High-Dose Chemotherapy Followed by Autologous Stem Cell Transplantation for Metastatic Rhabdomyosarcoma—A Systematic Review

Abstract

IntroductionPatients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The aim of this systematic review is to investigate whether high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) in patients with metastatic RMS has additional benefit or harm compared to standard chemotherapy.MethodsSystematic literature searches were performed in MEDLINE, EMBASE, and The Cochrane Library. All databases were searched from inception to February 2010. PubMed was searched in June 2010 for a last update. In addition to randomized and non-randomized controlled trials, case series and case reports were included to complement results from scant data. The primary outcome was overall survival. A meta-analysis was performed using the hazard ratio as primary effect measure, which was estimated from Cox proportional hazard models or from summary statistics of Kaplan Meier product-limit estimations.ResultsA total of 40 studies with 287 transplant patients with metastatic RMS (age range 0 to 32 years) were included in the assessment. We identified 3 non-randomized controlled trials. The 3-year overall survival ranged from 22% to 53% in the transplant groups vs. 18% to 55% in the control groups. Meta-analysis on overall survival in controlled trials showed no difference between treatments. Result of meta-analysis of pooled individual survival data of case series and case reports, and results from uncontrolled studies with aggregate data were in the range of those from controlled data. The risk of bias was high in all studies due to methodological flaws.ConclusionsHDCT followed by autologous HSCT in patients with RMS remains an experimental treatment. At present, it does not appear justifiable to use this treatment except in appropriately designed controlled trials.

Consensus and controversies regarding the treatment of rhabdomyosarcoma

“…Furthermore, there is little published data demonstrating the efficacy of tyrosine kinase inhibitors in the treatment of relapsed RMS. Intensification of therapy followed by autologous or allogeneic stem cell transplantation has also not been routinely helpful, and is generally done only in the context of a clinical trial . Although the use of molecular profiling or patient‐derived xenografts to guide therapy is intuitively appealing and commonly done in the setting of recurrent disease, there are no prospective published data demonstrating that this strategy affects outcome for patients with relapsed RMS.…”

“…Intensification of therapy followed by autologous or allogeneic stem cell transplantation has also not been routinely helpful, and is generally done only in the context of a clinical trial. 57,58 Although the use of molecular profiling or patient-derived xenografts to guide therapy is intuitively appealing and commonly done in the setting of recurrent disease, there are no prospective published data demonstrating that this strategy affects outcome for patients with relapsed RMS. Similarly, the role of immunotherapy, including checkpoint inhibitors (e.g., agents that target PD-1, PD-L1, or CTLA-4), immunomodulatory agents, or chimeric antigen receptor T-cell therapy, are being evaluated but efficacy has not yet been established.…”

Cutaneous metastasis of rhabdomyosarcoma

“…Adults are rarely affected with two peaks of incidence: young adults and the elderly. 2,4 The most common anatomic sites of occurrence are, in order of frequency, the head and neck, the genitourinary tract and the extremities. It is classified into four histological types: (i) the embryonic form (60%); (ii) botryoid (6%); (iii) alveolar (30%) and (iv) pleomorphic (1%).…”

“…Cutaneous metastases are very rare, mainly in adults, and there are just two described cases. [4][5][6][7] The main prognosis factors include size and site of the tumour, possibility of resection, age of the patient and histological type.…”

Epidemiology and therapies for metastatic sarcoma

“…Bevacizumab and temsirolimus are also being evaluated in relapsed and refractory patients in a randomized fashion when added to vinorelbine and cyclophosphamide to estimate and compare event-free survival between groups (NCT#01222715). The role of higher dose chemotherapy with stem cell rescue has thus far not been validated 55,56. The pleomorphic and undifferentiated histologic subtypes of rhabdomyosarcoma, which are more common in older adults, are more resistant to chemotherapy and may present more commonly with metastatic disease.…”