Jörg Beyer

Publications of Jörg Beyer

• Sequential Versus Single High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Tumors: Long-Term Results of a Prospective Randomized Trial.

  Authors: Anja Lorch, Antje Kleinhans, Andrew Kramar, Christian K Kollmannsberger, Jörg T Hartmann, Carsten Bokemeyer, Oliver Rick, Jörg Beyer

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 01/2012;

  PURPOSETo evaluate the long-term survival rates in patients with relapsed or refractory germ cell tumors (GCTs) after single or sequential high-dose chemotherapy (HDCT). PATIENTS AND METHODSBetweenPURPOSETo evaluate the long-term survival rates in patients with relapsed or refractory germ cell tumors (GCTs) after single or sequential high-dose chemotherapy (HDCT). PATIENTS AND METHODSBetween November 1999 and November 2004, 211 patients with relapsed or refractory GCT were randomly assigned to treatment with either one cycle of cisplatin 100 mg/m(2), etoposide 375 mg/m(2), and ifosfamide 6 g/m(2) (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m(2) and etoposide 1,500 mg/m(2) (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m(2), etoposide 1,800 mg/m(2), and cyclophosphamide 6,400 mg/m(2) (CEC, arm B) followed by autologous stem-cell reinfusion. Long-term progression-free survival (PFS) and overall survival (OS) 6 years after random assignment of the last patient were compared by using the log-rank test.ResultsOverall, 108 and 103 patients were randomly assigned to arms A and B, respectivelyl. The study was stopped prematurely because of excess treatment-related mortality in arm B (14%) compared with that in arm A (4%; P = .01). As of December 2010, nine (5%) of 211 patients were lost to follow-up; 94 (45%) of 211 are alive and 88 (94%) of 94 patients are progression free. Five-year PFS is 47% (95% CI, 37% to 56%) in arm A and 45% (95% CI, 35% to 55%) in arm B (hazard ratio [HR], 1.16; 95% CI, 0.79 to 1.70; P = .454). Five-year OS is 49% (95% CI, 40% to 59%) in arm A and 39% (95% CI, 30% to 49%) in arm B (HR, 1.42; 95% CI, 0.99 to 2.05; P = .057). CONCLUSIONPatients with relapsed or refractory GCT achieve durable long-term survival after single as well as sequential HDCT. Fewer early deaths related to toxicity translated into superior long-term OS after sequential HDCT.

• Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database.

  Authors: Anja Lorch, Caroline Bascoul-Mollevi, Andrew Kramar, Lawrence Einhorn, Andrea Necchi, Christophe Massard, Ugo De Giorgi, Aude Fléchon, Kim Margolin, Jean-Pierre Lotz, Jose Ramon Germà-Lluch, Thomas Powles, Christian Kollmannsberger, Jörg Beyer

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 03/2011; 29(16):2178-84.

  Conventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experienceConventional-dose chemotherapy (CDCT) and high-dose chemotherapy (HDCT) may both be successfully used as salvage treatment for patients with metastatic germ cell tumors (GCTs) who experience progression with first-line treatment. Data on 1,984 patients with GCTs who experienced progression after at least three cisplatin-based cycles and were treated with either cisplatin-based CDCT or carboplatin-based HDCT chemotherapy were collected from 38 centers or groups worldwide. Of 1,984 patients, 1,594 (80%) were eligible, and among the eligible patients, 1,435 (90%) could reliably be classified into one of the following five prognostic categories based on prior prognostic classification: very low (n = 76), low (n = 257), intermediate (n = 646), high (n = 351), and very high risk (n = 105). Within each of the five categories, the progression-free survival (PFS) and overall survival (OS) after CDCT and HDCT were compared using the Cox model adjusted for significant distributional differences between important variables. Overall, 773 patients received CDCT, and 821 patients received HDCT. Both treatment modalities were used with similar frequencies within each prognostic category. The hazard ratio for PFS was 0.44 (95% CI, 0.39 to 0.51) stratified on prognostic category, and the hazard ratio for OS was 0.65 (95% CI, 0.56 to 0.75), favoring HDCT. These results were consistent within each prognostic category except among low-risk patients, for whom similar OS was observed between the two treatment groups. This retrospective analysis suggests a benefit from HDCT given as intensification of first salvage treatment in male patients with GCTs and emphasizes the need for another prospective randomized trial comparing CDCT to HDCT in this patient population.

