Total nodal irradiation in patients with severe treatment-refractory chronic graft-versus-host disease after allogeneic stem cell transplantation: Response rates and immunomodulatory effects.

BACKGROUND AND PURPOSE: The use of total nodal irradiation (TNI) has been reported as an immunomodulatory therapy for different diseases including chronic graft-versus-host disease (cGVHD). MATERIAL AND METHODS: We retrospectively analyzed 13 patients with treatment-refractory cGVHD receiving TNI with 1×1Gy from 2001 to 2014. In 10 of 13 patients immunomodulatory effects of TNI were measured. RESULTS: At time of TNI all patients had severe cGVHD (involving the skin: n=12), fascia (n=6), oral mucosa (n=8), eye (n=8), and lung (n=5). Nine of 13 patients had corticosteroid-refractory cGVHD. In 7 of 13 patients (54%) a partial response (PR) could be achieved. In 3 patients (23%) cGVHD manifestations remained stable, 2 patients progressed. One patient was not evaluable due to follow-up <1 month. At 3 months after TNI, best responses could be achieved in skin, and oral involvement including steroid sparing activity. TNI was well tolerated with adverse effects limited to reversible thrombocytopenia and neutropenia. Immunomodulatory effects on peripheral blood cells could be demonstrated including an increase of CD4+ T cells in the group of responders. CONCLUSIONS: TNI represents an effective immunomodulating therapy in treatment-refractory cGVHD.

Tumor-Induced Osteomalacia: an Up-to-Date Review.

Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. TIO is usually induced by small, slowly growing tumors of mesenchymal origin (phosphaturic mesenchymal tumor mixed connective tissue variant [PMTMCT]). Nonspecific symptoms including fatigue, bone pain, and musculoskeletal weakness make the diagnosis elusive and often lead to a delay in treatment. The prognosis of TIO is excellent following complete resection of the neoplasm, which leads to the rapid and complete reversal of all symptoms. If the tumor cannot be detected, treatment relies on supplementation with phosphate and active vitamin D compounds. Subsequent radiotherapy in case of incompletely resected tumors or definitive radiotherapy in unresectable tumors is an important treatment option to avoid recurrence or metastasis even though this occurs rarely. Due to the risk of recurrence or late metastases, long-term monitoring is required even in TIO patients diagnosed with a benign tumor.

Tumor-Induced Osteomalacia: Increased Level of FGF-23 in a Patient with a Phosphaturic Mesenchymal Tumor at the Tibia Expressing Periostin.

In our case, a 45-year-old male patient had multiple fractures accompanied by hypophosphatemia. FGF-23 levels were significantly increased, and total body magnetic resonance imaging (MRI) revealed a tumor mass located at the distal tibia leading to the diagnosis of tumor-induced osteomalacia (TIO). After resection of the tumor, hypophosphatemia and the increased levels of FGF-23 normalized within a few days. Subsequent microscopic examination and immunohistochemical analysis revealed a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT) showing a positive expression of somatostatin receptor 2A (SSTR2A), CD68, and Periostin. Electron microscopy demonstrated a poorly differentiated mesenchymal tumor with a multifocal giant cell component and evidence of neurosecretory-granules. However, the resected margins showed no tumor-free tissue, and therefore a subsequent postoperative radiotherapy was performed. The patient is still in complete remission after 34 months. Tumor resection of PMTMCTs is the therapy of choice. Subsequent radiotherapy in case of incompletely resected tumors can be an important option to avoid recurrence or metastasis even though this occurs rarely. The prognostic value of expression of Periostin has to be evaluated more precisely in a larger series of patients with TIO.