Nonmyeloablative stem cell transplantation in patients with ALL and AML results in low nonrelapse mortality despite high rate of infections and GVHD.

Abstract

28 patients with high-risk acute lymphoblastic (ALL) or acute myelogenous leukemia (AML) underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors because of one or several contraindications against myeloablative conditioning. Out of 28 patients, nine (32%) had pulmonary or hepatosplenic infiltrates due to invasive fungal infections (IFI) before NST. Out of a total of 28 patients, 17 (61%) had uncontrolled leukemia before NST. Conditioning was performed with fludarabine 180 mg/m(2), busulfan 8 mg/kg and antithymocyte globulin 40 mg/kg. After NST, fever of unknown origin, sepsis or pneumonia developed in 18/28 patients (64%) overall. IFI reactivated in 3/9 patients after NST. Out of, 28 patients, 13 (46%) had late onset of acute graft-versus-host disease (GvHD), which developed at a median of 83 days after NST. GvHD frequently developed after donor lymphocyte infusions. After a median follow-up of 8 months (2-46 months), 14/28 patients (50%) have died from relapse and 1/28 patients (4%) has died from sepsis. Among 28 patients, 13 (46%) are alive in complete remission (CR). Six of 17 patients (35%) with uncontrolled disease and 7/11 patients (63%) with CR before NST are alive in CR. Probability of overall survival at 2 years is 38%. In summary, NST offers a therapeutic alternative to patients with high-risk ALL or AML, who have contraindications against conventional high-dose conditioning. Low NRM was encountered despite high morbidity, but relapse rate was high. Therefore, controlled studies are necessary to elucidate the place of NST in the therapy of high-risk acute leukemias.