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Use of intravenous mycophenolate mofetil for graft-versus-host disease prophylaxis in an allogeneic hematopoietic stem cell transplant recipient with an allergic reaction to cyclosporine and tacrolimus

Bone Marrow Transplantation volume 38, pages 253–254 (2006)Cite this article

Most graft-versus-host disease (GHVD) prophylaxis regimens utilized during allogeneic hematopoietic stem cell transplantation (HSCT) contain either cyclosporine (CSA) or tacrolimus alone or in combination with other agents. An allergic reaction to either of these agents is extremely rare, possibly due to the immunosuppression induced by the conditioning regimen. In the event of a reaction involving both agents, however, the optimal choice of GVHD prophylaxis is unclear.

A 7-year-old boy of Chinese descent with an on-therapy bone marrow relapse of B-precursor acute lymphoblastic leukemia was admitted for allogeneic HSCT from his human lymphocyte antigen-identical sister. He had a prior history of multiple food allergies, including reactions to nuts and sesame. His conditioning regimen consisted of total body irradiation delivered over 4 days in 11 fractions of 120 cGy each (total dose 1320 cGy), followed by one dose of intravenous etoposide (60 mg/kg over 4 h).1 He was initially ordered to receive intravenous CSA (5 mg/kg) given over 20 h starting on Day −2, then tapered per institutional protocol, followed by methotrexate (15 mg/m2 on Days +1, 10 mg/m2 on Day +3, +6 and +11) for his GHVD prophylaxis regimen.2 Within minutes of starting CSA, he developed angioedema of the lips and respiratory distress. The infusion was halted and he received diphenhydramine and hydrocortisone (HC), with resolution of his symptoms. The following day, his GVHD prophylaxis was switched to intravenous tacrolimus (0.03 mg/kg) given over 24 h.2 Approximately 12 h into the infusion, he developed generalized urticaria. Again, the infusion was halted, and he was treated with diphenhydramine and HC, with resolution of his symptoms. After 12 h, he was pre-medicated with diphenhydramine and HC, and the tacrolimus restarted. Once again, urticaria developed. Having established that the patient was having severe allergic reactions to both intravenous CSA and tacrolimus, we were forced to switch either to an alternate route of delivery or to another immunosuppressive medication. Owing to his mucositis, we were concerned that the patient would have poor or erratic absorption of oral tacrolimus or oral CSA; therefore, we decided to utilize intravenous mycophenolate mofetil (MMF), starting at a dose of 15 mg/kg/dose every 12 h.3 Owing to undetectable levels of mycophenolate acid (MPA, Mayo Labs, Rochester, MN, USA), his dosing interval was escalated first to every 8 h, then his total dose was increased to 600 mg/m2 and finally, 900 mg/m2, which ultimately resulted in a level of 0.9 μg/ml3. He received a total of 6.4 × 106 CD34+ bone marrow cells/kg from his sister. His immediate post transplant phase was complicated only by grade II mucositis. He had neutrophil engraftment (ANC>500/μl for 2 consecutive days) on Day +24. Owing to severe nasal hemorrhages, his platelet counts were kept greater than 35 000 with his last platelet transfusion on Day +32. On Day +24, his mucositis had significantly resolved and he was switched to oral tacrolimus, which he tolerated without any allergic reaction. He was discharged on Day +30. Analysis of variable nucleotide tandem repeats (VNTRs) on Day +23 showed 100% of blood CD3+ cells and 95% of marrow CD34+ cells were of donor origin. He is now Day +118 and has no evidence of acute GVHD. His VNTRs continue to show 98–100% donor engraftment.

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  1. Division of Pediatric Stem Cell Transplantation, Stanford University School of Medicine, Palo Alto, CA, USA

    C C Dvorak, E Callard & R Agarwal

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Dvorak, C., Callard, E. & Agarwal, R. Use of intravenous mycophenolate mofetil for graft-versus-host disease prophylaxis in an allogeneic hematopoietic stem cell transplant recipient with an allergic reaction to cyclosporine and tacrolimus. Bone Marrow Transplant 38, 253–254 (2006). https://doi.org/10.1038/sj.bmt.1705422

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