• Interdisciplinary evidence-based recommendations for the follow-up of early stage seminomatous testicular germ cell cancer patients.

  Authors: Rainer Souchon, Michael Hartmann, Susanne Krege, Anja Lorch, Frank Mayer, Maria De Santis, Silke Gillessen, Jörg Beyer, Richard Cathomas

  Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. 02/2011; 187(3):158-66.

  To provide guidance regarding follow-up procedures after initial treatment of early stage testicular seminoma (clinical stages (CS) I-II A/B) based on current published evidence complemented byTo provide guidance regarding follow-up procedures after initial treatment of early stage testicular seminoma (clinical stages (CS) I-II A/B) based on current published evidence complemented by expert opinion. An interdisciplinary, multinational working group consisting of urologists, medical oncologists, and radiation oncologists analyzed the published evidence regarding follow-up procedures in various stages of seminomatous and nonseminomatous testicular cancers. Focusing on radiooncological aspects, the recommendations contained herein are restricted to early stage seminoma (with radiotherapy being a standard treatment option). In particular, extent, frequency, and duration of imaging at follow-up were analyzed concerning relapse patterns, risk factors, and mode of relapse detection. Active surveillance, adjuvant carboplatin or radiotherapy are equally accepted options for CS I seminoma but they result in different relapse rates and patterns. Usually relapses occur within the first 2(-6) years. Routinely performed follow-up using computerized tomography (CT) after adjuvant treatment yield only low detection rates of recurrences. Therefore, there is no evidence to maintain routine examinations every 3-4 months. After treatment of stage IIA/B, detection rates of relapses or progression identified solely by routinely performed CT during follow-up are low. Considering lifelong cure rates of up to 99% for patients treated for seminoma CS I-IIA/B, the negative impact of unnecessary ionizing radiation exposure has to be considered. The presented recommendations for various follow-up scenarios for early stage seminoma strongly promote the restrictive use of imaging procedures that utilize ionizing radiation (especially CT), due to its potential to induce secondary malignancies.

• Is high dose therapy superior to conventional dose therapy as initial treatment for relapsed germ cell tumors? The TIGER Trial.

  Authors: Darren R Feldman, Robert Huddart, Emma Hall, Jörg Beyer, Thomas Powles

  Journal of Cancer. 01/2011; 2:374-7.

  Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses,Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT) and high dose therapy (HDT) are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP) with sequential HDT (TICE). The planned open labelled randomised phase III study (TIGER) is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint). It is hoped that this large study will conclusively resolve the uncertainty which currently exists.

• Prognostic factors in patients with metastatic germ cell tumors who experienced treatment failure with cisplatin-based first-line chemotherapy.

  Authors: Anja Lorch, Jörg Beyer, Caroline Bascoul-Mollevi, Andrew Kramar, Lawrence H Einhorn, Andrea Necchi, Christophe Massard, Ugo De Giorgi, Aude Fléchon, Kim A Margolin, Jean-Pierre Lotz, Jose Ramon Germa Lluch, Thomas Powles, Christian K Kollmannsberger

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 10/2010; 28(33):4906-11.

  To develop a prognostic model in patients with germ cell tumors (GCT) who experience treatment failure with cisplatin-based first-line chemotherapy. Data from 1,984 patients with GCT who progressedTo develop a prognostic model in patients with germ cell tumors (GCT) who experience treatment failure with cisplatin-based first-line chemotherapy. Data from 1,984 patients with GCT who progressed after at least three cisplatin-based cycles and were treated with cisplatin-based conventional-dose or carboplatin-based high-dose salvage chemotherapy was retrospectively collected from 38 centers/groups worldwide. One thousand five hundred ninety-four (80%) of 1,984 eligible patients were randomly divided into a training set of 1,067 patients (67%) and a validation set of 527 patients (33%). Seminomas were set aside for posthoc analyses. Primary end point was the 2-year progression-free survival after salvage treatment. Overall, 990 patients (62%) relapsed and 604 patients (38%) remained relapse free. Histology, primary tumor location, response, and progression-free interval after first-line treatment, as well as levels of alpha fetoprotein, human chorionic gonadotrophin, and the presence of liver, bone, or brain metastases at salvage were identified as independent prognostic variables and used to build a prognostic model in the training set. Survival rates in the training and validation set were very similar. The estimated 2-year progression-free survival rates in patients not included in the training set was 75% in very low risk, 51% in low risk, 40% in intermediate risk, 26% in high risk, and only 6% in very high-risk patients. Due to missing values in individual variables, 69 patients could not reliably be classified into one of these categories. Prognostic variables are important in patients with GCT who experienced treatment failure with cisplatin-based first-line chemotherapy and can be used to construct a prognostic model to guide salvage strategies.

