Loss of chimerism following allogenic haematopoietic progenitor cell transplantation in children: a silent alarm

Introduction: Allogenic haematopietic progenitor cell transplantation (Allo-HPCT) is the cornerstone in the treatment of a wide spectrum of hematological malignancies in children. Its success is highly affected by recurrence of the underlying disease. Chimerism follow up is essential to find out patients at higher risk of recurrence. Objective: To analyze the impact of chimerism status at days +30, +60 and +90 post Allo HPCT regarding clinical outcome Material and Methods: We retrospectively reviewed 91 patients (male = 51 and female = 40) with underlying malignancies who underwent Allo-HPCT between November 1987 and September 2008. Patient age ranged from 0.5 to 19 years (median = 7.58). Diagnosis included Acute Lymphoblastic Leukemia (ALL = 53), Acute Myeloid Leukemia (AML = 30) and others (O = 6). Chimerism status was determined by quantitative polymerase chain reaction (PCR) of variable number of tandem repeats (VNTR) at days +30, +60 and +90 after Allo HPCT. Chimerism was defined as Complete Chimerism (CC) when there was no evidence of autologous cell at any time post transplant, as Mixed Chimerism (MC) when both recipient and donor cells where found and Null Chimerism (NC) when complete autologous reconstitution was seen. Results: 31 out of 91 patients (ALL = 18, AML = 12, O = 1) relapsed after Allo-HPCT. Median time to relapse was 114 days (25-844). All relapsed patients eventually died (Disease progression (DP) = 27, Sepsis (S) = 2, Graft Versus Host Disease (GVHD) = 2). 28 other children died in remission (S = 4, GVHD = 2, Viral Infections = 3, Other = 19). Mean follow up was 833.5 days ± 1238.1. At day +30 median relapse-free-survival was 14,53 months in patients with CC, 12.3 months with MC and 2.07 months in children with NC (p