Influence of the intensity of the conditioning regimen on the characteristics of acute and chronic graft‐versus‐host disease after allogeneic transplantation

Abstract

SummaryThe graft‐versus‐host disease (GVHD) characteristics of 150 consecutive patients undergoing reduced intensity conditioning allogeneic (allo‐RIC) transplants and 88 patients undergoing myeloablative conditioning regimen were analysed. All patients received the same GVHD prophylaxis and peripheral blood stem cells from a human leucocyte antigen identical sibling. The cumulative incidence of acute GVHD (aGVHD) was 67% and 44% in the myeloablative and allo‐RIC regimen groups, respectively (P < 0·001), and was 39% vs. 29%, respectively (P = 0·043), for grades 2–4 aGVHD. Only conditioning type (myeloablative versus allo‐RIC) significantly influenced the incidence of aGVHD in multivariate analysis: Hazard ratio (HR) = 2·16 [95% confidence interval (CI): 1·52–3·07], P < 0·0001. The cumulative incidence of chronic GVHD (cGVHD) was 63% and 71% among myeloablative and allo‐RIC patients respectively (P = 0·084). This trend was because of the higher incidence of limited cGVHD, but not extensive cGVHD among allo‐RIC recipients [HR = 3·3 (95% CI: 1·42–8·08), P = 0·0017]. Moreover, among patients who developed cGVHD, the cumulative incidence of limited cGVHD was significantly lower in the myeloablative group than in the allo‐RIC group (7% vs. 25%, P = 0·007). Duration of immunosuppression was shorter among allo‐RIC patients (35·5% vs. 68·8% required systemic immunosuppression 36 months after transplant, P = 0·028). Although prospective controlled trials are required to further evaluate the effect of the conditioning regimen on GVHD, our results suggest that RIC modifies the incidence and characteristics of both acute and cGVHD after allogeneic transplantation, and decreases the immunosuppression requirements in long‐term follow up when compared with myeloablative conditioning.

UVA (UVA-1) therapy for the treatment of acute GVHD of the skin

“…In our analysis, patients with RIC demonstrated a later median onset of acute GVHD compared with non-RIC patients. This observation is in accordance with that reported by Perez-Simon et al 29 Although it has been reported that RIC decreases the incidence and severity of acute GVHD when compared with non-RIC, [29][30][31] we could not demonstrate an influence of the type of conditioning regimen on the severity of acute cutaneous GVHD. However, patients with RIC required more treatment sessions and a higher median dose of UVA-1 irradiation for treatment of acute GVHD of the skin (mainly grade 1) compared with patients with non-RIC HCT.…”

Reduced intensity compared with high dose conditioning for allotransplantation in acute myeloid leukemia and myelodysplastic syndrome: A comparative clinical analysis

“…These data add to an increasing body of evidence [19][20][21][22] that RI HSCT can be clinically potent with an antileukemia effect capable of inducing and maintaining a long term remission in these aggressive myeloid malignancies. The preferred intensity within the spectrum of RI or non-MA conditioning regimens for myeloid leukemia continues to be a subject of study [16,23]. Regimens sufficiently nontoxic, but with antileukemic potency to effectively cyto-reduce the tumor mass while still permissive of donor engraftment and the ensuing immunological graft versus leukemia effect await evaluation in prospective clinical trials.…”

MTX or mycophenolate mofetil with CsA as GVHD prophylaxis after reduced-intensity conditioning PBSCT from HLA-identical siblings

“…12,13 Briefly, fludarabine 150 mg/m 2 was combined with BU 8-10 mg/kg for myeloid malignancies (8 mg/kg for patients 465 years old; there were five patients in the CsA/MTX group and four in the CsA/ MMF group) or melphalan 70-140 mg/m 2 (for multiple myeloma and lymphoid malignancies, respectively).…”

“…All patients were included in a series of consecutive allo-RIC trials designed for patients who were not eligible for a conventional highdose myeloablative conditioning, as reported elsewhere in detail. 12,13 All patients received an HLA-identical sibling allo-RIC and PBSC as the stem cell source without in vivo/ ex vivo T-cell depletion. All participants gave written informed consent, and the studies were approved by the national and local ethics committees.…”