Allogeneic Hematopoietic Stem Cell Transplantation for Adult AML Patients with Granulocytic Sarcoma
Authors: Shimizu Hiroaki , Saitoh Takayuki , Tanaka Masatsugu , Mori Takehiko , Kawai Nobutaka , Sakura Toru , Kanda Yoshinobu , Nakaseko Chiaki , Yano Shingo , Fujita Hiroyuki , Fujisawa Shin , Miyawaki Shuichi , Kanamori Heiwa , Okamoto Shinichiro 
Published: October 2019

Abstract
Abstract 2035

Background:
Recently, we described that adult AML patients with granulocytic sarcoma (GS) at diagnosis presented unique characteristics including younger age, higher WBC counts, and higher frequency of French-British-American M4 and M5 morphology than those without GS. Furthermore, GS adversely affected the relapse rate and disease free survival. However, the appropriate therapeutic strategy, especially indication of allogeneic hematopoieteic stem cell transplantation (allo-HSCT), has remained unclear. Here, we present a large-scale retrospective analysis of 503 adult AML patients who underwent allo-HSCT that compared the clinical characteristics and treatment outcomes of patients with GS to those without GS.

Patients and Methods:
This study included 503 consecutive adult AML patients (median age 44 (15–73), male/female; 301/202), excluding patients with acute promyelocytic leukemia, who received allo-HSCT for the first time between January 2000 and December 2008 at 9 institutions participating in the Kanto Study Group for Cell Therapy (KSGCT). GS group was consisted of patients in whom GS occurred any time in the clinical course until transplantation, such as at diagnosis, relapse, and disease progression. The c2-test was used for comparison of binary variables. The Mann-Whitney U test was used for comparison of continuous variables. overall survival (OS) and leukemia free survival (LFS) were estimated by the Kaplan-Meier method, and compared using the log-rank test. The Cox proportional hazards regression model was used for multivariate analysis of prognostic factors. P < 0.05 was considered as statistically significance.

Results:
Of the 503 patients, 44 patients (8.7%) had GS before transplantation. All factors including patients' characteristics and transplantation procedure were not significantly different in each group, but the patients in GS group were significantly younger (GS: median 34 years; range, 17–60 years vs. non-GS: median 46 years; range, 15–73 years; p=0.002). Treatment outcomes, GS vs. non-GS: The cumulative incidences of grade II-‡W acute GVHD, chronic GVHD, and NRM at 1 year were not significantly different in each group. The 5-year OS rate did not differ significantly between the GS and non-GS groups (47% vs. 44%, respectively; p=0.621). The 5-year LFS rate also did not differ significantly (41% vs. 38%, respectively; p=0.646). Since patients in GS group were significantly younger as mentioned above, we performed a subgroup analysis on 336 patients aged 50 or younger; 37 patients in GS group and 298 in non-GS group. Age was not significantly different between the two groups. In this subgroup, too, there was no significant difference in both the 5-year OS rate and the 5-year LFS rate. Treatment outcomes in GS group: Patients in CR at allo-HSCT achieved the significantly superior 5-year OS rate and LFS rate compared to those in non-CR, (OS: 75% vs. 24%, respectively; p=0.002), (LFS: 60% vs. 24%, respectively; p=0.046). In contrast, the prognosis of 10 patients who performed allo-HSCT with accompanying GS was dismal; 9 patients experienced a relapse within 6 months. 5-year OS rate and LFS of 8 patients, who received prior local irradiation for GS, did not significantly differ from those who did not. Both acute and chronic GVHD did not significantly affect the OS and LFS rates, respectively. Twenty-four patients (55%) experienced a relapse after allo-HSCT. Regarding the sites of relapse, only GS, only bone marrow, and both bone marrow and GS were involved in 1 patient (4%), 13 (54%), and 10 (42%), respectively. In 10 patients (91%) out of 11 with GS at relapse, GS occurred at the same site between before and after allo-HSCT. Multivariate analysis identified age and disease status as independent prognostic factors for OS.

Conclusion:
Patients with GS, who treated with allo-HSCT, could achieve the comparable prognosis to those without GS despite poor prognosis of GS. Notably, an excellent treatment outcome was brought about in patients received allo-HSCT in CR. This study suggests that allo-HSCT during an appropriated period may overcome this unfavorable disease.

Disclosures:
No relevant conflicts of interest to declare.