• High dose chemotherapy as salvage treatment for unresectable late relapse germ cell tumors.

  Authors: Anja Lorch, Oliver Rick, Thomas Wündisch, Jörg-Thomas Hartmann, Carsten Bokemeyer, Jörg Beyer

  The Journal of urology. 07/2010; 184(1):168-73.

  We assessed the activity of high dose chemotherapy in patients with unresectable late relapse germ cell tumors. A total of 35 patients with late relapse were included in a group of 216 treated withWe assessed the activity of high dose chemotherapy in patients with unresectable late relapse germ cell tumors. A total of 35 patients with late relapse were included in a group of 216 treated with high dose chemotherapy as first or subsequent salvage treatment in a prospective, randomized, multicenter phase III trial comparing single vs sequential high dose chemotherapy. Late relapse was defined as unequivocal evidence of relapse more than 2 years after completion of cisplatin based chemotherapy. All patients were considered to have unresectable, progressive, late relapse germ cell tumors. Responders were scheduled for surgical resection of all residual lesions when technically feasible. We identified 4 late relapse groups, including late relapse in 20 of 35 patients (57%) after first line treatment (group 1), in 4 (11%) after first salvage treatment (group 2), in 4 (11%) after initial and after first salvage treatment (group 3), and in 7 (20%) after first line treatment and salvage treatment with rapid progression thereafter who were randomized to a high dose chemotherapy trial (group 4). Median time to late relapse was 4.7 years (range 2.1 to 18.3) in all groups. Resection of all residual lesions could be done in 15 of 35 patients (43%). At a median followup of 5.6 years (range 1.9 to 8.5) 5 of 35 patients (14%) had no progression, resulting in 15% projected progression-free survival. Management for unresectable late relapse germ cell tumors remains controversial. High dose chemotherapy followed by resection of all residual lesions can result in long-term remission in individuals.

• Interdisciplinary evidence-based recommendations for the follow-up of testicular cancer patients: a joint effort.

  Authors: Richard Cathomas, Daniel Helbling, Frank Stenner, Christian Rothermundt, Cyrill Rentsch, Osama Shahin, Hans-Helge Seifert, Kathrin Zaugg, Anja Lorch, Frank Mayer, Jörg Beyer, Maria De Santis, Silke Gillessen

  Swiss medical weekly. 06/2010; 140(25-26):356-69.

  Detailed recommendations for the treatment of testicular cancer exist and due to the stringent application of the standard therapies, most patients can nowadays be cured. Moreover in the treatment ofDetailed recommendations for the treatment of testicular cancer exist and due to the stringent application of the standard therapies, most patients can nowadays be cured. Moreover in the treatment of early stage disease, active surveillance is now a cornerstone of treatment. Hence there is a clear need for recommendations regarding the long term follow-up of these young patients. These have to be safe, feasible and the intensity of procedures have to reflect the known risk of recurrence. Different proposals have been published but they differ widely especially in terms of frequency and modality of imaging. In the last few years, new evidence has become available regarding the relapse pattern of different disease stages of testicular cancer, the use of imaging in follow-up and the risks of excessive radiation due to imaging, in particular with CT scans. In this article, an interdisciplinary, multinational working group has reviewed the evidence and based on this has formulated practical recommendations for the follow-up of patients with testicular cancer.

• Patterns of relapse after chemotherapy in patients with high-risk non-seminomatous germ cell tumor.

  Authors: Karin Oechsle, Anja Lorch, Friedemann Honecker, Christian Kollmannsberger, Jörg T Hartmann, Ina Boehlke, Jörg Beyer, Carsten Bokemeyer

  Oncology. 03/2010; 78(1):47-53.

