Abstract
Background
Follicular lymphoma (FL) occurs predominantly at advanced age, with an annual incidence of 3–5 cases per 100 000 inhabitants in Western countries. The clinical course is heterogeneous.
Methods
For this new guideline, systematic literature searches were conducted in medical databases (MEDLINE, PubMed Central) (up to November 2017) and in the Guidelines International Network (G-I-N), and recent publications were added.
Results
The results of 21 systematic reviews with meta-analyses, 75 randomized controlled trials, and 58 prospective and retrospective studies were evaluated. Lymph-node biopsy is necessary for initial diagnosis of FL. CT scanning of the neck, thorax, and abdomen should be performed to assess how far the disease has spread, together with bone marrow biopsy and, if required, PET/CT. In early FL (stages I and II; 10–15 %), potentially curative radiotherapy combined with an anti-CD 20 antibody is recommended. In advanced disease (stages III and IV), watchful waiting is indicated for patients who have no clinical symptoms and a low tumor burden. Patients with clinical symptoms and/or high tumor burden should receive chemotherapy in combination with an anti-CD 20 antibody, followed by 2 years’ maintenance treatment with an anti-CD 20 antibody.
Conclusion
Given the good long-term prognosis of FL, the treatment must be chosen with care and thorough follow-up is necessary to ensure detection of late sequelae such as second malignancies or organ damage.
Follicular lymphoma (FL) is a malignancy that develops from the B-cell lineage in the lymphatic system. After diffuse large-cell B-cell lymphoma, FL is the second most common malignant lymphoma in Western countries. The incidence is between three and five cases per 100 000 inhabitants per year and has risen in recent years (1). FL affects particularly the older age groups (mean age at diagnosis >60 years) and is characterized by a heterogeneous clinical presentation and a very variable prognosis. Some patients have no or only minor symptoms for years and initially do not require treatment. Others, however, present with symptoms at diagnosis or shortly after and will have to undergo treatment (2– 4). The S3 clinical practice guideline that has been developed for Germany for the first time provides an overview of the current recommendations for the diagnosis, therapy, and follow-up of follicular lymphoma.
Methods
Guideline conceptualization and development
The German clinical practice guideline for follicular lymphoma was developed by an interdisciplinary group of clinicians, methodologists, patient representatives, and representatives from 24 scientific medical societies (see eMethods), the Deutsche Studiengruppe niedrig-maligne Lymphome (GLSG, German Low Grade Lymphoma Study Group), and the German Lymphoma Alliance (GLA). The scientific medical society in charge was the German Society of Hematology and Medical Oncology (DGHO); the guideline was published by the guideline program oncology of the Association of the Scientific Medical Societies in Germany (AWMF), the German Cancer Society (DKG), and the German Cancer Aid (DKH). The latter provided the funding for the guideline project. The guideline program oncology accompanied the development of the guideline methodologically and provided AWMF certified guideline advisers as moderators.
After key questions and patient relevant endpoints had been defined, the methodological process was set out. The quality of the evidence (confidence in the effect estimates) was evaluated by using the GRADE approach—depending on the endpoint prioritized beforehand (etable). For the remaining statements/recommendations, the development process was decided on the basis of expert consensus of the guideline group.
eTable. Recommendation grades and confidence in the evidence by endpoint according to GRADE.
| Strength of recommendation | Description | Expression | |||
| A | Strong recommendation | Should/must | |||
| B | Recommendation | Should | |||
| 0 | Recommendation not definite/open to interpretation | Can | |||
| Confidence in the evidence | Description | Symbol | |||
| High confidence | We are very certain that the true effect is close to the estimated effect. |  |
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| Moderate confidence | We have moderate confidence in the effect estimate: the true effect is probably close to the estimate, but there is a possibility that it differs to a relevant degree. | |
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 |
| Low confidence | Our confidence in the effect estimate is limited: the true effect may well be different from the estimate to a relevant degree. | |
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| Very low confidence | We have very little confidence in the effect estimate: the true effect probably differs from the estimated effect to a relevant degree. | |
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GRADE, Guidelines Recommendation Assessment Development
A detailed description of the methods including the management of conflicts of interests can be found in the guideline report (https://www.awmf.org/uploads/tx_szleitlinien/018–033OLk_S3_Follikulaeres_Lymphom_2020–06.pdf).
Results
A systematic literature search identified a total of 8508 potentially relevant publications. Of these, 21 (23 publications) systematic reviews with meta-analyses, 75 (97 publications) randomized controlled trials, and 58 (68 publications) prospective or retrospective studies were included to address the defined key questions. The eFigure shows as an example the specific literature search strategy for randomized controlled trials that were evaluated for the guideline.
eFigure.
