Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study

Abstract

Objective: To describe long-term outcomes of children with early-infantile Krabbe disease who underwent hematopoietic stem cell transplantation (HSCT) in the first 7 weeks of life.

Methods: In this prospective longitudinal study, evaluations performed at baseline and follow-up included brain imaging, neurodiagnostic tests, and neurobehavioral evaluations.

Results: Of the 18 patients in this study (11 girls, 7 boys; mean follow-up 9.5 years, range 4-15), 5 died (3 of peritransplant complications, 1 of a surgical complication unrelated to Krabbe disease, 1 of disease progression). One of the surviving patients has normal cognitive function and 10 continue to develop cognitive skills at a slightly slower rate than normal. All surviving patients continue to gain receptive language skills, with 7 falling within the normal range. Ten patients receive speech therapy, and 2 of these patients require augmentative communication devices. Gross motor development varies widely, but 3 patients can walk independently, and 7 walk with assistive devices. Spasticity ranges from mild to severe, and 12 patients wear orthotics. Fine motor skills are generally preserved. Brain myelination and atrophy stabilized in 8 patients, improved in 4 patients, and worsened in 1 patient. Nerve conduction velocities initially improved but continue to be abnormal in most patients.

Conclusions: The surviving patients function at a much higher level than untreated children or symptomatic children who underwent HSCT. These results show that early HSCT changes the natural history of this disease by improving both lifespan and functional abilities.

Classification of evidence: This study provides Class IV evidence that for children with early-infantile Krabbe disease, early HSCT improves lifespan and functional abilities.

Figure 1. Survival of children with early-infantile Krabbe disease after hematopoietic stem cell transplantation

Kaplan-Meier curve of survival for 18 children who underwent hematopoietic stem cell transplantation for infantile Krabbe disease before 7 weeks of age.

Figure 2. Growth after hematopoietic stem cell transplantation for children with early-infantile Krabbe disease

Growth charts show weight gain for the (A) 6 boys and (B) 10 girls with follow-up data after hematopoietic stem cell transplantation before 7 weeks of age. The inset in the upper left corner of each graph magnifies and highlights growth during the first 24 months of age. The red lines represent individual patients. The gray and blue lines represent standard growth curves (blue = 50th percentile, gray lines = 3rd, 5th, 10th, 25th, 75th, 90th, 95th, and 97th percentiles). Additional graphs are included in the supplemental material.

Figure 3. Development after hematopoietic stem cell transplantation for early-infantile Krabbe disease before 7 weeks of age

For the 15 children with follow-up data, we used age-equivalent scores (i.e., developmental age) for (A) cognitive development and (B) gross motor function to allow comparisons across tests and monitor development over time. The colored lines represent individual patients. The shaded gray area represents typical development. Additional graphs showing adaptive behavior, receptive language, expressive language, and fine motor function are included in the supplemental material.