[Show abstract][Hide abstract] ABSTRACT: We present the case of a 38-year-old woman diagnosed with metastatic adenocarcinoma of the biliary tract in the 18th week of pregnancy. Chemotherapy based on cisplatin and gemcitabine was administered, reaching disease stabilization until late-preterm delivery at 35 + 0 weeks of gestation. The infant was healthy and showed no malformations. Her head circumference was small, yet no neurological and behavioral defects have been detected. Development was normal during 14 months of follow-up. We discuss the implications of metastatic cancer in pregnancy with focus on therapeutic options for metastatic adenocarcinoma of the biliary tract. In this context, available data for the active regimens in biliary tract cancers-platinum compounds and gemcitabine-are discussed. This report is the fourth in the literature detailing the application of gemcitabine during pregnancy and the first presenting longer term follow-up, complementing available evidence that gemcitabine-based regimens are feasible in this situation.
[Show abstract][Hide abstract] ABSTRACT: The Advanced Breast Cancer Second International Consensus Conference (ABC2) on diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 7-9, 2013. The focus of the conference was inoperable, locally advanced breast cancer. The diagnosis and treatment of metastatic breast cancer had already been discussed 2 years before at the ABC1 Consensus and were only updated regarding special issues as part of this year's ABC2 Consensus. Like 2 years ago, a working group of German breast cancer experts commented on the voting results of the ABC panelists, with special consideration of the German guidelines for the diagnosis and treatment of breast cancer (German Gynecological Oncology Working Group (AGO) recommendations, S3 Guideline) in order to adapt them for daily clinical practice in Germany. The goal of both the ABC Consensus and the German comments is to facilitate evidence-based therapy decisions.
Breast Care 02/2014; 9(1):52-9. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer biology multiple drug candidates have been developed to modulate additional molecular targets which may associate with specific biomarker profiles. Accordingly, exploratory biomarkers are increasingly incorporated in early clinical trials, thus demanding a new process of patient selection. Here, we describe the implementation of preemptive, multiplexed biomarker profiling linked to standard diagnostic algorithms for metastatic breast cancer patients treated at the West German Cancer Center. Profiling for experimental biomarkers was prospectively offered to patients with metastatic breast cancer who met generic clinical trial inclusion criteria. Formalin-fixed, paraffin-embedded tumor samples were retrieved and studied for potentially "actionable" biomarkers related to active clinical trials by immunohistochemistry, amplicon sequencing, and in situ hybridization. The clinical course of those "profiled" patients was closely monitored to offer trial participation whenever applicable. Here, we report results from the first 131 patients enrolled in this program. PIK3CA mutations (23 %) and amplifications (2 %), loss of PTEN expression (13 %), and FGFR1 amplifications (8 %) were detected next to established biomarkers such as estrogen (67 %) and progesterone receptor expression (52 %), and HER2 overexpression or amplification (23 %). So far 16 "profiled" patients (12 %) have been enrolled in biomarker-stratified early clinical trials. Preemptive profiling of investigational biomarkers can be integrated into the diagnostic algorithm of a large Comprehensive Cancer Center. Extensive administrative efforts are required to successfully enroll "profiled" patients with metastatic breast cancer in early clinical trials stratified by exploratory biomarkers.
Breast Cancer Research and Treatment 10/2013; · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Multiple investigational drugs are currently explored in cancer patient populations defined by specific biomarkers. This demands a new process of patient selection for clinical trials.
Starting January 1, 2012, preemptive biomarker profiling was offered at the West German Cancer Center to all patients with advanced non-small-cell lung (NSCLC) or colorectal cancer (CRC), who met generic study inclusion criteria. Tumour specimens were subjected to prespecified profiling algorithms to detect 'actionable biomarkers' by amplicon sequencing, in situ hybridisation and immunohistochemistry. The clinical course was closely monitored to offer trial participation whenever applicable.
