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Table 1 Myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for hematological malignancies, especially for acute lymphoblastic leukemia

From: Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning

Regimen No. of ALL Mean age (range) Donor Stem cell source Disease status at HSCT Survival rate Relapse rate TRM/NRM aGVHD cGVHD Remarks Reference
ETP 60 mg/kg × 1 + TBI 1.2 Gy × 11 13 16 (6–36) MRD BM CR2, IF, or relapse 54 % (100 d) 15 % 31 % 23 % ND It was not clear whether ETP 60 mg/kg was better than ETP 30 mg/kg according to a phase I/II (dose-finding) study using 25 to 70 mg/kg of ETP. Blume KG, et al. Blood 1987;69:1015.
ETP 50 to 70 mg/kg × 1 + TBI 2 Gy × 6 17 19 (4–38) MRD BM Non-CR1, IF, or relapse except 1 65 % (182 d) 6 % 35 % 85 % 50 % Anti-leukemic effect was observed in a phase I/II study with ETP + BI, but the rejection rate was high. Thus, the immunosuppressive effect was worse than CY + TBI. A dose of more than 60 mg/kg of ETP was too toxic. Schmitz N, et al. Blood 1988;72: 1567.
ETP 36 mg/kg or 52 mg/kg × 1 + CY 67 mg/kg or 103 mg/kg × 1 + TBI 2 Gy × 6 7 15 (6–35) MRD BM Relapse 0 % (899 d)   ND ND ND ETP (36 mg/kg) + CY (67 mg/kg) + TBI was well tolerated for allogeneic HSCT (phase I study). Petersen FB, et al. Bone Marrow Transplant. 1992; 10:83.
ETP 60 mg/kg × 1 + TBI 1.2 Gy × 11 25/122 2–48 MRD BM CR2: 8 3-Y DFS: 63 % 8 % 4 % ND ND ETP + TBI appeared to be better for a good-risk group than for a poor-risk one according to a randomized controlled study. Hepatic toxicity and severe mucositis were marked with ETP of 60 mg/kg. The age range for the patients with ALL was shown, but the mean was unclear. Blume KG, et al. Blood 1993;81: 2187.
CR3, Non-CR: 17 12 % 40 % 12 % ND ND
BU 1 mg/kg × 16 + CY 60 mg/kg × 2 23/122 5–48 CR2: 6 4 % 17 % 4 % ND ND
CR3, Non-CR: 17 17 % 34 % 22 % ND ND
ETP 60 mg/kg × 1 + TBI 1.2 Gy × 11 34 27 (1–45) MRD BM CR1 3-Y DFS: 64 % 12 % ND 18 % (gr.II) 38 % A relatively good outcome was observed in a phase II study, but relapse and TRM rates were high. Thirty of the 34 patients were high-risk. Snyder DS, et al. Blood 1993;82: 2920.
       High-risk
       <20 y 3-Y DFS : 100 % 0 %
       20 y 3-Y DFS: 54 % 17 %
ETP 30–60 mg/kg × 1 + CY 60–200 mg/kg × 2 + TBI 1.2Gy × 11 (1.5 Gy × 8) 20/44 18 (1–54) MRD BM ND Early death: standard-risk 2/18 high-risk 2/26 ND ND ND ND Fourty-four patients with hematological malignancies were analyzed in a retrospective study. Among them, 20 patients were ALL. Sixty to 65 mg/kg of ETP resulted in a fatal toxicity, but 30 to 50 mg/kg did not. Fifty mg/kg of ETP was considered to be the maximally tolerated dose. Spitzer TR, et al. Int. J. Radiat. Oncol. Biol. Phys. 1994;29:39
ETP 25–60 mg/kg × 2 10/32 18 (3–49) MRD BM ND Early death: standard-risk 1/12 high-risk 5/20 ND
BU 1 mg/kg × 12–16
Standard   20 (1–39) MRD BM CR2: 20 7-Y OS: 52 % 34 % 25 % 48 % (gr.II) 41 % A retrospective study suggested that high-dose conditioning regimens did not improve the outcome of patients transplanted for high-risk leukemia. Mengarelli A, et al. Haematologica 2002;87:52.
