Early “Mini” Donor Lymphocyte Infusions after Reduced-Intensity Conditioning in Allogeneic Transplant of Highly Purified CD34⁺ Cells from HLA-Identical Donors in Pediatric Leukemia Patients.

To maximize graft-versus-leukemia (GvL) effect while minimizing transplant-related morbidity and mortality (TRM), we designed a study of allogeneic CD34⁺ selected PBSC transplantation followed by donor lymphocyte infusion (DLI). PBSC CD34⁺ selection was performed with the CliniMACS device. Between June 2004 and July 2005, fifteen consecutive patients (5 females and 10 males) aged between 1–16 years (median 5 years) diagnosed of AML (6) and ALL (9) were conditioned with fludarabine 30 mg/m²/day x 5 days and melphalan 140 mg/m²/day x 1 day. Status at transplantation was 1^st CR 10, 2^nd CR 4 and 3^th CR 1. GvHD prophylaxis consisted of CsA + short Mtx in 13 cases and CsA in 2. Patients were grafted with a median number of 6.9 x 10⁶/Kg CD34⁺ cells (range: 1.5–30.9 x 10⁶/Kg) and 15.6 x 10³ CD3⁺ cells (range: 2–59.2 x 10³/Kg). All patients engrafted. Median time to neutrophil and platelet engraftment was 12 days (range: 9–15 days) and 13 days (range: 9–42 days), respectively. DLI of 0.5 x 10⁵/Kg CD3⁺ cells were scheduled on day +15, +30 and +60. A total of 40 DLI were performed. One patient had acute GvHD grade I after the 2^nd DLI that resolved with topical steroid treatment and another one developed graft hypoplasia after first DLI resolved after G-CSF treatment. One patient died of a sepsis on day +15 (TRM 6% ± 5%). Two patients relapsed, one with an isolated CNS relapse (6 months postransplant) and the other with a medullar relapse (3 months). With a median follow-up of 6 months (range: 3–13 months) the disease free survival was 75% ± 13% and overall survival 87% ± 8%. The preliminary results of our transplantation strategy are encouraging. A large prospective study is needed to substantiate these results.