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.

  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% 
  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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