Summary:One-hundred and two patients with good risk myeloid leukemia (CML first chronic phase or AML first CR) were transplanted from HLA-related donors after conditioning with (n ‫؍‬ 45) or without anti-thymocyte globulin (ATG) (n ‫؍‬ 57). One graft failure was observed in the non-ATG and none in the ATG group. The median time to leukocyte engraftment (Ͼ1 ؋ 10 9 /l) was 16 (range 12-33) in the ATG group and 17 days (range 11-29) in the non-ATG group (NS) and for platelet engraftment (Ͼ20 ؋ 10 9 /l) 24 and 19 days (P ‫؍‬ 0.002), respectively. Acute GVHD grade II-IV was observed in 47% of the non-ATG and in 20% of the ATG group (P ‫؍‬ 0.004). Grade III/IV GVHD occurred in 7% of the ATG and in 32% of the non-ATG group (P ‫؍‬ 0.002). Chronic GVHD was seen in 36% and 67% (P ‫؍‬ 0.005), respectively. After a median follow-up of 48 months (range 2-128), the 5-year estimated OS is 66% (95% KI: 51-81%) for the ATG group and 59% (95% KI: 46-72%) for the non-ATG group (NS). The 5-year estimated DFS is 64% (95% KI: 50-78%) for ATG and 55% (95% KI: 43-67%) for the non-ATG regimen (NS). The 5-year probability of relapse was 5% in the ATG and 15% in the non-ATG group (NS). ATG as part of the conditioning regimen leads to a significant reduction in GVHD without increase of relapse in patients with myeloid leukemia after stem cell transplantation from HLA-related donors. Allogeneic stem cell transplantation from HLA-identical siblings for patients suffering from acute or chronic myeloid leukemia has become a curative treatment option. Transplant-related mortality as the cause of death is approximately 30%, and most deaths are related directly or indirectly to acute or chronic graft-versus-host disease (GVHD). Allogeneic stem cell transplantation from HLAidentical siblings with an unmanipulated graft resulted in an incidence of acute GVHD of approximately 30 to 60%. 1 Several investigators have shown that removal of T cells from the graft by ex vivo T cell depletion resulted in a dramatic decrease in GVHD. However, it became rapidly apparent that T cell depletion resulted in a high incidence of graft failure and an increased risk of leukemia relapse. [2][3][4][5][6] Partial or selective depletion of different subpopulations of T cells, or T cell depletion with T cell add-back has been investigated and resulted either in enhanced graft failure or increased risk of GVHD after T cell add-back. [7][8][9] Other forms of T cell depletion including T cell depletion with monoclonal antibodies either in vivo or ex vivo have been investigated extensively, resulting in a decrease of GVHD, but a relatively high incidence of graft failure has been observed. 10,11 By adding monoclonal anti-52 antibodies to the conditioning regimen to deplete residual host T cells, the problem of graft failure has been partly overcome. 12 Another strategy of in vivo T cell depletion is the use of anti-thymocyte globulin as part of the conditioning regimen. We and others have recently shown that ATG as part of the preparative regimen in unrelated stem cell tran...

Summary:We compared two doses of recombinant human granulocyte-stimulating factor (G-CSF) for stem cell mobilisation in 90 healthy donors for allogeneic stem cell transplantation in a retrospective analysis. Group I (n = 46) received 10 g/kg G-CSF (filgrastim) given as 5 g/kg twice daily, and group II (n = 44) received 16 g/kg, given as 8 g/kg twice daily with a 12-h interval. The groups were well-balanced for age and bodyweight. G-CSF application was performed on an outpatient basis, and leukapheresis was started in all donors on day 5. The most frequent side-effects of G-CSF were grade I/II, bone pain, headache and fatigue in both groups, whereas grade III of bone pain, headache and fatigue occurred in the 2 ؋ 8 g/kg group only. One serious non-fatal event with non-traumatic spleen rupture occurred in the 2 ؋ 5 g/kg group. The CD34 + cell count in the first apheresis of all donors was 5.1 ؋ 10 6 /kg donor weight (range, 1.5-19.3). The CD34 + cell harvest was higher in the 2 ؋ 8 g/kg group than in the 2 ؋ 5 g/kg group (7.1 ؋ 10 6 /kg vs 4.9 ؋ 10 6 /kg; P = 0.09). The target of collecting Ͼ5.0 ؋ 10 6 CD34 + cells/kg donor weight with one apheresis procedure was achieved in 45% of group I and in 61% of group II, respectively. Administering G-CSF at a dosage of 8 g/kg twice daily leads to a higher CD34 + cell yield than a dosage of 2 ؋ 5 g/kg, but is associated with increased toxicity and higher cost.

