Acute graft versus host disease in hematopoietic stem cell alotransplant recipients

Abstract

Introduction: The transplantation of hematopoietic stem cells (HSCT) is a therapeutic intervention where the hematopoietic stem cells and the cells originating from them are being removed and replaced by the normal stem cells of donor or the patient him/her-self. HSCT today represent standardized biological manipulation for treating malignant, genetic and autoimmune diseases. The application of allogeneic hematopoietic stem cell transplantation (HSCT) is limited by life-threatening complications such as severe or acute graft-versus-host disease (GVHD). Despite intensive prophylaxis with immunosuppressive agents, the incidence of GVHD occurs in 9-50% of patients undergoing transplant with an identical HLA sibling matched donor and 75% of patients undergoing unrelated HLA donors.

Aim of study: To evaluate our experiences in GVHD prophylaxis and treatment after alloHSCT, GVHD incidence and prognostic factors and administration of new immunosuppressive regiments. Can we recognize clinical parameters which are associated with occurrence and severity of graft-versus-host disease?

Patients and methods: Starting from September 2000 till September 2010, 63 patients (36 males and 27 females) at the age of 16-56 (median range 33 years) with hematological malignancies were treated with alloHSCT on Department of Hematology, Clinical Centre, Skopje. In 10 patients bone marrow was used as source of stem cells and in 53 patients stem cells were obtained from peripheral blood. From the group of 63 patients, 26 patients had active disease at the time of transplantation. GVHD prophylaxis was accomplished with combination of cyclosporine and methotrexate (Seattle regimen) or more intensive immunosuppression regiments.

Results: GVHD was noticed in 30 patients (47.6%) and in 33 patients (52.4%) a manifestation of GVHD was noticed. Acute GVHD was noticed in 24 patients (38%) and chronic GVHD in 20 patients (31.7%) The remaining 32 patients (45%) achieved complete clinical and hematological remission. Lethal outcome was confirmed in 31(49%) patients (9 from chrGVHD, 6 from acute GVHD, 16 from disease relapse).

Conclusion: The incidence of acute GVHD in our study was 38% and 31% for chronic GVHD. The most common GVHD reaction was registered in female donors and male recipients, with higher GVHD incidence in elderly patients. In all patients stem cells were obtained from peripheral blood. Active disease, sex, source of hematopoietic cells, age and conditional regiments are the most significant predictive factors with the high incidence of GVHD.