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Increased Transplant Related Mortality and Poor Donor Cell Chimerism in African American Children Undergoing Umbilical Cord Blood Transplantation. Institutional Experience at Lurie Children's Hospital of Chicago
We retrospectively evaluated all CBT to see if there is a correlation between patient ethnicity & transplant outcomes.
Between 1/1995 & 1/2011 we performed 145 CBT for the treatment of malignant (95), non-malignant (50) conditions. Conditioning regimen: TBI + VP16 + Cy (79); TBI + TT + VP16 + Cy (16); Bu ± Cy ± FLUD (31); Cy ± TT or VP16 (12); other combinations (20).
Malignancies: ALL (47), AML (29), other (19); Pt status: PR (7), CR1 (39), CR2 (42), CR3 (7).
Non-malignancies: Immunodeficiency (22); BM failure (10); Metabolic (6); Histiocytic (6); Hemoglobinopathy (6).
Cohort was 65 F, 80 M; median age 3.8 yr (0.1 - 20.6), wt 15.5 kg (3.0 - 73.0).
Ethnicity: Caucasian (52), Hispanic (44), African American (31), Asian (13), Mid Eastern (5).
HLA match: 6/6 (15), 5/6 (38), 4/6 (83), 3/6 (9).
Median cell dose/Kg: 0.64^8 TNC, 0.56^8 MNC & 0.70^6 CD34.
GvHD prophylaxis: MTX + ATG + CSA/FK506 ± PRED (92); MMF + ATG + CSA (16); CSA/FK506 + ATG ± PRED (37).
Statistical analyses were done using Fisher's Exact and log-rank tests, column stats, and T- test. Significance was determined at p-value of 0.05.
Overall Outcomes:
ANC >500 cells/µL was achieved in 70.3% of pts at 23 days (1 - 60); 66.2% achieved PLT count of >20,000 at 42 days (14 - 100); and 64.8% achieved >95% chimerism at 28 days (13 - 99). 100- day TRM was 22%. 84 pts (58%) are survivors. EFS > 1, 3 & 5 yr was 50%, 41% & 37% respectively, OS was 60%, 48% & 43%. 34 pts (23%) are event free for > 10 yr. Median follow up was 2.6 yr (1.2 - 16.4 yr). Grade II- IV acute GVHD was seen in 66 pts (46%), chronic GVHD in 8 (6%).
Table 1: Group Variables.
Variable
| African American (31)
| All Others (114)
| P-value
| ||
Median
| Range
| Median
| Range
| ||
Age
| 4.0
| 0.2- 20.6
| 3.6
| 0.1- 17.4
| 0.11
|
TNC/Kg^8
| 0.54
| 0.05- 2.75
| 0.68
| 0.12- 4.27
| 0.19
|
MNC/Kg ^8
| 0.44
| 0.04- 2.55
| 0.57
| 0.08- 3.84
| 0.23
|
CD34/Kg^6
| 0.60
| 0.02- 7.6
| 0.80
| 0.02- 8.7
| 0.80
|
| N=
| %
| N=
| %
|
|
HLA 3/6, 4/6, 5/6, 6/6
| 4, 19, 6, 2
| 13, 61, 19, 7
| 5, 64, 32, 13
| 4, 56, 28, 11
| 0.18
|
Malignancy: Non-Malignancy
| 21, 10
| 67.7, 32.3
| 74, 40
| 64.9, 35.1
| 0.83
|
TBI: No TBI
| 24, 7
| 77.4, 22.6
| 71, 43
| 62.3, 37.7
| 0.14
|
Table 2: Group Outcomes.
Outcomes
| African American (31)
| All Others (114)
| P-value
| ||
Median
| R=
| Median
| R=
| ||
Days to ANC
| 28
| 1- 51
| 23
| 15- 60
| 0.31
|
Days to PLT Engraft
| 45
| 25-81
| 42
| 14- 105
| 0.93
|
Days to Chimerism
| 28
| 19- 97
| 29
| 13- 100
| 0.67
|
| N=
| %
| N=
| %
|
|
Alive, Died
| 17, 14
| 54.8, 45.2
| 67, 47
| 58.8, 41.2
| 0.69
|
Relapse
| 1 of 31
| 4.8
| 16 of 64
| 21.6
| 0.11
|
aGVHD
| 11
| 35.5
| 55
| 48.2
| 0.23
|
cGVHD
| 2
| 6.4
| 6
| 5.3
| 0.68
|
ANC Engraft
| 20
| 64.5
| 82
| 71.9
| 0.51
|
PLT Engraft
| 17
| 54.8
| 79
| 69.3
| 0.14
|
Chimerism >95%
| 15
| 48.4
| 79
| 69.3
| 0.031
|
TRM
| 12
| 38.7
| 20
| 17.5
| 0.012
|
Graph 1: K-M Survival.
Conclusion:
Children of African American ethnicity had statistically significant increased Transplant Related Mortality and showed poor chimerism compared to other groups. There was no other statistical significance between the two groups with respect to age, diagnosis, HLA match, cell dose, conditioning, survival, relapse, engraftment or GVHD. Also, there was no difference in transplant outcomes of the other individual ethnic groups.