  We investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumorWe investigated the pattern of relapse after chemotherapy in patients with high-risk germ cell tumor (GCT) to critically review common follow-up procedures including close monitoring of serum tumor markers and radiologic procedures. 645 patients received first-line (434 patients) or salvage platinum-based (211 patients) high-dose chemotherapy in three multicenter trials. Retrospective analysis comprised 77 patients after first-line and 61 after salvage chemotherapy, who had achieved at least a partial remission but progressed afterwards. At relapse, 24% of the patients presented with an isolated elevation in serum tumor markers, 26% with pathologic radiologic confirmation with negative tumor markers, and 42% with elevated tumor markers and radiologically confirmed progression. Relapse was detected by clinical symptoms in 8%. 46% relapsed within 3 months and 97% within 2 years. Relapse pattern did not correlate with tumor marker status or metastasis location prior to chemotherapy, line of chemotherapy, response status after chemotherapy or time point of relapse. In high-risk GCT patients, relapse after chemotherapy is detected either by tumor marker elevation alone, radiologic imaging alone or both, in one third each. Close monitoring including serum tumor markers, radiologic imaging and clinical examination appears warranted within the first 2 years.

• European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): part II.

  Authors: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl [......] Niels E Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase

  European urology. 04/2008; 53(3):497-513.

  OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world.OBJECTIVES: The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands. METHODS: Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

• European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I.

  Authors: Susanne Krege, Jörg Beyer, Rainer Souchon, Peter Albers, Walter Albrecht, Ferran Algaba, Michael Bamberg, István Bodrogi, Carsten Bokemeyer, Eva Cavallin-Ståhl [......] Niels E Skakkebaek, Aslam Sohaib, Sergei Tjulandin, Padraig Warde, Stefan Weinknecht, Lothar Weissbach, Christian Wittekind, Eva Winter, Lori Wood, Hans von der Maase

  European urology. 04/2008; 53(3):478-96.

  OBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. InOBJECTIVES: The first consensus report presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in the year 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, Amsterdam, The Netherlands. METHODS: Medical oncologists, urological surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference, and incorporated the new data into updated and revised guidelines. As for the first meeting, the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update. RESULTS: The first part of the consensus paper describes the clinical presentation of the primary tumor, its treatment, the importance and treatment of testicular intraepithelial neoplasia (TIN), histological classification, staging and prognostic factors, and treatment of stage I seminoma and non-seminoma. CONCLUSIONS: Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early- and advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

• Phase I/II study of sequential dose-intensified ifosfamide, cisplatin, and etoposide plus paclitaxel as induction chemotherapy for poor prognosis germ cell tumors by the German Testicular Cancer Study Group.

  Authors: Jörg T Hartmann, Thomas Gauler, Bernd Metzner, Arthur Gerl, Jochen Casper, Oliver Rick, Marius Horger, Jan Schleicher, Günter Derigs, Regine Mayer-Steinacker, Jörg Beyer, Markus A Kuczyk, Carsten Bokemeyer

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 01/2008; 25(36):5742-7.

  PURPOSE: To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) forPURPOSE: To evaluate the feasibility and the toxicity of sequential, dose-intensified chemotherapy combined with paclitaxel plus peripheral blood-derived hematopoietic stem-cell support (PBSC) for patients with untreated metastatic germ cell tumors (GCTs) who have poor International Germ Cell Consensus Cancer Group prognostic features. PATIENTS AND METHODS: Paclitaxel was added to high-dose (HD) etoposide, ifosfamide, and cisplatin (VIP; etoposide 1,500 mg/m2, ifosfamide 10,000 mg/m2, and cisplatin 100 mg/m2; cumulative dose; days -6 through -2 per cycle) at three dose levels (135, 175, and 225 mg/m2) applied on day -6. Cycles were supported by PBSC and granulocyte colony-stimulating factor. One cycle of standard VIP was administered before start of HD-VIP plus paclitaxel cycles to collect autologous PBSC. RESULTS: Fifty-two of 53 patients receiving 152 cycles were assessable. As expected, myelosuppression was the major adverse effect. Median durations of leukocytes less than 1,000/microL and thrombocytes less than 25,000/microL were 6 and 4 days, respectively, independently of the dose of paclitaxel applied. WHO grade 2 neurotoxicity and grade 3 encephalopathy were observed in 5% of patients each. Other main adverse effects observed were stomatitis, diarrhea, and obstipation. Seventy-nine percent of patients achieved a favorable response to chemotherapy plus secondary surgery. After a median follow-up time of 41 months in surviving patients, the calculated 2- and 5-year survival rates were 77.6% (95% CI, 65.4% to 89.9%) and 75.2% (95% CI, 62.5% to 87.8%), respectively. CONCLUSION: Dose-intensive, sequential HD-VIP plus paclitaxel up to a dose of 225 mg/m2 in patients with poor prognosis GCT is a feasible approach. The regimen warrants investigation for its therapeutic potential in an expanded cohort of poor prognosis GCT patients.

