Neurocognitive Function in Pediatric Stem Cell Transplant Recipients Following Low Dose Single Fraction Total Body Radiation and Cyclophosphamide

Background

Neurocognitive function is vulnerable in the formative pediatric years to transplant conditioning regimen especially those using fractionated total body irradiation (FTBI). However, FTBI improves disease free survival (DFS) in lymphoid malignancies.  Our institution has previously described a novel conditioning regimen using low dose single fraction TBI (SDTBI) delivered at a high dose rate. DFS was comparable to recipients of fractionated TBI, and early toxicities were minimal (Druley, BMT 2009). Our hypothesis is that SDTBI based myeloablative conditioning is associated with less neurotoxicity and can preserve neurocognitive functions in children.

Aim

To review neurocognitive function in children following SDTBI (550 cGy) and cyclophosphamide- based myeloablative transplant conditioning for hematologic malignancies pre and 1 year post transplant.

 Methods

A total of 45 consecutive children transplanted for hematologic malignancies (ALL, AML, NHL) between March 1998 and January 2006 that survived beyond 1 year after transplant were identified. The conditioning regimen consisted of cyclophophamide 50 mg/kg on days -3 and -2, and SDTBI (550 cGy) on day -1. Fifteen had neurocognitive testing completed before and at least 1 year post transplant.  This testing comprised of a comparative analysis of IQ and neurocognitive function using Wechsler intelligence scales selected based on the child’s age. 

Result

Full scale (FSIQ), verbal (VIQ), and performance or non-verbal (PIQ) IQs were compared. Using a greater than 1 SD loss (or greater than 15 point loss) criterion as a gross marker for significant decline at the individual patient level. Fifteen patients had an average age was 10.7 years (range 1-20.5). No patient showed a decline in FSIQ with the exception of one. This child underwent a second myeloablative transplant one year after the first; FSIQ declined by 16 points. One child’s VIQ declined 23 points; two others’ PIQ declined by 16 and 21 points, respectively.

Conclusion

Among a limited cohort of SDTBI BMT, the majority showed an overall stability or lack of significant decline in neurocognitive function one year post transplant. In contrast, previous reports show decline one year post transplant in children receiving FTBI (Phipps S et al, JCO 2008; Shah et al, PBC 2008). These data provide an initial insight into the effects of SDTBI based conditioning on neurocognition in children. Future studies will expand the analysis to further analyze exposure to CNS toxic treatments and to examine more detailed cognitive measures for domain specific trends.We will also look at patients that received FTBI and Bulsulfan/cyclosphosphamide.