Long-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

Abstract

The online version of this article has a Supplementary Appendix. BackgroundDue to increased rates of secondary solid organ cancer in patients with severe aplastic anemia who received an irradiation-based conditioning regimen, we decided some years ago to use the combination of cyclophosphamide and antithymocyte globulin. We report the long-term follow up of patients who underwent hematopoietic stem cell transplantation from an HLAmatched sibling donor after this conditioning regimen. Design and MethodsWe analyzed 61 consecutive patients transplanted from June 1991 to February 2010, following conditioning with cyclophosphamide (200 mg/kg) and antithymocyte globulin (2.5 mg/kg/day x 5 days). ResultsMedian age was 21 years (range 4-43); 41 of the 61 patients were adults. Median duration of the disease before hematopoietic stem cell transplantation was 93 days. All but 2 patients received bone marrow as the source of stem cells and all but 2 engrafted. Cumulative incidence of acute grade II-IV graft-versus-host disease was 23% (95%CI 13-34) and 18 developed chronic graft-versus-host disease (cumulative incidence 32% at 72 months, 95% CI 20-46). In multivariate analysis, a higher number of infused CD3 cells was associated with an increased risk of developing chronic graft-versus-host disease (P=0.017). With a median follow up of 73 months (range 8-233), the estimated 6-year overall survival was 87% (95% CI 78-97). At 72 months, the cumulative incidence of avascular necrosis was 21% and 12 patients presented with endocrine dysfunction (cumulative incidence of 19%). Only one patient developed a secondary malignancy (Hodgkin's lymphoma) during follow up. ConclusionsCyclophosphamide and antithymocyte globulin is an effective conditioning regimen for patients with severe aplastic anemia and is associated with low treatment-related mortality. Long-term complications include avascular necrosis and endocrine dysfunction.Key words: hematopoietic stem cell transplantation, severe aplastic anemia, long-term outcomes. Haematologica 2012;97(5):710-716. doi:10.3324/haematol.2011 This is an open-access paper. Citation: Konopacki J, Porcher R, Robin M, Bieri S, Cayuela J-M, Larghero J, XhaardLong-term follow up after allogeneic stem cell transplantation in patients with severe aplastic anemia after cyclophosphamide plus antithymocyte globulin conditioning

Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation

“…30 Moreover, the low occurrence of tumors after MFD transplant is in keeping with that seen in recent studies with a longer follow up. 31 However, given the young age of our patients, tumor occurrence needs to be carefully monitored during long-term follow up. Reports in literature indicate that a second course of IST after previous failure provides an overall success rate of 30-70% 3,32-34 but a far weaker hematopoietic reconstitution than after HSCT.…”

Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation

“…10 Chronic GVHD (cGVHD) remains a problem for 30-50% of patients, and this impacts not only on survival but also on quality of life after HSCT. 8,18 Risk factors for cGVHD include older age, previous acute GVHD (aGVHD) and PBSC source. 19,20 Alemtuzumab, a CD52 MoAb, has been evaluated in a multicenter retrospective study in 50 patients receiving a MSD or MUD transplant for SAA.…”

Allogeneic stem cell transplantation using alemtuzumab-containing regimens in severe aplastic anemia

“…In contrast to HSCT for haematological malignancy, graft failure remains a significant problem in SAA, especially in patients, who have been heavily transfused and are alloimmunized to major and minor HLA antigens. Graft failure occurs in up to 10 % of MSD and 15 % of MUD HSCT patients [3,6,8,10].…”

“…A recent retrospective EBMT study of 1,886 patients showed that the addition of ATG improved OS after MSD HSCT [6]; a previous prospective randomized study from the CIBMTR showed no significant difference in OS when ATG was added to CY 200 mg/kg, but that study was underpowered due to relatively low number of patients enrolled [4]. However, ATGbased conditioning is associated with up to 30 % incidence of chronic GVHD [3][4][5][6], and severe chronic GVHD impacts quality of life as well as OS (Table 1).…”

“…Improved HLA matching and better conditioning regimens have also contributed to improved outcomes after MUD HSCT. Long-term survival is seen in 80-90 % of patients following MSD HSCT [3][4][5][6] and 75-80 % for MUD HSCT in SAA [7][8][9][10].…”