Abstract 2853

Introduction:

Splenectomy may be an effective therapeutic option for treating massive splenomegaly in patients with MPNs. There is still limited data on its short- and long-term benefits and risks. Objective: To describe short-term outcomes, complications and impact on survival and transformation to acute myeloid leukemia (AML) in patients with MPNs who underwent splenectomy.

Methods:

First, efficacy and short-term complications were analyzed in 94 patients with different MPNs who underwent splenectomy at MD Anderson between 1981–2009. Second, medical records of 696 patients with myelofibrosis (MF) seen at MD Anderson between 1966–2009 were reviewed (among which 91 underwent splenectomy either at or outside MD Anderson) to evaluate the long-term impact of splenectomy on overall survival (OS) and transformation-free survival (TFS). Improvement in anemia and thrombocytopenia were defined by the International Working Group on Myelofibrosis Research and Treatment response criteria. Survival was estimated by Kaplan-Meier method, and hazard ratios (HR) were determined by Cox multivariate analysis. Splenectomy was analyzed as a time-dependent covariate. Risk in patients with MF was determined by the Dynamic International Prognostic Scoring System (DIPSS). Accelerated phase (AP) criteria in MF were determined as thrombocytopenia <50×109/L, chromosome 17 abnormalities and blasts >10% in peripheral blood (PB) or bone marrow (BM).

Results:

Splenectomy improved spleen pain, anemia and thrombocytopenia in 84%, 47% and 66% of patients, respectively. Among patients with MF, improvement in anemia and thrombocytopenia was seen in 44% and 75% of patients, respectively. Hematological complications included post-operative leukocytosis (76%) and thrombocytosis (43%), developing within a median time of 1 day and 5 days post-surgery, respectively. Early (<7 days) intervention for control of elevated white blood cell and/or platelet count was needed in 37% of patients. Forty-six percent of patients developed non-hematological clinical complications, and the most common was venous thromboembolism (VTE; 16%). VTE sites included portal vein (N=11), supra-hepatic vein (N=3) and superior vena cava, pulmonary embolism and splenic vein (N=1 each). Post-operative mortality was 5%. Median survival post-splenectomy was 19.2 months, and 5-year survival 16.1%. In the second cohort of patients with MF, requirement for splenectomy was associated with decreased OS (HR=2.84, p<0.0001) and TFS (HR=2.79, p<0.0001). In the multivariable model, the time dependent covariate splenectomyremained an independent risk factor for inferior OS and TFS in patients with MF, alongside male sex, transfusion dependency, DIPSS score and AP criteria (Table).

Conclusions:

Splenectomyis a possible therapeutic option for patients with MF and other MPNs, and its greatest benefits are related to improvement in spleen pain and discomfort, anemia and thrombocytopenia. However, in patients with MF it appears to be associated with increased mortality and risk of transformation to AML.

Table:

Cox multivariable analysis for TFS and OS

CovariateHR (95% CI)P
TFS   
Splenectomy (yes vs. no) 2.53 (1.86–3.44) <0.0001 
Male sex (yes vs. no) 2.10 (1.62–2.73) <0.0001 
Transfusion dependency (yes vs. no) 1.48 (1.14–1.92) 0.003 
DIPSS risk category   
    • Intermediate-1 (vs. Low) 1.92 (1.07–3.45) 0.02 
    • Intermediate-2 (vs. Low) 1.94 (1.07–3.52) 0.02 
    • High (vs. Low) 2.53 (1.35–4.73) 0.004 
AP Criteria   
    • Present (vs. Absent) 2.39 (1.80–3.17) <0.0001 
    • Unclassifiable (vs. Absent) 0.84 (0.52–1.34) 0.46 
OS   
Splenectomy (yes vs. no) 2.54 (1.86–3.48) <0.0001 
Male sex (yes vs. no) 2.17 (1.65–2.85) <0.0001 
Transfusion dependency (yes vs. no) 1.51 (1.16–1.97) 0.002 
DIPSS risk category   
    • Intermediate-1 (vs. Low) 2.06 (1.09–3.88) 0.02 
    • Intermediate-2 (vs. Low) 2.09 (1.10–3.98) 0.02 
    • High (vs. Low) 2.93 (1.50–5.72) 0.002 
AP Criteria   
    • Present (vs. Absent) 2.53 (1.89–3.38) <0.0001 
    • Unclassifiable (vs. Absent) 0.97 (0.59–1.57) 0.91 
CovariateHR (95% CI)P
TFS   
Splenectomy (yes vs. no) 2.53 (1.86–3.44) <0.0001 
Male sex (yes vs. no) 2.10 (1.62–2.73) <0.0001 
Transfusion dependency (yes vs. no) 1.48 (1.14–1.92) 0.003 
DIPSS risk category   
    • Intermediate-1 (vs. Low) 1.92 (1.07–3.45) 0.02 
    • Intermediate-2 (vs. Low) 1.94 (1.07–3.52) 0.02 
    • High (vs. Low) 2.53 (1.35–4.73) 0.004 
AP Criteria   
    • Present (vs. Absent) 2.39 (1.80–3.17) <0.0001 
    • Unclassifiable (vs. Absent) 0.84 (0.52–1.34) 0.46 
OS   
Splenectomy (yes vs. no) 2.54 (1.86–3.48) <0.0001 
Male sex (yes vs. no) 2.17 (1.65–2.85) <0.0001 
Transfusion dependency (yes vs. no) 1.51 (1.16–1.97) 0.002 
DIPSS risk category   
    • Intermediate-1 (vs. Low) 2.06 (1.09–3.88) 0.02 
    • Intermediate-2 (vs. Low) 2.09 (1.10–3.98) 0.02 
    • High (vs. Low) 2.93 (1.50–5.72) 0.002 
AP Criteria   
    • Present (vs. Absent) 2.53 (1.89–3.38) <0.0001 
    • Unclassifiable (vs. Absent) 0.97 (0.59–1.57) 0.91 
Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.

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