Flow chart showing the specific literature search for randomized controlled trials
The extended version and the abbreviated version as well as the guideline reports can be found at www.awmf.org and www.leitlinienprogramm-onkologie.de/leitlinien/follikulaeres-lymphom/. The guideline is also available digitally in the app for the guideline program oncology (www.leitlinienprogramm-onkologie.de/app/).
Diagnosis and staging
Follicular lymphomas are usually characterized by slowly progressive growth. Accordingly, many patients remain asymptomatic for a long time, particularly in the early stages. Characteristic symptoms are mostly painless swollen lymph nodes on the neck or axilla, also in the abdomen, more rarely in the inguinal region. Additionally, some patients experience non-specific losses in performance (38%) and fatigue (34%) (2). B-symptoms (fevers, night sweats, weight loss) are found in less than a quarter of patients, with night sweats being the most common of the three B-symptoms, followed by weight loss in 19% and a fever in 8% of patients (2).
Swollen lymph nodes that last for several weeks or increase should prompt a histological investigation. As large a tissue specimen as possible should be harvested, and a completely excised lymph node is preferable to a punch biopsy (expert consensus [EC]). A cytological aspirate is not sufficient for diagnosis (EC). Histology should be complemented by immunohistochemistry in order to confirm the B-cell nature of the lymphoma (CD20, CD79a), the germinal center phenotype (CD10, BCL6), and criteria of malignancy (for example, lowered intrafollicular proliferation, BCL2-expression). The histological diagnosis should be made by a pathologist with extensive hemopathological experience (EC).
After confirming a diagnosis of follicular lymphoma, the stage and therapeutic requirement are determined by appropriate investigations. Since most patients do not have clinical symptoms that necessitate immediate therapy, the following investigations should be undertaken within 4–6 weeks (EC) (box 1).
BOX 1. Diagnostic investigations*.
Medical history
Physical examination
Computed tomography scanning of neck, thorax, abdomen, using contrast medium (where possible)
If required, additionally sonography
Bone marrow punch biopsy and aspirate
-
Laboratory tests:
Blood count – including differential blood count
Lactate dehydrogenase
Liver function and kidney function tests
ß2 microglobulin
* Strong consensus
If the physical examination, bone marrow biopsy, and existing imaging findings including computed tomography (CT) or alternatively, magnetic resonance imaging (MRI), do not provide any indications of stage III or IV, any planned curative radiotherapy should be preceded by positron emission tomography (PET/CT) to determine the spread of the lymphoma and to define the size of the area to be irradiated (EC) (5, 6). Since PET/CT is not covered by the statutory health insurance system, cost reimbursement may not be granted.
Primary treatment
The treatment of follicular lymphoma should be guided by the stage according to the Ann Arbor classification (table 1) and in advanced stages III and IV also by the clinical symptoms (7).
Table 1. Spread of malignant lymphomas according to the Ann Arbor staging system.
| Stage | Involvement | Extranodal (E) status |
| I | Involvement of the lymph nodes in one lymph node region | A single localized, extralymphatic manifestation without lymph node involvement |
| II | Involvement of two or more lymph node regions on the same side of the diaphragm | Localized involvement of an extranodal organ or extranodal localization and one or several lymph node regions on the same side of the diaphragm |
| III | Involvement of lymph node regions on both sides of the diaphragm | Localized involvement of extralymphatic organs accompanied by lymph node involvement on both sides of the diaphragm |
| IV | Diffuse extralymphatic involvement; liver involvement is always considered as diffuse involvement | Not applicable |
Treatment in the early stages
Radiotherapy is an effective method for achieving local remission (8, 9). But when using radiotherapy as the sole treatment modality in the early stages I and II, recurrences outside the radiation field are frequently observed (10, 11), which suggests that a proportion of patients has a more extensive lymphoma spread than the initial staging may indicate. For this reason, several studies have investigated the combination of radiotherapy with systemic therapy—such as chemotherapy or antibody therapy. Both additional therapeutic modalities were found to be beneficial (12– 14), with antibody therapy being the preferred method because of its lower toxicity. For this reason, therapy with curative intent in stages I and II should be given as radiotherapy in combination with rituximab (recommendation grade B; caution: off-label use of rituximab). Radiotherapy should comprise “involved site” radiotherapy (EC). A recently published study reported for this approach a plateauing of progression free survival after five years in 75% for a follow-up period of more than five years (14).