Within 12 months, 267 patients (188 NSCLC, 79 CRC) were profiled. Estimated additional cost for biomarker profiling was 219615.51 EUR excluding histopathology workup and administration. The most prevalent biomarkers in pulmonary adenocarcinoma were KRAS mutations (29%), loss of PTEN expression (18%), EGFR mutations (9%), HER2 amplification (5%) and BRAF mutations (3%), while the prevalence of ALK translocations and PIK3CA mutations was extremely low. In pulmonary squamous cell carcinoma FGFR1 amplifications were found in 15%, PTEN expression was lost in 20% and DDR2 was mutated in a single case. KRAS mutations (41%) predominated in CRC, followed by loss of PTEN expression (16%), PIK3CA (5%) and BRAF (5%) mutations. So far 13 patients (5%) have entered biomarker-stratified clinical trials. Therapeutic decisions for approved drugs were guided in another 45 patients (17%).
Preemptive biomarker profiling can be implemented into the diagnostic algorithm of a large Comprehensive Cancer Center. Substantial investments in diagnostics and administration are required.
European journal of cancer (Oxford, England: 1990) 07/2013; · 4.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland. The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year's St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.
Breast Care 06/2013; 8(3):221-9. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A group of German breast cancer experts (medical oncologists and gynaecologists) reviewed and commented on the results of the first international 'Advanced Breast Cancer First Consensus Conference' (ABC1) for the diagnosis and treatment of advanced breast cancer. The ABC1 Conference is an initiative of the European School of Oncology (ESO) Metastatic Breast Cancer Task Force in cooperation with the EBCC (European Breast Cancer Conference), ESMO (European Society of Medical Oncology) and the American JNCI (Journal of the National Cancer Institute). The main focus of the ABC1 Conference was metastatic breast cancer (stage IV). The ABC1 consensus is based on the vote of 33 breast cancer experts from different countries and has been specified as a guideline for therapeutic practice by the German expert group. It is the objective of the ABC1 consensus as well as of the German comments to provide an internationally standardized and evidence-based foundation for qualified decision-making in the treatment of metastatic breast cancer.
Breast Care 02/2012; 7(1):52-59. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the efficacy and safety of oral and i.v. vinorelbine plus trastuzumab as first-line regimen in a patient-convenient application for human epidermal growth factor receptor 2 (HER2)-overexpressing patients with metastatic breast cancer.
Forty-two women were enrolled in a multicenter study. The patients received i.v. vinorelbine at a dose of 25 mg/m(2) on day 1 followed by oral vinorelbine at a dose of 60 mg/m(2) on days 8 and 15 in a 3-week cycle. Standard dose trastuzumab was given at 3-week intervals.
Complete response was observed in 7 patients (18.9%) and partial response in 19 patients (51.4%), for an overall response rate of 70.3% [95% confidence interval (CI) 53.0-84.1]. The disease control rate reached 91.9% (95% CI 78.1-98.3). The median time to progression was 9.3 months, while median overall survival reached 35.6 months. Hematological and non-hematological toxic effects were acceptable with grade 3-4 leukopenia of 14% and neutropenia of 38%; cardiac toxicity did not reach the level of clinical relevance.
The combination of i.v. and oral vinorelbine plus trastuzumab demonstrates high activity and good tolerability in first-line treatment of HER2-overexpressing metastatic breast cancer. In addition, it offers convenience for the patients with only one i.v. treatment every 3 weeks.
Annals of Oncology 03/2011; 22(3):603-8. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Effective treatment options for patients with metastatic breast cancer (MBC) resistant/refractory to anthracyclines and/or taxanes are limited. Intravenous and oral combination of vinorelbine (VRL) and capecitabine were shown to be feasible and effective in first-line MBC. In order to evaluate the activity of the combination of an all oral regimen in a more advanced setting, we investigated a regimen combining oral VRL and capecitabine in a phase II study as second-line chemotherapy of MBC patients previously treated with anthracyclines and taxanes.
