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Impact of Conditioning Intensity with or without Total Body Irradiation on Acute Graft-Versus-Host Disease and Clinical Outcomes

Track: Poster Abstracts
Saturday, March 1, 2014, 6:45 PM-7:45 PM
Longhorn Hall E (Exhibit Level 1) (Gaylord Texan)
Hideki Nakasone, MD, PhD , Saitama Medical Center, Jichi Medical University, Saitama, Japan
Takahiro Fukuda, MD , Department of Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan
Junya Kanda, MD, PhD , Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan
Takehiko Mori , Division of Hematology, Keio University School of Medicine, Tokyo, Japan
Takanori Teshima, MD , Department of Hematology, Hokkaido University Graduate School of Medicine, Sapporo-City, Japan
Shingo Yano , Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
Naoyuki Uchida, MD , Department of Hematology, Toranomon Hospital, Tokyo, Japan
Kazuhiko Kakihana , Hematology Division, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Tokyo, Japan
Tetsuya Eto , Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan
Shin-Ichiro Mori, MD , Hematology-Oncology Department, St Luke's International Hospital, Tokyo, Japan
Tokiko Nagamura, MD, PhD , Department of Cell Processing and Transfusion, Institute of Medical Science, University of Tokyo, Tokyo, Japan
Tatsuo Ichinohe , Kyoto University, Kyoto, Japan
Yoshiko Atsuta, MD, PhD , Department of HSCT, Data Management / Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan
Makoto Murata , Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background:

Impacts of conditioning intensity and total body irradiation (TBI) on acute graft-versus-host disease (aGVHD) still remains a matter of debate, because the selection of reduced intensity (RIC) or myeloablative conditioning (MAC) is generally determined based on patient / donor characteristics such as age, HLA mismatch, and donor types.

Methods:

We analyzed 5471 recipients (>15 years old) with AML,ALL,CML or MDS who received allogeneic HCT between 2006 and 2009, using JSHCT registry database. Conditioning is classified as High TBI(>8Gy)-MAC, Low TBI-MAC, nonTBI-MAC, Low TBI-RIC and nonTBI-RIC. The impact of the types of conditioning on aGVHD and other outcomes were assessed. Subgroup analyses were also performed according to donor types: HLA-matched related (MRD, n=1374), HLA-mismatched related (MMRD, n=429), HLA matched unrelated (MUD, n=1508), HLA mismatched unrelated donor (MMUD, n=820), and cord blood (CBT, n=1340).

Results:

The High TBI-MAC group included younger age and more acute lymphoblastic leukemia. The Low TBI-MAC and -RIC groups included more CBT and HLA mismatched BMT/PBSCT. There was a significant difference in the incidence of aGVHD2-4: 39% in High TBI-MAC, 41% in Low TBI-MAC, 31% in nonTBI-MAC, 37% in Low TBI-RIC, and 32% in nonTBI-RIC, respectively (P<0.001). In multivariate analysis, TBI-containing conditionings were significantly associated with an increased risk of aGVHD2-4: HR was 1.34 in High TBI-MAC (P<0.001), 1.50 in Low TBI-MAC (P<0.01), 1.23 in Low TBI-RIC (P=0.011), and 1.21 in nonTBI-RIC (P=0.051) in comparison with nonTBI-MAC. Subgroup analyses revealed that the adverse impact of High TBI-MAC on aGVHD2-4 was observed only in HLA-matched BMT/PBSCT and CBT (HR=1.61 in MRD, P<0.001; HR=1.44 in MUD, P<0.01; HR=1.76 in CBT, P=0.042), while it disappeared in HLA-mismatched BMT/PBSCT (HR=0.72 in MMRD, P=0.72; HR=1.16 in MMUD, P=0.35). Other conditionings had no significant impact on aGVHD2-4 in subgroup analyses. For non-relapse mortality, a favorable impact of High TBI-MAC was observed in MMUD (HR=0.66 in High TBI-MAC, P=0.027), while any adverse impact of TBI-conditioning on relapse/NRM was not observed in any donor types. Finally, the conditioning types had no impact on overall survival (OS) in MRD, MUD, and CBT. Conversely, favorable impacts of TBI-conditioning on OS were observed in MMRD (High TBI-MAC, HR=0.54, P<0.01; Low TBI-RIC, HR=0.48, P<0.01) and MMUD (High TBI-MAC, HR=0.72, P=0.026; Low TBI-RIC, HR=0.65, P=0.015) in comparison with nonTBI-MAC. However, the impact of Low TBI-RIC was not different from that of nonTBI-RIC, when we focused only on RIC,

Conclusion:

The adverse impact of High TBI-MAC on aGVHD2-4 incidence was observed only in HLA-matched BMT/PBSCT and CBT, but not in mismatched BMT/PBSCT. In mismatched HCT, High TBI-MAC rather had a favorable impact on OS and should not be avoided as long as there is no contraindication.

Disclosures:
Nothing To Disclose
See more of: Poster Session 2: GVH/GVL
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