Umbilical cord blood transplantation in pediatric patients: Results of the prospective, multi-institutional Cord Blood Transplantation Study (COBLT)

In 1996, NHLBI sponsored COBLT, a prospective study that established 3 cord blood banks that banked ∼8000 CBUs, and funded 28 transplant centers to participate in a clinical trial with the primary endpoint of 180-day post-transplant overall survival (OS). The trial enrolled 316 pediatric pts with median age 4.6 years (range 0.1-17.9), 61% M, 37% minorities, 44% CMV+ and 71% with a malignant (malign) disease, who received a single CBU. CBUs had to be at least 4 of 6 HLA match (intermediate resolution A and B and high resolution [HR] DRB1) and provide a total nucleated cell dose (TNC) ≥1.0 × 107/kg. Approximately 50% of Caucasian and Hispanic pts received a CBU matched at HLA 5-6/6, but only 15% of African-Americans and 36% of Asians were matched at HLA 5-6/6. HR HLA types were retrospectively determined for HLA -A, -B, -DRB1 (292 pairs) and -C and -DQB1 (270 pairs). Only 30% of pairs were HR HLA matched at 8-10 alleles. The median pre-cryopreservation TNC and CD34+ cell dose were 6.8 × 107/kg (range 1.5-50.4) and 2.3 × 105/kg (range 0.1-20.1), respectively. The cumulative incidence (CINC) of neutrophil recovery (>500, day 42) and of platelet engraftment (>50000, day 180) was 81% and 54%, respectively. By day +100, the CINC of grades II-IV aGVHD was 40%. The CINC of cGVHD was 21% at 2 yrs. The probability of OS at 180 days post-transplant was 69% (95% CI 64%, 74%). For pts with malignant disease, disease-free survival at 1 year was 50% (95% CI 43%, 56%). Based on Cox proportional hazards models, the success of transplantation was predominantly dependent on pt characteristics: pts with non-malign disease, CMV seronegativity, and males had improved outcomes. CD34+ dose was associated with improved neutrophil and platelet engraftment. In multivariate analyses, TNC (95% pts had ≥2.5 × 107/kg), HLA match (4/6 vs 5 or 6/6 types at transplant) or HR HLA match (<8/10 vs ≥8/10) were not significantly associated with any of the end points. In conclusion, HLA 4-6 of 6 matched CBUs with ≥2.5 × 107/kg TNC provide excellent transplant results for pediatric patients with malign (OS 57% [95% CI 50%, 63%] at 1 year) and non-malign (OS 71% [95% CI 61%, 80%] at 1 year) diseases. In 1996, NHLBI sponsored COBLT, a prospective study that established 3 cord blood banks that banked ∼8000 CBUs, and funded 28 transplant centers to participate in a clinical trial with the primary endpoint of 180-day post-transplant overall survival (OS). The trial enrolled 316 pediatric pts with median age 4.6 years (range 0.1-17.9), 61% M, 37% minorities, 44% CMV+ and 71% with a malignant (malign) disease, who received a single CBU. CBUs had to be at least 4 of 6 HLA match (intermediate resolution A and B and high resolution [HR] DRB1) and provide a total nucleated cell dose (TNC) ≥1.0 × 107/kg. Approximately 50% of Caucasian and Hispanic pts received a CBU matched at HLA 5-6/6, but only 15% of African-Americans and 36% of Asians were matched at HLA 5-6/6. HR HLA types were retrospectively determined for HLA -A, -B, -DRB1 (292 pairs) and -C and -DQB1 (270 pairs). Only 30% of pairs were HR HLA matched at 8-10 alleles. The median pre-cryopreservation TNC and CD34+ cell dose were 6.8 × 107/kg (range 1.5-50.4) and 2.3 × 105/kg (range 0.1-20.1), respectively. The cumulative incidence (CINC) of neutrophil recovery (>500, day 42) and of platelet engraftment (>50000, day 180) was 81% and 54%, respectively. By day +100, the CINC of grades II-IV aGVHD was 40%. The CINC of cGVHD was 21% at 2 yrs. The probability of OS at 180 days post-transplant was 69% (95% CI 64%, 74%). For pts with malignant disease, disease-free survival at 1 year was 50% (95% CI 43%, 56%). Based on Cox proportional hazards models, the success of transplantation was predominantly dependent on pt characteristics: pts with non-malign disease, CMV seronegativity, and males had improved outcomes. CD34+ dose was associated with improved neutrophil and platelet engraftment. In multivariate analyses, TNC (95% pts had ≥2.5 × 107/kg), HLA match (4/6 vs 5 or 6/6 types at transplant) or HR HLA match (<8/10 vs ≥8/10) were not significantly associated with any of the end points. In conclusion, HLA 4-6 of 6 matched CBUs with ≥2.5 × 107/kg TNC provide excellent transplant results for pediatric patients with malign (OS 57% [95% CI 50%, 63%] at 1 year) and non-malign (OS 71% [95% CI 61%, 80%] at 1 year) diseases.