Treatment in the advanced stages
In the advances stages III and IV therapy does not aim to cure but to alleviate disease-related symptoms and prolong progression free survival and as far as is possible overall survival. The timing and choice of first-line therapy depend on clinical symptoms, clinical course, and the tumor burden. The latter is defined according to the modified GELF (Groupe d’Étude des Lymphomes Folliculaires) criteria (box 2), 15, 16).
BOX 2. BOX 2.
Modified GELF criteria for determining tumor burden
The absence of the following symptoms defines a low tumor burden
B symptoms (weight loss > 10 % over 6 months and/or fever > 38° Celsius over 2 weeks without any sign of an infection and/or night sweats)
Hematopoetic failure (increasing anemia with hemoglobin < 10 g/dL and/or thrombocytopenia < 100 000 cells/µL)
Very large lymphoma conglomerations (largest diameter > 7 cm, so called “bulky disease”)
Rapidly progressive lymph node enlargement
Lymphoma related compression syndrome
Lymphoma related pleural effusion or ascites
GELF, Groupe d‘Étude des Lymphomes Folliculaires
Strategy in case of low tumor burden without clinical symptoms
Because of the indolent course of follicular lymphomas, watchful waiting is the approach of choice in patients at the advanced stages III and IV without clinical symptoms and a low tumor burden. A prospective randomized trials compared such a “watch and wait” approach with a short course of rituximab (given as four applications) and a third arm, in which rituximab was applied for a total of two years (17). Initial results from this study show a significantly prolonged time to progression in patients in both rituximab arms. But the follow-up periods were short, and overall survival after three years did not differ. The question that also remains unanswered is whether the early administration of rituximab in asymptomatic patients may have a negative effect on treatment required at a later stage.
An analysis of the National LymphoCare Study, reflecting real life healthcare conditions, confirmed that the “watch and wait” strategy does not put affected patients at any disadvantage (18). Because of these data, early initiation of therapy of asymptomatic patients with a low tumor burden is not indicated outside clinical trials, and for this group of patients, a “watch and wait” strategy continues to be the recommended approach (recommendation grade A).
Treatment in patients with a high tumor burden and/or clinical symptoms
In patients with a high tumor burden and/or clinical symptoms, therapy should be initiated (EC). In accordance with the encouraging results of four large prospectively randomized trials, such patients should initially be treated with a combination of an anti-CD20-antibody plus chemotherapy as long as no contraindications exist to such a therapy (recommendation grade A) (table 2) (19– 22).
Table 2. Comparison of chemotherapy versus chemotherapy plus rituximab in RCTs.
| OR | PFS | OS | ||||
| CVP R-CVP Marcus 2008 (21) |
64 % 81 % |
(p < 0.0001) | 18 mo 48 mo |
(p < 0.001) | 77 % 83 % |
(p = 0.029) |
| CHOP R-CHOP Hiddemann 2005 (19) |
90 % 96 % |
(p = 0.011) | 31 mo n. r. |
(p = 0.0006) | 90 % 95 % |
(p = 0.016) |
| MCP R-MCP Herold 2007 (20) |
75 % 92 % |
(p = 0.0009) | 29 mo n. r. |
(p < 0.0001) | 74 % 87 % |
(p = 0.0096) |
| CHVP+IFN R-CHVP+IFN Salles 2008 (22) |
72 % 81 % |
(p < 0.0001) | 35 mo n. r. |
(p < 0.0001) | 79 % 84 % |
(p = 0.029) |
CHOP, cyclosphosphamide, hydroxydaunorubicin, vincristine, prednisone;
CHVP, cyclophosphamide, hydroxydaunorubicin, VP 16, prednisone;
CVP, cyclophosphamide, vincristine, prednisone; IFN, interferon alpha;
MCP, mitoxantrone, cyclophosphamide, prednisone; mo, months; n. r., not reached;
OR, overall response; OS, overall survival; PFS, progression-free survival
R; rituximab; RCT, randomized controlled trial
The chemotherapeutic options should include bendamustine and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone (recommendation grade B) (Caution: off-label use of bendamustine). The selection should be guided by the patient’s individual risk profile—for example, a cardiac comorbidity—and/or the patient’s wishes. It should be borne in mind that CHOP has a higher acute toxicity especially in the form of neutropenia (65–74%) and neutropenic fevers (7–11%), whereas bendamustine leads to long-term immunosuppression and is therefore associated with infectious complications (20–26%) (23), and prophylaxis for Pneumocystis carinii pneumonia and viral infections should be given longer-term, at least to the end of maintenance treatment.