• Germ-cell tumors.

  Authors: Anja Lorch, Jörg Beyer, Carsten Bokemeyer

  The New England journal of medicine. 11/2007; 357(17):1772-3; author reply 1773-4.

• Single versus sequential high-dose chemotherapy in patients with relapsed or refractory germ cell tumors: a prospective randomized multicenter trial of the German Testicular Cancer Study Group.

  Authors: Anja Lorch, Christian Kollmannsberger, Joerg Thomas Hartmann, Bernd Metzner, Ingo G H Schmidt-Wolf, Wolfgang E Berdel, Florian Weissinger, Jan Schleicher, Gerlinde Egerer, Antje Haas, Rebekka Schirren, Jörg Beyer, Carsten Bokemeyer, Oliver Rick

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 07/2007; 25(19):2778-84.

  PURPOSE: To compare single versus sequential high-dose chemotherapy (HDCT) as first or subsequent salvage treatment in patients with relapsed or refractory germ cell tumors (GCTs). PATIENTS ANDPURPOSE: To compare single versus sequential high-dose chemotherapy (HDCT) as first or subsequent salvage treatment in patients with relapsed or refractory germ cell tumors (GCTs). PATIENTS AND METHODS: Between November 1999 and November 2004, 230 patients were planned to be recruited in a prospective, randomized, multicenter trial comparing one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2, and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE; arm A) versus three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2, and cyclophosphamide 6,400 mg/m2 (CEC; arm B). RESULTS: The study was stopped prematurely after recruitment of 216 patients as a result of excess treatment-related mortality in arm B. One hundred eleven (51%) of 216 patients were randomly assigned to sequential HDCT, and 105 (47%) of 216 patients were randomly assigned to single HDCT. Five (2%) of 216 patients had to be excluded because of non-GCT histologies at review. With a median follow-up time of 36 months, 109 (52%) of 211 patients were alive, and 91 (43%) of 211 patients were progression free. At 1 year, event-free, progression-free, and overall survival rates were 40%, 53%, and 80%, respectively, in arm A compared with 37%, 49%, and 61%, respectively, in arm B (P > .05 for all comparisons). Treatment-related deaths, mainly as a result of sepsis and cardiac toxicity, were less frequent in arm A (four of 108 patients, 4%) compared with arm B (16 of 103 patients, 16%; P < .01). CONCLUSION: We found no difference in survival probabilities between single HDCT using CE and sequential HDCT using CEC. Sequential HDCT was better tolerated and resulted in fewer treatment-related deaths.

• Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR-ligand mismatch after dose-reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma.

  Authors: Nicolaus Kröger, Bronwen Shaw, Simona Iacobelli, Tatjana Zabelina, Karl Peggs, Avichai Shimoni, Arnon Nagler, Thomas Binder, Thomas Eiermann, Alejandro Madrigal, Rainer Schwerdtfeger, Michael Kiehl, Herbert Gottfried Sayer, Jörg Beyer, Martin Bornhäuser, Francis Ayuk, Axel Rolf Zander, David I Marks

  British journal of haematology. 07/2005; 129(5):631-43.

