title: Growth factors and DLI in adult haploidentical transplant: a three-step pilot study towards patient and disease status adjusted management.
abstract: Haploidentical transplant is now established as a procedure of choice for patients who lack a compatible donor. However, they are still referred too late, heavily pretreated, at very advanced stages. We initiated a three-step phase I study trying improve transplant-related mortality, relapse rate, and immunity: G-CSF + DLI, GM-CSF + DLI, patient- and disease-adapted strategy. Thirty-three consecutive leukemia patients, aged 18-55, were investigated (20 very poor risk, 11 poor risk, and 2 better risk). GvH type NK alloreactivity was chosen when possible (18/33) and balanced across the three groups. In the first nine patients, G-CSF was used and escalated prophylactic DLI started at month 1. Thus, G-CSF and 1-3 DLI (10(4) CD3/kg) is safe. It results in faster CD4 recovery and a low rate of infections. However, it was insufficient to induce a GVL effect. In the next 12 patients, GM-CSF was used plus 1 DLI (10(4) CD3/kg) at day 30 unless aGVHD (3 patients). The comparison between the two first groups can be summarized as follows: G-CSF + DLI: TRM at day 100: 0, RR: 6/9, severe aGVHD: 0. GM-CSF + 1 DLI group: RR: 1/12, TRM at day 100: 3, aGVHD > 1: 9/12, price to pay: GVHD resulting in five deaths in total. Step 3 (13 patients) consists of a patient-adapted strategy: no more aspecific DLI (selected anti-CMV and aspergillus DLI planned in all patients); in myeloid disorders with NK alloreactivity: no GF. In the other cases, GM-CSF (at a reduced total dose of 500 mug) is given the follow-up of these 13 patients, although promising is currently short (median 5 months). Overall, TRM at day 100 is 3/29, reflecting the good tolerance of the conditioning in a heavily pretreated population (median age: 43). NRR mortality (8/26) at 1 year is greater in the GM-CSF + DLI group, reflecting the impact of severe aGVHD. We conclude that the third strategy might improve the outcome without exposing patients to unnecessary severe GVHD.
authors.affiliation: Department of Hematology, Institut Jules Bordet, University of Brussels (ULB), Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Lewalle
authors.forename: A
authors.initials: A
authors.lastname: Delforge
authors.forename: M
authors.initials: M
authors.lastname: Aoun
authors.forename: P
authors.initials: P
authors.lastname: Crombez
authors.forename: V
authors.initials: V
authors.lastname: de Wilde
authors.forename: K
authors.initials: K
authors.lastname: Theunissen
authors.forename: L
authors.initials: L
authors.lastname: Lagneaux
authors.forename: B
authors.initials: B
authors.lastname: Nowak
authors.forename: V
authors.initials: V
authors.lastname: Misplon
authors.forename: D
authors.initials: D
authors.lastname: Bron
authors.forename: P
authors.initials: P
authors.lastname: Martiat
mesh_terms: D000293:Adolescent; D000328:Adult; D006086:Graft vs Host Disease / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006239:Haplotypes; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007938:Leukemia / Q000276:immunology / Q000534:rehabilitation / Q000628:therapy*; D017710:Lymphocyte Transfusion / Q000379:methods / Q000401:mortality; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000401:mortality; D023822:Tissue Engineering; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality
chemical_list: D016179:Granulocyte Colony-Stimulating Factor