A three or more drug combination as effective therapy for moderate or severe chronic graft-versus-host disease

Abstract

Summary:We analyzed the results of a three or more drug combination as treatment for moderate or severe cGVHD developing after transplantation for thalassemia, in 45 patients with median age of 11 (range 2-26) years. Eighteen patients received a three drug regimen with cyclosporine (CsA), methylprednisolone (MP) and azathioprine (AZ) as first line therapy, 16 patients received this regimen as salvage therapy and 11 patients were given a four or five drug regimen with CsA, MP, AZ, cyclophosphamide (CY) and/or methotrexate (MTX) mainly as salvage therapy. The overall complete response (CR) rate was 77.3%, with 94% of CR in patients receiving the three drug regimen as first line, 88% in patients receiving it as salvage therapy and 36.6% in patients given the four or five drug regimen. The probability of CR in patients given the three drug regimen as first or salvage therapy or the four/five drug regimen was 89%, 53% and 30%, while the probability of survival was 89%, 65% and 58%, respectively. The incidence of treatment failure was low in our patients. Patients treated with the three drug regimen as first line therapy had less treatment-related complications than patients receiving this regimen as salvage therapy or patients given the four or five drug regimen. The main causes of treatment-related mortality (20%) were infectious complications. This retrospective study showed that a three or more drug combination is safe and effective for treatment of moderate or severe cGVHD at least in younger patients. Bone Marrow Transplantation (2001) 27, 45-51. Keywords: chronic graft-versus-host disease; bone marrow transplantation; thalassemia; multiagent immunosuppressive treatment Chronic graft-versus-host disease (cGVHD) is the most common late complication of allogeneic hematopoietic stem cell transplantation and its associated immunodeficiency and infection are major causes of morbidity and mortality following transplant. With the increasing number of allogeneic matched, mismatched and unrelated bone

Low-dose methotrexate for the treatment of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

“…Gaziev et al used three or more drugs in combination for the treatment of cGVHD. They found that patients receiving the three drug regimen as first line therapy had higher CR rates and fewer complications than did those receiving this combination as salvage treatment 12 while we found that MTX therapy effected a rapid response. GVHD-related symptoms in most patients improved within a few days and were controlled within 2-3 weeks after initiation of MTX.…”

“…To date, MTX has always been used as a single agent in the prevention of aGVHD after allo-HSCT, or as part of a combined regimen for treating cGVHD in both adult and pediatric patients. [10][11][12][13][14] There are no published data on the efficacy and the safety of low-dose MTX treatment in patients with acute or chronic GVHD.…”

Chronic graft versus host disease

“…Notably, an overall clinical summary scale of mild, moderate, or severe chronic GvHD was the best predictor of survival based on Akaike's information criterion, a qualitative biostatistical method of comparing prognostic schemes (Lee et al , 2002a). However, formal definitions for the mild, moderate and severe categories have not been established (Gaziev et al , 2001).…”

IHRW: An Improved Hypergraph Random Walk Model for Predicting Three-Drug Therapy

“…The combination of the three drugs has fewer complications and lower mortality than the combination of multiple drugs. This retrospective study (Gaziev et al ., 2001) showed that the combination of three or more drugs is safe and effective for the treatment of moderate or severe cGVHD at least in younger patients. Therefore, we propose a method called IHRW to combine known potent drug combinations and unlabeled drug combinations for large-scale prediction of potential efficacious drug combinations.…”