Higher levels of minimal residual disease in peripheral blood than bone marrow before 1st and 2nd relapse/regrowth in a patient with high‑risk neuroblastoma: A case report

Abstract

More than half of patients with high-risk neuroblastoma (HR-NB) experience relapse/regrowth due to the activation of chemoresistant minimal residual disease (MRD). MRD in patients with HR-NB can be evaluated by quantitating neuroblastoma-associated mRNAs (NB-mRNAs) in bone marrow (BM) and peripheral blood (PB) samples. Although several sets of NB-mRNAs have been shown to possess a prognostic value for MRD in BM samples (BM-MRD), MRD in PB samples (PB-MRD) is considered to be low and difficult to evaluate. The present report describes an HR-NB case presenting higher PB-MRD than BM-MRD before 1st and 2nd relapse/regrowth. A 3-year-old female presented with an abdominal mass, was diagnosed with HR-NB, and treated according to the nationwide standard protocol for HR-NB. Following systemic induction and consolidation therapy with local therapy, the patient achieved complete remission but experienced a 1st relapse/regrowth 6 months after maintenance therapy. The patient partially responded to salvage chemotherapy and anti-GD2 immunotherapy but had a 2nd relapse/regrowth 14 months after the 1st relapse/regrowth. Consecutive PB-MRD and BM-MRD monitoring revealed that PB-MRD was lower than BM-MRD at diagnosis (100 times) and 1st and 2nd relapse/regrowth (1,000 and 3 times) but became higher than BM-MRD before 1st and 2nd relapse/regrowth. The present case highlights that PB-MRD can become higher than BM-MRD before relapse/regrowth of patients with HR-NB.

Keywords: bone marrow; minimal residual disease; neuroblastoma; neuroblastoma-associated mRNAs; peripheral blood; relapse/regrowth.

Figure 1.

(A) CT images of an abdominal tumor at diagnosis. A tumor with a diameter of ~6 cm (white arrows) was detected in the left adrenal gland. (B) Pathological examination of the adrenal tumor. Small round tumor cells were arranged in nests separated by slender fibers (original magnification, ×200). Immunostaining was positive for synaptophysin (original magnification, ×400). (C) Representative MIBG images during the entire course of treatment. MIBG-avid lesions were detected in left adrenal gland, right and left upper carpal bones, spine, pelvis, and right and left thigh bones at 0 months, disappeared at 12 months, and reappeared in the left upper carpal bones, spine, pelvis, and right and left thigh bones at 23 months and in the left thigh bone at 37 months. H&E, hematoxylin and eosin staining; MIBG, metaiodobenzylguanidine.

Figure 2.

Consecutive PB-MRD and BM-MRD monitoring. Month 0 was defined as the time of diagnosis. 7NB-mRNAs, 7 neuroblastoma-associated mRNAs; 13CRA, 13-cis-retinoic acid; BM-MRD, MRD in bone marrow samples; CR, complete response; GD2, anti-GD2 immunotherapy; HDC, high-dose chemotherapy; IC, induction chemotherapy; LT, local therapy; MRD, minimal residual disease; MRD ratio, PB-MRD/BM-MRD; PB-MRD, MRD in peripheral blood samples; PD, progressive disease; PR, partial response; SC, salvage chemotherapy.