Long-term results of autologous marrow transplantation for relapsed or refractory male or female germ cell tumors

Abstract

Summary:Twenty-one patients with relapsed or refractory germ cell tumors were treated with high-dose chemotherapy and marrow transplantation (HDC/BMT) from 1982-1993. Primary sites of disease were testis (17), ovary (three), and pineal gland (one). Pathology included dysgerminoma (one), choriocarcinoma with adenocarcinoma (one), seminoma (four), and nonseminoma or mixed germ cell tumor (15). Nineteen had at least two prior chemotherapy regimens and eight had cisplatinrefractory disease defined as progression within 4 weeks of a cycle of cisplatin-based chemotherapy. HDC regimens were mostly combinations of cyclophosphamide with etoposide and cisplatin or carboplatin. There were only two treatment-related deaths (aspergillosis and interstitial pneumonitis). Times to engraftment of granulocytes (21 ± 8.3 days) and platelets (32 ± 20.2 days) were reasonable with only the last nine patients receiving growth factors. At a minimum of 4 years follow-up, eight patients have died of disease, six of whom were cisplatin-refractory prior to transplant. Eleven patients (52% overall) are alive and continuously free of disease after 4-10 years including one of three with refractory ovarian germ cell tumor. HDC/BMT provides significant long-term disease-free survival as salvage therapy for both male and female relapsed germ cell tumor patients who are not refractory to cisplatin. Keywords: germ cell tumors; bone marrow transplantation; relapsed; cisplatin-refractory Metastatic germ cell tumors in both male and female patients are potentially curable with cisplatin-based combination chemotherapy with or without additional surgery. 1 Patients who relapse or fail first-line therapy, however, only have a 15-25% successful salvage rate with second-line conventional chemotherapy (cisplatin and ifosfamide combinations). 2,3 Initial experience with high-dose chemotherapy using carboplatin-and etoposide-containing regimens showed that 10-15% of heavily pretreated (two or more salvage chemotherapy regimens) patients could still obtain long-term remissions. [4][5][6][7][8][9] Recently, data on 283 heavCorrespondence: RA Mandanas, 920 SL Young Blvd WP2010, Oklahoma City, OK 73104, USA Received 23 June 1997; accepted 2 October 1997 ily pretreated patients with disseminated germ cell tumors from four large centers in the USA and Europe have been analyzed retrospectively for prognostic variables that predict a poor outcome with high-dose chemotherapy and hematopoietic stem cell support. 10 The resulting model categorized patients into three groups based on the number of prognostic factors present and allows the separation of poor (3-5 risk factors) risk patients from good (0 risk factors) and intermediate (1 or 2 risk factors) risk patients who might still have a beneficial outcome (27-51% 2-year failure-free survival) following high-dose chemotherapy and autologous stem cell support. Female patients with ovarian germ cell neoplasms were excluded from this analysis and although published data on high-dose chemotherapy with stem cell support f...

First-line high-dose chemotherapy for patients with poor prognosis extragonadal germ cell tumors: the experience of the European Bone Marrow Transplantation (EBMT) Solid Tumors Working Party

“…6 High-dose chemotherapy (HDCT) with hematopoietic progenitor cell support (HPCS) was initially studied in relapsed or refractory GCT. [7][8][9] In the last few years, several attempts have been made to improve the outcome of patients with poor prognosis NSGCT, including the use of HDCT with HPCS as first-line treatment. [10][11][12] To better characterize this issue, we reviewed the large database of the patients registered with the European Group for Blood and Marrow Transplantation (EBMT) with first-line HDCT with HPCS in patients with poor prognosis GCT, reclassified according to IGCCCG classification, and analyzed long-term survival data.…”

Long-term haematological recovery following high-dose chemotherapy with autologous bone marrow transplantation or peripheral stem cell transplantation in patients with solid tumours

“…1 HDC with ABMT or PSCT is not considered standard treatment for solid tumours, therefore benefits have to be studied in randomised studies and balanced against the risks of the treatment, both in the short and long term. 2 Solid tumours treated with HDC followed by ABMT or PSCT include breast cancer, 3,4 ovarian carcinoma, [5][6][7] relapsed germ cell tumours [8][9][10] and childhood sarcomas. 11,12 In the last decade, a shift from bone marrow to peripheral blood as the source of haematopoietic stem cells has occurred.…”

Long-term follow-up of patients with poor prognosis germ cell tumor treated with early high-dose chemotherapy with hematopoietic progenitor cell support: a single-center experience

“…Other studies with HDCT in GCT patients have associated male and female patients. [20][21][22] The results with chemotherapy in advanced ovarian GCT are generally good, but probably less than male GCT with similar clinical features. 23 In the current report, one toxic death occurred in 18 GCT patients treated with early HDCT.…”