Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

Abstract

BackgroundReduced intensity conditioning regimens permit the delivery of a potentially curative graft-versus-leukemia effect in older patients with acute myeloid leukemia. Although T-cell depletion is increasingly used to reduce the risk of graft-versus-host disease its impact on the graft-versusleukemia effect and long-term outcome post-transplant is unknown. Design and MethodsWe have characterized pre-and post-transplant factors determining overall survival in 168 patients with acute myeloid leukemia transplanted using an alemtuzumab based reduced intensity conditioning regimen with a median duration of follow-up of 37 months. ResultsThe 3-year overall survival for patients transplanted in CR1 or CR2/CR3 was 50% (95% CI, 38% to 62%) and 44% (95% CI, 31% to 56%), respectively compared to 15% (95% CI, 2% to 36%) for patients with relapsed/refractory disease. Multivariate analysis demonstrated that both survival and disease relapse were influenced by status at transplant (P=0.008) and presentation cytogenetics (P=0.01). Increased exposure to cyclosporine A (CsA) in the first 21 days post-transplant was associated with an increased relapse risk (P<0.0001) and decreased overall survival (P<0.0001). ConclusionsDisease stage, presentation karyotype and post-transplant CsA exposure are important predictors of outcome in patients undergoing a T-cell depleted reduced intensity conditioning allograft for acute myeloid leukemia. These data confirm the presence of a potent graft-versusleukemia effect after a T-cell depleted reduced intensity conditioning allograft in acute myeloid leukemia and identify CsA exposure as a manipulable determinant of outcome in this setting.Key words: reduced intensity conditioning, graft-versus-leukemia, acute myeloid leukemia. leukemia. Haematologica 2010;95:989-995. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Craddock C, Nagra S, Peniket A, Brookes C, Buckley L, Nikolousis E, Duncan N, Tauro S, Yin J, Liakopoulou E, Kottaridis P, Snowden J, Milligan D, Cook G, Tholouli E, Littlewood T, Peggs K, Vyas P, Clark F, Cook M, MacKinnon S, and Russell N. Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid Factors predicting long-term survival after T-cell depleted reduced intensity allogeneic stem cell transplantation for acute myeloid leukemia

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

“…28 Given the close relationship between GVHD and GVL, this study sought to assess the impact of GVHD on outcome in a large and rather homogeneous cohort of AML patients given PBSC after various RIC, and particularly at assessing the impact of GVHD on survival given the divergent results observed in studies containing fewer number of patients. [10][11][12][20][21][22][23][24] Several observations could be drawn from the current findings. First, current study observed a positive impact (that is, lower risk of relapse translating into better LFS) of grade I acute GVHD on transplantation outcomes in patients given RIC allo-SCT for AML.…”

“…However, this is a delicate balance as a number of prior studies have shown a lower risk of relapse in AML patients who experienced chronic GVHD after RIC allo-SCT compared with those patients who did not, [10][11][12]20,21 while some other studies failed to find such an association. 22,23 A recent analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed the impact of GVHD in a cohort of patients with AML or myelodysplastic syndrome given various graft types after RIC conditioning. 24 In a landmark analysis at 1 year after transplantation (n ¼ 630), relapse incidence was reduced only in the group of patients with prior both acute and chronic GVHD, while acute and/or chronic GVHD had no significant impact on disease-free survival.…”

Prophylactic donor lymphocyte infusion in patients with high-risk acute myeloid leukemia: ready for prime time?

“…Low exposure to CNI the first weeks after transplantation 13 -Increases GV-AML effects -Increases risk of GvHD?…”

“…11,12 Given the poor prognosis of patients who experience relapse after allo-HCT, several groups of investigators have assessed various post-transplant approaches aimed at preventing disease relapse in high-risk AML patients (Table 1). These approaches include decreasing the level of post-grafting immunosuppression, 13 preemptive (i.e., administered in patients with post-transplant evidence of minimal residual disease or low / decreasing donor chimerism levels) or prophylactic administration of diseasespecific medications such as demethylating agents 14 or FLT3 inhibitors, 15 or preemptive 16,17 or prophylactic DLI. 18,19 In this issue of Bone Marrow Transplantation, Jedlickova et al 20 report the results of a retrospective analysis assessing the safety and efficacy of prophylactic DLI in a cohort of 46 high-risk AML patients given grafts following a sequential treatment consisting of chemotherapy (FLAMSA) followed by RIC allo-HCT.…”

Impact of pre-transplant co-morbidities on outcome after alemtuzumab-based reduced intensity conditioning allo-SCT in elderly patients: A British Society of Blood and Marrow Transplantation study

“…17,23 Taken together, with the profoundly adverse impact of multiple co-morbidities on transplant outcome, our data allow the identification of a population of older patients with active disease in whom allogeneic transplantation is very unlikely to deliver a survival benefit. As a consequence, these data now inform clinical practice at the reporting centres and patients with a HCT-CI of greater than 1 are only transplanted in exceptional circumstances or according to an investigational protocol.…”