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Addition Of Thiotepa To The Conditioning Regimen Significantly Improves Transplant Outcomes In Children Undergoing Cord Blood Transplantation For Non-Malignant Disease. Lurie Children's Hospital Of Chicago's Experience
We retrospectively evaluated all CBT performed for non-malignant conditions to determine if there is any correlation between transplant outcomes & conditioning, including Total body irradiation, Fludarabine, Cyclophosphamide, Etoposide & Thiotepa.
Between 1/1995 & 1/2011, 50 CBT were performed. Conditioning: TBI + VP16 + Cy (11); TBI + TT ± VP16 + Cy (4); TT + FLUD ± Bu ± VP16 (6); Bu + Cy (11); Bu + FLUD (15); VP + Cy (2); no conditioning (1). Diagnoses: Immunodeficiency (22), BM failure (10), Metabolic disease (6), Histiocytic disease (6), Hemoglobinopathy (6).
There were 20 F, 30 M. Median age 1.0 yr (0.1 – 17.4), wt 9.15 kg (3.0 - 52.0). HLA match: 6/6 (7), 5/6 (13), 4/6 (27), 3/6 (3). Median cell dose/Kg: TNC 0.89^8, MNC 0.77^8, CD34 0.99^6. CBU were processed per Rubenstein et al. GvHD prophylaxis: MTX + ATG + CSA (18); MMF + ATG + CSA (13); no MTX/MMF (19); PRED or FK506 (10).
Statistical analyses were done using Fisher's Exact, Log-Rank, & Column stats. Significance was determined at p-value of 0.05.
Overall Results:
62% achieved ANC >500 cells/µL at 20 days (11 - 40); 56% had PLT >20,000 at 40 d (14 - 100); & 52% achieved >95% chimerism at 43 d (13 - 169). 13 pts died from day + 100 TRM. 30 pts are survivors at this time. EFS > 1, 3, 5 yr was 44, 32 & 30%, with OS of 62, 46 & 42%. 8 pts are event free >10 yr. Median follow up was 2.0 yr (0.2- 14.6 yr). Acute GVHD grade II - IV was seen in 12, there was no chronic GVHD.
Table 1: Group Variables.
Variables
| Thiotepa (10)
| No Thiotepa (40)
| P-value
| ||
Median
| Range
| Median
| Range
| ||
Age (yr)
| 1.1
| 0.3- 15.5
| 0.9
| 0.1- 17.4
| 0.79
|
Infused TNC/kg^8
| 1.21
| 0.37- 3.18
| 0.85
| 0.05- 4.27
| 0.52
|
Infused MNC/kg^8
| 1.06
| 0.31- 2.83
| 0.73
| 0.04- 3.84
| 0.49
|
Infused CD34/kg^6
| 0.83
| 0.10- 8.7
| 0.99
| 0.02- 7.6
| 0.31
|
| N=
| Percent
| N=
| Percent
|
|
HLA Match 3/6, 4/6, 5/6, 6/6
| 0, 5, 5, 0
| 0, 50, 50, 0
| 3, 22, 8,7
| 8, 55, 20, 17
| 0.20
|
TBI
| 4
| 40
| 11
| 27.5
| 0.46
|
Table 2: Group Outcomes.
Outcomes
| Thiotepa (10)
| No Thiotepa (40)
| P-value
| ||
N=
| %
| N=
| %
| ||
Alive
| 9
| 90
| 21
| 52.5
| 0.037
|
TRM
| 0
| 0
| 13
| 32.5
| 0.045
|
Non-Engraft
| 1
| 10
| 13
| 32.5
| 0.07
|
Transplant Event
| 2
| 20
| 24
| 60
| 0.035
|
ANC Engraft
| 9
| 90
| 22
| 55
| 0.07
|
PLT Engraft
| 9
| 90
| 19
| 47.5
| 0.029
|
Chimerism >95%
| 9
| 90
| 17
| 42.5
| 0.006
|
EFS >5 yr
| 9
| 90
| 16
| 40
| 0.038
|
OS >5 yr
| 10
| 100
| 15
| 37.5
| 0.039
|
Ac GVHD
| 4
| 40
| 8
| 20
| 0.23
|
Figures: K-M.
 |  |
Conclusion:
In this cohort patients who received Thiotepa in addition to other conditioning showed statistically significant transplant outcomes. There was no TRM. 5 yr OS was 100%, EFS 90%. Thiotepa recipients had better and rapid chimerism, and the engraftment percent were statistically significant. No other statistical significance was seen between the two groups with respect to age, HLA match, cell dose, aGVHD, or TBI or other conditioning. In conclusion, addition of Thiotepa to conditioning regimen dramatically changes transplant outcomes of pediatric non malignancy patients undergoing cord blood transplantation.