BONE-MARROW TRANSPLANTATION FOR THE TREATMENT OF HEMATOLOGICAL DISORDERS IN DOWNS-SYNDROME - TOXICITY AND OUTCOME

We report 18 patients with Down's syndrome who underwent bone marrow t ransplantation, and review nine previously published patients. The ind ications for transplant in the combined group of 27 patients were acut e lymphoblastic leukaemia in 14 cases (52%), acute myeloid leukaemia i n 11 cases (41%) and aplastic anemia in two cases (7%). Transplants we re autologous in five cases (19%) and allogeneic in 22 cases (81%); of the 22 allogeneic transplants, 16 donors were HLA-matched siblings. I n all patients the conditioning regimen included total body irradiatio n of 7.5 Gy or more, and/or contained cyclophosphamide of 120 mg/kg or more. Seven patients (26%) had fatal pulmonary disease including pneu monitis and pulmonary hemorrhage. Five patients (19%) had significant airway problems including three with severe mucositis who required int ubation for airway protection, one with severe mucositis with partial airway obstruction that required observation in the intensive care uni t but did not require intubation, and one with Candida albicans laryng itis with development of a glottic web. Nineteen patients (70%) surviv ed beyond 100 days post-transplant. There was no clear association bet ween 100-day survival and the use of any particular agent or regimen u sed 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, cycl osporin A, and methotrexate. There appeared to be more early deaths in patients who received the combination of cyclophosphamide and total b ody irradiation, compared with those receiving the combination of buls ulfan and cyclophosphamide or those receiving the combination of cytos ine arabinoside and total body irradiation. Also, the use of methotrex ate was associated with a greater number of early deaths, compared wit h cyclosporin A. At 3 years, life table estimates of freedom from rela pse, relapse-free survival and survival were 75%, 44% and 48%, respect ively. The estimated cumulative risk of death due to a non-leukaemic c ause at 3 years was 39%. The data show that Down syndrome patients can tolerate the commonly used transplant conditioning regimens with acce ptable toxicity; however, there is a strong suggestion in the data tha t the rates of life-threatening and fatal toxicity are higher than wou ld be expected to occur in patients without Down's syndrome. Patients, vith Down's syndrome may have a predisposition to fatal pulmonary comp lications and reversible airway problems during the immediate posttran splant period.