Hyperacute Graft-Versus-Host Disease: Analysis of Risk Factors, Clinical Manifestations and Outcomes.

Objective: To evaluate risk factors, clinical manifestations and outcome of hyperacute or early acute graft-versus host disease (GVHD), defined as that occurring within 14 days after hematopoietic stem cell (HSC) transplantation.

Methods: A total of 815 consecutive patients transplanted at UT MD Anderson Cancer Center between 1/1998 and 9/2002 were retrospectively analyzed.

Results: Of 381 patients presenting with acute GVHD, 22% (n=83) had biopsy-proven hyperacute GVHD. Grade I GVHD occurred in 12% of these patients, grade II in 53%, grade III in 13% and grade IV in 22%. The proportion of grade II-IV GVHD in this group was significantly higher (88%) than in the 298 patients presenting with acute GVHD between days 15 and 100 (64%, p value <0.001). The majority of patients with hyperacute GVHD had skin involvement (89%), followed by GI (43%), and liver GVHD (19%). Skin involvement was significantly more common (89% vs 76%, p value 0.01), and more severe (stage III or IV 63% vs 32%, p value <0.001) in the hyperacute group. There was no statistical difference in frequency and severity of visceral involvement. Risk factors for hyperacute GVHD were evaluated using Cox proportional hazards model. On univariate analysis, a mismatched (MM) related (HR=4.4, p value<0.001) matched unrelated (MUD) graft (HR=2.4, p value<0.001) and a myeloablative preparative regimen with or without TBI (HR=2.5, p value<0.001) were significantly associated with a higher rate of hyperacute GVHD. These effects remained significant in a multivariate model. Donor’s age greater than 40 years was associated with a lower rate of hyperacute GVHD (HR=0.6,p value=0.05), and there was a trend for increased rates for patients receiving sex mismatched grafts, solid tumor transplants or multiple (>5) chemotherapy regimens before transplant. Age, disease status, GVHD prophylaxis, or stem cell source (BM vs peripheral HSC) were not associated with hyperacute GVHD. Overall mortality was significantly higher within 6 months post transplant for patients with hyperacute GVHD (HR=2.2, p value <0.001) compared to all other patients, or to patients developing acute GVHD after day 14 (HR=1.6, p = 0.009). GVHD-related death was also significantly higher (HR=2.3, p=0.007) in the hyperacute GVHD group.

Conclusions: Hyperacute GVHD occurs in a substantial proportion of patients undersgoing HSC transplant, even prior to neutrophil engraftment. Skin involvement, grades 3–4 GVHD and a higher mortality are common features of this syndrome . Patients at high risk or with a diagnosis of hyperacute GVHD should be included in clinical studies whenever possible.