Outcomes in Patients with Chronic Myelomonocytic Leukemia: Analysis of 279 Patients.
Authors: Borthakur Gautam , Beran Miloslav , Liu Jun , Verma Dushyant , Dong Xiao Q , Rondon Gabriela , Champlin Richard E. , Kantarjian Hagop , Popat Uday R 
Published: October 2019

Background: Chronic myelomonocytice leukemia is characterized by peripheral blood/bone marrow monocytosis and variable degree of dysplasia. The World Health Organization classification includes it in a myelodysplastic/myeloproliferative disorder category. We have reported earlier on a predictive model (MDAPS) based on hemoglobin, presence of circulating immature cells, absolute lymphocyte count and blast percentage and this has been validated in prospective group (Beran,M. et al. Leuk Lymphoma.2007;48:1150). In recent times hypomethylating agents are reported to have activity in this disease. Five year estimated survival with stem cell transplant is in the 20% range.

Patients and Method: We performed an analysis of 279 patients seen at MD Anderson Cancer Center between the years 1999–2007. We also included 26 (9%) patients who underwent SCT in the analysis. Patients were assigned a score according to the International Prognostic Scoring System (IPSS) used for patients with myelodysplastic syndrome. Cox proportional hazard regression models were used for each variable. Log transformations were used for WBC, platelet counts, lactate dehydrogenase levels and absolute monocyte counts. Stepwise model selection was employed to fit a multivariable model.

Results: Median age of patients is 68 years (range, 30–89), WBC count 14.5 x106/ml (range, 1.7–99), hemoglobin 10.3 gm/dL (range, 5.9–16.4), platelet count 98 x106/ml, beta 2 micrglobulin 4.1 mg/L (range, 1.2–20), absolute monocyte count 2.9 x106/ml (range, 1–40.2). Median survival is 15.7 months [95% confidence interval (CI); 13.9–18.8]. In univariate analysis patients undergoing stem cell transplantation survived longer than the others (hazards ratio 0.59, 95% CI 0.3–0.9) (Fig.1). Survivals at 2 and 5 years were 40.5% (95% CI, 0.22–0.72) and 24.3 (95% CI, 0.1–0.6) respectively in patients undergoing transplant versus 34.3% (95% CI, 0.27–0.42) and 8.9% (95% CI, 0.05–0.17) for others. Additionally WBC, creatinine, LDH, absolute monocyte count, hemoglobin and platelet count were laboratory parameters significantly associated with survival (Table 1). Splenomegaly, higher IPSS score (1.5 and above) and poor-risk cytogenetics (−5 and or −7, 8 abnormality) predicted for worse survival. Multivariate analysis indicated that lower hemoglobin level and platelet count and higher absolute monocyte count predicted for worse survival. Further analysis including treatment as a variable is in progress.

Conclusion: Survival of patients with CMML has not improved despite availability of agents with activity in this disease. SCT may improve outcome but larger number of patients is needed for definitive answer.

Table 1. Univariate analysis

Variable HR(95%CI) p-value Age 1.01 (1.00–1.03) 0.10 WBC 1.44 (1.22–1.70) <.0001 Hemoglobin 0.84 (0.78–0.91) <.0001 Platelet 0.80 (0.70–0.92) 0.001 Creatinine 1.17 (1.06–1.28) 0.001 LDH 1.35 (1.04–1.77) 0.03 Absolute Monocyte count 1.47 (1.24–1.74) <.0001 Bone marrow blast percentage 1.04 (1.01–1.07) 0.01 Normal spleen size 0.69 (0.49–0.96) 0.03 IPSS (1.5 or higher) 2.23 (1.35–3.67) 0.002 SCT 0.53 (0.30–0.93) 0.03 Cytogenetics (−5, −5 and −7, −7,+8) 2.09 (1.43–3.05) 0.0001

Fig. 1: Survival analysis according to stem cell transplant status Fig. 1:. Survival analysis according to stem cell transplant status