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

Abstract

Mycophenolate mofetil (MMF) in combination with CsA seems to lead to earlier post transplant hematological recovery and less mucositis than MTX, with a similar incidence of GVHD. In this study we analyzed the post transplant outcomes of two cohorts of patients who underwent an HLA-identical sibling reduced intensity conditioning transplantation (allo-RIC) with GVHD prophylaxis consisting of CsA in combination with either MMF or a short course of MTX. We included 145 consecutive allo-RIC transplants performed between April 2000 and August 2007. The median follow-up for survivors was 41 months (4-105 months). The study group included 91 males. Median age was 55 years (range 18-71 years). Diagnoses included myeloid (n ¼ 65) and lymphoid (n ¼ 80) malignancies. GVHD prophylaxis consisted of CsA/MMF in 52 and CsA/MTX in 93 patients. The conditioning regimen was based on fludarabine in combination with BU (n ¼ 59) or melphalan (n ¼ 86). The occurrence of grade 2-4 mucositis was higher in the CsA/MTX group than in the CsA/MMF group (57 vs 23%, P ¼ 0.001). The cumulative incidence of acute and chronic GVHD was similar, 48 vs 50% and 71 vs 68%, respectively (P40.7). The 2-year relapse and OS were similar in the CsA/MTX and CsA/MMF groups (29 vs 21%, P ¼ 0.3 and 52 vs 51%, P ¼ 0.7, respectively). Our results support further prospective studies comparing the use of the CsA/MMF combination with CsA/MTX as GVHD prophylaxis in HLA-identical sibling donor allo-RIC recipients.

Use of immunoglobulins in the prevention of GvHD in a xenogeneic NOD/SCID/γc− mouse model

“…[31][32][33][34][35][36] and despite first-line prophylaxis usually consisting of CsA and MTX, GvHD still occurs in 10-50% of patients depending on the HLA disparity between host and donor. 29,52 Although CsA is considered a cornerstone in GvHD prophylaxis, we showed that its reduction of GvHD-related mortality was comparable to that observed by IVIG in our model. In a clinical setting, IVIG are used with CsA and other immunosuppressive drugs, although in our model IVIG and CsA were used alone.…”

The impact of graft-versus-host disease prophylaxis in reduced-intensity conditioning allogeneic stem cell transplant in acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

“…The type and dose of post-transplant immunosuppression in the context of non-ATG-containing, fludarabinebased RIC from HLA-identical sibling donors was recently evaluated by Piñana et al 18 The authors found similar posttransplant outcomes with either a combination of CsA and MTX or of CsA and MMF. In our study, we also observed similar outcomes in the group of patients who received MTX or MMF and CsA without ATG (data not shown), but this group had a higher risk of chronic GVHD leading to worse survivals.…”

“…Transplantation outcomes were similar in the two groups with the exception of a higher incidence of grade 2-4 mucositis with CsA + MTX. 18 In this study, we retrospectively investigated the impact of the intensity of the GVHD prophylaxis on the posttransplant outcomes of a homogeneous cohort of 228 adult patients over 50 years old with de novo acute myeloid leukemia in first complete remission given haematopoietic stem cells from HLA-identical siblings following fludarabine and 2 days of intravenous busulfan (Flu-ivBu2) RIC. We analyzed the impact of the use of ATG with CsA compared to a combination of ATG and CsA + MTX or MMF versus CsA and MTX or MMF with no ATG as post-transplant GVHD prophylaxis.…”

Cyclosporine Plus Methotrexate or Cyclosporine Plus Mycophenolate Mofetil as Graft Versus Host Disease Prophylaxis in Acute Leukemia Transplant: Comparison of Toxicity, Engraftment Kinetics and Transplant Outcome

“…These include use of immunosuppressive drugs singly and in combination [14,15], tailoring the dose of CsA depending on blood levels [16,17] and evaluation of newer immunosuppressive agents in comparison with standard agents [5][6][7][8][9][10]. CsA combined with either MTX or MMF is the most widely used immunosuppressive drug [5,6,8].…”

“…Mycophenolate mofetil (MMF), a pro-drug of mycophenolic acid, inhibit T cell activation and proliferation and has been used in combination with CsA for GVHD prophylaxis [8][9][10]. Compared to MTX, MMF has been shown to be less toxic when used in combination with CsA for GVHD prophylaxis [8].…”