We report 18 patients with
Down's syndrome who underwent
bone marrow transplantation, and review nine previously published patients. The indications for transplant in the combined group of 27 patients were acute lymphoblastic leukaemia in 14 cases (52%), acute myeloid leukaemia in 11 cases (41%) and
aplastic anemia in two cases (7%). Transplants were autologous in five cases (19%) and allogeneic in 22 cases (81%); of the 22 allogeneic transplants, 16 donors were HLA-matched siblings. In all patients the conditioning regimen included total body irradiation of 7.5 Gy or more, and/or contained
cyclophosphamide of 120 mg/kg or more. Seven patients (26%) had fatal
pulmonary disease including
pneumonitis and pulmonary
hemorrhage. Five patients (19%) had significant airway problems including three with severe
mucositis who required intubation for airway protection, one with severe
mucositis with partial
airway obstruction that required observation in the intensive care unit but did not require intubation, and one with Candida albicans
laryngitis with development of a glottic web. Nineteen patients (70%) survived beyond 100 days post-transplant. There was no clear association between 100-day survival and the use of any particular agent or regimen used for conditioning or
graft-versus-host disease prophylaxis, and the majority of patients tolerated high-dose
cyclophosphamide, high-dose
cytosine arabinoside, high-dose
busulfan, total body irradiation,
cyclosporin A, and
methotrexate. There appeared to be more early deaths in patients who received the combination of
cyclophosphamide and total body irradiation, compared with those receiving the combination of
busulfan and
cyclophosphamide or those receiving the combination of
cytosine arabinoside and total body irradiation. Also, the use of
methotrexate was associated with a greater number of early deaths, compared with
cyclosporin A. At 3 years, life table estimates of freedom from relapse, relapse-free survival and survival were 75%, 44% and 48%, respectively. The estimated cumulative risk of death due to a non-leukaemic cause at 3 years was 39%. The data show that
Down syndrome patients can tolerate the commonly used transplant conditioning regimens with acceptable toxicity; however, there is a strong suggestion in the data that the rates of life-threatening and fatal toxicity are higher than would be expected to occur in patients without
Down's syndrome. Patients with
Down's syndrome may have a predisposition to fatal pulmonary complications and reversible airway problems during the immediate post-transplant period.