Wolfgang Dörffel

Publications (12)100.49 Total impact

• Article: Treatment of Children and Adolescents With Hodgkin Lymphoma Without Radiotherapy for Patients in Complete Remission After Chemotherapy: Final Results of the Multinational Trial GPOH-HD95.

  Wolfgang Dörffel, Ursula Rühl, Heike Lüders, Alexander Claviez, Marion Albrecht, Jos Bökkerink, Harald Holte, Jonas Karlen, Georg Mann, Heinz Marciniak, Felix Niggli, Kjeld Schmiegelow, Ernst-Wilhelm Schwarze, Richard Pötter, Lutz Wickmann, Günther Schellong
  [show abstract] [hide abstract]
  ABSTRACT: PURPOSETo minimize the risk of late effects in pediatric Hodgkin lymphoma (HL) by omitting radiotherapy (RT) in patients in complete remission (CR) after chemotherapy and reducing the standard radiation dose to 20 Gy in patients in incomplete remission. PATIENTS AND METHODS Between 1995 and 2001, 925 patients with classical HL (cHL) were registered from seven European countries in German Society of Pediatric Oncology and Hematology Hodgkin Lymphoma Trial 95. Patients in treatment group 1 (TG1; early stages) received two cycles of vincristine, prednisone, procarbazine, and doxorubicin or vincristine, prednisone, etoposide, and doxorubicin chemotherapy; additional two or four cycles of cyclophosphamide, vincristine, prednisone, and procarbazine were added in TG2 (intermediate stages) or TG3 (advanced stages), respectively. Patients in CR (assessed by computed tomography or magnetic resonance imaging) did not undergo RT. Those with tumor volume reduction more than 75% received reduced involved-field RT with 20 Gy and an additional 10- or 15-Gy boost only for larger residuals.ResultsRates of overall survival, progression-free survival (PFS), and event-free survival at 10 years were (± SE) 96.3% ± 0.6%, 88.2% ± 1.1%, and 85.4% ± 1.3%, respectively. PFS for TG1 patients without or with RT was 97.0% ± 2.1% versus 92.2% ± 1.7% (P = .214) but was unsatisfactory for nonirradiated patients in TG2 (68.5% ± 7.4% v 91.4% ± 1.9%; P < .0001), with similar but not significant results in TG3 (82.6% ± 5.4% v 88.7% ± 2.0%, P = .259). Reduction of the standard radiation dose from 25 to 20 Gy did not increase failure rate. CONCLUSIONRT can be omitted in early stage HL in so defined CR following this chemotherapy. RT with 20(-35) Gy proved to be sufficient in patients with incomplete remission following chemotherapy.
  Journal of Clinical Oncology 03/2013; · 18.37 Impact Factor
• Article: Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for Hodgkin disease in children and adolescents: report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies.

  Günther Schellong, Marianne Riepenhausen, Christian Bruch, Stefan Kotthoff, Johannes Vogt, Tobias Bölling, Karin Dieckmann, Richard Pötter, Achim Heinecke, Jürgen Brämswig, Wolfgang Dörffel
  [show abstract] [hide abstract]
  ABSTRACT: To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results.
  Pediatric Blood & Cancer 12/2010; 55(6):1145-52. · 1.89 Impact Factor
• Article: Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study.

