A 32-year-old male was diagnosed with Guillain Barre syndrome at the local hospital 32 months ago; he had weakness in both lower limbs and was unable to walk autonomously. After receiving gamma globulin (0.4 g/kg for 5 days), weakness in both lower limbs remained and he was unable to stand autonomously. Eight months after the initial diagnosis, the weakness of the limbs became worse: the patient was able to raise the upper limbs but could not hold objects. His fine movements were poor, and he experienced numbness of the distal extremities and pain in both feet. On April 8th, 2021, he was referred to the neurology department of our hospital.
Physical examination revealed skin pigmentation and white nails (Fig. 1). Muscle strength in both upper limbs was weak. The strength of the proximal muscles of both lower limbs was grade IV, and that of the distal muscles was grade 0. Hyperalgesia occurred below 20 cm above the wrist of the left upper limb, in the right upper limb, and in both lower limbs. The ONLS score was 5 points for both upper limbs and 7 points for both lower limbs. Electromyography was performed to assess neurogenic injury. Blood tests revealed the following: platelet count, 527×109/L (reference range, 100–300×109/L), hemoglobin, 179 g/L (reference range, 120–160g/L), and VEGF, 503.37 pg/ml (reference range, < 160.00). Immunofixation electrophoresis revealed the presence of IgG-λ type M protein. There were no abnormalities with respect to bone marrow cell morphology, bone marrow flow cytometry, genes related to bone marrow proliferative neoplasms, antinuclear antibodies, or thyroid function. Positron emission tomography-computed tomography (PET-CT) indicated bone destruction in the sacrum, with localized soft tissue masses measuring 3.6×7.9 cm and showing increased glucose metabolism (Fig. 2A). Pathological examination of the tumor puncture revealed diffuse clonal proliferation of round cells; immunohistochemical staining identified these as Ki67 (5%+), λ (+), κ (-), CD138 (+), CD38 (+), IgG (+), IgA (-), suggesting plasmacytoma (Fig. 2B to H). A 17p13.1 deletion was identified by fluorescence in situ hybridization (Fig. 2I). Therefore, we diagnosed POEMS syndrome with SP of the bone harboring a 17p deletion.
The patient received 4 cycles of Dara-Rd as induction therapy. During each 28-day cycle, he received Dara (16 mg/kilogram body weight once weekly during cycles 1 and 2; and every 2 weeks during cycles 3 through 4), lenalidomide (25 mg on Days 1 through 21), and oral dexamethasone (40 mg on Days 1, 8, 15, and 22). After induction, the size of the mass located in sacral vertebrae (1 and 2) reduced to 3.6×7.2 cm, which was slightly smaller than that measured initially (Fig. 3A, B). Blood test results returned to normal, with a platelet count of 298×109/L, hemoglobin at 128 g/L, and VEGF at 43.48 pg/mL (Fig. 3C). Immunofixation electrophoresis was negative and the peripheral neuropathy had improved. Significantly The ONLS score decreased to 4 points for both upper limbs and to 5 points for both lower limbs. According to the response criteria for POEMS syndrome1, HRCR and VCR was achieved.
On August 7th, 2021, he received intermediate-dose cyclophosphamide (3 g/m2) and G-CSF mobilization. A total of 4.22×108/kg mononuclear cells were collected, of which CD34 + cells comprised 6.54× 106/kg.
Considering that the plasmacytoma was isolated and showed no obvious change after induction, he received local radiotherapy (DT 5000cGy/25f) to the sacral lesion.
On January 1st, 2022, he received 200 mg/m2 of melphalan as a conditioning regimen, and an infusion of 3.27×106/kg of CD34 + cells. G-CSF was administered (5 ug/kg) on Day + 6 to promote granulocyte implantation, and was discontinued until the white blood cell count exceeded 10×109/L. During implantation, he suffered from transient febrile neutropenia and diarrhea. The time until neutrophil recovery was 13 days, and that to platelet recovery was 24 days.
After successful implantation, the patient received two cycles of Dara-Rd consolidation (Fig. 4A). PET-CT revealed a reduction in glucose metabolism in the primary sacral bone lesions (to background levels) (Fig. 4B). Immunofixation electrophoresis remained negative and the neuropathy improved significantly. Electromyography showed that the neurogenic damage to limbs was significantly reduced. The ONLS score was 3 for both upper limbs and 2 for both lower limbs. Up until to the final follow-up, the patient had remained on the oral lenalidomide (10 mg/day) for 18 months, and remains in continuous HRCR and VCR.