A New Prognostic Scoring System Including Transfusion Dependency and Cytogenetic Abnormalities for Patients with Chronic Myelomonocytic Leukemia.
Authors: Such Esperanza , Cervera Jose , Nomdedeu Benet , Pedro Carmen , Bueno Javier , Bernal Teresa , Carbonell Felix , Belkaid Mohamed , Senent Leonor , Sole Francesc , Luño Elisa , Vallespi Teresa , Collado Rosa , Ardanaz Teresa , Ramos Fernando , Tormo Mar , Sancho-Tello Reyes , del Cañizo Maria Consuelo , Xicoy Blanca , Marco Victor , Gomez Valle , Bonanad Santiago , Valencia Ana , Mallo Mar , Benlloch Luis , Sanz Guillermo 
Published: October 2019

Abstract
Abstract 1750
Poster Board I-776
Chronic myelomonocytic leukemia (CMML) is a clonal disorder sharing features of both myelodysplastic syndromes (MDS) and chronic myeloproliferative disorders (MPD). The natural course of CMML is highly variable. Several small series have suggested the prognostic importance of different characteristics but a widely accepted prognostic scoring system for CMML is not available. The main aims of the study were to identify prognostic factors, including cytogenetic findings, for overall survival (OS) and acute leukemic (AL) transformation in a large series of patients with CMML and to develop an easily applicable prognostic scoring index for estimating outcome and planning treatment in the individual patient. Five hundred and seventy-two patients diagnosed of CMML according to FAB and WHO criteria in 25 centers belonging to the Spanish Registry of MDS were included in the study. Actuarial curves of OS and risk of AL evolution were built by Kaplan-Meier method and differences between curves compared with log-rank tests. Multivariate analyses of OS and risk of AL evolution were performed by Cox proportional hazards regression method. The weights assigned to the variables included in the final prognostic scoring system were based on the regression coefficients from the proportional hazards models. Median age was 73 yr and 397 (69%) were males. According to FAB criteria 61% of the patients had MDS-CMML (absolute WBC count '13 × 109/L) and 39% MPD-CMML and by WHO classification 86% were CMML-1 (blasts <10% in bone marrow and <5% in blood) and 14% CMML-2. Karyotype was available in 419 patients (abnormal in 113) and RBC transfusion dependency in 415 (222 transfusion-dependent). With a median follow-up of 33 months, the median OS was 25 months. Seventy-five patients evolved to AL and the cumulative risk to AL transformation was 25% at 5 yr. In univariate analyses patients with CMML-2, presence of 2–3 cytopenias, MPD-CMML, hemoglobin <10 g/L, poor-risk cytogenetics (defined as trisomy 8 or complex karyotype), and RBC transfusion dependency had both a shorter OS and higher risk of AL evolution (P<0.001 in all cases). Additionally, patients with serum LDH level >480 U/L (P<0.001), monocytes >3 × 109/L (P<0.001), platelets '100 × 109/L (P=0.001), serum ferritin level >500 ng/mL (P<0.01), and males (P=0.01) also had a poorer OS. In multivariate analyses the most relevant variables for OS were WHO (P<0.001) and FAB classifications (P<0.001), RBC transfusion dependency (P<0.001), LDH level (P<0.001), hemoglobin level (P<0.001), and cytogenetics (P=0.001). For AL transformation risk the only independent factors were WHO (P<0.001) and FAB classifications (P<0.001), RBC transfusion dependency (P<0.001), and cytogenetics (P=0.01). A prognostic scoring system using WHO (CMML-2, 1.5 points) and FAB classifications (MPD-CMML, 1 point), RBC transfusion dependency (dependent, 1 point), LDH level (>480 U/L, 1 point) and cytogenetic risk group (high-risk, 1 point) was developed (overall risk, 0 – 5.5 points). This scoring system was able to stratify patients into 4 risk groups (low, 0 points; intermediate-1, 1–1.5 points; intermediate-2, 2 points; and high, 2.5 – 5.5 points) with significantly different probabilities of death (median OS, 105, 38, 22, and 11 mo, respectively; P<0.001; Figure) and AL evolution (cumulative risk at 5 yr, 3%, 24%, 33%, and 40%, respectively; P=0.001). The results of this study confirm the prognostic impact of FAB and WHO subtypes and serum LDH level and recognize for the first time the relevance of RBC transfusion dependency and specific chromosomal abnormalities in CMML. Finally, they offer a simple and powerful index for assessing prognosis and planning therapy in CMML.
Figure Overall survival curve according to the CMML Score System. Blue: low, 0 points; Green: intermediate-1, 1-1.5 points: Yellow: intermediate-2, 2 points: and Purple: high, 2.5-5.5 points. Figure. Overall survival curve according to the CMML Score System. Blue: low, 0 points; Green: intermediate-1, 1-1.5 points: Yellow: intermediate-2, 2 points: and Purple: high, 2.5-5.5 points.

Disclosures
No relevant conflicts of interest to declare.