Favorable effect on acute and chronic graft-versus-host disease with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow transplantation from HLA-identical sibling donors for acquired aplastic anemia

Abstract

Between August 1989 and November 2003, 33 patients at our center with acquired aplastic anemia underwent bone marrow transplantation (BMT) from HLA-identical sibling donors with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies (MoAb) for conditioning. The median age at BMT was 17 years (range, 4-46 years). Before BMT, 58% were heavily transfused (>50 transfusions), and 42% had previously experienced treatment failure with antithymocyte globulin-based immunosuppressive therapy. Unmanipulated bone marrow was used as the source of stem cells in all patients except 1. Graft-versus-host disease (GVHD) prophylaxis was with cyclosporine alone in 19 (58%) patients; 14 received anti-CD52 MoAb in addition to cyclosporine. The conditioning regimen was well tolerated without significant acute toxicity. Graft failure was seen in 8 patients (primary, n = 4; secondary, n = 4). Of those whose grafts failed, 4 survived long-term (complete autologous recovery, n = 2; rescue with previously stored marrow, n = 1; second allograft, n = 1). The cumulative incidence of graft failure and grade II to IV acute and chronic GVHD was 24%, 14%, and 4%, respectively. None developed extensive chronic GVHD. With a median follow-up of 59 months, the 5-year survival was 81% (95% confidence interval, 68%-96%). No unexpected early or late infectious or noninfectious complications were observed. We conclude that the conditioning regimen containing cyclophosphamide and anti-CD52 MoAb is well tolerated and effective for acquired aplastic anemia with HLA-matched sibling donors. The favorable effect on the incidence and severity of GVHD is noteworthy in this study and warrants further investigation.

Graft-versus-host disease following marrow transplantation for aplastic anemia: different impact of two GVHD prevention strategies

“…[10][11][12] Previous observations in patients with AA also showed that the risk of graft failure was higher when in vivo anti-CD52 antibodies were administered both before and after stem cell infusion. 8 Graft rejection was reduced when anti-CD52 antibodies were administered only before stem cell infusion, indicating that the timing of anti-CD52 antibodies may be an important factor. 8 In addition to different dosing schedules, previous studies used a high dose of anti-CD52 antibodies (75-100 mg).…”

“…8 Graft rejection was reduced when anti-CD52 antibodies were administered only before stem cell infusion, indicating that the timing of anti-CD52 antibodies may be an important factor. 8 In addition to different dosing schedules, previous studies used a high dose of anti-CD52 antibodies (75-100 mg). 8,9,13 Reducing the dose of anti-CD52 antibodies may decrease the incidence of infectious complications.…”

“…Previous studies from St George's Hospital in London reported a favorable effect on acute and chronic GVHD in matched sibling donor and matched unrelated donor BMT for AA using in vivo anti-CD52 monoclonal antibodies (Campath-1G antibodies and alemtuzumab). 8,9 The main concerns with the use of anti-CD52 antibodies include a high risk of graft failure 8 and increased risk of infectious complications. [10][11][12] Previous observations in patients with AA also showed that the risk of graft failure was higher when in vivo anti-CD52 antibodies were administered both before and after stem cell infusion.…”

“…8 In addition to different dosing schedules, previous studies used a high dose of anti-CD52 antibodies (75-100 mg). 8,9,13 Reducing the dose of anti-CD52 antibodies may decrease the incidence of infectious complications. Recently, a study from Sweden in patients with hematological malignancies suggested that a lower dose of alemtuzumab (30 mg) results in a lower risk of infectious complications and faster immune reconstitution.…”

Impact of intensity of conditioning therapy in patients aged 40–60 years with AML/myelodysplastic syndrome undergoing allogeneic transplantation

“…Transfusion and other supportive care were also carried out as earlier described. 23,24 Patients who received Alemtuzumab as part of their GVHD prophylaxis also received 3 months of antifungal prophylaxis (voriconazle, itraconazole or posaconazole) and antiviral prophylaxis (acyclovir). Post transplant G-CSF was not routinely administered.…”