Could Cord Blood Transplantation Cure Refractory Severe Aplastic Anemia?

In children and young adults with refractory severe aplastic anemia (SAA) without matched, unrelated donors, cord blood transplantation was associated with low rates of engraftment failure and high rates of one-year overall survival (OS), according to a small, prospective, phase II study published in Blood.

“Most [patients with] refractory SAA do not respond to eltrombopag or other secondline treatment and are therefore exposed to life-threatening infections and bleeding,” lead author Régis Peffault de Latour, MD, PhD, of Saint-Louis Hospital in Paris, told ASH Clinical News. “Cord blood transplantation with at least 4×107 frozen nucleated cells/kg is a valuable curative option in young patients with refractory idiopathic SAA and no available matched unrelated donors.”

This study enrolled 29 patients (median age = 16 years; range = 9-23 years) who presented with primary-refractory SAA approximately six months following firstline immunosuppressive therapy, consisting of anti-thymocyte globulin and cyclosporine. Those with relapsed SAA who were refractory to secondline immunosuppressive therapy and without a matched unrelated donor were also eligible for inclusion if they had one or two unrelated units of cord blood containing more than 4×107 frozen nucleated cells/kg available.

Pre-transplant conditioning consisted of:

  • fludarabine 30 mg/m2 per day (day 6 to day 3)
  • cyclophosphamide 30 mg/kg per day (day 6 to day 3)
  • anti-thymocyte globulin 2.5 mg/kg per day (day 3 and day 2) for a total dose of 5 mg/kg
  • 2 Gy total body irradiation (day 2)

Time from diagnosis to transplant was long (median = 12 months; range = 8.7-17.8 months) and most patients had at least 20 platelet and red blood cell transfusions, reflecting “heavily refractory disease,” the authors noted. (See TABLE for patients’ pre-transplant characteristics.)

The study’s primary endpoint was one-year survival rates of at least 50 percent. Secondary endpoints included cumulative incidences of engraftment, acute and chronic GVHD, infections, and SAA relapse.

Three patients did not undergo transplant: One patient had a male unrelated donor available (n=1), one was diagnosed with dyskeratosis congenita (n=1), and one patient died from septic shock. After a median follow-up of 38.8 months (range = 29.9-53.8 months), the rate of one-year survival was 88.5 percent (n=23; p<0.0001) among the 26 patients undergoing transplant. In the intention-to-transplant analysis (which comprised all study participant), the study also met its primary endpoint with a one-year OS rate of 84.7 percent (p<0.0001).

The researchers also reported a one-year treatment-related mortality rate of 11.5 percent; two patients died from infections arising from nonengraftment and one died from GVHD. Another patient died from severe GVHD at 13.9 months, leading to a two-year survival rate of 84.6 percent.

Twenty-three patients (88%) experienced engraftment. In the remaining three patients, engraftment failed because of:

  • death at day 71 (n=1)
  • death at day 92 following a second haploidentical hematopoietic cell transplantation (HCT; n=1)
  • survival at 31 months following a second haploidentical HCT (n=1)

Almost half of patients (n=10; 45.8%) experienced grade 2-4 acute GVHD; nine patients (36%) developed chronic GVHD.

Overall, 18 of the 22 patients alive at last follow-up had stopped active immunosuppression at a median of 18 months post-transplant (range not provided). However, three patients had extensive chronic GVHD. “These results justify using a minimal anti-thymocyte globulin dose of 5 mg/kg, … which may also lower non-engraftment rates,” the authors wrote.

A limitation of this analysis is the relatively small cohort of predominantly young patients, which reduces generalizability of the findings across the broader SAA population. The use of cord blood transplantation is another limitation, according to the researchers, as it can increase the rate of severe or potentially fatal infections.

“Longer-term follow-up is still recommended in these patients to identify possible complications that may require specific management,” Dr. de Latour noted. “Unfortunately, not all patients with SAA have eligible cord blood units available, justifying new prospective clinical trials evaluating transplant with mismatched unrelated donor or haploidentical donor to all pediatric and young [patients with] SAA.”

The authors report no financial conflicts.


Peffault de Latour R, Chevret S, Jubert C, et al. Unrelated cord blood transplantation in patients with acquired refractory aplastic anemia: a nationwide phase II study. Blood. 2018 May 14. [Epub ahead of print]