TBI 2 Gy × 6 + CY 120 mg/kg × 2 7/38 CR3: 9
1st Rel.: 5
Adv.: 4
BU 16 mg/kg × 4 + CY 120 mg/kg × 2 24/38
BU 16 mg/kg × 4 + CY 120 mg/kg × 4 7/38
Alternative   23 (3–44) MRD BM: 60 CR2: 47 7-Y OS: 25 % 58 % 32 % 47 % (gr.II) 44 %   
ETP 60 mg/kg × 1 + TBI 2 Gy × 6 TBI 2 Gy × 6 + CY 120 mg/kg × 2 43/66 PB: 6 CR3: 9
1st Rel.: 6
Adv.: 13
BU 16 mg/kg × 4 + CY 120 mg/kg × 2 +IDA 42 mg/m2 × 2
BU-CY + VP 20 mg/kg × 1
BU-CY + Ara-C 2 g/m2 × 4
ETP 40 mg/kg × 1 + CY 60 mg/kg × 2 + TBI 2 Gy × 6 39 34 (15–52) MRD: 35 BM CR1 6-Y OS: 41 % 10 % 15 % ND ND Autologous HSCT by ETP + CY + TBI regimen showed 41 % of 6-Y OS in a prospective study, whereas allogeneic BMT with the same regimen showed a 6-Y OS of 75 %. This result suggested a possibility of GVL effect. ETP was administered in 4 consecutive infusions of 10 mg/kg lasting 2 hours each. Hunault M, et al. Blood 2004;104:3028.
MUD: 4 (<50 years old: 75 %)
ETP 15 mg/kg × 2 + CY 60 mg/kg × 2 + TBI 2 Gy × 6 37 26 (15–58) MRD: 13 BM: 3 CR1: 28 3-Y OS: 89 % 8 % 5 % 78 % (gr.II: 41 %) 55 % (ext.: 36 %) Excellent outcome was observed in addition to low relapse and TRM rates in a retrospective study. Shigematsu A, et al. Biol. Blood Marrow Transplant. 2008;14:568.
MUD: 18 PB: 4 CR2: 7
MMRD: 2 CB: 1 Non-CR: 2
MMUD: 4
ETP 15 mg/kg × 2 + CY 60 mg/kg × 2 + TBI 2 Gy × 6 or 3 Gy × 4 35 28 (15–58) MRD:16 BM: 29 CR1: 28 5-Y OS:82 % 14 % 3 % 71 % (gr.II: 37 %) 46 % (ext.: 30 %) A retrospective analysis in Japan showed ETP + CY + TBI was associated with lower relapse and NRM rates, resulting in better survival than that with CY + TBI. Shigematsu A, et al. Int. J. Hematol. 2011;94:463.
MUD: 11 PB: 6 CR2:7
MMUD: 6
Unknown: 2
CY 60 mg/kg × 2 + TBI 2 Gy × 6 or 3 Gy × 4 494 34 (15–59) MRD: 235 BM: 405 CR1: 414 5-Y OS: 55 % 29 % 16 % 62 % (gr.II: 37 %) 45 % (ext.: 27 %)   
MUD: 180 PB: 89 CR2: 80
MMRD: 1
MMUD: 70
Unknown: 2
ETP 15 mg/kg × 2 + CY 60 mg/kg × 2 + TBI 2 Gy × 6 50 34 (17–49) MRD: 26 BM: 40 CR1: 47 1-Y OS: 80 % 10 % 14 % 66 % (gr.II: 58 %; gr.III: 12 %) 56 % (ext.: 38 %) A prospective multi-center phase II study in Japan confirmed the excellent outcome of ETP + CY + TBI for adult ALL patients. Shimemastu A, et al. Transplant. Direct. 2015;1:1
MUD: 24 PB: 10 CR2: 3 2-Y OS: 67 %
1-Y EFS: 76 %
2-Y EFS: 65 %
  1. No. the number of patients, ALL acute lymphoblastic leukemia, HSCT hematopoietic stem cell transplantation, TRM transplant-related mortality, NRM non-relapse mortality, aGVHD acute graft-versus-host disease, cGVHD chronic graft-versus-host disease, ETP etoposide, TBI total body irradiation, MRD matched related donor, BM bone marrow, CR complete remission, IF involved field, d day, ND not determined, CY cyclophosphamide, Auto autologous, BU busulfan, Y year, DFS disease-free survival, MUD matched unrelated donor, OS overall survival, GVL graft versus-leukemia, MMRD mismatched related donor, MMUD mismatched unrelated donor, CB cord blood, PB peripheral blood, ext. extensive type of cGVHD, gr. grade