Delayed and Sudden Lymphocyte Recovery Is the Predictive Sign of Primary Graft Failure Following CBT, Single Institute Analysis of 105 CBT

Background: Primary graft failure (pGF) after cord blood transplantation (CBT) still occurs in roughly 10% of cases. Although associated with a poor prognosis, cases diagnosed early have an increased possibility of rescue with re-transplantation. We considered an early stage diagnostic method by elucidating mechanisms underlying post-CBT pGF.

Patients and Method: We analyzed 105 cases of single-unit CBT at our institution. For pGF cases, we analyzed WBC dynamics (neutrophils, lymphocytes), chimerism, and fever, and compared these parameters with delayed (>day 28) or normal (≤day 28) engraftment cases.

Results: Of the evaluable 102 cases, 59 were normal engraftment cases, 33 were delayed engraftment cases, and 10 were pGF cases. Of the 10 pGF cases, 7 showed essentially no blood cell count recovery by day 14, and sudden lymphocyte recovery at a median of day 18 (range, 15-24) followed by graft rejection. Of the 4 assessed for chimerism at the time of lymphocyte increase, all showed recipient-derived cells. 3 of the 10 pGF cases never achieved WBC≥100/μL by day 28. For engraftment cases, lymphocyte number peaked at day 12, and almost cases assessed for chimerism showed donor-derived cells. Only 1 of the 67 cases which showed WBC >100/μL on day 12 indicated pGF, whereas pGF was observed in 9 of the 33 cases in which WBC was <100/μL (p<0.001). 72 cases had febrile episodes which were associated with pre-engraftment immune reaction. The proportion of febrile (≥38°C) cases was peaked at day 8 for normal engraftment cases, day 11 for delayed engraftment cases, and day 12.5 for pGF cases.

Conclusions: pGF likelihood should be considered for cases of delayed timing of non-infectious fever, cases for which WBC recovery is not seen at around day 12, and cases of sudden lymphocyte recovery at around day 18.