Risk Factors for Response after Initial Therapy for Acute Graft-Versus-Host-Disease (aGVHD).

Introduction: Acute GVHD remains the most important early complication and limitation to allogeneic hematopoietic stem cell transplantation (HSCT). Although far from optimal, corticosteroids remain initial standard therapy with an overall response rate of 50%. Steroid resistant patients have a dismal prognosis, with mortality rates reaching 90%. Objective: To identify the subgroup of patients that would not benefit from initial therapy with corticosteroids. Thus, accrual of these patients into clinical studies would be mandatory. Methods: Retrospective evaluation of all (N= 287) patients who developed biopsy proven aGVHD after allogeneic HSCT at the University of Texas M. D. Anderson Cancer Center from 1998 through 2002. All patients received initial therapy for aGVHD with methylprednisolone. Prognostic factors for response (CR/PR) to initial therapy with corticosteroids were evaluated using logistic regression analysis including age, gender, donor/patient sex mismatch (F/M), donor type, cell type, intensity of conditioning regimen, diagnosis, disease status at transplant, number of prior chemotherapy regimens, number of prior autologous HSCT, CD34+ cell dose infused, time of onset of aGVHD and grade at initiation of first line therapy. Results: At the time of first line therapy, 89/287 patients (31%) had grade I aGVHD, 141 (49%) had grade II, and 57 (20%) had grade III–IV. Overall response to first line therapy was 56% and was comparable between patients with grade I and II aGVHD. Grade III–IV aGVHD (CR/PR 39% vs. 60%, p=0.003) and hyperacute GVHD (occurring by day +14) (CR/PR 42% vs. 61%, p=0.007) were the most significant prognostic factors for failure. Sex mismatch was associated with significantly lower response rate in patients with grade III–IV (CR/PR 12% vs. 49%, p=0.02) but not in patients with grade I–II (CR/PR 61% vs. 60%, p=0.9). Failure to respond to first line therapy was the most significant predictor of non-relapse mortality at one and two years after initiation of first line therapy (p<0.001) for all GVHD grades. Conclusions: Hyperacute GVHD and sex mismatch are significant predictors of response to first line therapy. Response to first line therapy has a strong and independent effect on survival. These factors should be integrated in prognostic scoring systems of aGVHD, which would allow identification of patients who would not benefit from standard therapeutic approaches. | Overall (N=287) | | | | | | | | |:---------------------------------------------:| --- | ------ | --------- | ------------------ | ------- | ------------------ | ------- | | | n | %CR/PR | p value | | | | | | CR: complete remission, PR: partial remission | | Grade at First Line | | | | | | | | | I | 89 | 65% | Reference | | | | | | II | 141 | 57% | 0.2 | | | | | | III/IV | 57 | 39% | 0.003 | | | | | | | | | | Grade I/II (N=230) | | Grade III/IV(N=57) | | | | | | | n, %CR/PR | p value | n, %CR/PR | p value | | Hyperacute GVHD | | | | | | | | | Yes | 73 | 42% | | 60, 48% | | 13, 15% | | | No | 214 | 61% | 0.007 | 170, 65% | 0.03 | 44, 45% | 0.05 | | Donor/Patient sex mismatch | | | | | | | | | Yes | 73 | 51% | | 57, 61% | | 16, 12% | | | No | 214 | 58% | 0.3 | 173, 60% | 0.9 | 41, 49% | 0.02 | Response To First Line Therapy