ORIGINAL ARTICLE Intensification of GVHD prophylaxis with low-dose ATG-F before allogeneic PBSC transplantation from HLA-identical siblings in adult patients with hematological malignancies: results from a retrospective analysis F Bonifazi 1 , G Bandini 1 , M Arpinati 1 , G Tolomelli 1 , M Stanzani 1 , MR Motta 1 , S Rizzi 1 , V Giudice 2 , E Dan 1 , E Massari 1 , P Tazzari 2 , A Bontadini 3 , P Pagliaro 2 and M Baccarani 1 Several studies have shown that chronic GVHD (cGVHD) is more frequent in patients receiving transplants from PBSC than in those receiving BM. In the setting of PBSC-unrelated transplants, the addition of anti-T-cell globulin (ATG) has shown a significant decrease in incidence/severity of cGVHD, without an increase in relapses or infections. However, no prospective data are yet available in the sibling setting. We retrospectively analyzed the effects of intensification of standard GVHD prophylaxis (CsA þ MTX) by the addition of low-dose ATG in 245 patients receiving a transplant from HLA-identical sibling. From 1996 to 2001, patients received PBSC as the preferred source (group 2), and then ATG was added before transplant (group 3) because of a high cGVHD rate. Patients receiving BM in the same time period were analyzed as a control group (group 1). The incidence of grade IIIÀIV acute GVHD and cGVHD was not significantly different in the three groups, but extensive cGVHD was highest in group 2 (38%) compared with group 3 (21%) or group 1 (28%; P ¼ 0.03). OS, TRM and time to relapse/progression were similar in the three groups. Our analysis shows that adding ATG to PBSC sibling allogeneic transplants can lower cGVHD, without an increase of relapse. Further prospective studies are needed to confirm these findings. Bone Marrow Transplantation (2012) 47, 1105--1111; doi:10.1038/bmt.2011.225; published online 21 November 2011 Keywords: GVHD; hematopoietic SCT; TRM; ATG; sibling transplants INTRODUCTION The first reports of allogeneic PBSC transplants appeared in 1995. 1-3 Since then, their use has grown so rapidly that already by 2001 they had become the preferred source of hematopoietic stem cells. 4 Many studies, 5 - 11 including those with extended observa- tion of the early series 12 - 15 and two meta-analyses, 16,17 conclu- sively showed that PBSC transplants are associated with high rates of chronic GVHD (cGVHD), especially of the extensive type, with a substantial impact on quality of life. 18,19 However, the true benefits of cGVHD on relapse and more generally on transplant outcome are still controversial. Recently, some authors have compared the value of PBSC with BM transplants, and concluded that additional studies with longer follow-up are necessary to establish which source will produce the best OS or disease-free survival. 20 On the other hand, Pidala et al., 21 in their decision analysis paper, demonstrated with a multistate model that PBSC transplants are superior to BM and lead to a gain in life expectancy in all the conditions that are associated with a relapse risk greater than 5%. Extensive cGVHD remains a problem, and several strategies can be applied to minimize it; the majority of transplants performed with PBSC relied on the classical combination of a calcineurin inhibitor---CsA or tacrolimus---and MTX, or, more recently, in reduced intensity conditioning (RIC) regimens, on CsA or tacrolimus and mycophenolate mofetil. One way to intensify GVHD prophylaxis without hampering the beneficial anti-leukemic effect associated with GVHD is to use anti-T-cell globulins (ATGs). The results from a recent, prospective, randomized study in the unrelated setting, 22 with more than 80% of transplants being from PBSC, confirmed this hypothesis. The authors showed that the addition of ATG (ATG-Fresenius (ATG-F), 60 mg/kg as total dose) resulted in a lower incidence of acute grade III--IV GVHD (11.7% vs 24.5%) and a lower 2-year incidence of cGVHD (12.2% vs 42.6%), without significant effects on relapse. However, survival, TRM and mortality from infections were not different. To our knowledge, no phase III studies are yet reported in the sibling setting. Here, we describe 245 consecutive adult patients with hematological malignancies receiving a fully HLA-identical sibling transplant and the same GVHD prophylaxis, transplanted between 1996 and 2006. From 1996 to 2001, the preferred stem cell source was PBSC (group 2); after that date, because of the high incidence of cGVHD, 23 ATG-F was added (group 3) in the conditioning regimen; patients receiving BM, because of donor ineligibility for PBSC collection, were analyzed as the control group (group 1). Received 22 July 2011; revised and accepted 10 October 2011; published online 21 November 2011 1 Institute of Hematology and Medical Oncology, ‘L and A Sera ` gnoli’, St Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; 2 Department of Transfusion Medicine, St Orsola-Malpighi Hospital, Bologna, Italy and 3 Immunogenetics Unit, St Orsola-Malpighi hospital, Bologna, Italy. Correspondence: Dr F Bonifazi, Institute of Hematology and Medical Oncology, ‘L and A Sera `gnoli’, St Orsola-Malpighi Hospital, University of Bologna, via Massarenti 9, Bologna 40138, Italy. E-mail: francesca.bonifazi@unibo.it Bone Marrow Transplantation (2012) 47, 1105 - 1111 & 2012 Macmillan Publishers Limited All rights reserved 0268-3369/12 www.nature.com/bmt