Long-term small-fiber neuropathy and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation

J Cancer Res Clin Oncol. 2020 Aug;146(8):2143-2152. doi: 10.1007/s00432-020-03216-8. Epub 2020 Apr 28.

Abstract

Purpose: We aimed at describing for the first time peripheral small-fiber neurotoxicity and pain sensitization in survivors of pediatric acute lymphoblastic leukemia after stem cell transplantation (SCT).

Methods: In a cross-sectional, retrospective, single-center study, we assessed 25 relapse-free long-term survivors (median age at SCT: 11 ± 4.9 years; median time between SCT and testing: 8.25 years, 19 males) using a reduced version of the pediatric-modified total neuropathy score for clinical assessment and Quantitative Sensory Testing (QST).

Inclusion criteria: [Formula: see text] 6 years old at testing, [Formula: see text] 18 years old at time of SCT, [Formula: see text] 1 year between SCT and testing.

Results: Nine patients (36%) had peripheral neuropathy as defined by the clinical red-pmTNS (≥ 4). The QST parameters mechanical pain sensitivity, mechanical detection threshold, thermal sensory limen, vibration detection threshold and pressure pain threshold were significantly abnormal in the survivor cohort (p < 0.0038). Except for one, all survivors showed at least one abnormal QST parameter. When using QST, signs of small and large fiber dysfunction were present in 22 (88%) and 17 (68%) survivors, respectively. More than half of all survivors were found to experience pathologic sensitization to pain.

Conclusions and implications for cancer survivors: Survivors of pediatric acute lymphoblastic leukemia after SCT are at high risk for long-term peripheral neuropathy with a dominating small-fiber and pain sensitization pattern.

Keywords: Acute lymphoblastic leukemia; Chemotherapy-induced peripheral neuropathy; Pain sensitization; Quantitative sensory testing; Small- and large nerve fibers.

MeSH terms

  • Adolescent
  • Adult
  • Cancer Pain / diagnosis
  • Cancer Pain / etiology*
  • Cancer Survivors*
  • Central Nervous System Sensitization*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Retrospective Studies
  • Small Fiber Neuropathy / diagnosis
  • Small Fiber Neuropathy / etiology*
  • Young Adult