Transplantation of CD34+ selected peripheral blood to HLA-identical sibling patients with aplastic anaemia: results from a single institution

Abstract

Summary:We evaluated the use of CD34 þ selected allogeneic peripheral blood as a source of hematopoietic progenitors for allogeneic transplantation in 11 patients with aplastic anemia (AA). The median age was 17 years (range, 6-49), and the median time between diagnosis and transplant 1 month (range, 1-24). Conditioning consisted of cyclophosphamide (50 mg/kg per day) on days À7 to À4 and antithymocyte globulin (30 mg/kg per day) on days À4 to À2 in nine patients. Total lymphoid irradiation was added to the preparative regimen for two. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and prednisone. Median doses of CD34 þ and CD3 þ cells infused were 3.91 Â 10 6 and 0.3 Â 10 6 /kg, respectively. The median time taken to achieve a neutrophil count 40.5 Â 10 9 /l was 12 days and to recover a platelet count 420 Â 10 9 /l, 13 days. Two patients developed acute GVHD grade I-II and one developed limited chronic GVHD. There were two treatment-related deaths. At a median follow-up of 44 months (range, 4-73), nine patients were alive with sustained and complete engraftment. This is a promising procedure in patients with AA, resulting in a rapid hematopoietic recovery, a low transplant-related mortality, and a low incidence of GVHD.

Long-Term Outcome of Fludarabine-Based Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Debilitating Paroxysmal Nocturnal Hemoglobinuria

“…Subsequent studies have clearly demonstrated the superiority in reduced incidence of GVHD with bone marrow as the preferred graft source in other bone marrow failure conditions(21). T-cell depletion following peripheral blood HCT using a variety of different in vitro and in vivo strategies has demonstrated success in lowering the incidence of chronic-GVHD following peripheral blood HCT for severe aplastic anemia(22–24), although in some cases the risk of graft rejection has been excessively high(25). To reduce the risk of rejection in allogeneic HCT for PNH and aplastic anemia associated with complete ex vivo T-cell depletion or uncontrolled in vivo T-cell depletion, we are exploring a strategy whereby high numbers of mobilized CD34+ selected peripheral blood cells are combined with non-mobilized T-cells at a T-cell dose that matches cell numbers typically infused following a bone marrow harvest (ClinicalTrials.gov Identifier: NCT01174108).…”

An update on the management of severe idiopathic aplastic anaemia in children

“…An IBMTR analysis of children and adolescents undergoing AHSCT with PBSC or BM for haematological malignancy demonstrated an increase in chronic GVHD, treatment‐related mortality, treatment failure and mortality with PBSC (Eapen et al , 2004) Similar data confined to AA is currently unavailable. A number of groups have reported encouraging results using CD34 + selected PBSC as a source of haematopoietic progenitors from alternate donors for AA patients and even from haploidentical parents (Kremens et al , 2001; Benesch et al , 2004; de la Rubia et al , 2005).…”

Successful engraftment after infusion of multiple low doses of CD34+ cells from a poorly matched sibling donor in a patient with severe aplastic anemia

“…After the first transplantation, it took 12 days to engraft the ANC, 8 days after the fourth PBSC infusion, and 7 days after the cord blood transplant. Additionally, de la Rubia et al showed that the median time taken to achieve engraftment with neutrophil counts >0.5×10 9 /L was 12 days (range, 9–13 days) [14]. From this, the first peripherally infused stem cells (CD34+ 0.36×10 6 cells/kg) were considered to have a major influence on engraftment in the present case.…”