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©The Author(s) 2019.
World J Clin Oncol. Feb 24, 2019; 10(2): 86-97
Published online Feb 24, 2019. doi: 10.5306/wjco.v10.i2.86
Published online Feb 24, 2019. doi: 10.5306/wjco.v10.i2.86
Table 1 Conditioning regimen descriptions
Conditioning regimen | Number of patients | Protocol |
Myeloablative without TBI (MA-noTBI) | 38 | Bu 12.8 mg/kg intravenous total dose and Cy 120 mg/kg total dose |
Myeloablative with TBI (MA + TBI) | 51 | Cy 120 mg/kg total dose and TBI 1000-1350 cGy |
Reduced intensity conditioning without TBI (RIC-noTBI) | 118 | Flu 125 mg/m2 total dose and Mel 140 mg/m2 total dose |
Reduced intensity conditioning with TBI (RIC + TBI) | 40 | Flu 160 mg/m2 total dose, Mel 50-75 mg/m2 total dose, and TBI 400 cGy |
Table 2 Patient characteristics for each of four conditioning regimen groups, n (%)
MA-noTBI (n = 38) | MA+TBI (n = 51) | RIC-noTBI (n = 118) | RIC+TBI (n = 40) | P | |
Age at BMT | < 0.0001 | ||||
Median-years (range) | 47 (26-58) | 36 (19-51) | 54 (23-73) | 61 (23-71) | |
< 40 | 6 (16) | 29 (57) | 22 (19) | 3 (8) | |
≥ 40 | 32 (84) | 22 (43) | 96 (81) | 37 (93) | |
Gender | NS | ||||
Female | 21 (55) | 19 (37) | 45 (38) | 22 (55) | |
Male | 17 (45) | 32 (63) | 73 (62) | 18 (45) | |
Diagnosis | < 0.0001 | ||||
ALL | 0 | 20 (39) | 7 (6) | 6 (15) | |
AML | 11 (29) | 28 (55) | 58 (49) | 14 (35) | |
CML | 7 (18) | 1 (2) | 3 (3) | 1 (3) | |
MDS/MPD | 11 (29) | 1 (2) | 23 (19) | 10 (25) | |
NHL/CLL/PLL | 8 (21) | 1 (2) | 25 (21) | 8 (20) | |
Other | 1 (3) | 0 | 2 (2) | 1 (3) | |
Karnofsky Performance Status | 0.03 | ||||
≤ 70 | 8 (21) | 8 (16) | 35 (30) | 13 (33) | |
80 | 13 (34) | 15 (29) | 51 (43) | 14 (35) | |
≥ 90 | 17 (45) | 28 (55) | 32 (27) | 13 (33) | |
BMT Regimen | < 0.0001 | ||||
BuCy | 36 (95) | 0 | 0 | 0 | |
CyTBI | 0 | 47 (92) | 0 | 0 | |
FluCy | 0 | 0 | 12 (10) | 0 | |
FluMel | 0 | 0 | 102 (86) | 0 | |
FluMelTBI | 0 | 0 | 0 | 40 (100) | |
Other | 2 (5) | 4 (8) | 4 (3) | 0 | |
Sex Match | NS | ||||
Matched | 24 (63) | 30 (59) | 70 (59) | 27 (68) | |
Mismatched | 14 (37) | 21 (41) | 48 (41) | 13 (33) | |
Donor | < 0.0001 | ||||
HLA Matched Related | 33 (87) | 31 (61) | 54 (46) | 17 (43) | |
HLA Matched Unrelated | 5 (13) | 20 (39) | 64 (54) | 23 (58) | |
GvHD Prophylaxis | < 0.0001 | ||||
TacMtx | 18 (47) | 35 (69) | 33 (28) | 0 | |
TacMMF | 4 (11) | 2 (4) | 18 (15) | 0 | |
TacmMtxMMF | 15 (39) | 7 (14) | 64 (54) | 40 (100) | |
Single Agent | 1 (3) | 7 (14) | 3 (3) | 0 | |
CMV Status | NS | ||||
R+D+ | 6 (16) | 8 (16) | 28 (24) | 9 (23) | |
R+D- | 14 (37) | 12 (24) | 35 (30) | 12 (30) | |
R-D+ | 0 | 8 (16) | 18 (15) | 4 (10) | |
R-D- | 18 (47) | 23 (45) | 37 (31) | 15 (38) | |
BMI kg/m2 | NS | ||||
Normal (< 30) | 15 (39) | 25 (49) | 34 (29) | 13 (33) | |
Overweight (25-< 30) | 12 (32) | 14 (27) | 40 (34) | 15 (38) | |
Obese (≥ 30-< 35) | 7 (18) | 7 (14) | 28 (24) | 7 (18) | |
Morbid (≥ 35) | 4 (11) | 5 (10) | 16 (14) | 5 (13) |
Table 3 Time to neutrophil and platelet engraftment by CD34+ dose for each conditioning regimen group
Conditioning group | ||||
MA-noTBI (n = 38) | MA + TBI (n = 51) | RIC-noTBI (n = 118) | RIC + TBI (n = 40) | |
Median days to engraftment (range) | ||||
Absolute neutrophil count > 500/mm3 | ||||
CD34+ dose > 4 × 106/kg | 14 (10-22) | 14 (9-28) | 14 (3-36) | 15 (10-22) |
CD34+ dose < 4 × 106/kg | 14.5 (12-19) | 19 (13-28) | 15 (10-21) | 18 (16-24) |
P | NS | NS | NS | 0.01 |
Platelet count > 20000/mm3 | ||||
CD34+ dose > 4 × 106/kg | 17 (3-171) | 20 (13-81) | 17 (3-1515) | 17 (10-866) |
