Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia

Abstract

Graft rejection has been a problem after marrow grafts for patients with aplastic anemia who were conditioned with cyclophosphamide (CY). Rejection lessened when patients were given the marrow donor“s peripheral blood buffy-coat cells in addition to the marrow, but this result was achieved at the price of more chronic graft-versus-host disease (GVHD). Results with second transplants suggested that CY alternating with antithymocyte globulin (ATG) was more immunosuppressive than CY alone. Therefore, the current study explored CY and ATG without buffy-coat cell transfusions in 39 patients with aplastic anemia given marrow transplants from HLA-identical family members (siblings in 38 cases, father in 1 case). We hoped both to minimize the risks of graft rejection and of chronic GVHD and to improve survival. Patients were 2 to 52 years of age (median, 24.5); 87% had received previous transfusions, and 41% had therapy with immunosuppressive agents before transplant. They were administered four daily doses of CY (total, 200 mg/kg) alternating with three doses of ATG (total, 90 mg/kg) followed by an HLA-identical marrow graft. Methotrexate and cyclosporine were administered to prevent GVHD. Two patients rejected their grafts (5%), and both were successfully retransplanted. Acute (grade 2 or 3) GVHD occurred in 15% and chronic GVHD in 34% of patients. The actuarial survival rate at 3 years was 92%, which compares favorably to the 72% survival rate in 39 historical patients who were matched with current patients for age and risk factors for rejection and GVHD. CY/ATG is a well-tolerated and effective conditioning program for marrow grafting in aplastic anemia that, when combined with GVHD prevention by methotrexate/cyclosporine, results in excellent survival.

What Role Is There for Antithymocyte Globulin in Allogeneic Nonmyeloablative Canine Hematopoietic Cell Transplantation?

“…Antithymocyte globulin (ATG) is a mixture of polyclonal antibodies with potent immunosuppressive effects [9]. ATG has been used in combination with reduced-intensity [10][11][12] and nonmyeloablative [13,14] conditioning regimens for allogeneic HCT.…”

Transplantation of highly purified CD34+ progenitor cells from alternative donors in children with refractory severe aplastic anaemia

“…Although the conditioning regimen varied due to each transplant centres preference, all nine patients engrafted with the used regimens and the use of large numbers of CD34 + stem cells might be more important than the conditioning regimen to facilitate engraftment. With conventional transplants from HLA-identical siblings or unrelated donors, engraftment failures occur in 5-25% of patients with SAA undergoing HCT (McCann et al, 1994;Storb et al, 1994;Doney et al, 1997;Deeg et al, 1999;Kojima et al, 2002). In addition, 20-52% of these patients experience severe acute GVHD after unrelated donor transplantation (Deeg et al, 1999;Bacigalupo et al, 2000b;Kojima et al, 2002).…”

Bone marrow transplantation in children with severe aplastic anemia using a conditioning regimen containing 3 Gy of total body irradiation, cyclophosphamide with or without antithymocyte globulin

“…The clinical data of patients after BMT are shown in Table 2. Fifteen of 17 patients (88%) engrafted on median of day 18 (range, [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. The platelet and reticulocyte recovery was achieved on median of day 39 (range, 15-160) and day 35 (range, 13-88), respectively.…”