Sirolimus and mycophenolate mofetil as GVHD prophylaxis in myeloablative, matched-related donor hematopoietic cell transplantation

L Johnston, M Florek, R Armstrong, J S McCune, S Arai, J Brown, G Laport, R Lowsky, D Miklos, J Shizuru, K Sheehan, P Lavori, R Negrin, L Johnston, M Florek, R Armstrong, J S McCune, S Arai, J Brown, G Laport, R Lowsky, D Miklos, J Shizuru, K Sheehan, P Lavori, R Negrin

Abstract

We investigated sirolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis in patients with advanced hematological malignancies receiving myeloablative hematopoietic cell transplantation (HCT) from HLA-identical sibling donors. On the basis of pre-study stopping rules, the trial was closed to accrual after enrollment of 11 adult patients. In all, 7 of the 11 patients received BU-containing preparative regimens. Sirolimus was discontinued in three patients because of the toxicity-related events of severe sinusoidal obstructive syndrome, portal vein thrombosis, altered mental status and in one patient because of the risk of poor wound healing. In all, 6 of the 11 patients developed grade II-IV acute GVHD (AGVHD) a median of 15.5 days post HCT. Two of three patients with grade IV AGVHD had sirolimus discontinued by 9 days post HCT. All patients responded to AGVHD therapy without GVHD-related deaths. There were two non-relapse- and two relapse-related deaths. At a median follow-up of 38 months (2-47 months), 7 of 11 patients were alive without disease. MMF and sirolimus GVHD prophylaxis did not reduce the risk of AGVHD, however, there were no GVHD-related deaths. The severe toxicities in the patients receiving the BU-containing preparative regimens limited the continued use of sirolimus and MMF for the prevention of AGVHD.

Figures

Figure 1
Figure 1
Analyses of FoxP3 expressing CD4+ T cells on the peripheral blood of ten study (sirolimus and mycophenolate mofetil) graft-versus-host disease (GVHD) prophylaxis patients and 15 control (calcineurin inhibitor-containing) GVHD prophylaxis patients at time points post-transplant. The pretransplant analyses are on the GCSF-mobilized peripheral blood of the patient donors.

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Source: PubMed

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