Comparative Analysis of Sibling Donor Reduced Intensity Conditioning Regimen for High Risk AML/MDS Using Anti-Thymocyte Globulin Versus Alemtuzumab for T-Cell Depletion.

Abstract 3362

Poster Board III-250

Several groups have used in-vivo T-cell depletion in conjunction with RIC HSCT protocols in an attempt to improve engraftment and reduce the incidence of graft-versus-host disease. However, the potential benefits of this approach are potentially offset by an attenuation of the graft-versus-leukaemia effect. While, anti-thymocyte globulin(ATG) and alemtuzumab are commonly used in RIC HSCT protocols, there is limited data available on the comparative effects of either form of T-cell depletion on clinical outcomes.

We performed a retrospective analysis on 65 patients with high risk AML/MDS who underwent a HLA-matched sibling donor RIC HSCT receiving either ATG or alemtuzumab. All patients received fludarabine (30mg/m² x 5 days intravenously), and either oral busulphan (4mg/kg x 2 days) or IV busulphan (3.2mg/kg x 2 days). From Jan 2002-Jun 2005, 41 patients received GvHD prophylaxis with alemtuzumab (20mg x 5 days intravenously) followed by cyclosporin A post-transplant. From Jun 2005 onwards, 21 patients received GvHD prophylaxis with ATG (Thymoglobulin, Genzyme) (total 6mg/kg over 3 days intravenously) followed by methotrexate and cyclosporine A post-transplant. All patients had either MDS RAEB I/II (n=26), or de novo/secondary AML (n=39). The median recipient age was 57 years (range:39–65) for ATG and 56.0yrs (39-72) for alemtuzumab. All ATG patients received PBSC with a median CD34 cell dose of 5.15×10⁶/kg (2.04 – 9.23). 37/41 alemtuzumab patients received PSBC with median CD34 cell dose of 5.10×10⁶/kg (1.86 – 13.9). Both groups were matched for donor/recipient age, disease type, cytogenetic risk, disease stage at transplantation, cell dose. Median follow-up (for survivors) was 721 days (range: 187–1138) for ATG group and 2082 days (1094-3233) for the alemtuzumab group.

Median time to neutrophil (>0.5×10 9/kg) and platelet (>20×10 9/kg) regeneration was 13 days and 14 days respectively, with no significant difference between both arms. There was 1 case of primary graft failure with ATG but none in patients receiving alemtuzumab. Lymphoid (CD3) engraftment was significantly slower in the alemtuzumab arm, with only 41% vs 75% patients attaining full donor chimerism(>95% donor) at day 100. There was no significant difference in the incidence of grade II-IV acute GvHD (ATG: 15%, Alemtuzumab 9%). However, patients who received ATG had a significantly higher incidence of chronic extensive GvHD (34% vs 6%, p=0.03). In addition, a significantly larger proportion of patients receiving alemtuzumab required subsequent DLI therapy (68% vs 19%). On univariate analysis, there was no significant difference in 2-year OS, and TRM between the alemtuzumab vs ATG group (56.1%+/-8% vs 73.7%+/-10%, p=0.25), and (19.5%+/-7% vs 10.6% +/- 7%, p=0.43). However, the use of ATG was associated with a significantly lower 2-year relapse incidence (28.4%+/-15% vs 51.5%+/-8%, p=0.04), and superior DFS (63.6%+/-14% vs 39.0%+/-8%, p=0.03).

In summary, our experience indicates that in patients with high risk MDS or AML undergoing a sibling donor RIC HSCT, use of ATG confers a higher incidence of extensive chronic GvHD with a consequently lower relapse incidence and more favourable DFS when compared with alemtuzumab. In the setting of sibling RIC HSCT, the use of ATG for T-cell depletion may thus be more suitable for patients with more aggressive disease. In contrast the use of alemtuzumab at the dose reported may be more suitable for treatment of patients with stable/lower-risk disease, or for the treatment of non-haematological malignancies. Further studies with regards to dose titration of both ATG and alemtuzumab in specific disease settings are warranted.