Mobilization of peripheral blood progenitor cells by disease-specific chemotherapy in patients with soft tissue sarcoma

Abstract

Summary:We investigated peripheral blood progenitor cell (PBPC) mobilization by disease-specific chemotherapy in patients with metastatic soft tissue sarcoma (STS). Nine patients, five females and four males, aged 12-51 years, pretreated by one to nine courses of cytotoxic chemotherapy, underwent STS-specific mobilization followed by G-CSF at 5 g/kg/day. PBPC were collected by 19 conventional-volume aphereses (8-12 l) with one to four procedures in individual patients. Leukaphereses started on median day 15 (range 13-18) from the first day of mobilization chemotherapy at medians of 25.8 ؋ 10 3 WBC/ l (6.8-46.9), 3.5 ؋ 10 3 MNC/ l (1.1-8.8), 122 ؋ 10 3 platelets/ l (72-293) and 30.7 CD34 ؉ cells/ l (6.7-207.8). Cumulative harvests resulted in medians of 4.6 ؋ 10 8 MNC/kg (3.0-6.4), 2.9 ؋ 10 6 CD34 ؉ cells/kg (1.1-11.1) and 12.0 ؋ 10 4 CFU-GM/kg (2.0-37.8). Eight patients underwent high-dose chemotherapy (HDCT) followed by PBPC rescue. Seven patients recovered hematopoiesis at medians of 12 days (8-15) for ANC Ͼ0.5 ؋ 10 3 / l and 14 days (8-27) for platelets Ͼ20 ؋ 10 3 / l. One patient, who received 1.6 ؋ 10 6 CD34 ؉ cells/kg, exhibited delayed ANC recovery on day ؉37 and failed to recover platelets until hospital discharge on day +55. We conclude that in patients with metastatic STS, who are pretreated by standard chemotherapy, PBPC can be mobilized by a further course of STS-specific chemotherapy plus G-CSF. One to four conventional-volume aphereses result in PBPC autografts that can serve as hematopoietic rescue for patients scheduled for HDCT. Keywords: soft tissue sarcoma; blood progenitor cells; disease-specific mobilization Soft tissue sarcomas (STS), arising from the extraskeletal connective tissue of the body, occur at a rate of 0.7% of all adult cancers. 1 Radical surgery, often combined with radiotherapy, can be curative in up to 60% of patients. However, prognosis of patients with metastatic or recurrent STS is poor, and most of them will die from progressive Treatment of patients who do not respond to these drugs is very difficult because only few salvage regimens exist. 6,7 There is strong evidence for a dose-response relationship for doxorubicin and ifosfamide. 8,9 For optimal response rates it seems essential to achieve a dose intensity of greater than 65 mg/m 2 for doxorubicin and greater than 5 g/m 2 for ifosfamide. 10,11 In the last decade, hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have entered clinical trials in an attempt to administer escalated-dose chemotherapy regimens without inducing fatal neutropenia. 12,13 More recently, the use of hematopoietic stem/progenitor cells has circumvented myelotoxicity as the dose-limiting toxicity in clinical trials. 14,15 The aim of this study was to demonstrate peripheral blood progenitor cell (PBPC) mobilization by diseasespecific chemotherapy in pretreated patients with metastatic STS scheduled for high-dose chemotherapy (HDCT). Patients and methods Pa...

Peripheral blood progenitor cell (PBPC) mobilization in heavily pretreated patients with germ cell tumors: a report of 34 cases

“…Mobilization of PBPC is usually performed by the administration of highdose cyclophosphamide and growth factors in various malignant diseases. The possibility of using disease-specific chemotherapy has been demonstrated recently by Schwella et al 16 in nine patients affected by soft tissue sarcomas. In our series, the choice of mobilization regimen was determined by disease response to premobilization chemo- Vinblastine is a vinca alkaloid tested extensively in the past three decades, whose primary toxicity is leukopenia.…”

Leukapheresis after high‐dose chemotherapy and autologous peripheral blood progenitor cell transplantation: a novel approach to harvest a second autograft

“…For the timing of collections, measurements of CD34+ cells were performed by flow-cytometry, as previously described. 1 4 Leukapheresis started after CDCT or after HDCT when numbers of PB CD34+ cells exceeded 10 per L. 15 To determine the time when leukapheresis started (first apheresis day), counting of days began on the day that followed CDCT or HDCT. No post-HDCT collections were performed in patients with circulating CD34+ cells less than 10 per L. These patients were classified as poor mobilizers.…”