Cyclosporine A and Mycophenolate Mofetil vs Cyclosporine A and Methotrexate for graft-versus-host disease prophylaxis after stem cell transplantation from HLA-identical siblings

Abstract

Summary:The combination of Cyclosporin A (CSA) and Methotrexate (MTX) is considered to be the standard regimen for the prevention of graft-versus-host disease (GVHD) after stem cell transplantation (SCT) from HLA-identical siblings. Mycophenolate Mofetil (MMF) has been widely used for GVHD prophylaxis after nonmyeloablative SCT, but experience following myeloablative therapy is still limited. We retrospectively compared CSA/MTX and CSA/MMF in 93 patients (median age 35 years, range 17-59 years, male subjects 48, female subjects 45) with acute myeloid leukemia (n ¼ 33), myelodysplastic syndrome (MDS) (n ¼ 3), acute lymphoblastic leukemia (ALL) (n ¼ 20) or chronic myeloid leukemia (n ¼ 37) who received CSA/MMF (n ¼ 26) or CSA/MTX (n ¼ 67) as GVHD prophylaxis following high-dose therapy and allogeneic SCT from HLA-identical siblings. No statistically significant differences were found in overall survival, relapse rate, treatment-related mortality and acute or chronic GVHD. Time to myeloid recovery was significantly shorter in patients who received CSA/MMF. We conclude that the combination of CSA/MMF appears equivalent to CSA/MTX for GVHD prophylaxis in patients receiving conventional-intensity SCT from HLA-identical siblings.

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

“…In line with several studies comparing the introduction of MMF instead of MTX as GVHD prophylaxis in Table 2 Cause of death according to the GVHD prophylaxis allo-HSCT, 5,10,21 in this retrospective study we report a similar incidence of GVHD and possibly a somewhat improved toxicity profile in favor of the CsA/MMF combination. It is important to note, however, that earlier studies comparing the impact of such combinations on the toxicity profile, the incidence of GVHD and transplantrelated mortality, had considerable limitations.…”

“…In combination with CsA, it has shown a good safety profile in phase II trials. 5,10,11 However, no differences in the rate of acute GVHD (aGVHD) were obtained after conventional high-dose allo-HSCT compared with standard CsA/MTX prophylaxis. 10,11 A recent study by Neumann et al 5 showed that CsA/MMF was as efficient as CsA/MTX for GVHD prophylaxis, but with faster hematopoietic recovery.…”

“…3,4 However, MTX delays hematopoietic engraftment, worsens oral mucositis and may be associated with pulmonary and renal toxicity after allo-HSCT. [5][6][7][8] In patients undergoing allo-RIC, reducing procedure-related toxicities may be of great importance, as these patients usually have greater comorbidities. Thus, in an attempt to reduce any MTX-associated toxicities, mycophenolate mofetil (MMF) has replaced MTX in RIC regimens in recent years.…”

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

“…22,23 Studies on the use of MMF as part of GVHD prophylaxis have been limited in size and mostly inconclusive, as most investigators reported insufficient plasma levels of the active metabolite MPA. [3][4][5]8,24,25 Most of these studies revealed a favorable toxicity profile of combinations of MMF with calcineurin inhibitors compared to regimens incorporating MTX. Encouraging results were reported by Nash et al, 7 who demonstrated that the rate of GVHD Targeting mycophenolate mofetil for GVHD prophylaxis I Haentzschel et al after transplantation from matched-sibling donors could be significantly reduced by using higher MMF doses up to 60 mg/kg daily.…”

Cyclosporine in combination with mycophenolate mofetil versus methotrexate for graft versus host disease prevention in myeloablative HLA‐identical sibling donor allogeneic hematopoietic cell transplantation

“…A study comparing Tac and MMF to Tac and MTX in both sibling and unrelated donor myeloablative HCT also demonstrated no difference in 100 day incidence of grade 2-4 GVHD, with a significant reduction in toxicities, but a higher incidence of grade 3-4 GVHD, primarily in unrelated donor transplants [15]. Additional small retrospective studies evaluating MMF in myeloablative transplant recipients have also confirmed improved toxicity and GVHD incidence and survival outcomes that are comparable to MTX [16,17]. On the basis of these data, we have routinely employed MMF in myeloablative MSD donor allogeneic HCT for GVHD prophylaxis at our institution.…”