  Christine Mauz-Körholz, Dirk Hasenclever, Wolfgang Dörffel, Kathrin Ruschke, Tanja Pelz, Antje Voigt, Martina Stiefel, Melanie Winkler, Constanze Vilser, Karin Dieckmann, Jonas Karlén, Eva Bergsträsser, Alexander Fosså, Georg Mann, Michael Hummel, Wolfram Klapper, Harald Stein, Dirk Vordermark, Regine Kluge, Dieter Körholz
  [show abstract] [hide abstract]
  ABSTRACT: Vincristine, etoposide, prednisone, and doxorubicin (OEPA)-cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) is derived from standard vincristine, procarbazine, prednisone, and doxorubicin (OPPA)-cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) chemotherapy by replacing procarbazine with etoposide and dacarbazine for a potentially less gonadotoxic regimen for boys with Hodgkin's lymphoma (HL). Five hundred seventy-three pediatric patients with classical HL were enrolled onto the German Society of Pediatric Oncology and Hematology-Hodgkin's Disease (GPOH-HD) -2002 study between November 2002 and December 2005. Boys received two courses of OEPA and girls received two courses of OPPA for induction. Treatment group (TG) -2 (intermediate stages) and TG-3 (advanced stages) patients received further two or four cycles COPP (girls) or COPDAC (boys), respectively. After chemotherapy all patients received involved-field irradiation with 19.8 Gy, except for patients with early-stage disease (TG-1) in complete remission. Five hundred seventy-three patients (287 males and 286 females) were less than 18 years old and fulfilled all inclusion criteria; 195 patients (34.0%) were allocated to TG-1, 139 (24.3%) were allocated to TG-2, and 239 (41.7%) were allocated to TG-3. Toxicity of OEPA-COPDAC was tolerable overall. Hematotoxicity was more pronounced with OEPA than OPPA, whereas it was less pronounced with COPDAC compared with COPP. The median observation time was 58.6 months. Overall survival and event-free survival (EFS) rates (+/- SE) at 5 years were 97.4% +/- 0.7% and 89.0% +/- 1.4%, respectively. In TG-1, overall EFS was 92.0% +/- 2.0%. EFS of patients without irradiation (93.2% +/- 3.3%) was similar to that of irradiated patients (91.7% +/- 2.5%), confirming results of the previous GPOH-HD-95 study. In TG-2+3, EFS did not significantly differ between boys and girls (90.2% +/- 2.3 v 84.7% +/- 2.7, respectively; P = .12). In TG-2+3, results in boys and girls are superimposable. OPPA-COPP and OEPA-COPDAC seem to be exchangeable regimens in intermediate- and advanced-stage classical HL in pediatric patients.
  Journal of Clinical Oncology 08/2010; 28(23):3680-6. · 18.37 Impact Factor
• Source

  Available from: Dirk Hasenclever

  Article: Resection alone in 58 children with limited stage, lymphocyte‐predominant Hodgkin lymphoma–experience from the European network group on pediatric Hodgkin lymphoma

  Christine Mauz-Körholz MD, Stephanie Gorde-Grosjean MD, Dirk Hasenclever PhD, Ananth Shankar MD, Wolfgang Dörffel MD, W. Hamish Wallace MD, Günther Schellong MD, Alain Robert MD, Dieter Körholz MD, Odile Oberlin MD, [......], Dirk Hasenclever, Ananth Shankar, Wolfgang Dörffel, W. Hamish Wallace, Günther Schellong, Alain Robert, Dieter Körholz, Odile Oberlin, Georgina W. Hall, Judith Landman‐Parker
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND.Lymphocyte-predominant Hodgkin lymphoma (LPHL) is a rare, CD20-positive, good prognostic lymphoma in children. Patients with early-stage LPHL who underwent successful surgical lymph node resection alone have been reported. To clarify the optimum treatment strategy in children, European study groups were asked to report their experience of surgery alone used in the treatment of pediatric LPHL.METHODS.Data from 58 patients were collected by the French Society for Pediatric Cancers, the German-Austrian Pediatric Study Group/German Society of Pediatric Oncology and Hematology (Germany), and the Children's Cancer and Leukaemia Group (United Kingdom). In total, there were 50 boys and 8 girls, and the median age was 11 years (age range, 4-17 years). Fifty-four patients had stage IA disease, 2 patients had stage IIA disease, and 2 patients had stage IIIA disease.RESULTS.With a median follow-up of 43 months (range, 2-202 months), the overall survival rate was 100%, and the progression-free survival (PFS) rate was 57%. Fifty-one of 58 patients achieved complete remission (CR) after surgery. In the CR group, the overall PFS rate was 67% (95% confidence interval, 51-82%). All seven patients who had residual disease after initial surgery developed recurrences (P = .003). Among 18 patients with stage IA LPHL who developed recurrent disease, 11 patients had local recurrences, and 7 patients recurred in stage IIA. One patient with stage IIIA disease presented with high-grade B-cell non-Hodgkin lymphoma at 10 years of follow-up.CONCLUSIONS.When complete resection was achieved, a substantial proportion of patients with surgically treated, early-stage LPHL experienced long-term remission and actually may have been cured. Cancer 2007. © 2007 American Cancer Society.
  Cancer 06/2007; 110(1):179 - 185. · 4.77 Impact Factor
• Article: Characterization and expression of CT45 in Hodgkin's lymphoma.

