Table I.
Recipient, Donor and Graft properties influencing aGVHD risk.
| Recipient/Donor Properties | Characteristic | Impact* | Study population (n) | Reference |
|---|---|---|---|---|
| Recipient Age | NSA | Related, Unrelated (5561) | (Jagasia, et al 2012) | |
| >30 years | HR=1.5 [1.4–1.7] | Unrelated (3857) | (Lee, et al 2007) | |
| >42 years | RR=1.7 [1.6–2.5] | Related (315) | (Urbano-Ispizua, et al 2002) | |
| >40 years | HR=1.4 [1.2–1.8] | Related (1960) | (Hahn, et al 2008) | |
|
| ||||
| Indication for transplant | CML | HR=2 [1.1–3.6] | Related (493) | (Remberger, et al 2002) |
| HR=1.4 [1.2–1.6] | Related (1960) | (Hahn, et al 2008) | ||
| OR=1.5 [1.1–2.0] (unrelated donor only) | Related, Unrelated (5561) | (Jagasia, et al 2012) | ||
|
| ||||
| Use of unrelated donor | Use of unrelated donor | 2.6 [1.8–3.7] | Related, Unrelated (1481) | (Stern, et al 2006) |
| RR=2.4 [2.1–2.8] | Related, Unrelated (4566) | (Arora, et al 2009) | ||
| HR=1.7 [1.5–1.8] | Related, Unrelated (2941) | (Flowers, et al 2011) | ||
|
| ||||
| HLA Match | Any mismatch (on best available HLA typing) | HR=2 [1.8–2.2] | Related, Unrelated (2941) | (Flowers, et al 2011) |
| HR=3.1 [1.1–8.6] (4/6 vs. 5–6/6) | Unrelated Cord Blood; Paediatric (88) | (Geyer, et al 2011) | ||
| NSA (4/6 vs. 5/6 vs. 6/6) | Unrelated Cord Blood (265) | (MacMillan, et al 2009) | ||
| Any mismatch at HLA-A, -B, -C, or DRB1 | HR=1.5 (1 mismatch); HR=1.8 (2 mismatches) | Unrelated (1874) | (Flomenberg, et al 2004) | |
| RR=2.6 [2.2–3.2] | Related, Unrelated (4566) | (Arora, et al 2009) | ||
| OR=1.3 [1.1–1.5] (unrelated donor only) | Related, Unrelated (5561) | (Jagasia, et al 2012) | ||
| NSA (Any degree of mismatch) | Unrelated, Cord Blood (803) | (Eapen, et al 2011) | ||
| C antigen mismatch; B allele or antigen mismatch | ↑ aGVHD | Unrelated (1933) | (Woolfrey, et al 2011) | |
| >1 mismatch at HLA-A, -B, -C, -DRB1 or -DQB1 | HR=2.5 [1.4–4.5] (severe GVHD) | Unrelated (334) | (Loiseau, et al 2007) | |
| Any mismatch at HLA-A, -B, -C, DRB1 or DP | HR=1.2 [1.1–1.4] (1 mismatch); | Unrelated (3857) | (Lee, et al 2007) | |
| HR=1.6 [1.5–1.8] (2 mismatches) | ||||
| DQ mismatch | NSA | Unrelated (1933) | (Woolfrey, et al 2011) | |
| DQ or DP mismatch | NSA [0.85–1.26] | Unrelated (1874) | (Flomenberg, et al 2004) | |
| DP mismatch, when adjusted for other mismatch | HR=1.3 [1.1–1.5] | Unrelated (5929) | (Shaw, et al 2007) | |
|
| ||||
| ABO Blood Group | Minor ABO mismatch | HR=2.9 [1.4–6.0] | Unrelated (154) | (Ludajic, et al 2009) |
| ABO incompatibility | NSA | Related, Unrelated (1856) | (Wang, et al 2010) | |
| NSA | Related, Unrelated (5561) | (Jagasia, et al 2012) | ||
|
| ||||
| Gender Disparity | Female donor to male recipient | RR=1.3 [1.02–1.7] | Related, Unrelated (1481) | (Stern, et al 2006) |
| HR=1.1 [1.04–1.2] | Related, Unrelated (2941) | (Flowers, et al 2011) | ||
| Alloimmunized female donor to male recipient | HR=3.6 [1.4–9.0] | Related, Unrelated; Reduced Intensity (111) | (Remberger, et al 2008) | |
|
| ||||
| Graft Properties | ||||
| Stem cell source | PBSC or BM use | NSA | Unrelated (513) | (Anasetti, et al 2011) |
| NSA | Related, Unrelated (2941) | (Flowers, et al 2011) | ||
| Use of umbilical cord blood | ||||
| Matched related cord blood vs. matched related marrow | RR=0.4 [0.2–0.7] | Related; Cord blood (2165) | (Rocha, et al 2000) | |
| Compared to matched unrelated marrow |
HR=0.45 [0.2–0.96] (Matched cord blood) NSA [0.4–1.3] (1–2 Mismatched cord) |
