Purpose: This study evaluated the feasibility of performing haploidentical CD34+ selected transplants for children with Down's syndrome (DS) and recurrent leukemia.
Patients and methods: Within a cohort of 15 children, two patients had DS. Transplantation of CD34+ cells from haploidentical parents was performed after the children were conditioned with fractionated total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and a short course of methotrexate.
Results: The preparative regimen was well tolerated, and engraftment of polymorphonuclear cells and platelets took place promptly (by day 20) in both patients with DS. However, both patients with DS experienced severe grade IV GVHD that was limited to the skin and was refractory to salvage with high-dose methylprednisolone therapy. In one patient, GVHD responded to second-line salvage therapy with ATG, but the patient died on day 234 from leukemic relapse. The second patient had GVHD that did not respond to ATG and died of multisystem organ failure and refractory GVHD on day 44. Two of two DS patients had steroid refractory severe acute GVHD of the skin, while only one of 11 evaluated and identically treated non-DS patients had severe GVHD (p < 0.05).
Conclusion: These observations in patients who underwent mismatched bone marrow transplantation suggests that patients with DS have an increased risk of severe acute GVHD of the skin in this context.