AT ENDO 2015

SAN DIEGO (FRONTLINE MEDICAL NEWS) – Remain vigilant for endocrine side effects after reduced-intensity conditioning for hematopoietic stem cell transplants in children.

Traditionally, hematopoietic stem cell transplants (HSCT) for leukemia and other malignancies are preceded by myeloablation with high-dose chemotherapy and radiation. Over the past decade, however, that approach has been supplanted by reduced-intensity conditioning (RIC), a gentler method for less aggressive diseases that don’t require a cancer to be wiped out before HSCT. RIC usually involves low-dose chemotherapy without radiation.

The hope is to reduce side effects with the gentler approach, but that’s not always how it works, according to a retrospective study of 120 children followed for a mean of 3.2 years at the Cincinnati Children’s Hospital Medical Center, which was presented at a poster session at the meeting of the Endocrine Society.

The children had RIC with campath, fludarabine, and melphalan – but no radiation – prior to one HSCT for hemophagocytic lymphohistiocytosis/X-linked lymphoproliferative syndrome (HLH/XLP), primary immune deficiency, or other generally nonmalignant conditions.

During follow-up, almost a quarter had thyroid problems and nearly three-fourths were vitamin-D deficient. Children less than 2 years old when transplanted started to catch up to their peers on growth charts, but children over 2 years old fell further behind. Hypogonadism might be a problem, too; the investigators plan to follow the children to see how they fare during puberty.

“We were surprised” by the results, said senior investigator Dr. Susan Rose, professor of endocrinology at the University of Cincinnati.

“We really thought that, with [RIC], not as many of them would have problems after their transplants, and they would grow better. [Many] were coming off steroids” after the procedure, “which usually leads children to have catch-up growth. Instead, we are seeing their growth is slower than normal. The occurrence of endocrinopathy after [RIC] is probably lower than with high-dose chemotherapy combined with radiation, but we still have to monitor [these children] and not be cavalier” about follow-up, she said.

“We can’t expect there to be no or fewer endocrine complications just because there was a less intensive [conditioning] regimen. We must, as endocrinologists, be vigilant about monitoring and screening” these patients, said endocrinologist and lead author Dr. Jonathan Howell, assistant professor of pediatrics at the university.

The children were an average of 6 years old when transplanted. They were shorter than average both before (height-for-age Z-score [HAZ] = –1.33) and after (HAZ = –1.35).

Children with HLH/XLP who were under 2 years old at transplant improved from an HAZ of –3.36 to –1.35 afterwards, but older children fell from an HAZ of –0.61 to –0.99.

Older children with HLH/XLP lost weight after transplant (body mass index Z-score [BMI-Z], 1.29 vs. 0.61), as did those transplanted for metabolic or genetic disorders (BMI-Z, 0.56 vs. –0.77). There was a trend towards increased BMI-Z in toddlers.

Seventy-seven children had their thyroids checked after HSCT: 11 had primary hypothyroidism, five had central hypothyroidism, and two were hyperthyroid. Also, 48 of the 68 children assessed for 25-OH vitamin D had levels below 30 ng/mL.

Fourteen children broke bones after their transplants and six were diagnosed with avascular necrosis. The team is looking into whether it had something to do with endocrine dysfunction.

The investigators had no disclosures and no external funding for their work.


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