Unrelated, Cord Blood; Paediatric (785) | (Eapen, et al 2007) | |
| Compared to matched marrow/mismatched marrow |
NSA [0.6–1.1] (vs. matched marrow) HR=0.7 [0.4–0.99] (vs. mismatched marrow) |
Unrelated, Cord Blood (600) | (Laughlin, et al 2004) | |
| 2 vs. 1 cord blood unit | RR=2 [1.2–3.4] | Unrelated Cord Blood (265) | (MacMillan, et al 2009) | |
| Use of haplo-identical donor | ||||
| Compared to mismatched unrelated donor | NSA | Haplo-identical, Mismatched Unrelated (35) | (Cho, et al 2012) | |
| Compared to matched related, matched unrelated donors | NSA | Related, Unrelated, Haplo-identical (90) | (Burroughs, et al 2008) | |
|
| ||||
| Stem cell dose | High CD34+ cell dose | HR=2.6 [1.3–5.3] | Related (315) | (Urbano-Ispizua, et al 2002) |
| CD34+ cell dose | NSA | Unrelated (932) | (Pulsipher, et al 2009) | |
|
| ||||
| Treg | Low Treg content in graft | ↑ aGVHD | Related (32) | (Rezvani, et al 2006) |
| RR=5 [1.9–16.7] | Related (58) | (Wolf, et al 2007) | ||
|
| ||||
| Conditioning/Post-transplant management | ||||
| Conditioning intensity | Use of Reduced Intensity Conditioning | HR=0.3 [0.1–0.7] | Related (137) | (Couriel, et al 2004b) |
| OR=0.09 [0.01–0.6] | Related (110) | (Mlynarczewska, et al 2004) | ||
| ↓ aGVHD | Related, Unrelated (5561) | (Jagasia, et al 2012) | ||
| HR=0.2 [0.1–0.5] | Unrelated Cord Blood; Paediatric (88) | (Geyer, et al 2011) | ||
|
| ||||
| Conditioning-related Toxicity | No oral intake for >9 days | OR=7.7 [1.4–40.7] (severe GVHD) | Related, Unrelated (231) | (Mattsson, et al 2006) |
| Presence of diarrhoea (>5.5 days duration, >7.94 ml/kg mean (days -3 to 0), or >8.94 ml/kg max) | OR=6–12 | Related (101) | (Liu, et al 2010) | |
|
| ||||
| TBI use in conditioning | Use of TBI | HR=1.4 [1.2–1.7] | Related (1960) | (Hahn, et al 2008) |
| HR=1.5 [1.3–1.5] | Related, Unrelated (2941) | (Flowers, et al 2011) | ||
|
| ||||
| GVHD prophylaxis | Single agent GVHD prophylaxis | OR=2.5 [1.3–4.8] | Related (493) | (Remberger, et al 2002) |
| Use of calcineurin inhibitor monotherapy | OR=2 [1.1–3.7] | Related, Unrelated (304) | (Wermke, et al 2010) | |
| Use of Tacrolimus in GVHD prophylaxis | OR=0.6 [0.5–0.9] (related donor) OR=0.8 [0.7–0.9] (unrelated donor) |
Related, Unrelated (5561) | (Jagasia, et al 2012) | |
| Use of Tacrolimus and methotrexate (compared to cyclosporine and methotrexate) | RR=0.6 | Related (329) | (Ratanatharathorn, et al 1998) | |
| ↓ aGVHD | Unrelated (180) | (Nash, et al 2000) | ||
| In vivo T-cell depletion | ||||
| With anti-thymocyte globulin | HR=0.2 [0.1–0.4] | Unrelated; Reduced Intensity (111) | (Remberger, et al 2008) | |
| RR=0.5 [0.3–0.9] | Unrelated Cord Blood (265) | (MacMillan, et al 2009) | ||
| OR=0.3 [0.2–0.6] | Related, Unrelated (304) | (Wermke, et al 2010) | ||
| NSA [0.7–1.04] | Related, Unrelated (1676) | (Soiffer, et al 2011) | ||
| With alemtuzumab |
HR=0.4 [0.3–0.6] (vs. T-cell replete) HR=0.4 [0.3–0.5] (vs. ATG) |
Related, Unrelated (1676) | (Soiffer, et al 2011) | |
| NSA (vs. ATG) | Related, Unrelated (108) | (Norlin and Remberger 2011) | ||
*
Relative risk (RR), hazard ratio (HR) or odds ratio (OR) provided when reported, otherwise increased or decreased risk is reported. Confidence intervals, when provided, are in brackets.
aGVHD - acute graft-versus-host disease; TBI – Total body irradiation; CML – Chronic myeloid leukaemia; ATG – antithymocyte globulin; NSA – No significant association; RR – Relative risk; HR – Hazard ratio; OR – Odds ratio