Clinical Significance of Granulocytic Sarcoma in Patients with Acute Myeloid Leukemia.

Granulocytic sarcoma (GS) are extramedullary tumors composed of malignant granulocytic precursor cells and is rare, accounting for 3-9%. Its prognostic impact in adults has been controversially discussed. The objectives of this study were to describe the frequency, presenting characteristics, and the survival in AML patients with GS.

Between January, 1990 and April, 2008 434 patients (median age 57 (15-86), male/female; 260/174) diagnosed as AML were included. Pretreatment factors were investigated in all 434 patients. Treatment outcomes were investigated in 248 eligible patients who were received intensive chemotherapy on Japan Adult Leukemia Study Group protocols AML92, AML95, AML97, or AML201, excluded patients with acute promyelocytic leukemia and dead within 30 days of the diagnosis. The χ2-test was used for the binary variable comparison. The Mann-Whitney U test was used for the continuous variable comparison. Overall survival (OS) and disease free survival (DFS) were estimated by the Kaplan-Meier method, and compared using the log-rank test. The Cox proportional hazards regression model was used for the multivariate analysis of prognostic factors. P < 0.05 was considered to indicate a statistical significance.

1. Pretreatment factors zIn all 434 patients 45 patients (10.4%) were with GS at diagnosis (GS group) and 389 patients without GS (non-GS group). Patients in GS group were significantly younger than non-GS group (44.2±18.3 vs 54.2±17.0; p<0.001), and presented with higher white blood cell counts (p=0.03). No significant differences in sex and lactate dehydrogenase levels demonstrated. Patients in GS group had higher frequency of French-American-British M4 (p=0.001) and M5 (p=0.045) morphology. No significant difference in the expression of any surface marker, the distribution of cytogenetic risk groups, and the frequency of each cytogenetic change including t(8;21), 11q23, inv(16), and the complex karyotype demonstrated. Results 2. Treatment outcomes zIn 248 eligible patients (median age 51 (15-69), male/female; 155/93), 41 patients were with GS and 207 patients without GS. Patients in each group did not differ significantly in distribution of age, sex, and undergoing allogenic hematopoietic stem cell transplantation. CR rates within two courses of induction therapy did not differ significantly (75.6% vs 84.1%; p=0.192) between GS group and non-GS group, however GS group had significantly higher relapse rates compared to non-GS group (74.2% vs 54.7%; p=0.042). 5-year OS did not differ significantly (41% vs 39%; p=0.342), however GS group had a significantly shorter 5-year DFS compared to non-GS group (12% vs 27%; p=0.022). Multivariate analysis of OS showed an independent prognostic significance of only age and cytogenetic risk groups, not GS. Thus that of DFS showed an independent prognostic significance of GS besides age and cytogenetic risk groups.

This study shows that adult AML patients with GS are associated with younger age, higher WBC counts, and monocytic differentiation of leukemia cells. GS adversely affects relapse rate and DFS. Recognition of GS may be a useful tool to identify a subset of adult AML patients with higher risk disease.

No relevant conflicts of interest to declare.