  We compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cellWe compared antithymocyte globulin (ATG) with alemtuzumab in 73 patients with multiple myeloma, who underwent reduced conditioning with melphalan/fludarabine, followed by allogeneic stem cell transplantation from human leucocyte antigen-matched or -mismatched unrelated donors. The ATG group had more prior high-dose chemotherapies (P < 0.001), while bone marrow was used more as the stem cell source in the alemtuzumab group (P < 0.001). Alemtuzumab resulted in faster engraftment of leucocytes (P = 0.03) and platelets (P = 0.02) and in a lower incidence of acute graft versus host disease (GvHD) grades II-IV (24% vs. 47%, P = 0.06). More cytomegalovirus (CMV) seropositive patients in the alemtuzumab group experienced CMV reactivation (100% vs. 47%, P = 0.001). The cumulative incidence of treatment-related mortality at 2 years was 26% [95% confidence interval (CI) = 12-37%] for ATG vs. 28% (95% CI = 15-55%) for alemtuzumab, P = 0.7. There was no significant difference in the estimated 2-year overall and progression-free survival between ATG and alemtuzumab: 54% (95% CI: 39-75%) vs. 45% (95% CI: 28-73%) and 30% (95% CI: 16-55%) vs. 36% (95% CI: 20-62%) respectively. In multivariate analysis, treatment with alemtuzumab had a higher risk for relapse (hazard ratio: 2.37; P = 0.05) while killer immunoglobulin-like receptor (KIR)-ligand mismatch was protective for relapse (P < 0.0001). We conclude that alemtuzumab produced less acute GvHD, but higher probability of relapse. The data implicated a major role of KIR-ligand mismatched transplantation in multiple myeloma.

• Repeat retroperitoneal lymphadenectomy in advanced testicular cancer.

  Authors: Axel Heidenreich, Carsten Ohlmann, Axel Hegele, Jörg Beyer

  European urology. 02/2005; 47(1):64-71.

  OBJECTIVES: Repeat retroperitoneal lymph node dissection (RPLND) for the treatment of metastatic testicular cancer is an uncommonly performed procedure. We evaluated the location, pathohistologicalOBJECTIVES: Repeat retroperitoneal lymph node dissection (RPLND) for the treatment of metastatic testicular cancer is an uncommonly performed procedure. We evaluated the location, pathohistological results, postoperative complications and therapeutic outcome in 17 patients being referred for repeat RPLND after failure of the primary retroperitoneal approach. PATIENTS AND METHODS: 18 patients underwent repeat RPLND after failed primary RPLND or residual tumour resection. We retrospectively analyzed preoperative patient characteristics, operative and pathohistological data from primary and repeat RPLND, morbidity and oncological outcome after surgery. RESULTS: All patients had nonseminomatous primaries with metastatic retroperitoneal lymph nodes; 4 and 14 patients had undergone primary RPLND and residual tumor resection (RTR), respectively, for metastatic testicular cancer. Prior to repeat RPLND all patients had undergone 4 cycles of salvage chemotherapy for locoregional recurrences only with negative tumour markers at time of surgery. All patients demonstrated residual masses requiring repeat RPLND. Retroperitoneal recurrences were located at multiple sites: retrocaval area with infiltration of the vena cava, interaortocaval and paraaortic region, retrocrural space, suprahilar region, outfield metastases in the iliac region. Two cases required resection of the vena cava due to infiltration, in one case an aortic graft and an iliac graft was necessary due to tumour infiltration of the adventitial layer of the vessels; nephrectomy and resection of the sigmoid was required in another 2 patients. The most significant complication was chylous ascites 1 and prolonged paralytic ileus in 1 patient. Pathohistological examination of the resected specimen revealed viable germ cell tumour elements in 4 patients (22.2%), necrosis/fibrosis in 8 patients (44.4%) and mature teratoma in 6 patients (33.3%). At a mean follow-up of 22 (1-45) months, the disease specific survival rate was 89% with significant differences between patients with necrosis (100%), mature teratoma (85%) and viable cancer (50%). CONCLUSION: Recurrences after RPLND usually reflect inadequate primary surgery especially in the retrocaval and suprahilar region. Repeat RPLND is safe and effective in the majority of patients; however, it requires careful preoperative planning with regard to potential involvement of adjacent vascular and visceral structures making close interdisciplinary collaboration necessary in many cases. Repeat RPLND is a mandatory surgery to be performed at centres of expertise.

• Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma.

  Authors: Nicolaus Kröger, Jose A Perez-Simon, Han Myint, Hans Klingemann, Avichai Shimoni, Arnon Nagler, Rodrigo Martino, Adrian Alegre, Jose F Tomas, Rainer Schwerdtfeger, Michael Kiehl, Axel Fauser, Herbert Gottfried Sayer, Angel Leon, Jörg Beyer, Tatjana Zabelina, Francis Ayuk, Jesus F San Miguel, Ronald Brand, Axel Rolf Zander

  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 10/2004; 10(10):698-708.

