ABSTRACT
Congestive heart failure and subclinical left ventricular systolic dysfunction (LVSD) affect long-term survivors of hematopoietic stem cell transplant (HSCT). Echocardiographic measurements of global longitudinal and circumferential strain have shown promise in identifying subclinical LVSD in cancer survivors. We analyzed echocardiograms in 95 children and young adults with malignancies or bone marrow failure syndromes performed before HSCT and 1-6 years after HSCT. We additionally measured the biomarkers soluble suppression of tumorigenicity-2 (sST-2) and cardiac troponin-I (cTn-I) in the same children through 49 days post HSCT. Ejection fraction (EF) after HSCT was unchanged from baseline (baseline: z-score -0.73 vs long-term follow up: -0.44, P=0.11). Global longitudinal strain was unchanged from baseline (-20.66 vs -20.74%, P=0.90) as was global circumferential strain (-24.3 vs -23.5%, P=0.32). Levels of sST-2 were elevated at all time points compared with baseline samples and cTn-I was elevated at days 14 and 28. Cardiac biomarkers at any time point did not correlate with long-term follow-up EF. In children and young adult survivors of HSCT, EF was unchanged in the first years after HSCT. Elevation in cardiac biomarkers occurring after HSCT suggest subclinical cardiac injury occurs in many patients and long-term monitoring for LVSD should continue.
Subject(s)
Heart Failure , Hematopoietic Stem Cell Transplantation , Stroke Volume , Survivors , Ventricular Dysfunction, Left , Adolescent , Adult , Anemia, Aplastic/blood , Anemia, Aplastic/physiopathology , Anemia, Aplastic/therapy , Bone Marrow Diseases/blood , Bone Marrow Diseases/physiopathology , Bone Marrow Diseases/therapy , Bone Marrow Failure Disorders , Child , Child, Preschool , Female , Follow-Up Studies , Heart Failure/blood , Heart Failure/physiopathology , Hemoglobinuria, Paroxysmal/blood , Hemoglobinuria, Paroxysmal/physiopathology , Hemoglobinuria, Paroxysmal/therapy , Humans , Infant , Interleukin-1 Receptor-Like 1 Protein/blood , Male , Neoplasms/blood , Neoplasms/physiopathology , Neoplasms/therapy , Troponin I/blood , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/physiopathology , Young AdultABSTRACT
We hypothesized that subclinical cardiac injury in the peri-transplant period is more frequent than currently appreciated in children and young adults. We performed echocardiographic screening on 227 consecutive patients prior to hematopoietic stem cell transplantation (HSCT), and 7, 30 and 100 days after transplant. We measured cardiac biomarkers cardiac troponin-I (cTn-I), and soluble suppressor of tumorigenicity 2 (sST2) prior to transplant, during conditioning, and days +7, +14, +28 and +49 in 26 patients. We subsequently analyzed levels of cTn-I every 48-72 h in 15 consecutive children during conditioning. Thirty-two percent (73/227) of patients had a new abnormality on echocardiogram. New left ventricular systolic dysfunction (LVSD) occurred in 6.2% of subjects and new pericardial effusion in 27.3%. Eight of 227 (3.5%) patients underwent pericardial drain placement, and 5 (2.2%) received medical therapy for clinically occult LVSD. cTn-I was elevated in 53.0% of all samples and sST2 in 38.2%. At least one sample had a detectable cTn-I in 84.6% of patients and an elevated sST2 in 76.9%. Thirteen of fifteen patients monitored frequently during condition had elevation of cTn-I. Echocardiographic and biochemical abnormalities are frequent in the peri-HSCT period. Echocardiogram does not detect all subclinical cardiac injuries that may become clinically relevant over longer periods.
Subject(s)
Heart Injuries/etiology , Hematopoietic Stem Cell Transplantation/adverse effects , Adolescent , Adult , Biomarkers/blood , Child , Child, Preschool , Echocardiography , Female , Heart Injuries/diagnosis , Humans , Infant , Interleukin-1 Receptor-Like 1 Protein/blood , Male , Pericardial Effusion/etiology , Time Factors , Troponin I/blood , Ventricular Dysfunction, Left/etiology , Young AdultSubject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Respiratory Syncytial Virus Infections/etiology , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Hematopoietic Stem Cell Transplantation/mortality , Humans , Immunosuppression Therapy/adverse effects , Infant , Male , Respiratory Syncytial Virus Infections/mortality , Retrospective Studies , Ribavirin , Risk Factors , Transplantation, Homologous , Young AdultABSTRACT
Myeloablative conditioning regimens for hematopoietic stem cell transplant (HSCT) are known to affect endocrine function, but little is known regarding reduced intensity conditioning (RIC) regimens. We retrospectively reviewed 114 children and young adults after single RIC HSCT. The analysis was grouped by age (<2 and ⩾2 years) and diagnosis (hemophagocytic lymphohistiocystosis/X-linked lymphoproliferative syndrome (HLH/XLP), other immune disorders, metabolic/genetic disorders). All groups displayed short stature by mean height-adjusted Z-score (HAZ) before (-1.29) and after HSCT (HAZ -1.38, P=0.47). After HSCT, younger children with HLH/XLP grew better (HAZ -3.41 vs -1.65, P=0.006), whereas older subjects had decline in growth (HAZ -0.8 vs -1.01, P=0.06). Those with steroid therapy beyond standard GVHD prophylaxis were shorter than those without (P 0.04). After HSCT, older subjects with HLH/XLP became thinner with a mean body mass index (BMI) Z-score of 1.20 vs 0.64, P=0.02, and similar to metabolic/genetic disorders (BMI-Z= 0.59 vs -0.99, P<0.001). BMI increased among younger children in these same groups. Thyroid function was abnormal in 24% (18/76). 25-OH vitamin D levels were insufficient in 73% (49/65), with low bone mineral density in 8 of 19 evaluable subjects. Despite RIC, children and young adults still have significant late endocrine effects. Further research is required to compare post-transplant endocrine effects after RIC to those after standard chemotherapy protocols.
