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Toxicity associated with the hematopoietic stem cell transplant (HSCT) process commonly results in a need for critical care resources. Identifying biomarkers associated with critical illness in HSCT patients may improve outcomes. Brain natriuretic peptide (BNP) has become a useful marker of cardiopulmonary disease in many settings. The value of BNP levels early in the HSCT process in children is largely unknown.
Hypothesis:
Children with elevated BNP levels during the first 14 days after HSCT will be at higher risk for toxicity and more likely to require critical care resources during the first 100 days after HSCT.
Methods:
A multicenter, prospective study recruited pediatric allogeneic HSCT patients from 5 tertiary care centers. BNP levels were assessed at the start of conditioning, at Day-1, and at Days +1, +7, +14, +21, +28, and +100 after HSCT. Patients were followed for 100 days after HSCT. Outcome variables included the need for inotropic support, supplemental oxygen, PICU admission and survival. Odds ratios were determined to assess the relationship of elevated BNP levels with these outcomes. An elevated BNP level was defined a priori as > 100 pg/mL.
Results:
Fifty one patients were enrolled. The median age was 12 years (IQR 6-15). There were 29 males. Forty patients (78%) were transplanted for malignant diseases. Thirty eight of the 51 patients (75%) had at least 1 BNP level > 100 within 14 days of transplant. The median BNP levels were 21, 28.5, 65, 56, 105, 55, 36 and 24 pg/mL at baseline, Day-1, +1, +7, +14, +21, +28 and +100 of HSCT respectively. A BNP level > 100 was associated with a need for oxygen (p=0.003) and PICU admission (p=0.02), but not inotropic support. Overall, 23 of the 51 patients (45%) required oxygen. Of these 23, all but one (96%) had at least one BNP level > 100 during the first 14 days post HSCT. In contrast, only 16 of the 28 patients (57%) who did not require oxygen had a BNP level > 100 during that time frame (Odds ratio 16.5, 95% CI (1.9 – 140.1)). Nineteen of the 51 patients (37%) required admission to the PICU. Of these 19, 18 patients (95%) had at least one BNP > 100 within the first 14 days of HSCT. In contrast, only 20 of the 32 patients (63%) who did not require PICU admission had a BNP level > 100 during that time frame (Odds ratio 10.8, 95% CI (1.3 – 91.5)). Six patients (12%) died due to transplant related mortality in the first 100 days; 5 of these (83%) had a BNP level >100 during the first 14 days.
Conclusions:
BNP levels peaked at Day +14 after allogeneic HSCT in this study. Children who required critical care resources (oxygen and PICU admission) almost invariably demonstrated an elevated BNP during the first 14 days after HSCT. This information may be useful clinically and for risk stratification in studies of pediatric HSCT patients. The etiology of the rise in BNP requires further study.