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Graft-Versus-Host Disease (GVHD) After Double-Unit Cord Blood Transplantation (DCBT) Is Associated with Unique Clinical Features Including a Higher Incidence of Grade III-IV Acute GVHD (aGVHD) in Children

Year: 2012

Type: article

Abstract: GVHD is a serious complication and common cause of transplant-related mortality after DCBT. However, relatively little is known about DCBT GVHD manifestations, treatment response, and risk factors. We evaluated 108 DCBT recipients (median 37 years, range 0.9-69) transplanted for high-risk hematologic malignancies with myeloablative (n = 81) or non-myeloablative (n = 27) conditioning, 4-6/6 HLA-matched grafts, calcineurin-inhibitor/mycophenolate mofetil, and no ATG. With a median follow-up of 28 months, the cumulative incidences of day 180 grade II-IV and III-IV aGVHD were 52% (95%CI:42-62) and 24% (95%CI:15-32), respectively. The median onset was 40 days (range 14-161), and the gut was most commonly affected (43/54, 80%). Twenty-five patients with mainly grade II gut aGVHD were treated with budesonide alone, 26 patients with predominantly grade III-IV aGVHD received systemic corticosteroids, and treatment response was achieved in over 80% by day 56 of therapy. However, 41 patients had active GVHD after day 100 with the majority (61%) having aGVHD, particularly of the gut. Classical chronic GVHD was uncommon. Univariate analysis of the association between patient/graft characteristics and grade III-IV aGVHD showed the only significant factor associated with a higher severe aGVHD incidence was age 0-15 years. Multivariate Cox regression analysis was performed (Table). Younger age was independently associated with a higher severe aGVHD incidence whereas better engrafting unit-recipient 8-9/10 HLA-allele match was protective. There was a trend toward better unit-unit HLA-match being associated with worse aGVHD, but, surprisingly, total infused TNC/kg had no relationship. The 2-year PFS of 72% (95%CI:51-94) in children was higher than the 56% (95%CI:45-66) in adults despite their greater incidence of severe aGVHD. We conclude that aGVHD after DCBT is common, predominantly affects the gut, has a high treatment response, children are at a higher risk for severe disease, and late GVHD frequently has acute features. While survival is promising, improved prophylaxis and treatment are needed. A possible approach to reduce aGVHD in pediatric DCBT recipients with adequate CB unit doses would be to prioritize high resolution HLA-match. Moreover, our data does not currently support an upper limit of infused TNC/kg in DCBT recipients. Further investigation of the biology underlying these unique observations should be a priority.TableMultivariate AnalysisCharacteristicCumulative Incidence (95% CI)Hazard RatioP ValueAge (years)0-15 (n = 18)41% (17-65)2.6 (1.0-6.4)0.042≥ 16 (n = 90)20% (12 -29)Reference-Engrafting Unit-Recipient 10 Allele HLA-Match2-7/10 (n = 83)27% (17-37)Reference-8-9/10 (n = 25)12% (0-25)0.3 (0.1-1.0)0.053Unit-Unit 10 Allele HLA-Match0-5/10 (n = 59)20% (9-29)Reference-6-10/10 (n = 49)29% (16-42)2.2 (1.0-5.0)0.062Total TNC x107/kg< 5.0 (n = 68)20% (10-29)Reference-≥ 5.0 (n = 40)31% (16-46)1.2 (0.5-2.8)0.617 Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2011.12.532