Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease

We investigated the use of 'prophylactic' donor lymphocyte infusions (DLI) containing 1 x 10(7) CD3(+) cells, given at 30, 60 and 90 days post-allogen eic blood and marrow transplantation (BMT), following conditioning with flu darabine 30 mg/m(2)/4 days and melphalan 70 mg/m(2)/2 days. GVHD prophylaxi s consisted of cyclosporin A (CsA) 2 mg/kg daily with early tapering by day 60. Our goals were the rapid achievement of chimerism and disease control, providing an immunological platform for DLIs to treat refractory patients with hematological malignancies. Twelve heavily pre-treated patients with l ife expectancy less than 6 months were studied; none were in remission. Dia gnoses were AML (n = 4), MDS (n = 1), ALL (n = 3), CML (n = 3) and multiple myeloma (n = 1). Response rate was 75%. Three patients are alive at a medi an of 450 days (range, 450-540). Two patients are in remission of CML in bl ast crisis and AML for more than 14 months. Median survival is 116 days (ra nge, 25-648). Six patients received 12 DLIs; three patients developed acute GVHD after the first infusion and were excluded from further DLIs, but no GVHD occurred among patients receiving subsequent DLIs. One patient with CM L in blast crisis went into CR after the first DLI. The overall incidence o f acute GVHD was 70%. Primary causes of death were infections (n = 3), acut e GVHD (n = 3), chronic GVHD (n = 1) and disease relapse (n = 2). We observ ed high response and chimerism rates at the expense of an excessive inciden ce of GVHD. DLI given at day +30 post BMT caused GVHD in 50% of the patient s, and its role in this setting remains unclear.