Peripheral Blood Stem Cells Versus Bone Marrow Grafts For HLA-Matched Unrelated Donor Transplantation In Adult Patients With Acute Myeloid Leukemia; The Role Of Low-Dose Rabbit Anti-Thymocyte Globuline In The Prophylaxis Of Graft-Versus-Host Disease
Authors: Shin Seung-Hwan , Kim Jung-Ho , Jeon Young-Woo , Yoon Jae-Ho , Yahng Seung-Ah , Lee Sung-Eun , Cho Byung-Sik , Eom Ki-Sung , Kim Yoo-Jin , Lee Seok , Min Chang-Ki , Cho Seok-Goo , Kim Dong-Wook , Lee Jong-Wook , Min Woo-Sung , Park Chong-Won , Kim Hee-Je 
Published: October 2019

Abstract

Background
In the setting of unrelated donor stem cell transplantation (URD-SCT), several data showed that peripheral blood stem cells (PBSC) resulted in faster engraftment but increased the risk of acute or chronic graft-versus-host disease (GVHD), while other transplant outcomes were comparable. However, there are some limitations in these data due to heterogeneous diseases or registry data characterized by various other treatment strategies. Notably, we have added low-dose rabbit anti-thymocyte globuline (ATG) only to the patients who received URD-SCT with PBSC because of their higher risk of developing GVHD. In this setting, we compared the long-term outcomes of URD-SCT using PBSC and bone marrow (BM) and studied the role of low-dose rabbit ATG in the prophylaxis of GVHD.

Methods
Between March 2004 and April 2012, 115 adult patients with AML underwent myeloablative (n=87) or reduced-intensity (n=28) conditioning HLA-matched URD-SCT with PBSC (n=70) or BM (n=45) grafts. All patients received tacrolimus and short-course methotrexate for GVHD prophylaxis. Low-dose rabbit ATG (Thymoglobuline®, 1.25 mg/kg for 2 days) was added only to the patients who received URD-SCT with PBSC grafts. The median follow-up of survivors was 44 months (range, 2-100) for PBSC transplants and 54 months (range, 8-105) for BM transplants (P=0.01).

Results
Baseline characteristics were not significantly different between the two groups except for total-body irradiation conditioning regimen (72.9% vs. 91.1%; P=0.02). PBSC transplants showed faster recovery of neutrophil (11 days vs. 13 days; P=0.03) and platelet (12 days vs. 18 days; P=0.01) counts than BM transplants. No difference was observed in the cumulative incidence of acute GVHD (grade ≥2) at 100 days (54.3% vs. 64.4%; P=0.38) and chronic GVHD at 4 years (61.4% vs. 60.0%; P=0.88) between the two groups. In spite of adding low-dose rabbit ATG, PBSC transplants did not show higher incidence of relapse compared to that of BM transplants (30.8% vs. 31.2%; P=0.53). Other transplant outcomes including non-relapse mortality (13.5% vs. 6.9%; P=0.24), disease-free survival (55.7% vs. 61.9%; P=0.80), and overall survival (63.3% vs. 63.2%; P=0.59) were comparable between the two groups. In multivariate analysis, graft source had no impact on transplantation outcomes. Regardless of graft source, transplants in ≥CR2 had higher relapse risk (hazard ratio, 2.45; 95 % CI, 1.04-5.76; P=0.04), poorer disease-free survival (hazard ratio, 2.68, 95% CI, 1.29-5.56; P=0.01) and overall survival (hazard ratio, 2.59; 95% CI, 1.20-5.59; P=0.02).

Conclusion
Adding low-dose rabbit ATG to the patients who received URD-SCT with PBSC may lower the incidence of acute and chronic GVHD comparably to that of URD-SCT with BM without increasing the incidence of relapse.

Disclosures:
No relevant conflicts of interest to declare.