Cyclosporine a and Mycophenolate Mofetil Vs Cyclosporine a and Methotrexate as Gvhd Prophylaxis in Reduced Intensity Conditioning Hematopoietic Stem Cell Transplantation from HLA-Identical Sibling Donor.

J.L.Piñana is supported by grants from the Instituto de Salud Carlos III (expedient CM06/00139, Ministerio de Sanidad)

Background: Cyclosporine A (Csa) with methotrexate (MTX) is the most common prophylactic regimen against acute graft versus host disease (aGVHD). Although some studies show that Mycophenolate Mofetil (MMF) in combination with Csa for patients undergoing allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is associated with early hematologic recovery, less toxicity as mucositis and no diferencies in terms of aGVHD. Limited data is available comparing these two combinations in reduced intensity conditioning Allo-HSCT (Allo-RIC). In this case-control study from two Spanish BMT centers, we retrospectively analyzed the introduction of MMF as GVHD prophylaxis in comparison with a short course of MTX in a large series of patients who underwent HLA identical sibling donor Allo-RIC.

Patients and methods: We include 145 consecutive Allo-RIC patients, who received peripheral blood (PB) as source of stem cells, between April 2000 and August 2007. The median follow-up for the whole group was 514 days (8 to 3170 days). The study group included 91 males and 54 females. Median age was 55 years (range 18 to 71 years). Diagnoses were acute leukemia/myelodisplastic syndrome/myeoloproliferative disorders) (n=37/15/13), multiple myeloma (n= 32), Hodgkin lymphoma (n= 6), chronic lymphocytic leukemia (n=15) and non-Hodgkin lymphoma (NHL) (n= 27). GVHD prophylaxis consisted of CsA/MMF in 52 and CsA/MTX in 93 patients. The conditioning regimen was based on fludarabine in combination with busulfan (59 recipients) or melphalan (86 cases).

Results: The occurrence of mucositis grade 2–4 was higher in the CsA/MTX group than in the CsA/MMF group (57% vs 23% p= 0.001). No significant differences were found between CsA/MMF and CsA/MTX groups in time to neutrophil recovery (15 +/−3 days vs 15 +/− 2days) (p= 0.5). Cumulate incidence of acute GVHD were 50% (95% C.I., 38–65) for CsA/MMF group and 48% (95% C.I. 39–60%) for CsA/MTX group (p= 0.9). Although chronic GVHD was also similar [71% (95% C.I. 58–86%) in CsA/MMF group vs 68% (95% C.I. 57–80%) in Csa/MTX group (p= 0.7)], we observed that the development of chronic GVHD was delayed in the CsA/MMF group [174 days (range 100–365) vs 134 days (range 84–302) p= 0.008)]. Non relapse mortality (NRM) at 100 days was higher in MTX group (6% vs 18%, p=0.04). However, relapse and overall survival at median follow-up were still similar between groups (25% vs 18%, p= 0.4 and 52% vs 51%, p=0.7, respectively).

Conclusion: We conclude that the combination Csa/MMF appears to be at least equivalent to the standard Csa/MTX GVHD prophylaxis in HLA identical sibling donor Allo-RIC. The toxicity profile of Csa/MMF was better, reflected by a significantly less incidence of mucositis.