Reduced-intensity conditioning using fludarabine with either antithymocyte globulin and BU, or low-dose TBI allowing allogeneic hematopoietic SCT

Abstract

In a single-center study, we analyzed the outcomes of 66 patients with advanced hematological malignancies receiving two reduced-intensity conditioning regimens for allogeneic transplantation: fludarabine and low-dose TBI (flu/TBI, n ¼ 25), or fludarabine, antithymocyte globulin and BU (flu/ATG/BU, n ¼ 41). The selection criteria were based on the hypothesis that flu/TBI patients were expected to achieve autologous recovery in the event of non-engraftment. Sixty-three patients (95%) engrafted. Regimen-related mortality at day 100 and 1 year was 6 and 15%, respectively. With median follow-up of 50.4 months, survival did not differ by regimen. Multivariate analysis confirmed that the type of regimen did not affect relapse. In patients achieving full donor chimerism by day 30, those conditioned with flu/TBI showed greater overall survival (P ¼ 0.02). Engraftment failure occurred in two patients (3%), both of whom received flu/TBI. We conclude that conditioning with flu/TBI or flu/ATG/BU yields comparable survival and remission outcomes. By contrast to our hypothesis, patients receiving flu/TBI who subsequently failed engraftment did not achieve autologous recovery. Yet, rapid attainment of full donor chimerism after flu/TBI is associated with greater survival than after flu/ATG/BU. Further, larger prospective randomized studies are required to define the advantage of one regimen over the other.

Reduced-intensity conditioning regimen with in vivo T-cell depletion for patients with haematological malignancies: results using unrelated and sibling donors

“…9,10 In conclusion, despite the limits of its retrospective nature, our study showed that fludarabine, i.v. BU and intermediate doses of ATG performed as well as using both matched and mismatched, unrelated or HLA-sibling donors.…”

In vivo T‐cell depletion with pretransplant low‐dose antithymocyte globulin is associated with reduced transplant‐related mortality and improved clinical outcome in patients receiving allogeneic hematopoietic stem cell transplantation from unrelated and partially matched related donors

“…To date, few data exist regarding the temporal trends of VTE incidence [3,8], or trends in VTE incidence according to age or gender [3,4]. The majority of studies published to date were conducted on a community-wide scale and therefore do not provide information on a national basis covering a range of distinct patient populations [3][4][5]8,9]. This study determined the national VTE prevalence patterns in the U.S. population within a 5-year period from 2002 to 2006 based on real-world data from patients in the MarketScan 1 Commercial and Medicare databases.…”

“…In particular, allogeneic HSCT from alternative donors with unmanipulated graft results in an increased risk of both acute and chronic GVHD compared with matched sibling donor transplants [1]. At the present, none of the GVHD prophylactic strategies currently in use, including calcineurin inhibitors [2], T-lymphocyte depletion, and monoclonal antibodies [3,4], have been proven to be of superior efficacy over another.The use of rabbit antithymocyte globulin (ATG; Thymoglobulin; Genzyme, Cambridge, MA) is effective in minimizing the incidence of GVHD after HSCT from both human leukocyte antigen (HLA)-identical sibling and unrelated volunteer donor [5][6][7][8][9][10]. Nevertheless, only a handful of studies have investigated the optimal dose of ATG and the timing [5,[11][12][13][14][15].The aim of this study was to analyze retrospectively the outcome of 90 adult patients with hematological malignancies who received HSCT from partially matched related or unrelated volunteer donors between October 1999 and October 2009 after a preparative regimen including moderate doses of ATG and to investigate whether the immunosuppressive effect is preserved without compromising GVHD control, engraftment kinetics, and transplant-related complications.Primary neutrophil engraftment, defined as an absolute neutrophil count (ANC) greater than 0.5 3 10 9 /L for 3 consecutive days, was achieved in 89 (99%) patients at a median of 17 days (range, 11-48) after transplantation.…”

“…The use of rabbit antithymocyte globulin (ATG; Thymoglobulin; Genzyme, Cambridge, MA) is effective in minimizing the incidence of GVHD after HSCT from both human leukocyte antigen (HLA)-identical sibling and unrelated volunteer donor [5][6][7][8][9][10]. Nevertheless, only a handful of studies have investigated the optimal dose of ATG and the timing [5,[11][12][13][14][15].…”