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

Abstract

We sought to compare two graft-versus-host disease (GVHD) prophylaxis regimen, cyclosporine and methotrexate (CsA?MTX) with CsA?mycophenolate mofetil (MMF) in 77 acute leukemia patients who underwent hematopoietic stem cell transplant (HSCT) between January 2008 and March 2013. Fifty-three patients received CsA?MTX while 24 received CsA?MMF. The incidence of grade 3-4 mucositis and grade 3-4 diarrhea was 74 and 6 % with CsA?MTX compared to 33 % and 21 % with CsA?MMF (P = 0.001 and 0.09 respectively). Forty-two (79 %) patients in CsA?MTX group required total parenteral nutrition compared to 14 (58 %) in CsA?MMF group (P = 0.09). The incidence of engraftment fever was 17 % with CsA?MTX and 41 % with CsA?MMF (P = 0.02). The median time to neutrophil and platelet engraftment was 14 days and 13 days with CsA?MTX compared to 12 days and 10 days with CsA?MMF (P = 0.003 and 0.08 respectively). The incidence of any grade and grade II-IV acute GVHD was 45 and 13 % with CsA?MTX compared to 42 and 29 % with CsA?MMF (P = NS). Incidence of overall and extensive chronic GVHD was 57 and 38 % with CsA?MTX compared to 42 and 17 % with CsA?MMF (P = NS). Incidence of relapse was 38 % with CsA?MTX compared to 33 % with CsA?MMF (P = NS). TRM was 6 % with CsA?MTX and 21 % with CsA?MMF (P = NS). At 2 years, overall survival (OS) was 64 % in CsA?MTX group compared to 46 % in CsA?MMF group (P = NS). We conclude that CsA?MMF is associated with lesser toxicity, faster myeloid engraftment and similar rates of acute and chronic GVHD, TRM, relapse and OS compared to CsA?MTX in acute leukemia transplant.

<p>Impact of Low-Dose rATG Prior to Matched Sibling Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies: Reduced Risk of Chronic Graft-versus-Host Disease and Improved Survival Outcomes</p>

“…4 Pharmacological GVHD prophylaxis in the form of the calcineurin inhibitor CsA in combination with MTX is currently the main regimen used in clinical practice; however, it imparts significant toxicities, including nephrotoxicity, neurotoxicity, hypertension, seizures, hypertrichosis, mucositis, etc. 5,27 Replacing CsA with tacrolimus does not significantly reduce the occurrence of GVHD, suggesting that optimizing conventional immunosuppressive regimens has limited benefit for enhancing the prevention of GVHD. 7,8 Another strategy employed as GVHD prophylaxis is T cell depletion in vitro, which may result in a higher incidence of graft failure and relapse, delayed immune reconstitution, and a higher incidence of CMV or EBV reactivation at the same time.…”