Hematopoietic stem cell transplantation following chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas

Peinemann F, Smith LA, Kromp M, Bartel C, Kröger N, Kulig M

Published Online:

February 16, 2011

Non-rhabdomyosarcoma soft tissue sarcomas are a group of rare cancers. Patients with inoperable or metastatic disease have a poor prognosis. It was believed higher doses of chemotherapy might improve patients' survival. However, high doses of chemotherapy stop the production of blood cells in the bone marrow and are not compatible with life. Stem cells collected from patients before high-dose chemotherapy can be transplanted back to the patient if the blood cell count gets too low. Due to a lack of research studies, it has not been proven that patients treated with this procedure lived longer than patients treated with standard chemotherapy.

We reviewed the published research on this treatment to investigate how effective and safe it is. Unfortunately we identified only one comparative study and the results of this study were not credible. Studies with aggregated data showed that two years after treatment between 20% to 60% of patients were still alive but the treatment had a high level of toxic side effects.

While the results of this systematic review may not be conclusive, they provide a summary of the current knowledge and highlight that more research is needed. Currently the research evidence says that patients with non-rhabdomyosarcoma soft tissue sarcomas should only be treated with high-dose chemotherapy and then autologous hematopoietic stem cell transplantation except within clinical trials.

Abstract (click to read)

Background:

Soft tissue sarcomas (STS) are a highly heterogeneous group of rare malignant solid tumors. Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise all STS except rhabdomyosarcoma. In patients with advanced local or metastatic disease, autologous hematopoietic stem cell transplantation (HSCT) applied after high-dose chemotherapy (HDCT) is a planned rescue therapy for HDCT-related severe hematologic toxicity.

Objectives:

To assess the effectiveness and safety of HDCT followed by autologous HSCT for all stages of soft tissue sarcomas in children and adults.

Search strategy:

We searched the electronic databases CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE and EMBASE (February 2010). Online trial registers, congress abstracts and reference lists of reviews were searched and expert panels and authors were contacted.

Selection criteria:

Terms representing STS and autologous HSCT were required in the title, abstract or keywords. In studies with aggregated data, participants with NRSTS and autologous HSCT had to constitute at least 80% of the data. Comparative non-randomized studies were included because randomized controlled trials (RCTs) were not expected. Case series and case reports were considered for an additional descriptive analysis.

Data collection and analysis:

Study data were recorded by two review authors independently. For studies with no comparator group, we synthesised results for studies reporting aggregate data and conducted a pooled analysis of individual participant data using the Kaplan-Meyer method. The primary outcomes were overall survival (OS) and treatment-related mortality (TRM).

Main results:

We included 54 studies, from 467 full texts articles screened (11.5%), reporting on 177 participants that received HSCT and 69 participants that received standard care. Only one study reported comparative data. In the one comparative study, OS at two years after HSCT was estimated as statistically significantly higher (62.3%) compared with participants that received standard care (23.2%). In a single-arm study, the OS two years after HSCT was reported as 20%. In a pooled analysis of the individual data of 54 participants, OS at two years was estimated as 49% (95% CI 34% to 64%). Data on TRM, secondary neoplasia and severe toxicity grade 3 to 4 after transplantation were sparse. All 54 studies had a high risk of bias.

Authors' conclusions:

Due to a lack of comparative studies, it is unclear whether participants with NRSTS have improved survival from autologous HSCT following HDCT. Owing to this current gap in knowledge, at present HDCT and autologous HSCT for NRSTS should only be used within controlled trials.

This record should be cited as:

Peinemann F, Smith LA, Kromp M, Bartel C, Kröger N, Kulig M. Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD008216. DOI: 10.1002/14651858.CD008216.pub3

Assessed as up to date:

January 4, 2011

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Primary Review Group:

Gynaecological Cancer Group

Health topics:

Cancer > Soft tissue sarcoma

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Hematopoietic stem cell transplantation following chemotherapy for non-rhabdomyosarcoma soft tissue sarcomas

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