Median transformation-free survival (TFS) was 16 months (range 0–127) and median overall survival (OS) was 20 months (range 0–130) for the whole cohort. There was no difference in OS (p=0.18) or TFS (p=0.24) by degree of fibrosis. OS was influenced by the IPSS score, median OS being 38, 21, 11 and 5 months for patients with Low, Int-1, Int-2 and High risk scores, respectively (p=0.01). Similarly, median TFS was 29, 18, 10 and 5 months for patients with Low, Int-1, Int-2 and High risk scores (p=0.007). For patients with t-MDS, median TFS and OS were 15 months both, not different from patients without previous history of chemotherapy and/or radiation therapy (p=0.84 and p=0.73, respectively).

Conclusion:
In our cohort of patients with a diagnosis of MDS with myelofibrosis, we found a higher prevalence of JAK2 mutations and splenomegaly than previously reported. More detailed mutation analysis is in progress. The degree of fibrosis did not influence survival in our patients. The median OS and TFS for patients with Low/Int-1 risk is inferior to that reported in the literature for patients with MDS without fibrosis with similar risk. Thus, early treatment strategies should be considered for patients with MDS who present with fibrotic features in the bone marrow.

Disclosures:
No relevant conflicts of interest to declare.