Forty patients (median age 52 years) with MBC received the combination of oral VRL 60 mg/m(2) on days 1, 8 and 15 plus capecitabine 1,000 mg/m(2) bid given from day 1 to day 14 in an open-label, international, multicentre, phase II study. Cycles were repeated every 3 weeks. The primary endpoint was response rate (RR) evaluated by an independent panel review. Secondary objectives included safety, duration of response, progression-free survival, overall survival and quality of life.
All the patients had received prior chemotherapy with anthracyclines and taxanes, 75% were refractory/resistant to anthracycline and/or taxane, 72.5% presented with visceral involvement and the last prior chemotherapy for 87.5% of the patients was for advanced disease setting. The median number of administered cycles per patient was 4 (range 1-31). Eight responses were documented and validated by an independent panel review, yielding RRs of 20% [95% CI: 9-35.6] in the intent-to-treat (treated) population and 23.5% [95% CI: 10.7-41.2] in the 34 evaluable patients. Median progression-free survival and median overall survival were 3.4 months [95% CI: 2.3-5.5] and 11.3 months [95% CI: 8.1-16.4], respectively. The principal toxicities were anaemia, neutropenia (rarely complicated; only one patient experienced febrile neutropenia), fatigue and gastrointestinal toxicities with very few grade 3-4 non-haematological toxicities.
In second-line treatment of MBC patients previously treated with anthracyclines and taxanes, oral VRL plus capecitabine is a safe regimen with an efficacy comparable to the other available combination regimens used in this heavily and resistant/refractory (75% of patients) pre-treated patients' population. Moreover, this well-tolerated combination offers the advantages of an all oral regimen.
Cancer Chemotherapy and Pharmacology 09/2009; 65(4):755-63. · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We analyzed circulating tumor cells (CTC) in blood of metastatic breast cancer patients (n = 42) and determined the ability of this method to predict therapy response.
CTC from blood were analyzed before and during therapy for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer. The estrogen (ER) and progesterone (PR) receptor expression was assessed by RT-PCR.
The overall detection rate for CTC was 52% (thereof 86% EpCAM; 86% MUC1; 32% HER2; 35% ER; 12% PR). CTC were ER, PR and HER2 negative in 45% (ER), 78% (PR) and 60% (HER-2) of patients with steroid receptor-positive tumors. 29% of patients with HER2-negative tumors had HER2-positive CTC. The test predicted therapy response in 78% of all cases. Persistence of CTC significantly correlated with shorter overall survival (P = 0.005).
Molecular profiling of CTC may offer superior prognostic information with regard to risk assessment for recurrence and predictive judgement of therapeutical regimens.
Breast Cancer Research and Treatment 09/2008; 115(3):581-90. · 4.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anthracyline-based chemotherapy is the treatment of choice for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL). However, anthracyclines have been associated with long-term cardiac toxicity.
We conducted a study using a sequential combination chemotherapy with a reduced cumulative dose of anthracyclines in younger patients with good-prognosis aggressive NHL. Chemotherapy consisted of one cycle of vincristine, ifosfamide, etoposide, and dexamethasone, followed by three cycles of epirubicin, cyclophosphamide, vincristine, and dexamethasone, and a fifth cycle containing carboplatin, etoposide, and dexamethasone. 86 patients were treated, 65 without and 21 with additional rituximab. Consolidating involved-field irradiation was applied in patients with stage I/II, bulky disease, or localized residual lymphoma.
Complete and partial remissions were achieved in 67 and 27% of patients, respectively, and the 3-year event-free and overall survival estimates were 75 and 87%. The survival estimates were substantially better in patients who received rituximab. Main toxicity was grade 3/4 leukocytopenia in 89% patients with neutropenic fever in 30%. Two patients died of septic shock.
The treatment appears to be effective in this group of patients. The hematological toxicities, particularly after the first and fifth cycle, require the use of G-CSF and/or a dose reduction in selected patients.
