Summary:The efficacy and safety of mycophenolate mofetil (MMF) in combination with CsA and prednisolone for the treatment of acute and chronic GVHD (aGVHD and cGVHD, respectively) after BMT and PBSCT from HLA-mismatched and -matched donors was evaluated in an open single center trial. Twenty-four patients, 17-48 years of age, with acute (n = 17) and chronic GVHD (n = 7) were treated with 2 g MMF daily in addition to CsA and prednisolone. Overall grade improvement of aGVHD was found in 11 of 17 (65%) patients treated with MMF. MMF therapy in the treatment of cGVHD led to moderate improvement in three of six patients with limited cGVHD. The most common adverse hematologic events of MMF were leukopenia (n = 6), anemia (n = 4) and thrombocytopenia (n = 3). Hematological adverse events were not severe and did not require the discontinuation of MMF. In this preliminary study, we have shown that MMF can be used safely for the treatment of aGVHD. In addition, the MMF therapy resulted in significant dose reduction of prednisolone for the treatment of GVHD. Keywords: mycophenolate mofetil; GVHD; bone marrow transplantation Allogeneic BMT is an effective therapy for a variety of malignant hematopoietic disorders. One of the limitations of such therapy is donor availability. Less than 30% of patients will have an HLA-matched related donor and Ͻ5% will have a one HLA locus mismatched related donor.1,2 HLA-matched unrelated donors (MUD) are an alternative for the patients lacking a suitable family member.3-5 However, the risks of developing aGVHD and cGVHD after MUD as well as after HLA-mismatched related transplants are significantly higher than after a BMT from an HLAmatched sibling. [6][7][8] The combination of immunosuppressive drugs, CsA, prednisolone and short-course MTX is an effective regimen for prevention of GVHD after BMT. 8,9 However, the incidence reported for aGVHD grades II-IV after transplan- tation from HLA-matched MUD is 78% and the incidence for grades III and IV is 36%. The incidence of cGVHD is 64%.10 Since GVHD contributes to morbidity and mortality after MUD BMT, more effective prophylaxis and therapy for this severe complication are needed. 11,12 MMF is a potent, uncompetitive, reversible inhibitor of eukaryotic inosine monophosphate dehydrogenase. It is an immunosuppressant that selectively inhibits proliferation of T and B lymphocytes and is successfully used for the prevention of acute rejection in primary cadaveric renal allograft recipients.13 However, very little is known about the effect of MMF in prevention or treatment of GVHD in experimental animals.14 In addition, no data on the use of MMF in the treatment of GVHD after BMT are available. The aim of our study was to evaluate the safety and efficacy of MMF in the treatment of aGVHD and cGVHD in patients after allogeneic BMT. Patients and methodsThis study included 24 patients given sibling BM (n = 6; four of which were HLA mismatched) or PBSCT (n = 3; two of which were mismatched) or allogeneic MUD BM (n = 14; two of which were HLA mismatched...

No abstract

Mycophenolate mofetil (MMF), a new immunosuppressive drug successfully used in renal and heart transplant recipients, was used in combination with cyclosporin A (CsA), methotrexate (MTX) and prednisolone for the prophylaxis of acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-mismatched, unrelated (n = 9) and related donors (n = 4) in an open single-centre phase II study. Thirteen patients, transplanted from HLA-mismatched donors of 18-57 yr of age, received 1 g MMF daily, starting at day 10, in addition to CsA and prednisolone for aGVHD prophylaxis. All patients were engrafted between days 13 and 15. Four of the 13 patients experienced aGVHD grade I/II (n = 2) and grade III (n = 2). All patients except 3 were alive on day 100 post-transplantation. No severe adverse effects of MMF were recorded. In our pilot study, we demonstrated that MMF can be used safely for the prophylaxis of aGVHD.

No abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare disease which, together with hemolytic uremic syndrome, is subsumed under thrombotic microangiopathy. After stem cell transplantation (SCT), this syndrome represents a possibly fatal complication with a higher incidence in allogeneic SCT than in autologous SCT. Although plasmapheresis offers an encouraging treatment modality in classic TTP, this seems less effective in bone marrow transplant-associated microangiopathy. This is probably due to a different etiology. We present a case of transplant-associated TTP with a fatal outcome despite multiple courses of plasmapheresis.