Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients

Abstract

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...

Thrombocytopenia and hemostatic disorders in chronic graft versus host disease

“…38 Mycophenolate mofetil is an established drug for treatment of both acute and chronic GVHD, and it could cause thrombocytopenia as a side effect. 41 Other drugs may cause thrombocytopenia by inducing antibodies against megakaryocytes and/or platelets, such as acetaminophen, amphotericin B, vancomycin, ranitidine, fluconazole, heparin, and others. 42 Many such drugs are used in cGVHD patients, so it is important to consider drug-induced thrombocytopenia as a possible cause of low platelet counts in the cGVHD setting.…”

Mycophenolate mofetil for the management of steroid-refractory acute graft vs host disease

“…[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Mycophenolate mofetil (MMF), whose metabolite mycophenolic acid inhibits the de novo synthesis of purines in lymphocytes, has probable efficacy in the treatment of aGVHD, based on three small case series that cumulatively reported 17 cases in which MMF was used for initial therapy for aGVHD, and 16 cases with glucocorticoidrefractory aGVHD. [31][32][33] Here, we report outcomes in a series of 27 recipients of allogeneic hematopoietic cell transplantation treated with MMF as salvage therapy for steroid-refractory aGVHD.…”

Targeting mycophenolate mofetil for graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation

“…1 To reduce GVHD-related mortality, prophylactic and therapeutic immunosuppressive regimen including mycophenolate mofetil (MMF) have been investigated in clinical studies. [2][3][4][5] One principal motivation of most investigators was to replace MTX by MMF to reduce the risk of mucosal, hematological and hepatic side effects associated with MTX.…”