Journal of Cancer Research and Clinical Oncology 09/2008; 135(3):459-66. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eine vielfältige klinische und zellbiologisch-experimentelle Forschungslandschaft trägt dazu bei, dass gerade beim metastasierten
Mammakarzinom die zunehmenden therapeutischen Alternativen einer medikamentösen Behandlung nicht nur einem steten Wandel unterworfen
sind, sondern glücklicherweise auch zu einer schrittweisen Verbesserung der Langzeitergebnisse führen . Wie bei der einzelnen
Patientin zu verfahren ist, wird durch die onkologischen Therapeuten oft recht unterschiedlich beurteilt. Auch aus Sicht der
Autoren sind bei den zahlreichen unterschiedlichen Situationen eines Langzeitverlaufs die Behandlungsmöglichkeiten heterogen.
Diese können durch die gegenwärtige Studienmedizin nur teilweise abgebildet werden . Deshalb sind Vorgaben durch vereinfachende
Leitlinien von Fachgesellschaften auch nicht immer befriedigend.
[Show abstract][Hide abstract] ABSTRACT: Eine vielfältige klinische und zellbiologisch-experimentelle Forschungslandschaft trägt dazu bei, dass gerade beim metastasierten Mammakarzinom die zunehmenden therapeutischen Alternativen einer medikamentösen Behandlung nicht nur einem steten Wandel unterworfen sind, sondern glücklicherweise auch zu einer schrittweisen Verbesserung der Langzeitergebnisse führen . Wie bei der einzelnen Patientin zu verfahren ist, wird durch die onkologischen Therapeuten oft recht unterschiedlich beurteilt. Auch aus Sicht der Autoren sind bei den zahlreichen unterschiedlichen Situationen eines Langzeitverlaufs die Behandlungsmöglichkeiten heterogen. Diese können durch die gegenwärtige Studienmedizin nur teilweise abgebildet werden . Deshalb sind Vorgaben durch vereinfachende Leitlinien von Fachgesellschaften auch nicht immer befriedigend.
[Show abstract][Hide abstract] ABSTRACT: High-dose chemotherapy (HD-CT) with autologous stem cell transplantation is considered to be the treatment of choice for relapsed high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL) patients, but the optimal treatment has not yet been defined. We evaluated a salvage treatment regimen consisting of conventional cycles with ifosfamide, etoposide, cytarabine, and dexamethasone (IVAD) followed by two cycles of HD-CT consisting of cyclophosphamide, melphalan, and etoposide (CMV) with autologous stem cell support in patients with relapsed or refractory NHL (n = 59) and HL (n = 16). Response to IVAD was complete remission (CR) in 16 patients (21%), partial remission (PR) in 39 patients (52%), stable disease (SD) in 18 patients (24%), and progressive disease (PD) in two patients (2.7%). Of 70 patients treated with HD-CT, 41 patients (59%) showed a CR, 20 patients a PR (29%), eight patients a SD (11%), and one patient a PD (1.4%). The 5-yr overall survival for the entire group of patients was 29%, and for patients with NHL and HL 25%, and 38%, respectively. The respective event-free survival probabilities at 5 yr were 22%, 16%, and 31%. Seven treatment-related deaths due to septicemia (three), cardiac arrhythmia (one), pneumonia (one), pneumonitis (one), and toxic epidermal necrolysis (one) were observed. In multivariate analysis, an International Prognostic Index of > or = 2 and resistant disease to first-line chemotherapy were poor independent prognostic factors for the subgroup of patients with NHL. In conclusion, these results indicate that IVAD/CMV is feasible as a salvage therapy for lymphoma patients. This treatment is currently evaluated with the addition of rituximab.
European Journal Of Haematology 02/2007; 78(2):93-101. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retrospective studies have shown that immunoassays measuring free light chains (FLC) in serum are useful for diagnosis and monitoring of multiple myeloma. This study prospectively evaluates the use of FLC assays and, for the first time, investigates the relationship between serum FLC concentrations and the presence and detectability of Bence Jones (BJ) proteins in the urine.
Three hundred seventy-eight paired samples of serum and urine were tested from 82 patients during the course of their disease. The sensitivities of serum FLC analysis and urine immunofixation electrophoresis (IFE) in detecting monoclonal FLC were compared. Serum FLC concentrations required for producing BJ proteins detected by IFE were determined.