  Hans-Jürgen Heidebrecht, Alexander Claviez, Marie Luise Kruse, Marc Pollmann, Friedrich Buck, Sönke Harder, Markus Tiemann, Wolfgang Dörffel, Reza Parwaresch
  [show abstract] [hide abstract]
  ABSTRACT: The monoclonal antibody Ki-A10 (IgG1) generated after immunization of mice with Hodgkin's lymphoma cell line L428 detects a nuclear antigen in human tissues with a restricted distribution pattern similar to cancer/testis antigens. The aim of this study was to characterize the antigen and to determine the expression profile in Hodgkin's lymphoma. The half-life and phosphorylation of the antigen were determined by radiolabeling. The antigen was characterized by immunopurification and sequencing. Demethylation of genes is used to induce cancer/testis antigens. Ki-A10-negative cells were treated with 5-aza-2'-deoxycytidine. The Ki-A10 expression in paraffin-embedded tumors was determined immunohistochemically. Immunopurification of the 25/22-kDa antigen and sequencing revealed a peptide of 14 amino acids corresponding to the gene product of the newly described gene family MGC27005, located on chromosome Xq26.3, now termed CT45. CT45 is significantly phosphorylated and down-regulated during mitosis. Demethylation of CT45-negative HeLa cells and stimulated peripheral blood lymphocytes induced CT45 expression. Except testis, immunohistochemical stainings of normal tissues, reactive lymphoid lesions, and most malignant tumors were negative. In comparison, 54 of 99 (55%) samples from pediatric and adolescent Hodgkin's lymphoma patients enrolled in the multicenter trial HD-95 stained Ki-A10 positive. Ki-A10 expression correlated with histologic subtypes (nodular sclerosis Hodgkin's lymphoma 68% versus mixed cellularity Hodgkin's lymphoma 40% versus nodular lymphocyte predominant Hodgkin's lymphoma 9%; P < 0.001). Ki-A10 is the first monoclonal antibody that detects CT45. As benign lymphoid lesions did not express CT45, the use of Ki-A10 antibody will facilitate the discrimination of Hodgkin's lymphoma from reactive lymphadenopathies.
  Clinical Cancer Research 08/2006; 12(16):4804-11. · 7.74 Impact Factor
• Chapter: Morbus Hodgkin

  Wolfgang Dörffel, Günther Schellong
  [show abstract] [hide abstract]
  ABSTRACT: Die Behandlung des Morbus Hodgkin bei Kindern geht seit den 70er-Jahren des vorigen Jahrhunderts im Vergleich zur Therapie bei erwachsenen Patienten eigene Wege. Führende pädiatrische Gruppen können schon seit den 80er-Jahren auf Heilungsraten über 90-95% verweisen. Die im Vergleich zu anderen onkologischen Erkrankungen besonders große Zahl langzeitüberlebender Patienten rückte aber auch die negativen Therapiefolgen stärker in den Blickpunkt. Seither ist es das Hauptanliegen der pädiatrischen Onkologen, die Therapie des Morbus Hodgkin in der Weise zu optimieren, dass die Patienten unter Beibehaltung gleichguter Heilungschancen weniger Spätfolgen der Behandlung erleiden. Auf diese Weise hat die Entwicklung der Therapie des Morbus Hodgkin bei Kindern und Jugendlichen eine Vorreiterrolle für die heute bei fast allen onkologischen Erkrankungen angestrebte maßgeschneiderte Behandlung gespielt, unter dem Motto: so viel wie nötig, so wenig als möglich.
  12/2005: pages 752-769;
• Article: Proliferation characteristics in pediatric Hodgkin's lymphoma point to a cell cycle arrest in the G(1) phase.

