Overall survival is similar with both approaches, but cord-blood transplantation offers advantages.
There is currently considerable interest in attempting to cure sickle cell disease (SCD) and thalassemia major (TM) by transplantation of healthy hematopoietic cells derived from either the bone marrow or cord blood. To determine which of these sources is optimal, international investigators conducted a retrospective, registry-based study that compared outcomes between 389 patients receiving bone-marrow transplantation (BMT; 130 with SCD and 259 with TM) and 96 patients receiving cord-blood transplantation (CBT; 30 with SCD and 66 with TM) from human leukocyte antigen (HLA)-identical siblings.
BMT recipients were older than CBT recipients (8.1 years vs. 5.9 years; P=0.02), heavier (23 kg vs. 19 kg; P=0.01), and treated less recently (1999 vs. 2001; P<0.01). BMT recipients were also more likely to have received antithymocyte globulin or antilymphocyte globulin (ATG/ALG; 67% vs. 54%; P<0.01) and methotrexate prophylaxis for graft-versus-host disease (GVHD; 76% vs. 30%; P<0.01). Thiotepa was used more often in patients receiving CBT (22% vs. 7%; P<0.01).
During a median follow-up of 70 months, 6-year overall survival was similar with BMT and CBT (95% and 97%), as was graft failure (7.4% and 10.4%). In successfully engrafted patients, neutrophil recovery was slower with CBT than BMT (23 days vs. 19 days;P=0.002), as was platelet recovery (38 days vs. 25 days; P=0.004); rates of infection and bleeding were similar with CBT and BMT. Treatment failures were more common in TM patients than SCD patients.
Long-term sustained mixed chimerism occurred more often with CBT (37% vs. 22%;P=0.01). Acute GVHD was more frequent with BMT than CBT (21% vs. 10%; P=0.04) and accounted for 8 deaths in the BMT group; no instances of grade IV GVHD or deaths occurred in CBT recipients. Chronic GVHD was also more common with BMT than CBT (11.8% vs. 7.1%); 12 BMT and no CBT recipients had extensive chronic GVHD. Disease-free survival was adversely affected by the use of methotrexate to prevent GVHD (P<0.001).
Comment: Although both bone-marrow transplantation and cord-blood transplantation are associated with high percentages of satisfactory outcomes, CBT has a number of advantages. These include significantly less graft-versus-host disease (and less need for methotrexate), directed-donor family banking, and ease of procurement. However, the scarcity of expert transplant centers, high cost, and need for a human leukocyte antigen–identical sibling are limitations of both CBT and BMT as curative therapy for hemoglobinopathies.