Successful double autografts for patients with relapsed clear cell sarcoma of the kidney

Abstract

Summary:Although the prognosis of clear cell sarcoma of the kidney (CCSK) has improved, when metastases occur the probability of cure is very low. We have treated two pediatric patients with relapsed CCSK, one with multiple bone metastases and another with brain metastases. After one or two courses of re-induction chemotherapy and radiation therapy to the sites of metastasis, they received double high-dose chemotherapy with autologous bone marrow rescue. Conditioning regimens were ifosphamide plus melphalan for the first autograft and busulfan plus thiotepa for the second. Hematological recovery was prompt, and no severe complications were observed. They are doing well without evidence of recurrence at 19 and 49 months after the second autograft, respectively. Keywords: clear cell sarcoma of the kidney (CCSK); bone marrow transplantation; childhood Clear cell sarcoma of the kidney (CCSK) was first described by Kidds 1 in 1970, and its histologic characteristics were defined thereafter. 2,3 It was also called bonemetastasizing renal tumor of childhood by Marsden et al 2 due to its unusual pattern of spread.Investigation of the efficacy of therapies for CCSK in the National Wilms' Tumor Study (NWTS)-1, NWTS-2 and NWTS-3 revealed that addition of doxorubicin to the combination of vincristine plus dactinomycin improved the 6-year relapse-free survival rate of this tumor. 3 However, about one-third of children with CCSK died due to treatment failure. The prognosis for relapsed cases is very poor and no convincing treatment strategy has been thus far established. 4 We present two patients with CCSK relapsing during the treatment of NWTS-3 who received intensive treatments including double autografts. They have remained in second remission longer than first remission. Case reports Case 1A 22-month-old boy presented in April 1992 with a history of vomiting and abdominal distention. A CT scan showed a large mass in the left renal fossa. Bone marrow aspiration, CT scan of the lung and brain, and bone scintigrams showed no metastases. A left radical nephrectomy was carried out and the resected kidney contained a large tumor which weighed 710 g and measured 11.2 × 11 × 8.9 cm. Microscopic examination showed nests or cords of cells separated by a network of small capillaries. The nuclei of the tumor cells were finely granular, imparting an 'empty' appearance compatible with CCSK.

Treatment and outcome of patients with relapsed clear cell sarcoma of the kidney: a combined SIOP and AIEOP study

“…Intensive treatment, including chemotherapy as well as achieving local control by complete surgery (where possible) and/or radiotherapy, seems to enhance consolidation of second CR. Summarising our study and previous reports, in total 24 relapsed CCSK patients received high-dose chemotherapy followed by ABMT, of which 12 patients (50%) were alive without disease after a median follow-up of 52 months (range, 9–103 months) (Kullendorff and Bekassy, 1997; Pein et al , 1998; Yumura-Yagi et al , 1998; Radulescu et al , 2008; Furtwängler et al , 2013). This seems to be promising, although it should be emphasised that this high-dose chemotherapy is mostly applied in a selected group of patients who already achieved a second CR.…”

“…Up until now, only three descriptive reports on clinical characteristics, treatment and outcome of relapsed CCSK have been published, including 11 patients in total (Table 1) (Kusumakumary et al , 1997; Yumura-Yagi et al , 1998; Radulescu et al , 2008). Therefore, data on clinical features of these patients are scarce and the contribution of chemotherapy, surgery, radiotherapy and high-dose chemotherapy followed by ABMT to optimal treatment of relapsed CCSK has not been established as yet.…”

Rationale for the treatment of children with CCSK in the UMBRELLA SIOP–RTSG 2016 protocol

“…Furthermore, treatment with high-dose chemotherapy (extremely high, potentially toxic doses of chemo therapy) followed by autologous stem cell transplantation (HD-ASCT) to consolidate the second complete remission seems to be of value 21,55 . In total, the outcomes of 24 patients with CCSK who experienced relapse and received HD-ASCT have been reported in the literature, of whom 50% were alive without disease after a median follow-up duration of 52 months, whereas the average 5-year OS of patients with relapsed CCSK is about 26% 21,[55][56][57][58] . Importantly, this HD-ASCT treatment was mostly given to a selected group of patients with relapsed disease who already achieved second complete remission; thus, the positive effect of HD-ASCT might (in part) be attributable to this selection of patients.…”

Brain Metastases

“…Jung et al in a study of 60 temporal bones with metastatic disease, found involvement of the facial nerve in 14 (23%) [105]. One study pointed out that only 50% of patients with tumoral invasion of the facial canal clinically had some degree of facial paralysis, although virtually all patients with tumor extension beyond the epineural sheath had complete paralysis [99].…”

“…The authors suggest that ICE chemotherapy, together with radiation therapy and surgery, provided a reasonable salvage treatment regimen for recurrent CCSK that has metastasized to the brain [102]. The role of high dosechemotherapy remains undefined, despite several encouraging reports [103][104][105].…”