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Table 2 Myeloablative conditioning regimens in allogeneic hematopoietic stem cell transplantation for Philadelphia chromosome-positive 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

5

28 (23–45)

MRD

BM

CR1: 4

OS: 60 % (≧171 d)

0 %

40 %

50 % (gr.≧II: 33 %)

ND

Intensified conditioning regimens followed by allogeneic HSCT were a preferred treatment modality for Ph + ALL according to a retrospective sutdy.

Forman SJ, et al. Blood 1987; 70:587

ETP 60 mg/kg × 1 + TBI 7.5 Gy × 1

1

Non-CR: 6

CY 100 mg/kg × 1 + TBI 1.2 Gy × 11

3

BU 1 mg/kg × 16 + CY 60 mg/kg × 1

1

BU + CY +TBI

67

28 (5–49)

MRD

BM

CR1: 33

2-Y DFS: 38 %

34 %

CR1: 42 %

Gr.≧II: 24 %

33 %

Allogeneic HSCT was feasible for Ph+ ALL patients according to a retrospective study using IBMTR data. The dose of conditioning regimens was not specified.

Barrett AJ, et al. Blood 1992; 79:3067.

Rel: 22

2-Y DFS: 41 %

32 %

Rel: 40 %

: 38 %

31 %

IF: 12

2-Y DFS: 25 %

57 %

IF : 42 %

: 45 %

22 %

CY 60 mg/kg × 2 + TBI 1.2 Gy × 11 (for patients ≧18 y)

15

25 (17–51)

MUD

BM

CR1: 7

2-Y DFS: 49 %

29 %

22 %

100 % (gr.≧II: 75 %)

62 % (ext. 54 %)

Unrelated HLA-matched donors were useful when related HLA-matched donors were not found in a retrospective study.

Sierra J, et al. Blood 1997; 90:1410.

CY 60 mg/kg × 2 + TBI 1.2 Gy × 12 (for children)

3

>CR1: 1

Non-CR: 10

ETP 50 mg/kg × 1 + TBI 1.2 Gy × 11+/–CY 60 mg/kg x 2

22

30 (6–42)

MRD

BM/PB

CR1

3-Y DFS: all 65 %

12 %

30 %

65 %

65 %

The relatively low relapse rate might reflect the enhanced anti-leukemic activity of ETP/TBI compared to other conditioning regimens in a retrospective study.

Snyder DS, et al. Leukemia 1999; 13:2053.

CY 60 mg/kg × 2 + TBI 1.2 Gy × 11

1

<1992 : 45 %

 

≧1992: 81 %

ETP 50 mg/kg × 1 +CY 60 mg/kg × 2 +TBI 2 Gy × 6 or TBI 10 Gy × 1

74

42 (17–56)

MRD: 43

BM

CR1

2-Y OS: 37 %

40 %

67 %

ND

ND

Allogeneic HSCT in CR1 was the best treatment option in Ph+ ALL according to a prospective study. Outcome was better in bcr/abl transcript-negative patients than in bcr-abl transcript-positive ones. The 2-Y OS, relapse, and TRM rates were 26 %, 74 %, and 91 %, respectively in 23 cases of autologous HSCT.

Dombret H, et al. Blood 2002;100:2357.

MUD: 8

2-Y OS: 63 %

25 %

38 %

ND

ND

CY 60 m/kg × 2 + TBI 2Gy × 6 (for adults)

Adults: 102

35 (1–53)

MRD: 79

BM/PB

CR1: 76

2-Y OS: all 37 %

44 %

38 %

Adults Gr.≧II: 52 %

43 % (ext.: 17 %)

A better outcome was correlated with remission status at transplant in a prospective study. The relapse rate decreased with the occurrence of acute GVHD. Bcr/abl transcript-positivity did not correlate to relapse rate.

Espérou H, et al. Bone Marrow Transplant. 2003;31:909.

Ara-C 3 g/m2 × 4 or 6 + Mel 140 mg/m2 × 1 +TBI 2 Gy × 6 (for children)

Children: 19

MUD: 42

>CR1: 45

CR1: 50 %

37 %

Children Gr.≧II: 53 %

39 % (ext.: 8 %)

CY 60 mg/kg × 2 + TBI 2 Gy × 6

166

37 (16–59)

MRD: 136

BM: 167

CR1: 93

5-Y OS

N.D.

N.D.

N.D.

N.D.

Allogeneic HSCT was the only procedure with curative potential for Ph+ ALL according to a retrospective study. Pre-transplant disease status was an important factor for better survival. Extensive cGVHD correlated with a better outcome, while severe aGVHD did not.

Yanada M. et al. Bone Marrow Transplant. 2005;36:867.

Non-TBI

31

MUD: 61

PB: 24

:>CR1 19

CR1: 34 %

BM + PB: 6

Non-CR: 85

>CR1: 21 %

5-Y OS

TBI (n = 166): 25 %

Non-TBI (n = 31): 8 %

ETP 60 mg/kg × 1 +TBI 1.2 Gy × 11

67

36 (2–57)

MRD

BM: 43

CR1:49

10-Y OS

 

CR1: 31 %

49 % (gr.≧II: 35 %)

38 % (ext.: 13 %)

Disease status at the time of HSCT was important according to a retrospective study. ETP + TBI with or without CY conferred long-term survival. Seventeen patients received imatinib before HSCT and received the drug after HSCT as well.

Laport GG, et al.: Blood 2008;112:903.

ETP 60 mg/kg × 1 + CY 60 mg/kg × 2 + TBI 1.2 Gy × 11

11

PB: 36

>CR1:30

CR1: 48 %

CR1: 28 %

>CR1: 54 %

  

ETP 60 mg/kg × 1+BU 1 mg/kg × 16 +TBI 1.2 Gy × 11

1

>CR1: 29 %

>CR1: 41 %

 
  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, CY cyclophosphamide, BU busulfan, MRD matched related donor, BM bone marrow, CR complete remission, OS overall survival, d day, gr. grade, ND not determined, Rel relapse, IF induction failure, DFS disease-free survival, ext. extensive type of chronic GVHD, IBMTR international bone marrow transplant registry, MUD matched unrelated donor, HLA human leukocyte antigen, PB peripheral blood, Ara-C cytosine arabinoside