Brain Natriuretic Peptide (BNP) Elevations In Allogeneic Stem Cell Transplant (ASCT) Recipients at the Time of WBC Engraftment. Correlation with Engraftment Syndrome and Cardiac Dysfunction.

Abstract 1309

Engraftment syndrome (ES) may occur in ASCT recipients at the time of neutrophil recovery and is suspected to reflect increased capillary permeability due to increases in proinflammatory cytokines. Clinical features of ES may include fever, weight gain, rash, hypoxia and pulmonary infiltrates, which are by definition non-cardiogenic and non-infectious in origin. We have observed elevations in BNP in ASCT recipients at the time of WBC engraftment who appear to meet clinical criteria for ES and therefore chose to monitor BNP at the time of hospital admission, on day + 0, and at engraftment to further characterize the relationship between conditioning intensity, ES and cardiac dysfunction.

A retrospective review was conducted of pretransplant cardiac features and transplant course in 139 patients undergoing ASCT between January, 2007 and April, 2010. Informative data was available for 122 transplants in 121 pts (74 males, 48 females). Median follow up of survivors was 266 days (minimum 100 days). Median age was 52 yrs (range 17–72). Transplant indication was AML 80 (66%), NHL 20 (16%), other 22 (18%). There were 58 (48%) matched related (MRD) and 64 (52%) unrelated donor (MUD) transplants. Graft source was PBSC (118) and BM (4). High dose (HD) therapy (Busulfan/Fludarabine or TBI/Cyclophosphamide [Cy]) was used in 61 transplants (50%), and reduced intensity (RI) conditioning (Busulfan/Fludarabine based or Pentostatin/TBI based) was used in 61 (50%). Tacrolimus and Mycophenolate were used for GVHD prophylaxis in 104 (85%), and Tacrolimus, Sirolimus, and Methotrexate were used in 18 (15%) mismatched transplants. Filgrastrim was routinely used from day +7 to engraftment. Forty pts (33%) had a history of HTN, CAD, CHF, or arrhythmias, 28 (25%) had received a high cumulative anthracycline dose (≥300 mg/m2 adriamycin equivalent), and 22 (18%) received HD Cy in the conditioning regimen. Results were analyzed according to a clinical diagnosis of ES noted in the medical record as well as by fulfillment of two or more diagnostic criteria (fever, rash, weight gain >2.5%, hypoxia/pulmonary infiltrate of noncardiac and noninfectious origin) present within 96 h of engraftment, as noted by Gorak et al. (BBMT 11:542, 2005).

Median admission BNP (nl<100pg/ml) was 57 pg/ml (range 40–386, n=99). Median Day 0 BNP was 59.50 pg/ml (range 40–2580, n=120). Median engraftment BNP was 216 pg/ml (range 40–11200, n=122). Abnormal BNP at admission, on day 0, and at engraftment was seen in 24%, 45% and 76% of pts respectively, with engraftment BNP>400 in 37%. The incidence of ES was 11% by clinical impression and 25% by definition criteria. Ninety four percent of pts with ES had abnormal BNP at engraftment and 61% had BNP >400. Seventy percent of pts with no evidence of ES or overt cardiac complications were noted to have abnormal BNP at engraftment, and 53% had BNP >400. Weight gain occurred in 27% of all pts and of these 90% had elevation in BNP. Six pts experienced acute cardiac complications at the time of WBC engraftment with markedly elevated BNP. There were no primary cardiac deaths.

A high cumulative anthracycline dose was associated with elevated BNP on day 0 and at WBC engraftment. High BNP on day 0 was also associated with reduced intensity conditioning but not with age. There was no correlation between cardiac history or HD Cy with elevations in BNP at any point. Elevated BNP at engraftment as well as presence of ES were significantly more common in MUD recipients. No correlation was observed between elevated engraftment BNP or presence of ES with acute GVHD or survival. One-year non relapse mortality was higher in pts with high anthracycline dose (28 vs. 18%%), high BNP at engraftment (22 vs. 7%), or MUD transplant (22 vs. 13%); High anthracycline dose was the only significant predictor of NRM in multivariate analysis. However, in the group of patients with normal BNP on day 0, a BNP >400 at engraftment was an independent predictor of both NRM and OS.

Conclusions: Elevations in BNP following ASCT are common and are associated with anthracycline exposure and MUD source. Marked elevations were noted in patients with or without ES or evidence of cardiac compromise and are of uncertain etiology. The high frequency of abnormal BNP in pts with ES and the prognostic value of a de novo elevation in BNP at the time of engraftment suggest the physiologic stress of WBC engraftment following ASCT has important cardiac consequences which deserve further study.