Summary:To evaluate the efficacy and toxicity of two different etoposide (VP-16) dosages (30 or 45 mg/kg) in combination with busulfan/cyclophosphamide as conditioning therapy followed by stem cell transplantation in acute myeloid leukemia (AML), 90 patients with AML received either 30 mg/kg (n = 60) or 45 mg/kg (n = 30) etoposide in combination with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The stem cell source was allogeneic related bone marrow (BM) (n = 53), allogeneic unrelated BM (n = 5), allogeneic unrelated peripheral blood (PBSC) (n = 2), syngeneic BM (n = 2), autologous BM purged (n = 9) or unpurged (n = 9), autologous PBSC (n = 10). Fifty-six patients (62%) were in first CR, 26 (29%) were Ͼ first CR, and eight (9%) were transplanted in relapse. Principal toxicities in both groups were mucositis and hepatotoxicity. Forty-five mg/kg etoposide resulted in greater hepatic toxicity (P = 0.03), and a higher incidence of VOD (23 vs 12%, P = 0.04) and acute GVHD grade III/IV (13 vs 5%, NS). The treatment-related mortality was 17% in the 30 mg/kg group and 33% in the 45 mg/kg group, mainly due to infections, intestinal pneumonia and GVHD. Hematological recovery of leukocytes 1/nl was comparable in both groups (17 vs 16 days). After a median follow-up of 16 months 19% in the 30 mg/kg group and 23% in the 45 mg/kg group relapsed. In patients who had undergone allogeneic related bone marrow transplantation in first CR no relapses occurred after a median follow-up of 3 years. For all patients the 3-year estimated disease-free survival was 62% in the 30 mg/kg group and 40% in the 45 mg/kg group (P = 0.03). For patients in first CR who underwent allogeneic related stem cell transplantation the 3 year disease-free survivals were 80% and 66%, respectively (P = 0.4). We conclude that etoposide 30 mg/kg or 45 mg/kg in combination with busulfan/cyclophosphamide is a highly active regimen 1-3 The use of allogeneic or autologous bone marrow transplantation increases the rate of long-term survival, although a substantial number of patients still relapse. 4,5 The relapse rate after autologous transplantation in first CR is about 50% and after allogeneic transplantation about 20%. 6 It is possible that improved preparative regimens will reduce these relapse rates. The most common preparative regimens in acute myeloid leukemia are busulfan and cyclophosphamide or TBI plus cyclophosphamide. 7,8 It has already been shown that an intensified preparative regimen can lower the relapse rate in allogeneic as well as in autologous transplantation. 5,9,10 We incorporated etoposide 45 or 30 mg/kg to a conditioning regimen consisting of busulfan (16 mg/kg) plus cyclophosphamide (120 mg/kg) to investigate the efficacy and toxicity of this new preparative regimen in patients with acute myeloid leukemia undergoing autologous or allogeneic stem cell transplantation. This combination was choosen based on the hypothesis that etoposide might have an additional antileukemic effect.11-13 It shows high antineoplastic activity against a ...

It is suggested that application of G-CSF twice daily leads to a higher CD34+ cell mobilization owing to a higher minimum serum level and therefore to a more continuous serum baseline level resulting in a more efficient CD34+ cell mobilization.