  Markus Tiemann, Alexander Claviez, Heike Lüders, Martin Zimmermann, Günther Schellong, Wolfgang Dörffel, Reza Parwaresch
  [show abstract] [hide abstract]
  ABSTRACT: This study was undertaken to determine the prognostic relevance of the proliferation rate in neoplastic cells in children and adolescents with Hodgkin's lymphoma. Paraffin-embedded biopsy specimens were immunostained with the proliferation-associated monoclonal antibodies Ki-S5 (Ki-67 antigen) and Ki-S2 (which detects the repp86 protein). Repp86 is a protein of about 100 kDa encoded by a gene located on human chromosome band 20q11.2. In contrast to the Ki-67 antigen, repp86 expression is restricted to the cell cycle phases G(2), S and M. Immunohistochemical results on diagnostic lymph node biopsy specimens from 224 patients included in two pediatric multicenter Hodgkin's trials, GPOH HD-90 and HD-95, were compared with clinical data. High Ki-67 antigen expression was a striking feature of Hodgkin's and Reed-Sternberg cells as well as lymphocytic and histiocytic cells (median: 80%, range: 20-100%), in contrast to low repp86 expression (median: 20%, range: 10-80%; P<0.001). The proliferation rate was independent of histological subtype, stage and presence of B symptoms. The probability of event-free and overall survival (+/-standard error) of all patients at 5 years was 91.6+/-2.0 and 98.1+/-1.0%, respectively. The proliferation rate of tumor cells did not influence the outcome. The difference between Ki-67 and repp86 expression in Hodgkin's and Reed-Sternberg or lymphocytic and histiocytic cells points to a possible cell cycle arrest in the G(1) phase, which may explain the obvious paradox of a highly proliferating but slowly growing paucicellular tumor. High Ki-67 expression does not seem to be an adverse prognostic factor in pediatric and adolescent patients with Hodgkin's lymphoma treated by effective risk-adapted chemo-radiotherapy regimens.
  Modern Pathology 12/2005; 18(11):1440-7. · 4.79 Impact Factor
• Article: Proliferation rate and outcome in children with T-cell rich B-cell lymphoma: a clinicopathologic study from the NHL-BFM-study group.

  Markus Tiemann, Marc-Oliver Riener, Alexander Claviez, Ulrike Meyer, Wolfgang Dörffel, Alfred Reiter, Reza Parwaresch
  [show abstract] [hide abstract]
  ABSTRACT: T-cell rich B-cell lymphoma (TCRBCL) is considered a rare variant of aggressive B-cell lymphoma characterized by few neoplastic cells and a large reactive infiltrate with striking similarities to nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL). In childhood, these tumors occur even less frequently. Biopsy specimens at diagnosis from 16 children (13 boys) with a median age of 12 years (range, 7 to 18) were immunophenotyped. The proliferation rate was assessed with monoclonal antibodies against Ki-67 and repp86 antigens and additional clonality analyses were performed. Ten patients had localized disease and only two had B symptoms. All patients showed high Ki-67 expression (median: 80%, range 40% to 90%), but low repp86 expression (median: 25%, range 10% to 50%). PCR-based clonality studies of the hypervariable CDR III region of the immunoglobuline heavy chain and the T-cell receptor gamma-chain genes demonstrated predominant clones in nine and five patients, respectively. Three patients had previous or concomitant NLPHL and two of them received initial treatment for Hodgkin's disease. All patients achieved remission after a brief polychemotherapy regimen. Two patients subsequently relapsed and one was rescued by salvage therapy including autologous stem cell transplantation. At a median follow-up of 23 months, 15 patients (94%) are alive. The striking contrast between the proliferation rates determined by Ki-67 and repp86 expression points to a possible arrest in the G1 cell cycle phase because repp86 expression is restricted to the S, G2 and M cell cycle phases. This G1 arrest may explain the paradoxon of high Ki-67 expression in a paucicellular lymphoma with a favorable prognosis in young patients.
  Leukemia and Lymphoma 10/2005; 46(9):1295-300. · 2.58 Impact Factor
• Article: Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group.

