Abstract
Compared to other hematopoietic stem cell sources, UCB carries an increased risk of graft failure (GF), a life-threatening complication of transplant. Timely recognition of GF could help plan potentially curative salvage therapy, such as second grafting [Ruggeri et al, Haematologica 2014]. This study was aimed at identifying patients at high risk of GF. We hypothesized that early chimerism results might be a useful prognosticator. Therefore, we examined the results of day 21 bone marrow (BM) and peripheral blood (PB) chimerism testing in 327 (123 single UCB and 204 double UCB) patients receiving myeloablative conditioning (2000-2013) for various hematological malignancies. Recursive partitioning analysis was used to determine the optimal cut off of day 21 chimerism for neutrophil engraftment. Chimierism ≥85% was observed in 283 and <85% in 44 patients. For all patients surviving >21 days without evidence of disease relapse the incidence of neutrophil recovery was 92% (95% CI 89-95%) by day 42. However, for those with <85% chimerism, the rate of GF was 42% (n=20) as compared to only 3% (n=9) among patients with ≥85% chimerism at day 21 (p<0.01). As expected, 1-year overall survival (OS) was very poor in the <85% chimerism (21% with complications of GF as the most common cause of death). In multiple regression analysis, <85% chimerism was associated with 3.7-fold less likelihood of achieving neutrophil recovery by day 42 (HR 0.27, 95% CI 0.18-0.41; p<0.01) after adjustment for number of UCB units (p=0.04), HLA disparity (p=0.15) and year of transplant (p=0.10). Chimerism was also an independent risk factor for 1-year treatment related mortality (TRM, 19% vs. 39%; p<0.01), disease-free survival (63% vs. 42%; p=0.03), and OS (69% vs. 42%; p<0.01) among engrafted subset of patients with chimerism ≥85% versus <85%, respectively. In multivariable analysis, <85% chimerism remained prognostic for increased 1-year TRM (HR 2.14, 95% CI 1.06-4.31; p=0.03), treatment failure (HR 1.85, 95% CI 1.05-3.25; p=0.03) and mortality (HR 2.19, 95% CI 1.23-3.87; p<0.01) for all engrafted patients with myeloablative UCB transplant. Chimerism, however, was not an independent predictor of grade II-IV acute GVHD at 100 days (p=0.41), 1-year relapse (p=0.78) or chronic GVHD (p=0.41). Our data indicate that chimerism <85% at day 21 is critically important prognostic factor for graft failure and survival after UCB transplant. These results argue for early evaluation in order to intervene at an earlier time point to enhance survival.
No relevant conflicts of interest to declare.
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