The outcomes of patients who experience the failure to reconstitute a trilineage of blood cells after initial neutrophil engraftment were evaluated in 178 patients with hematologic disorders, who underwent allogeneic HCT. Of 165 qualified patients (five with primary engraftment failure; eight deaths before day 60 of HCT), 43 (26%) satisfied the criteria for the initial (n=22; failure of platelet >20 000/microl or red blood cell transfusion independence/reticulocyte count >/=1.0% by day 60) or subsequent (n=21, ANC <500/microl for >/=3 days, platelet <20 000/microl for >/=7 days, or red blood cells transfusion/reticulocyte <1.0% after initial trilineage reconstitution) failure. GVHD was the most common clinical condition associated with cytopenia (n=24). In all, 20 patients (47%) recovered at least partially with a median of 52 days (range 8-323) later, with 12 of those 20 patients recovering completely. The eventual reconstitution failure rate was 14% (23/163 patients). The number of cell lineages involved in the cytopenia was the only independent variable that predicted partial recovery (1 lineage vs 2-3 lineages with odds ratio of 8.69 (95% CI 1.96-38.60), P=0.004). Five/20 patients with vs 20/23 patients without partial recovery died. Trilineage reconstitution failures after allogeneic HCT need systematic analysis in the future studies.