Unrelated Donor Umbilical Cord Blood Transplantation in Children with Acquired Aplastic Anemia. Korean Experience of 12 Cases.

Matched unrelated donor transplants have been reserved for patients with severe aplastic anemia (SAA) who fail a round of immunosuppressive therapy (IST). Despite the general acceptance of cord blood as an alternative stem cell source, unrelated donor cord blood transplantation (CBT) has not yet been recommended for SAA because of the high risk of graft failure and infectious complications. Only a few cases of successful CBT in SAA have been reported in the literature. From July, 2003 to Dec., 2005, twelve cases of unrelated donor CBTs in Korean children with acquired SAA were performed, and enrolled in this retrospective study. Two of them received double unit CBT. One patient who rejected a CBT received the second transplant with double unit CBT. All patients had no matched family donors. The median age and weight at the time of transplant were 7.0 years (2.8–18.8 years) and 23.3 kg (12.1–49.4 kg), respectively. Seven patients received previous IST including ATG/ALG plus cyclosporine (CyA). The median interval from the diagnosis to transplant was 20.5 months. The HLA discrepancy between the single unit umbilical cord blood and the patient was 0/6 in 1, 1/6 in 8, and 3/6 in 1. The conditioning regimen was heterogeneous, but included radiation in 3, and fludarabine in 3. The median infused nucleated cell dose was 3.3 × 10⁷/kg (0.3–9.4 × 10⁷/kg), and median CD34+ cell dose was 1.7 × 10⁵/kg (0.4–6.6 × 10⁵/kg) of recipient weight. Graft-versus-host disease (GvHD) prophylaxis was CyA plus methylprednisolone in 9 cases. Primary engraft failure was encountered in 3. The absolute neutrophil count ≥500/μL was achieved at 17.0 days (15–34 days), and platelet count ≥20,000/μL at 57.0 days (32–122 days), respectively. Complete donor chimerism was promptly observed in 8, with transient mixed chimerism in another patient. Acute GvHD ≥ II was observed in 5 cases, and extensive chronic GvHD was found in 2 among 8 evaluable cases. The 3-year overall survival was 74.1%, and 3-year estimated failure-free survival was 58.3%. The causes of death were sepsis, cytomegloviral pneumonitis, and chronic GvHD with intracranial hemorrhage in each patient. Cytomegaloviral disease was found in 3 cases. These results are comparable with those from unrelated donor BMT in refractory SAA. Considering the better tolerability of HLA mismatching, CBT should be considered as an alternative source of transplants. A randomized, prospective study comparing the 2nd-line IST, unrelated bone marrow transplants, or CBT is warranted to answer the best option for those who fail to 1st line IST without matched siblings.