  We evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated withWe evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated with melphalan/fludarabine followed by allogeneic stem cell transplantation. The cumulative risk at 1 year for treatment-related mortality (TRM) was 18% (95% confidence interval [CI], 12%-28%). In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16-6.74; P =.02), relapse (HR, 4.14; 95% CI, 2.04-8.38; P <.001), event-free survival (HR, 3.11; 95% CI, 1.77-5.46; P <.001), and overall survival (HR, 2.69; 95% CI, 1.35-5.35; P =.005). In addition, relapse was also significantly diminished by chronic graft-versus-host disease (GVHD) in a time-dependent Cox model (HR, 0.37; 95% CI, 0.16-0.87; P =.02). At transplantation, 8% of the patients were in complete remission, whereas 27% had progressive disease. After allografting, 49% achieved complete remission, and 38% achieved partial remission. In a subgroup of patients with chemosensitivity at transplantation and no relapse after prior high-dose chemotherapy who underwent transplantation with peripheral blood stem cells (n = 46), the cumulative risk of TRM at 1 year was only 8% (95% CI, 1%-54%). The 2-year estimated event-free and overall survival was 60% (95% CI, 42%-78%) and 75% (95% CI, 59%-91%), respectively, for related donors (n = 34) and was 81% (95% CI, 59%-100%) and 92% (95% CI, 76%-100%), respectively, for unrelated donors (n = 12).

• Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin's disease.

  Authors: Alexander Claviez, Thomas Klingebiel, Jörg Beyer, Wenzel Nürnberger, Gerhard Ehninger, Meinolf Suttorp, Peter Dreger, Wolfgang Dörffel, Norbert Schmitz

  Annals of hematology. 05/2004; 83(4):237-41.

  Despite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkin's disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (medianDespite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkin's disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (median age: 16 years, range: 11-19) received reduced intensity conditioning and allogeneic peripheral blood stem cell transplantation (PBSCT) after failure of stratified first-line chemotherapy, involved-field radiotherapy, and salvage chemotherapy including autologous PBSCT (two patients). For conditioning, fludarabine was combined with busulfan (8 or 12 mg/kg) and additional cyclophosphamide (three patients), or without cyclophosphamide (two patients), or melphalan (one patient). Two patients died of infections and one of progression. One patient remains in complete remission 59 months following transplantation. Two patients relapsed but responded after withdrawal of immunosuppression, chemotherapy, or donor lymphocyte infusions and are alive at 22 and 36 months post transplant, respectively. Allogeneic PBSCT, with reduced intensity conditioning, may be beneficial for selected patients with refractory HD.

• Bacterial contamination of ex vivo processed PBPC products under clean room conditions.

  Authors: Markus Ritter, Joachim Schwedler, Jörg Beyer, Kamran Movassaghi, Reinier Mutters, Andreas Neubauer, Nimrod Schwella

  Transfusion. 12/2003; 43(11):1587-95.

  BACKGROUND: Patients undergoing high-dose radio- and/or chemotherapy and autologous or allogeneic PBPC transplantation are at high risk for infections owing to profound immunosuppression. In thisBACKGROUND: Patients undergoing high-dose radio- and/or chemotherapy and autologous or allogeneic PBPC transplantation are at high risk for infections owing to profound immunosuppression. In this study, the rate of microbial contamination of ex vivo processed PBPC products was analyzed, comparing preparation under clean room conditions to standard laboratory conditions. STUDY DESIGN AND METHODS: After implementation of good manufacturing practice conditions in the two participating institutions, the microbial contamination rate of 366 PBPC harvests from 198 patients was determined under certified clean room conditions (Group A) from 2000 until 2002. To investigate influence of improved environmental conditions along with other parameters, this set of samples was compared with a historical control set of 1413 PBPC products, which have been processed ex vivo under a clean bench in a regular laboratory room and were harvested from 626 patients (Group B) from 1989 until 2000. RESULTS: In Group B microbial contamination was found in 74 PBPC products (5.2%) from 57 patients. In Group A microbial growth was detected in 3 leukapheresis products (0.8%) from 3 patients. After exclusion of PBPC products, which were probably contaminated before manipulation, statistical analysis showed a significant difference (chi2= 10.339; p < 0.001). CONCLUSION: These data suggest an impact of clean room conditions on the bacterial contamination rate of PBPC products. To identify confounding variables, variables like technique of leukapheresis, culture methodology, and microbial colonization of central venous catheters were taken into account. Further variables might be identified in following studies.