  Günther Schellong, Wolfgang Dörffel, Alexander Claviez, Dieter Körholz, Georg Mann, Hans-G Scheel-Walter, Jos P M Bökkerink, Marianne Riepenhausen, Heike Lüders, Richard Pötter, Ursula Rühl
  [show abstract] [hide abstract]
  ABSTRACT: To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). One hundred seventy-six patients with progression (n = 51) or first relapse (n = 125) were enrolled by 67 centers. The median time from initial diagnosis to progression/relapse was 1.1 year (range, 0.1 to 15.3 years), and the patients' median age was 14.7 years (range, 4.3 to 24.5 years). Salvage chemotherapy consisted of two to three cycles of IEP alternating with one to two cycles of ABVD supplemented in part by one to two cycles of cyclophosphamide, vincristine, procarbazine, and prednisone or lomustine (CCNU), etoposide, and prednimustine. Radiotherapy was given to involved areas using individualized doses. In the 1990s, additional high-dose chemotherapy with autologous stem-cell transplantation (SCT) was introduced for patients with unfavorable prognosis. Disease-free survival (DFS) and overall survival (OS) after 10 years are 62% and 75%, respectively (SE, 4% each). Of 176 patients, 73 suffered second events. The risk-factor analysis revealed the time to progression/relapse as the strongest prognostic factor (P = .0001). Patients with progression have an inferior outcome (DFS, 41%; OS, 51%), whereas patients with late relapse (> 12 months after end of therapy) do well (DFS, 86%; OS, 90%), although none of them received SCT in second remission. The result can be considered favorable. Whereas the salvage strategy for progressive disease has to be optimized further, it is possible to reduce intensity and avoid SCT in late relapses after Hodgkin's disease in childhood/adolescence.
  Journal of Clinical Oncology 09/2005; 23(25):6181-9. · 18.37 Impact Factor
• Article: Impact of latent Epstein-Barr virus infection on outcome in children and adolescents with Hodgkin's lymphoma.

  Alexander Claviez, Markus Tiemann, Heike Lüders, Matthias Krams, Reza Parwaresch, Günther Schellong, Wolfgang Dörffel
  [show abstract] [hide abstract]
  ABSTRACT: The prognostic significance of latent Epstein-Barr virus (EBV) infection in Hodgkin's lymphoma (HL) is debated controversially. Especially in the pediatric age group, no conclusive data are available. Eight hundred forty-two children and adolescents (median age, 13.7 years) from pediatric multicenter treatment studies HD-90 and HD-95 were studied for latent EBV infection in Hodgkin's and Reed-Sternberg cells by immunostaining against latent membrane protein 1 (LMP-1). Results were compared with established risk factors. Two hundred sixty-three patients (31%) were LMP positive. EBV infection correlated with sex (39% male v 23% female; P < .001), histologic subtype (69% mixed cellularity v 22% nodular sclerosis v 6% lymphocyte predominance; P < .001) and young age. With a median follow-up of 4.9 years, 820 patients (97%) are alive. Probability of overall survival at 10 years (+/- standard deviation) for EBV-negative and -positive patients was 98.1% +/- 0.6% and 95.1% +/- 1.4%, respectively (P = .017 by log-rank test). A negative effect of EBV infection became evident for patients with nodular sclerosis subtype Bennett II (P = .02), and those treated for advanced stages (P = .003). In multivariate analysis, LMP positivity was an independent factor for adverse outcome (RR = 3.08). Probability of failure-free survival (FFS) in LMP positive and negative patients was 89.1% +/- 2.3% and 84.1% +/- 3.9%, respectively (P = .86). With effective combined treatment modalities in pediatric HL, latent EBV infection has no influence on FFS but is associated with an inferior overall survival in crucial subgroups.
  Journal of Clinical Oncology 07/2005; 23(18):4048-56. · 18.37 Impact Factor
• Article: Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin's disease.

  Alexander Claviez, Thomas Klingebiel, Jörg Beyer, Wenzel Nürnberger, Gerhard Ehninger, Meinolf Suttorp, Peter Dreger, Wolfgang Dörffel, Norbert Schmitz
  [show abstract] [hide abstract]
  ABSTRACT: 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 (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.
  Annals of Hematology 05/2004; 83(4):237-41. · 2.62 Impact Factor
• Article: Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin’s disease

  Alexander Claviez, Thomas Klingebiel, Jörg Beyer, Wenzel Nürnberger, Gerhard Ehninger, Meinolf Suttorp, Peter Dreger, Wolfgang Dörffel, Norbert Schmitz
  [show abstract] [hide abstract]
  ABSTRACT: Despite high-dose chemotherapy and autografting, the outcome for patients with primary refractory Hodgkins disease (HD) or multiple relapses remains unsatisfactory. Six pediatric patients (median age: 16years, 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 12mg/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 59months following transplantation. Two patients relapsed but responded after withdrawal of immunosuppression, chemotherapy, or donor lymphocyte infusions and are alive at 22 and 36months post transplant, respectively. Allogeneic PBSCT, with reduced intensity conditioning, may be beneficial for selected patients with refractory HD.
  Annals of Hematology 03/2004; 83(4):237-241. · 2.62 Impact Factor