CD34+ dose < 4 × 106/kg | 19.5 (15-32) | 34 (20-228) | 22 (14-275) | 18 (11-20) |
P | NS | 0.001 | 0.01 | NS |
Table 4 Multivariable analysis shows no association of cell doses with overall survival or progression free survival, except for total nucleated cell dose in the reduced intensity conditioning + total body irradiation group
Variable | Overall survival1 | Progression free survival2 | ||||||||
All patients (n = 247) | MA-noTBI (n = 38) | MA + TBI (n = 51) | RIC-noTBI (n = 118) | RIC + TBI (n = 40) | All patients (n = 247) | MA-noTBI (n = 38) | MA + TBI (n = 51) | RIC-noTBI (n = 118) | RIC + TBI (n = 40) | |
CD3+ cell dose | ||||||||||
< Median HR | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
> Median HR | 1.1 | 1.0 | 0.5 | 1.3 | 0.8 | 1.0 | 1.1 | 0.4 | 1.4 | 0.6 |
95%CI | 0.8-1.5 | 0.4-2.6 | 0.2-1.1 | 0.8-2.1 | 0.3-2.2 | 0.7-1.4 | 0.4-2.6 | 0.2-1.0 | 0.8-2.2 | 0.2-1.7 |
P | NS | NS | NS | NS | NS | NS | NS | 0.05 | NS | NS |
CD4+ cell dose | ||||||||||
< Median HR | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
> Median HR | 1.2 | 1.1 | 0.6 | 1.2 | 2.0 | 1.1 | 1.1 | 0.5 | 0.3 | 1.5 |
95%CI | 0.8-1.7 | 0.4-2.6 | 0.2-1.3 | 0.8-1.0 | 0.7-6.0 | 0.8-1.6 | 0.5-2.6 | 0.2-1.2 | 0.8-2.1 | 0.5-4.3 |
P | NS | NS | NS | NS | NS | NS | NS | NS | NS | NS |
CD8+ cell dose | ||||||||||
< Median HR | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
> Median HR | 1.2 | 1.5 | 1.0 | 1.3 | 0.5 | 1.1 | 1.1 | 0.9 | 1.2 | 0.7 |
95%CI | 0.8-1.6 | 0.5-4.2 | 0.4-2.3 | 0.8-2.1 | 0.2-1.8 | 0.8-1.5 | 0.5-2.8 | 0.4-2.0 | 0.8-2.0 | 0.2-2.0 |
P | NS | NS | NS | NS | NS | NS | NS | NS | NS | NS |
TNC dose | ||||||||||
< Median HR | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
> Median HR | 0.8 | 1.0 | 0.7 | 0.9 | 0.2 | 0.8 | 1.1 | 0.7 | 1.1 | 0.2 |
95%CI | 0.6-1.2 | 0.4-2.4 | 0.3-1.9 | 0.5-1.5 | 0.1-0.8 | 0.6-1.2 | 0.4-2.5 | 0.3-1.6 | 0.6-1.8 | 0.1-0.8 |
P | NS | NS | NS | NS | 0.02 | NS | NS | NS | NS | 0.02 |
CD34+ cell dose | ||||||||||
< 4 × 106/kg HR | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
4-8 × 106/kg HR | 1.0 | 0.5 | 1.3 | 1.1 | 0.6 | 0.8 | 0.7 | 1.2 | 1.0 | 0.6 |
95%CI | 0.6-1.5 | 0.2-1.4 | 0.4-4.4 | 0.6-1.9 | 0.1-2.3 | 0.6-1.4 | 0.2-2.1 | 0.4-4.0 | 0.6-1.8 | 0.2-2.6 |
P | NS | NS | NS | NS | NS | NS | NS | NS | NS | NS |
> 8 × 106/kg HR | 1.0 | 1.3 | 0.7 | 1.1 | 0.5 | 0.9 | 1.5 | 0.6 | 1.1 | 0.5 |
95%CI | 0.6-1.5 | 0.4-4.0 | 0.2-2.3 | 0.5-2.0 | 0.1-2.4 | 0.6-1.4 | 0.5-4.6 | 0.2-2.0 | 0.6-2.0 | 0.1-2.6 |
P | NS | NS | NS | NS | NS | NS | NS | NS | NS | NS |
Table 5 Summary of correlations between cell doses demonstrating low correlation between total nucleated cell dose and CD8+ and CD34+ cell doses and moderate correlation with CD3+ and CD4+ cell doses
CD3+ dose | CD4+ dose | CD8+ dose | CD34+ dose | ||
CD4+ dose | |||||
R | 0.91 | ||||
R2 | 0.83 | ||||
P | < 0.0001 | ||||
CD8+ dose | |||||
R | 0.81 | 0.55 | |||
R2 | 0.66 | 0.30 | |||
P | < 0.0001 | < 0.0001 | |||
CD34+ dose | |||||
R | 0.20 | 0.21 | 0.11 | ||
R2 | 0.04 | 0.04 | 0.01 | ||
P | 0.0012 | 0.0009 | NS | ||
Total nucleated cell dose | |||||
R | 0.71 | 0.64 | 0.56 | 0.38 | |
R2 | 0.50 | 0.41 | 0.31 | 0.14 | |
P | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 |
- Citation: Burns M, Singh AK, Hoefer CC, Zhang Y, Wallace PK, Chen GL, Platek A, Winslow TB, Iovoli AJ, Choi C, Ross M, McCarthy PL, Hahn T. Impact of conditioning regimen on peripheral blood hematopoietic cell transplant. World J Clin Oncol 2019; 10(2): 86-97
- URL: https://www.wjgnet.com/2218-4333/full/v10/i2/86.htm
- DOI: https://dx.doi.org/10.5306/wjco.v10.i2.86