Abnormal FLC were present in 54% of serum samples compared with 25% by urine tests. In abnormal serum samples for kappa or lambda, the sensitivity of IFE to detect the respective BJ proteins in urine were 51% and 35% and the median serum FLC concentrations required to produce detectable BJ proteins were 113 and 278 mg/L. Renal excretions of monoclonal FLC increased with serum concentrations, but excretions significantly decreased at high serum concentrations combined with renal dysfunction.
Serum FLC assays are significantly more sensitive for detecting monoclonal FLC than urine IFE analysis. They also have the advantage of FLC quantification and are more reliable for monitoring disease course and response to treatment.
Clinical Cancer Research 01/2006; 11(24 Pt 1):8706-14. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nearly all national (AGO, DKG) and international guide lines (e. g. ASCO) for follow-up of breast cancer patients do not explicitly recommend regular laboratory and radiological/ultrasound screening procedures. According to these guide lines, follow-up should be focused on the breast, only patients with possibly tumour related symptoms should be screened for metastatic disease. The rejection of more time-consuming and costlier follow-up examinations remains a contradiction to established follow-up guide lines for other solid tumours. In addition, treatment options for metastatic breast cancer disease have improved continuously over the last years. However, treatment options are considerably limited in advanced disease, if e. g. symptoms like dyspnoea or jaundice are already present at first diagnosis of metastatic disease. Therefore we will review available data of older studies as well as discuss arguments for a systematic surveillance in high-risk breast cancer patients. Overall, symptom guided follow-up seems to be adequate for patients with small primary tumours, no lymph node involvement and therefore a high curative probability, whereas in the authors' opinion systematic surveillance should be recommended for high risk patients even in the absence of symptoms. All patients, however, should be fully informed about the possibility of metastatic disease development and should be enabled to select the quality of their postoperative follow-up.
Zentralblatt für Gynäkologie 09/2005; 127(4):213-6.
[Show abstract][Hide abstract] ABSTRACT: To define the maximum-tolerated dose (MTD) and to evaluate the dose-limiting toxicities (DLT) of the combination of capecitabine and vinorelbine in patients with metastatic breast cancer who relapse after adjuvant and/or first-line treatment. In addition, we aimed to obtain data on efficacy and safety at the recommended dose.
Patients with measurable metastatic breast cancer after failure of prior chemotherapy (including anthracyclines and/or taxanes) were eligible. Capecitabine was administered with a fixed dose of 1000 mg/m(2) orally twice daily for 2 weeks followed by 1 week rest. One treatment cycle consisted of 6 weeks of treatment containing two treatment periods of capecitabine. Vinorelbine was given intravenously at escalated doses of 25 mg/m(2) (dose level 1) and 30 mg/m(2) (dose level 2) on days 1 and 8, and 22 and 29.
Thirty-three patients received a total of 91 cycles of capecitabine and vinorelbine. The median number of administered cycles per patient was three (range one to six). Thirty-one patients were evaluable for toxicity. At dose level 2 four out of seven patients experienced DLTs (nausea/vomiting, febrile neutropenia, grade 4 neutropenia, infection and diarrhea); thus, the MTD was defined. In order to confirm the safety and efficacy, dose level 1 was extended to 24 patients. Two patients [8.3%; 95% confidence interval (CI) 1% to 27%] showed DLTs (hospitalization due to febrile neutropenia and prolonged neutropenia). The main toxicity was neutropenia, which was observed at National Cancer Institute Common Toxicity Criteria grade 3 and 4 in 39% of patients. The overall response rate for capecitabine and vinorelbine was 55% (95% CI 36% to 72.7%), including three patients with a complete remission. The median time to disease progression was 8 months (95% CI 4.3-11.7) with an overall survival of 19.2 months (95% CI 11.3-27.1) based on intention-to-treat analysis.
The combination of capecitabine and vinorelbine can be administered with manageable toxicity and showed significant efficacy for patients with metastatic breast cancer even after failure of a anthracycline- and/or taxane-based therapy.
