Poor growth, thyroid dysfunction and vitamin D deficiency remain prevalent despite reduced intensity chemotherapy for hematopoietic stem cell transplantation in children and young adults

Abstract

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.

Figure 1

Height-for-age z scores before and after RIC HSCT. After HSCT, younger children with HLH/XLP demonstrated improved linear growth (HAZ =−3.41 vs −1.65, p= 0.006), while older subjects showed decline in linear growth outcomes (HAZ =−0.8 vs −1.01, p= 0.06), although all patients remained short relative to normal growth in children (Figure 1). Bars represent mean and standard error. There were 102 subjects on study younger than age 14 at the time of BMT. 6 pre-BMT HAZ measurements were invalid due to CDC/WHO guidelines. 96 had valid pre-BMT HAZ measurement. 6 subjects were missing a post-BMT measurement and 1 was invalid. 95 had a valid post-BMT HAZ measurement.

Figure 2

Body mass index z-scores before and after RIC HSCT. After HSCT, older subjects with HLH/XLP had decreased BMI (BMI-Z= 1.20 vs. 0.64, p=0.02) which was similar to metabolic or genetic disorders (BMI-Z= 0.59 vs. −0.99, p<0.001). Bars represent mean and standard error. There were 114 subjects on study. 11 pre-BMT measurements were invalid due to CDC/WHO guidelines. 103 and two had valid pre-BMT BMIZ measurement. 12 subjects were missing a post-BMT measurement and 1 was invalid. 103 had a valid post-BMT HAZ measurement.