Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation: influence of Campath dose on lymphoid recovery, mixed chimerism and survival

Abstract

Sixty-nine consecutive patients (median age 54 years) were prospectively enrolled in a single-institution protocol for allogeneic transplantation with adjusted non-myeloablative fludarabine-melfalan-based conditioning including cyclosporin A and MMF, and one of three modes of serotherapy. Thirty-one donors (45%) were unrelated. The first cohort of 29 had ATG (Thymoglobulin 2 mg/kg  3 days), the subsequent 26 had Campath 30 mg  3 days subcutaneously, and the final cohort of 14 had 30 mg Campath once. The groups were similar as regards age, diagnosis and risk factors. Campath-patients had no acute toxicity, fewer days with fever and antibiotics, and required fewer transfusions than ATG-treated patients. 3-d-Campath patients showed lower lymphocyte counts from day þ 4, and CD4 þ , CD8 þ , CD19 þ and NK cells recovered slower than in ATG-treated patients. More Campath patients developed mixed chimerism that required DLI. 3-d-Campath induced more serious and opportunistic infections than ATG, which resulted in a greater non-relapse mortality and an impaired overall survival despite a low tumor-related mortality. The change of the Campath dosing schedule to one dose abrogated the deleterious effect of 3-d-Campath on immune recovery, severe infections and survival. Subcutaneous Campath is simple and provides strong immune suppression with no early toxicity, but dose limitation to 30 mg once is recommended.

Preemptive DLI without withdrawal of immunosuppression to promote complete donor T-cell chimerism results in favorable outcomes for high-risk older recipients of alemtuzumab-containing reduced-intensity unrelated donor allogeneic transplant: a prospective phase II trial

“…In order to prevent these complications, several groups have successfully reduced the alemtuzumab dose as part of the conditioning regimen for sibling and UD transplantation (total dose of 10-50 mg). [22][23][24][25] The schedule of pretransplant alemtuzumab, in addition to dose, will also have an effect on its biodistribution and clearance. 26 The earlier in the conditioning regimen that alemtuzumab is given, the less active drug that will be available post transplant.…”

Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML

“…Consequently, we intend to replace alemtuzumab with a reduced dose of rabbit ATG (Fresenius) resulting in a possibly milder immunosuppression post transplant. 25 Furthermore, we plan to prospectively study an intensified-conditioning regimen for patients up to 65 years old with addition of treosulfan, taking into account the aforementioned negative impact of age and, possibly, RIC 6 on outcome, as well as the active disease most of our patients have at the time of second allo-SCT.…”

Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia

“…Only one study has compared alemtuzumab with other agents for in vivo T-cell depletion. Juliusson et al (2006) found that patients who received alemtuzumab as part of the conditioning regimen initially had less initial toxicity with fewer fevers and lower transfusion requirements, the patients who received 30 mg/day for three consecutive days were more likely to have mixed chimerism post-transplant requiring DLI, and had more serious opportunistic infections which translated to greater non-relapse mortality. At the present time, the role of alemtuzumab in non-myeloablative stem cell transplant for CLL is uncertain.…”