• Infectious complications after allogeneic stem cell transplantation: epidemiology and interventional therapy strategies--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

  Authors: Hermann Einsele, Hartmut Bertz, Jörg Beyer, Michael G Kiehl, Volker Runde, Hans-Jochen Kolb, Ernst Holler, Robert Beck, Rainer Schwerdfeger, Ulrike Schumacher [......] Hans Martin, Joachim Kienast, Andrew J Ullmann, Georg Maschmeyer, William Krüger, Dietger Niederwieser, Hartmut Link, Christian A Schmidt, Helmut Oettle, Thomas Klingebiel

  Annals of hematology. 11/2003; 82 Suppl 2:S175-85.

  The risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during thatThe risk of infection after allogeneic stem cell transplantation is determined by the underlying disease, the intensity of previous treatments and complications that may have occurred during that time, but above all, the risk of infection is determined by the selected transplantation modality (e.g. HLA-match between the stem cell donor and recipient, T cell depletion of the graft, and others). In comparison with patients treated with high-dose chemotherapy and autologous stem cell transplantation, patients undergoing allogeneic stem cell transplantation are at a much higher risk of infection even after hematopoietic reconstitution, due to the delayed recovery of T and B cell functions. The rate at which immune function recovers after hematopoietic reconstitution greatly influences the incidence and type of post-transplant infectious complications. Infection-associated mortality, for example, is significantly higher following engraftment than during the short neutropenic period that immediately follows transplantation.

• Extragonadal germ cell tumors of the mediastinum and retroperitoneum: results from an international analysis.

  Authors: Carsten Bokemeyer, Craig R Nichols, Jean-P Droz, Hans J Schmoll, Alan Horwich, Arthur Gerl, Sophie D Fossa, Jörg Beyer, Jörg Pont, Lothar Kanz, Lawrence Einhorn, Jörg T Hartmann

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 05/2002; 20(7):1864-73.

  PURPOSE: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies. PATIENTS ANDPURPOSE: To characterize the clinical and biologic features of extragonadal germ cell tumor (EGCT) and to determine the overall outcome with currently available treatment strategies. PATIENTS AND METHODS: Of an unselected population of 635 consecutive patients treated from 1975 through 1996 at 11 cancer centers, 341 patients (54%) had primary mediastinal EGCT, and 283 patients (45%) had retroperitoneal EGCT. Five hundred twenty-four patients (83%) had a nonseminomatous germ cell tumor (GCT), and 104 patients (16%) had a seminomatous histology. RESULTS: After platinum-based induction chemotherapy with or without secondary surgery, 141 patients (49%) with mediastinal nonseminomas (median follow-up, 19 months; range, 1 to 178 months) and 144 patients (63%) with retroperitoneal nonseminoma (median follow-up, 29 months; range, 1 to 203 months) are alive (P =.0006). In contrast, the overall survival rate for patients with a seminomatous EGCT is 88%, with no difference between patients with mediastinal or retroperitoneal tumor location (median follow-up, 49 months; range, 4 to 193 months; respective 70 months; range, 1 to 211 months). A significantly lower progression-free survival rate was found in seminoma patients treated with initial radiotherapy alone compared with chemotherapy. Nonseminomatous histology, presence of nonpulmonary visceral metastases, primary mediastinal GCT location, and elevated beta-human chorionic gonadotropin were independent prognostic factors for shorter survival. Hematologic malignancies (n = 17) occurred without exception in patients with primary mediastinal nonseminoma. Sixteen patients developed a metachronous testicular cancer despite the use of platinum-based chemotherapy. CONCLUSION: Whereas patients with pure seminomatous EGCT histology have a long-term chance of cure of almost 90% irrespective of the primary tumor site, 45% of patients with mediastinal nonseminomas are alive at 5 years. This outcome is clearly inferior compared with patients with nonseminomatous retroperitoneal primary tumors.