Annals of Oncology 02/2005; 16(1):64-9. · 7.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this prospective trial was to study a combined-modality treatment including local consolidation by surgery or radiotherapy and high-dose chemotherapy (HDC) followed by peripheral-blood stem-cell (PBSC) transplantation. In all, 48 patients with oligometastatic breast cancer amenable to local treatment after induction chemotherapy with epirubicin and cyclophosphamide or paclitaxel and cisplatin, depending on prior adjuvant chemotherapy, were enrolled. The median follow-up was 41 months (range, 7-85 months). PBSC were collected in 47 patients, and 40 received one or two courses of HDC. Local therapy was given in 37 patients. No treatment-related deaths occurred. Of 47 evaluable patients, 36 (75% of intention-to-treat population) had no evidence of disease or complete remission after completion of therapy. Six patients (12.5%) had partial response, two patients (4%) no change, and three patients (6%) progressive disease. The median time to progression and overall survival was 17.5 (95% confidence interval (CI), 14-21 months) and 42.2 months (95% CI, 33-52 months), respectively, and 27% of patients were progression free after 5 years. In conclusion, patients with oligometastatic breast cancer can be treated safely with this combined modality protocol with promising relapse-free survivals.
Bone Marrow Transplantation 11/2004; 34(7):637-43. · 3.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Various chemotherapy regimens, combined with recombinant human granulocyte colony-stimulating factor(rhG-CSF) or recombinant granulocyte-macrophage CSF (rhGM-CSF) are used in cancer patients to mobilize and collect peripheral blood stem cells (PBSC). In this retrospective study, we evaluated and compared the efficacy of such regimens in 262 patients with different types of malignant diseases. The following chemotherapy regimens were applied: ifosfamide-etoposide-cisplatin or bleomycin (n = 96; mainly patients with testicular cancer); ifosfamide-etoposide plus or minus cytosine arabinoside (Ara-C) or vincristine (VCR)(n = 52; mainly patients with lymphoma); cyclophosphamide-anthracycline (n = 53; mainly patients with breast cancer); intermediate to high dose (ID-HD) cyclophosphamide (n = 37; mainly patients with breast or ovarian cancer. or multiple myeloma; and others (n = 24). rhG-CSF or rhGM-CSF, each at an average daily dose of 5 microg/kg body weight, were used in 166 and 96 patients, respectively. The study evaluated and compared the efficacy of these two cytokines. In patients receiving rhG-CSF, CD34+ cells could be collected earlier (median: day 14 versus day 16) and there was a significantly higher white blood cell count (WBC)(median 11,350 versus 5550/microl) and CD34+ cell count (median 88 versus 43/microl) at the start of apheresis, and a significantly higher CD34+ cell yield (median 7.4 x 10(6) versus 4.6 x 10(6)/kg) than in patients who receivedrhGM-CSF. Among the various chemotherapeutic regimens used, each combined with rhG-CSF, ifosfamide-etoposide plus or minus Ara-C or VCR mobilized a significantly higher number of CD34+ cells (median 119/microl) and produced a significantly higher harvest of these cells (median 13 x 10(6)/kg) than cyclophosphamide-anthracycline (median 87/microl and 7 x 10(6)/kg, respectively) or ID-HD cyclophosphamide (median 59/microl and 5 x I 0(6)/kg, respectively). Ifosfamide-etoposide plus or minus Ara-C or VCR was also superior to ifosfamide-etoposide-cisplatin or bleomycin (median 78/microl and 9 x 10(6)/kg, respectively), but at borderline significance. The outcome of PBSC mobilization and collection appeared to be negatively influenced by the number of relapses before the current salvage treatment. These data indicate that mobilization and collection of PBSCstrongly depend on the type of hematopoietic growth factor and chemotherapeutic regimen used. The data further show rhG-CSF is a more effective growth factor than rhGM-CSF and ifosfamide-etoposide-based regimens, particularly ifosfamide-etoposide plus or minus Ara-C or VCR, are highly effective regimens in mobilizing and collecting CD34+ cells.