Metastatic rhabdomyosarcoma cured after chemotherapy and allogeneic SCT

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Successful treatment of children with RMS requires multimodal therapy. However, despite advances in combined chemotherapy, radiation therapy and surgery, children with stage IV RMS have a uniformly poor outcome. 1 In case of nonembryonal histology in combination with metastatic involvement in three or more organ systems, the prognosis is dismal (3-year survival 5%). 2 Other unfavourable risk factors include the age at diagnosis of more than 10 years, bone or BM metastases and RMS of the extremities. Patients with more than two of these risk factors have a 5-year survival of 9%. 3 Most patients achieve a remission after conventional therapy, but relapse is frequent, indicating persistence of minimal residual disease. 4 Although RMS is a chemosensitive disease, the benefits of high-dose chemotherapy followed by autologous haematopoietic stem cell rescue for children with stage IV or relapsed RMS are not clear because randomized trials comparing this treatment with standard chemotherapy are lacking. In a meta-analysis of 389 patients identified from 22 publications, there was no significant survival advantage of high-dose chemotherapy followed by autologous haematopoietic stem cell rescue for patients with relapsed or metastatic RMS as compared with standard chemotherapy. 5 GVL effect is well documented after allogeneic SCT for haematological malignancies. Recently, the evidence of graft-versus-tumour effect has also been described in patients with a variety of solid tumours. 6 Only sporadic cases have been reported of allogeneic SCT in high-risk RMS patients. Wiegel et al. 7 report on two children with relapsed stage IV RMS who received allogeneic SCT after a myeloablative regimen in a non-remission status. Both patients died of disease progression. However, outcome of patients with ALL is also poor when allogeneic SCT is performed in a non-remission status or in a status with high levels of minimal residual disease. 8 Misawa et al. describe a patient with refractory RMS for which an allogeneic SCT was performed after a myeloablative regimen. The patient reached a PR. As tumour regression occurred after the reduction of immunosuppressants on day þ 30, the authors suggest the existence of a graft-versus-tumour effect. However, 80 days after transplantation, disease progression occurred. On day 165, the patient died of progressive disease in the final stage accompanied by fungal pneumonia. 9 In this letter we report, a patient with stage IV RMS who achieved CR and is in ongoing remission for 4 years after combined therapy followed by allogeneic SCT.An 8-year-old Caucasian girl was diagnosed with an alveolar RMS of the right gastrocnemical muscle (Figure 1). PAX-3 and PAX-7 fusion genes, which are specific for alveolar RMS were detected by reverse-transcription PCR. Staging revealed stage IV with extensive local, abdominal and thoracic lymph node metastases in combination with skeletal metastases (Figure 2). Bilateral crystal b...

Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment

“…The rationale for treating cancer patients with allogeneic grafts is a hypothesised graft- vs -tumour effect of donor-derived cytotoxic T cells and/or natural killer cells that may unavoidably be given during infusion of haematopoietic stem cells for immune reconstitution or intentionally thereafter as DLI ( Childs et al , 2000 ; Ueno et al , 2003 ; Bishop et al , 2004 ; Bregni et al , 2004 ; Kolb et al , 2004 ; Lundqvist and Childs, 2005 ; Mackensen et al , 2006 ; Rizzo et al , 2009 ; Reisner et al , 2011 ). Little is known about graft- vs -RMS effects in patients treated with allo-SCT and only few single-centre case experiences have been reported ( Misawa et al , 2003 ; Donker et al , 2009 ; Ohta et al , 2011 ). In this study, we evaluated individual therapy outcomes of 30 patients with advanced RMS of all subtypes who became eligible for experimental allo-SCT.…”

“…These observations suggest that allo-SCT and cellular immunotherapy may also improve outcome for RMS patients. However, little is known about graft- vs -RMS effects in patients treated with allo-SCT and only few single-centre case experiences have been reported ( Misawa et al , 2003 ; Donker et al , 2009 ; Ohta et al , 2011 ).…”

Childhood Rhabdomyosarcoma: New Insight on Biology and Treatment

“…Interestingly, the German HD CWS-96 trial demonstrated that patients who received oral maintenance chemotherapy had improved outcome compared to patients who received HDSCT [13•]. While there is increasing evidence that HDSCT is of little benefit, there is less evidence on the utility of allogeneic SCT for RMS patients other than isolated case reports [15].…”

Rhabdomyosarcoma in adolescent and young adult patients: current perspectives

“…For high-dose chemotherapy followed by autologous stem cell rescue, recent studies performed mainly in Europe have not demonstrated any significant benefit of this treatment approach compared to conventional treatment strategies 77–79. Other transplant strategies have mainly been reported as small case series or single case reports and will need further investigation as a clinical trial to validate their feasibility 80,81…”