Abstract
Background: Despite millions of donors in unrelated registries, many patients, in particular those belonging to ethnic minorities can not find a suitable donor in a timely fashion. In contrast, with an inventory of 250,000 banked cord blood unit, almost every patient will find a 4/6 cord blood unit matched by low resolution HLA-A and –B and high resolution –DRB1 typing. The current study evaluates the outcomes of umbilical cord blood transplants (UCBT) performed using a 4/6 matched donor treated at a single center.
Methods: Between August 1993 and November 2007 a total of 318 consecutive pediatric patients (under 21 years old) underwent UCBT from a single 4/6 unit after myeloablative conditioning regimen. The patients were a median of 6.1 (range 0.05–20.33) years and weighed a median of 21.2 (range 3.27–118.4) kg at transplant. Overall, 36.5% (n=116) were girls and 39.2% (n=123) were CMV seropositive. A significant proportion (34.6%) of patient identified as belonging to ethnic and racial minorities. Sixty-five percent (n=205) of the patients had malignant diseases including acute lymphoblastic leukemia (n=87), acute myeloid leukemia (n=58), infant leukemia (n=14), and others (n=46). The nonmalignant patients (n=113) included inherited metabolic disorders (n=75), primary immunodeficiency diseases (n=16), bone marrow failure syndromes (n=11), and others (n=11). The cellular composition of the donor cord blood unit showed a median pre-cryopreservation total nucleated cell (TNC) dose of 6.2×107/kg (range 0.9–38.2), infused TNC of 4.8×107/kg (range 0.5–27.4), infused CD34 of 1.8×105/kg (range 0.02–104.8), and infused CFU of 3.6×104/kg (range 0.0–49.9). Kaplan-Meier estimates of survival were calculated using log-rank test. Descriptive statistics were used for other analyses.
Results: The median time to engraftment (ANC>500/mm3 and platelets>50K/uL) were 25 and 83 days. By day 42, 87.4% had achieved ANC>500/mm3 and by day 180, 74.7% had achieved platelets>50K/uL. Acute grades III/IV GvHD developed in 15.5% while the incidence of extensive chronic GvHD at 2 years was 15.2% in evaluable patients. A total of 9.7% of patients had either primary graft failure (n=19) or autologous recovery (n=12). The probabilities of overall survival (OS) are presented in the table.
| . | . | N . | 1-yr OS . | 3-yr OS . | 5-yr OS . |
|---|---|---|---|---|---|
| Diagnosis Group | |||||
| Malignant | 205 | 52% | 44% | 43% | |
| Nonmalignant | 113 | 59% | 51% | 46% | |
| Patient CMV status | |||||
| Positive | 123 | 45% | 38% | 38% | |
| Negative | 190 | 62% | 52% | 49% | |
| TNC cryopreserved | x107/Kg | ||||
| <2.5 | 29 | 31% | 24% | 24% | |
| 2.5 – 4.99 | 92 | 51% | 43% | 43% | |
| 5.0 – 7.5 | 79 | 56% | 50% | 48% | |
| > 7.5 | 118 | 63% | 53% | 48% |
| . | . | N . | 1-yr OS . | 3-yr OS . | 5-yr OS . |
|---|---|---|---|---|---|
| Diagnosis Group | |||||
| Malignant | 205 | 52% | 44% | 43% | |
| Nonmalignant | 113 | 59% | 51% | 46% | |
| Patient CMV status | |||||
| Positive | 123 | 45% | 38% | 38% | |
| Negative | 190 | 62% | 52% | 49% | |
| TNC cryopreserved | x107/Kg | ||||
| <2.5 | 29 | 31% | 24% | 24% | |
| 2.5 – 4.99 | 92 | 51% | 43% | 43% | |
| 5.0 – 7.5 | 79 | 56% | 50% | 48% | |
| > 7.5 | 118 | 63% | 53% | 48% |
Conclusions: A 4/6 single donor unit is an effective graft source for patients younger than 21 yrs and should be seriously considered if the cryopreserved cell dose is more than 2.5×107TNC/kg. The use of 4/6 matched units will make transplant accessible to many more patients in particular those of ethnic and racial minorities who are unable to find a suitable adult unrelated donor.
Disclosures: No relevant conflicts of interest to declare.
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