Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia

Abstract

We analyzed the outcome of 692 patients with severe aplastic anemia (SAA) receiving transplants from HLA-matched siblings. A total of 134 grafts were peripheral blood progenitor cell (PBPC) grafts, and 558 were bone marrow (BM) grafts. Rates of hematopoietic recovery and grades 2 to 4 chronic graft-versushost disease (GVHD) were similar after PBPC and BM transplantations regardless of age at transplantation. In patients older than 20 years, chronic GVHD and overall mortality rates were similar after PBPC and BM transplantations. In patients younger than 20 years, rates of chronic GVHD (relative risk [RR] 2.82; P ‫؍‬ .002) and overall mortality (RR 2.04; P ‫؍‬ .024) were higher after transplantation of PBPCs than after transplantation of BM. In younger patients, the 5-year probabilities of overall survival were 73% and 85% after PBPC and BM transplantations, respectively. Corresponding probabilities for older patients were 52% and 64%. These data indicate that BM grafts are preferred to PBPC grafts in young patients undergoing HLAmatched sibling donor transplantation for SAA. IntroductionTransplantation of bone marrow (BM) from an HLA-matched sibling donor is an effective treatment for severe aplastic anemia (SAA) with long-term survival in excess of 80% and graft failure rates of approximately 10%. [1][2][3][4][5][6][7] Unpublished data (January 2007) from the European Group for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR) suggest approximately 60% of HLA-matched sibling donor transplantations for SAA now use peripheral blood progenitor cell (PBPC) grafts. A similar switch to PBPC over BM grafts is reported in leukemia transplantations. [8][9][10] The higher rate of chronic graft-versus-host disease (GVHD) may be offset by lower relapse rates in some settings. In contrast, there is no perceived benefit of chronic GVHD for SAA. Further, few data on PBPCs for SAA are reported. [11][12][13][14][15] In a preliminary analysis from our group, PBPC grafts appeared to contribute to higher mortality. 16 Here, we report chronic GVHD and long-term overall survival rates in 134 PBPC recipients and 558 BM recipients of HLA-matched sibling donor transplants for SAA. Patients, materials, and methods PatientsData on patients undergoing their first PBPC and BM HLA-matched sibling transplantation from 1995 to 2003 were obtained from the EBMT and the Statistical Center of the CIBMTR at the Medical College of Wisconsin. Only patients who received transplants at centers that provided a minimum of 12 months of follow-up on all their surviving patients were included. The Institutional Review Board of the Medical College of Wisconsin approved this study. Informed consent was obtained in accordance with the Declaration of Helsinki. Statistical methodsThe probabilities of hematopoietic recovery (neutrophil count Ն 0.5 ϫ 10 9 /L for 3 consecutive days and platelet count Ն 20 ϫ 10 9 /L for 7 days, unsupported) and acute and chronic GVHD were calculated using the cum...

The number of infused CD34+ cells does not influence the incidence of GVHD or the outcome of allogeneic PBSC transplantation, using reduced-intensity conditioning and antithymocyte globulin

“…Most of the published studies showed that allo-SCT with the use of PBSC as opposed to BM, is associated with a similar rate of acute GVHD (aGVHD), but an increased incidence of cGVHD. [1][2][3][4][5][6][7] Moreover, in accordance with these data, some studies also show better OS and disease-free survival (DFS) among patients with advanced leukemia after allogeneic PBSC transplantation (allo-PBSC). 4,8 This association has been explained mostly by the decreased incidence of relapse in patients with GVHD.…”

“…On the contrary, the vast majority of the published studies showed increased rates of cGVHD with the use of PBSC in comparison with BM grafts. [1][2][3][4][5][6][7] The influence of allo-PBSC on long-term survival remains more controversial and is mainly dependent on the disease status before transplantation. Some studies reported a favorable outcome after myeloablative allo-PBSC for patients with advanced myeloid leukemias, mostly because of decreased RRs.…”

Implications of CD34+ cell dose on clinical and haematological outcome of allo-SCT for acquired aplastic anaemia

“…For haematological disorders in general, investigators have found a greater risk of chronic GVHD with PBSC transplant in the setting of a large CD34 þ cell dose. [25][26][27] This may be due to increased type-2 cytokines and IL-10-producing monocytes, which together result in late immune dysregulation. 28 The notable reduction in the incidence of severe forms of GVHD could partly be attributed to the extensive use of alemtuzumab for conditioning in the majority of our patients.…”

The EBMT activity survey: 1990–2010

“…After it has been shown in observational studies that peripheral blood was associated with more chronic GVHD and poor survival in patients with marrow failure, the trend is now to prefer marrow as a stem cell source for this indication. 14,15 The use of marrow has increased from 48% in 2009 to 59% in 2010 for nonmalignant disorders.…”