Unrelated Cord Blood Transplantation (UCBT) in Children with Sickle Cell Disease (SCD): US Centers Experience.

Abstract

Abstract UCBT may be curative in patients (pts) with high-risk SCD. Unrelated cord blood units matched at >4/6 HLA are acceptable for UCBTs and available to most pts. We reviewed UCBTs in 7 children with SCD and cerebrovascular accidents performed in 4 centers (1998 to 2003): 4 pts were conditioned with conventional myeloablative regimens, and 3 pts with reduced-intensity regimens. The former received busulfan (BU), cyclophosphamide (CY) and anti-thymocyte globulin (ATG) (3 pts) or BU/CY/ATG plus fludarabine (FLU) (1 pt). Of 3 pts who received 4/6 HLA-matched UCBTs after BU/CY/ATG and GVHD prophylaxis with methylprednisone (MP) and cyclosporine (CSP) or tacrolimus (TAC), 2 have durable engraftment, 1 had autologous reconstitution (BMT2004; 34:405–11). A 5 yr old (yo) female with transfusion-induced alloimmunization received a 5/6 HLA-matched UCBT (6.2 X 10^7/kg nucleated [NC] cells) after BU/CY/ATG/FLU, followed by CSP and MP post-transplant. PMN engraftment and VNTR > 98% of donor origin were documented 24 and 37 days, respectively, after UCBT. Complications included elevated liver enzymes during conditioning, grade IV GVHD of skin, GI and liver, grade III mucositis, VOD, parainfluenza 3 infection, candidemia and adenovirus viremia. Pt died of severe acute GVHD and multi-organ failure 73 days after UCBT. Two different reduced-intensity regimens were used in the other 3 pts. An 8 yo male received a 4/6 HLA-matched UCBT (3.2 X 10^7/kg NC) after conditioning with alemtuzumab, rituximab, hydroxyurea, thiotepa and TBI (600cGy, with 300 cGy total dose to liver and kidneys) and received TAC and mycophenolate mofetil (MMF) post-transplant. This patient failed UCBT 8 months earlier (FLU/CY/ATG/TLI, 4/6 HLA). PMN engraftment and VNTR > 98% of donor origin was documented within 18 days after UCBT. Complications included grade I skin GVHD, grade 1 mucositis and parainfluenza 1 infection. This pt remains engrafted and fully active 1.6 ys after UCBT. A 4 yo female and a 16 yo male received 4/6 or 5/6 HLA-matched cord units, respectively, after BU or CY, ATG, FLU and total lymphoid irradiation (200 or 500 cGy) and received CSP and MMF post-transplant. Neither had evidence of donor engraftment, and autologous reconstitution was documented within 2 weeks after UCBT. Sustained donor engraftment occurred in 3/4 pts (75%) who underwent UCBT after myeloablative conditioning and 1/3 pts (33%) who underwent UCBT after reduced-intensity conditioning. Two of the 3 pts who engrafted after myeloablative preparative regimens developed acute grade III–IV GVHD, and 1 of these pts developed extensive chronic GVHD. The 1 pt who engrafted after a reduced-intensity preparative regimen developed grade I acute GVHD only. Significant viral infections (CMV 1 pt, adenovirus, parainfluenzavirus 2 pts each) occurred in 4 pts. In this limited experience, following various conditioning regimens, optimal GVHD and infection prevention remains a challenge. Both apparent lesser risk and documented durable engraftment may justify further development of non-myeloablative strategies for UCBT in children with high-risk SCD.