ASSOCIATION BETWEEN ANTIBODIES REACTIVE WITH NEUTROPHILS, RATE OF NEUTROPHIL ENGRAFTMENT, AND INCIDENCE OF POST-ENGRAFTMENT NEUTROPENIA FOLLOWING BMT

Previous reports have suggested that antibodies reactive with neutroph il (ARN) are frequently detectable in patients undergoing bone marrow or blood stem cell transplantation (BMT), and that such antibodies res ult in steroid-responsive delayed neutrophil engraftment or steroid-re sponsive post-engraftment neutropenia in some patients. However, the t rue incidence and significance of ARN in the BMT setting remain poorly established because most of the published data are in the form of ret rospective case reports. Therefore, we prospectively studied the incid ence of ARN, the rate of neutrophil engraftment, and the incidence of postengraftment neutropenia in a cohort of 40 BMT candidates. Sixteen of the 36 evaluable patients (44%) had detectable ARN following transp lant vs none of 25 concurrently studied healthy controls (P < 0.0001). Patients with detectable ARN in the post-transplant period recovered to an absolute neutrophil count (ANC) of 500 x 10(9)/l a median of 3.5 days later than patients without detectable ARN; multivariate analysi s controlling for the potential effects of diagnosis, conditioning reg imen, amount of prior therapy, and other factors revealed that only th e administration of hematopoietic growth factors (P = 0.008) and the p resence of ARN in the post-transplant period (P = 0.016) were independ ently predictive of the rate of neutrophil engraftment following BMT. Four of the 16 patients with detectable ARN (25%) satisfied previously published criteria for post-engraftment neutropenia, ie a fall in the ANC to less than 500 x 10(9)/l for at least 2 consecutive days, follo wing initial engraftment to an ANC of at least 1000 x 10(9)/l for at l east 2 consecutive days. In contrast, none of the 20 patients without detectable post-transplant ARN developed post-engraftment neutropenia. Multivariate analysis revealed that only the presence of ARN in the p ost-transplant period (P = 0.022) was independently predictive of post -engraftment neutropenia. All four patients with ARN-associated post-e ngraftment neutropenia responded to steroid-based therapy. These prosp ectively gathered data support previously published primarily case rep ort data suggesting that ARN occur frequently following BMT and are as sociated with an increased incidence of delayed neutrophil engraftment and post-engraftment neutropenia. As is the case in the non-transplan t setting, ARN-associated neutropenia occurring following BMT may resp ond to steroid-based therapy.