GVHD is a common and difficult to treat complication of allogeneic transplantation. Chronic GVHD is a major complication of allogeneic stem cell transplantation involving the skin, musculoskeletal system and liver. Chronic GVHD is mediated primarily by T-cells. However, recently there has been emerging evidence that B-cells are also involved. The support for this concept comes from the detection of antibodies to minor HLA antigens. Several phase II clinical trials evaluated Rituxan for the treatment of chronic GVHD based on the hypothesis that antibody suppression would be beneficial. In aggregate they show effectiveness.It is usually treated with steroids but recently a number of other drugs have been incorporated into the therapeutic armamentarium. Among them is Rituxan.
In the first study of Rituxan for GVHD, Rituxan (rituximab) produceds responses in patients with chronic graft-versus-host-disease (GVHD) involving the skin and musculoskeletal system. This trial included 21 patients who had steroid-refractory GVHD and were treated with 38 cycles of Rituxan. Twenty of the 21 patients were evaluable for response and one patient developed recurrent CML. Skin was involved in 81%, musculoskeletal system in 57%, Eye in 38%, oral mucosa in 33% and one patient had liver involvement. It was well tolerated:
70% of patients achieved a response against chronic GVHD.
Two patients achieved a complete disappearance of chronic GVHD.
Activity of Rituxan was limited to patients with GVHD that affected the skin or muscular/skeletal systems.
Total body surface involvement decreased from 42% to 20%.
Rheumatoid pain score improved from 4 to 1.5.
21% discontinued and 68% had >50% reduction in prednisone dosage.
The most common side effects associated with Rituxan were infections.
Responses to Rituxan lasted through one year following therapy.
One year after treatment with Rituxan, doses of the steroid prednisone were reduced approximately 75% in patients.
Oral and ocular chronic GVHD were not improved.
Decreasing antibody titers correlated with response.
The researchers concluded that Rituxan appears to be a promising treatment for patients with steroid-refractory chronic GVHD.
The status of experimental is difficult to apply to this treatment because phase III trials are not possible due to the low numbers of patients available for such studies. There is no expert consensus on performing such studies. There are phase II trials, for example: Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic NCT01044745.
A 2012 guideline(Dighan et al) says that Rituximab is suggested as a second line treatment option in refractory cutaneous or musculoskeletal chronic GvHD.
Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN, on behalf of the Haemato-oncology Task Force of the British Committee [trunc]. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol 2012 Jul;158(1):46-61. [125 references]
R . Kamble , M . Oholendt , G . CarrumRituximab Responsive Refractory Acute Graft-versus-Host Disease . Biology of Blood and Marrow Transplantation , Volume 12 , Issue 11 , Pages 1201 – 1202 2006
Stefan Deneberg etal, Relapse of preB-ALL after rituximab treatment for chronic graft versus host disease. Implications for its use?
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Maximilian Christopeit, Vincent Schütte, Sebastian Theurich, Thomas Weber, Wilfried Grothe, and Gerhard Behre, Rituximab reduces the incidence of acute graft-versus-host disease Blood 113: 3130-3131, 2009.
Rituxan is currently in a clinical study for GVHD: A Phase II Trial of Rituximab and Corticosteroid Therapy for Newly Diagnosed Chronic Graft Versus Host Disease , NCT00350545
Corey Cutler, David Miklos, Haesook T. Kim, Nathaniel Treister, Sook-Bin Woo, Don Bienfang, Lloyd B. Klickstein, Jesse Levin, Katherine Miller, Carol Reynolds, Rebecca Macdonell, Mildred Pasek, Stephanie J. Lee, Vincent Ho, Robert Soiffer, Joseph H. Antin, Jerome Ritz, and Edwin Alyea Rituximab for steroid-refractory chronic graft-versus-host disease Blood. 2006 July 15; 108(2): 756–762.
V Ratanatharathorn et al, Chronic graft-versus-host disease: clinical manifestation and therapy July (2) 2001, Volume 28, Number 2, Pages 121-129