ATLANTA—The first scoring system devised specifically for patients with unclassifiable cases of myelodysplastic syndrome (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) has identified several clinicopathologic factors helpful in predicting survival outcomes, according to a study presented during the 54th American Society of Hematology Annual Meeting and Exposition.

Specifically, by assigning 2 points each to an ANC of ≥8.5k/uL, the presence of peripheral blood blasts, hemoglobin ≤11.5g/dL, and LDH ≥550U/L and 3 points for age ≥65, the system provided “three well-separated prognostic groups,” noted Yang Liu, BA, from the Taussig Cancer Institute, Cleveland Clinic, Cleveland,  and colleagues.

These three groups—favorable (score 0-3), intermediate (score 4-6), and poor (score ≥7)—corresponded with a median overall survival of 67 months (n=34), 29 months (n=21), and 13 months (n-24), respectively (P<0.0001), among the 92 patients with unclassifiable cases seen at the Cleveland Clinic. A total of 52 (57%) patients had MDS/MPN-U and 40 (43%), MDS-U.

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According to the World Health Organization 2008 diagnostic criteria, patients with features of MDS and MDS/MPN who cannot be characterized with a specific subtype are otherwise classified as MDS-U and MDS/MPN-U. Criteria diagnostic of MDS include refractory cytopenia with unilineage dysplasia, refractory cytopenia with multilineage dysplasia, refractory anemia with excess blasts (RAEB)-1, RAEB-2, MDS-U and 5q- syndrome; MDS/MPN include chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myelogenous leukemia, and MDS/MPN-U.

“The natural history of patients who belong to these disease subtypes is heterogeneous,” Liu noted. “Although included in currently accepted prognostic scoring schemes like the International Prognostic Scoring System (IPSS) in MDS, Revised IPSS, and MD Anderson prognostic scoring schemes, they represent a minority of patients in the cohort.”

To date, no prognostic scoring system exists for unclassified cases of MDS and MDS/MPN. “Clinically, we observe stark differences in treatment responses and clinical outcomes between MDS/MPN-U and other MDS/MPN-subtypes, and MDS-U with other subtypes of MDS,” the investigators noted.

They collected hematologic, bone marrow, cytogenetic (metaphase cytogenetic [MC]/SNP-A) and survival data from 92 patients with unclassifiable cases seen at the Cleveland Clinic, including MDS/MPN-U (57%) and MDS-U (43%), and compared survival outcomes.

Median age at diagnosis was 69 years (range, 20-88 years); 65% were male. Median follow-up was 21 months. Median absolute neutrophil count (ANC) was 2.69k/uL; peripheral blood (PB) blasts were 0%, hemoglobin 9.6 g/dL, and LDH 260 U/L.

“The majority of MDS-U and MDS/MPN-U patients have new cytogenetic abnormalities found on SNP-karyotyping analysis,” Liu said. SNP-A karyotyping was completed for 65 patients, and new cytogenetic mutations were detected in 72% (including gains in 64%, losses in 57%, and uniparental disomy in 25%).

In 52% of patients, molecular mutations that typically confer poor prognosis in myeloid neoplasms, such as ASXL1, IDH1/2, EZH2, K/NRAS, CBL and TP53, were sequenced and revealed a mutational frequency of 18% in TET2, 14% in ASXL1, 6% in EZH2 exons 18-19, 2% in CBL, 2% in NRAS, and 4% in TP53. No mutations were found in IDH1/2 or KRAS.

Univariate analysis of clinicopathologic factors found ANC ≥8.5k/uL, presence of peripheral blood blasts, immature myeloid cells, and BM blasts, age ≥65 years, LDH ≥550 U/L, albumin ≤3.6 g/dL, IPSS Risk Group (Int-2/high vs int-1 vs low), IPSS-R Risk Group (high/very high vs low vs very low), WBC ≥15k/uL, Hgb ≤11.5 g/dL, percent of bone marrow cellularity >85%, and number of cytopenias (3 vs 2 vs 1 vs 0) were all significantly associated with overall survival (OS).

In multivariate analysis, independent predictors of OS in unclassifiable cases of MDS and MDS/MPN were age ≥65 years, ANC ≥8.5k/uL, Hgb ≤11.5 g/dL, presence of peripheral blood blasts, and LDH ≥550 U/L.