High-Dose Melphalan With Autologous Stem-Cell Rescue in Metastatic Rhabdomyosarcoma

Abstract

Purpose: The European Collaborative MMT4-91 trial was conducted as a prospective nonrandomized study to evaluate the potential benefit of high-dose melphalan as consolidation of first complete remission in children with stage IV rhabdomyosarcoma.Patients and Methods: Fifty-two patients in complete remission after six courses of chemotherapy received ''megatherapy'': 42 received melphalan alone, whereas 10 received melphalan in combination with etoposide, carboplatin/etoposide, or thiotepa/busulfan and etoposide. The outcome of this group of patients was compared with that observed in 44 patients who were also in complete remission after six courses of identical chemotherapy (plus surgery or radiotherapy) but went on to receive a total of up to 12 courses of conventional chemotherapy (four cycles). No differences were found between the two groups regarding clinical characteristics, chemotherapy received before complete remission, or response to chemotherapy. In particular, there was no significant difference between the groups for site of primary tumor, histologic subtype, age at presentation, presence of bone or bone marrow metastases, or number of metastases.Results: The 3-year event-free survival (EFS) and overall survival (OS) rates were 29.7% and 40%, respectively, for those receiving high-dose melphalan or other multiagent high-dose regimens and 19.2% and 27.7%, respectively, for those receiving standard chemotherapy. The difference was not statistically significant (P ‫؍‬ .3 and P ‫؍‬ .2 for EFS and OS, respectively). There was a significant prolongation in the time from the last day of high-dose chemotherapy or the end of chemotherapy cycle 4 to the time of relapse in those receiving megatherapy (168 days for patients receiving megatherapy v 104 days for those receiving standard therapy; P ‫؍‬ .05).Conclusion: The addition of a high-dose alkylating agent to consolidation therapy may have prolonged progression-free survival in this poor-risk patient group, but it did not significantly improve the ultimate outcome. J Clin Oncol 17:2796-2803. 1999 by AmericanSociety of Clinical Oncology. T HE OUTCOME OF treatment for children with metastatic rhabdomyosarcoma (RMS) remains disappointing. Despite intensification of conventional chemotherapy, there has been little evidence of any significant improvement in overall survival, which has remained at approximately 20% to 30%. 1,2 A preliminary analysis of prognostic factors in 175 children on the European Collaborative Studies MMT4-89 and MMT4-91 has shown the following factors to have a significant adverse impact on prognosis: presence of bone and bone marrow metastases; number of metastases; limbs, parameningeal head and neck, and ''other'' sites as primary sites; and age older than 10 years at presentation. In particular, on multivariate analysis, age, site of primary tumor, and bone marrow metastases each achieved statistical significance for prognostic impact. 3 Similar observations have been confirmed in recent analyses of the Intergroup Rhabdomyosarcoma Study...

Intensive chemotherapy for children and young adults with metastatic primitive neuroectodermal tumors of the soft tissue

“…19 In the MMT4 studies there was evidence that high-dose consolidation therapy with melphalan may have delayed relapse but it did not ultimately improve the survival of patients with metastatic rhabdomyosarcoma. 10 This conclusion has been confirmed in the group of patients with metastatic soft tissue PNET. However, the reduced use of local radiotherapy in the patients who were candidates for dose intensification may have undermined the efficacy of this strategy.…”

“…Benefit has been shown in the treatment of metastatic neuroblastoma 16 and, recently, promising results have also been reported in adult patients with advanced soft tissue sarcoma. 17 In children, previous experience failed to show a better outcome for metastatic rhabdomyosarcoma 10,18 or bony Ewing's sarcoma. 19 In the MMT4 studies there was evidence that high-dose consolidation therapy with melphalan may have delayed relapse but it did not ultimately improve the survival of patients with metastatic rhabdomyosarcoma.…”

“…10 The first protocol MMT4-89 explored an intensive regimen including most of the drugs active in soft tissue sarcomas. Treatment consisted of four identical 9-week cycles.…”

“…The results in patients with rhabdomyosarcoma have recently been published. 10 Here, we report the outcome of patients with extraosseous PNET included in MMT4 protocols.…”

Favorable NK cell activity after haploidentical hematopoietic stem cell transplantation in stage IV relapsed Ewing’s sarcoma patients

“…Metastatic relapsed or primarily metastatic EWS or rhabdomyosarcoma aged 410 years have a very poor prognosis, despite of intensive chemotherapy. [1][2][3][4][5] Most patients with extended disease undergo autologous stem cell transplantation during initial therapy. In disease persistence or recurrence, new treatment strategies are needed.…”