Haight, Ann E MD; Rudolph, Carrye Anne BS; Eckman, James R MD; Hsu, Lewis L MD, PhD; Bowman, Laura C MD; Chiang, Kuang-Yueh MD, PhD; Olson, Ellen RN, CPNP; Lauer, Mary RN, CPNP; Yeager, Andrew M MD; Adamkiewicz, Thomas MD; Lane, Peter MD; Olson, Thomas MD Author Information
Allogeneic BMT offers a cure to select patients with sickle cell disease (SCD), but the limited available long-term data and concerns about the risk-to-benefit ratio present dilemmas for families and clinicians. We report favorable outcomes in a large single institution experience with myeloablative matched sibling BMT for children with severe SCD between December 1993 and April 2003. Sixteen patients (12 male) with a median age 7.7 years (3.3–17.1) were transplanted for primary indications of CVA (n = 8), recurrent TIA (n = 1), recurrent ACS (n = 6), and frequent VOC pain (n = 1). Graft source was HLA-identical sibling marrow, with 9 HgbAS donors. Preparative regimen (BU 14 mg/kg, CTX 200 mg/kg, ATG 90 mg/kg) was well tolerated. Special measures included aggressive management of hypertension and hypomagnesemia, maintenance of Hgb 10–12 g/dl and platelets >50k, and prolonged antiepileptics while on CSA for GVHD prophylaxis. The initial 8 patients were treated on a multicenter consortium trial (Walters et al). With median follow-up 36 months (6–84), OS and DFS are 100% and there are no graft failures. Two patients have stable mixed chimerism (72 and 69% donor) with low HgbS (0 and 2.5%) and no clinical SCD. Median WBC engraftment was day 12.5 (10–21) and platelet engraftment day 31.5 (17–46). No patients experienced aGVHD. The two oldest patients had cGVHD related to medication non-compliance. Two of the 8 patients with prior CVA had serious CNS events, including seizure and hemorrhage on day 0 in a moya-moya patient and late progressive cerebrovascular disease in a patient with prior CVA. None had new clinical CVA. One patient (age 16.7 years) without prior CVA had a seizure attributed to "non-compliance rebound" with CSA. Infections included two episodes of Zoster, one early multiorganism bacteremia, and one late pneumococcal bacteremia. All patients have excellent functional status and attend school/college. These favorable outcomes have led our center to offer this transplant treatment as a standard-of-care with principles specific to SCD: 1)careful psychosocial screening and transplantation at a young age, 2)supportive measures to avoid CNS events, and 3) long-term follow-up with attention to infection and cerebrovascular disease that may relate to SCD rather than the BMT. In our experience, collaborative management with a comprehensive sickle cell program optimizes referral of appropriate patients, reduces peritransplant complications, and optimizes outcomes.
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