Cellcept/cyclosporine as prophylaxis against graft- versus-host disease in pediatric patients undergoing allogeneic stem cell transplantation

Traditionally, pediatric patients are prophylaxed against acute graft-versus-host disease (GvHD) with cyclosporine combined with either methotrexate Mtx) or methylprednisolone (Pred). Mtx worsens the severity of mucositis and renal insufficiency while pred causes muscle wasting, hypertension and increased infections. Cellcept (myophenolic acid) is a better tolerated, less toxic agent with synergistic immunosuppressive effects when combined with cyclosporine or tacrolimus. We explored its use in combination with cyclosporine in 21 pediatric patients undergoing allogeneic transplantation. Patients with both malignant (n = 7) and non-malignant (n = 14) conditions ranging in age from 2 weeks to 15 years were transplanted after myeloablative preparative regimens with either related bone marrow or cord blood (n = 7) or unrelated cord blood (n = 14), using cellcept and cyclosporine for GVHD prophylaxis. Cellcept and cyclosporine were administered intravenously through the first 40-60 days post transplant using cellcept at a dose of 15mg/kg/dose IV q8H beginning on day -2 or -3. The patient then transitioned to oral therapy at the same dose and schedule. There were no acute toxicities attributable to cellcept observed in patients on IV therapy. All patients required treatment with antihypertensive therapy(ies). Grossly infection rates did not vary from those previously observed in conventionally treated patients at our center. 18/21 patients engrafted neutrophils between day 9 and 52. Of the three patients who did not engraft, 2 died of infectious complications, one died of VOD and multi-system organ failure. Of the 18 patients, evaluable for GvHD follow-up ranged between 34 and 693 days (median 108 days), 6 patients had 0 grade I, 10 developed grade II, 1 grade III, and 1 grade 4 GVHD. Follow-up is too short to comment on the incidence of chronic GvHD, but to date, 4 of 7 patients followed for >100 days have developed chronic GvHD. While this data is early, it appears that the incidence of both acute and chronic GvHD are increased compared to previously reported series in patients treated with cellcept instead of mtx (related bone marrow transplantation) or pred (unrelated cord blood transplantation). Engraftment in UCBT recipients was not compromised with the use of IV cellcept administered in the peritransplant period. Additional patients will need to be tested with this regimen and longer follow-up is necessary to fully define the risks or benefits of this therapy.