The anti-CD20-antibodies of choice are rituximab or obinutuzumab (EC). In a prospective randomized study, a combination of obinutuzumab plus chemotherapy led for the primary endpoint progression free survival (PFS) to an extended PFS (after three years: 76% versus 69%, p=0.0012) compared with a combination containing rituximab, and was also found to be superior in certain subgroups. The obinutuzumab combination did, however, have a higher rate of adverse effects. Differences in overall survival were not observed (23, 24).
After complete or partial remission has been achieved, the initial treatment should be followed by two years of maintenance treatment with an anti-CD20-antibody (recommendation grade A). This recommendation is supported by several prospective randomized trials that consistently showed a statistically significantly prolonged progression free survival (PFS after 3 years: 75% versus 58%, p<0.0001 [25); median PFS: 10.5 years versus 4.1 years, p<0.001 [26]) but not overall survival (>12 years) (25– 27).
Therapy in the setting of tumor recurrence
To date one has to continue to assume that follicular lymphomas at advanced stages (III and IV) cannot be cured and recurrences occur regularly. In case of a recurrence, repeated lymph node biopsy should be undertaken in order to detect a possible transformation into a high malignant lymphoma or exclude such a transformation (EC). The further diagnostic evaluation resembles the approach taken in primary therapy (EC). The indication for initiating recurrence treatment also follows the recommendations for primary treatment.
The selection of therapy for the recurrence takes into account the type of previous therapy and maintenance therapy, the quality of the response to prior therapy, the time to recurrence, the clinical symptoms associated with the recurrence, the patient’s age and comorbidities, and the patient’s own wishes. In case of recurrence or progression after more than two years after chemo-immunotherapy, the identical chemo-immunotherapy can be used again (EC) (28, 29). If the lymphoma has become refractory to rituximab, an antibody switch to obinutuzumab is beneficial (30). In case of recurrence or progression after less than two years after chemo-immunotherapy, other therapeutic options (for example, high-dose therapy followed by autologous stem cell transplantation) can be deployed in suitable patients (EC) (31, 32).
New substances
In recent years, numerous new agents for the therapy of malignant lymphomas have been developed, some of which interfere with specific signaling pathways, attach defined surface structures, or have an immunomodulatory effect. We cannot go into more detail here. Results from clinical trials, however, indicate that chemotherapy-free therapeutic approaches may become a possibility with such agents, which have a higher specificity and efficacy while also having reduced toxicity (33– 35).
Follow-up
Follow-up aims to monitor the overall condition of the patient and the remission status of the lymphoma, but also to detect potential long term effects of the treatment.
In order to identify unfavorable early recurrences in a timely manner, control examinations should be undertaken every three months in the first two years after the end of therapy, and every six months from the third year onward (EC). To check the remission status after achieving complete or partial remission, CT scanning and where required PET/CT are the basis, which in case of symptoms or existing residual manifestations can be extended by using suitable additional investigations (EC). In the follow-up of asymptomatic patients, outside clinical trials, routine imaging using CT or PET/CT should not be undertaken after a progression free interval of more than two years.
The potential long term sequelae of the therapy include the development of secondary malignancies. This depends mainly on the treatment given previously. After a combination of mitoxantrone, cyclophosphamide, and predniso[lo]ne, the risk of secondary hematological neoplasms was notably higher than for CHOP (5% versus 1%) (36), whereas a Cochrane analysis founds no difference in the rate of secondary leukemias after autologous stem cell transplantation compared with conventional chemotherapy (37). On the basis of such uncertain data, patients with follicular lymphoma should be urgently advised to attend the generally recommended cancer screenings (EC).
No reliable data for follicular lymphoma exist regarding the long term injury to organs. Anthracycline induced cardiomyopathies are the exception; these occur at higher rates, with the risk of cardiac dysfunction being increased by a factor of 2.6–7 (38, 39). Because of the lack of data, the recommendation for late sequelae and organ toxicities was kept general and their evaluation recommended for the follow-up examinations.
Conclusions
The new S3 clinical practice guideline provides evidence based recommendations for the diagnosis, therapy, and follow-up of patients with follicular lymphoma. Recent studies, whose results were not yet available when the guideline was developed, are highly likely to necessitate updates and revisions to the guideline in the near future.
Supplementary Material
eMethods
Participating scientific medical societies, organizations, experts and others*
* The numbers in parentheses indicate the affiliation of the experts and others to the respective scientific medical societies and organizations
Organizations with a mandate
Organizations without mandate
Participants and experts
German Society of Hematology and Medical Oncology (DGHO) (in charge) (1)
German Society of Radiation Oncology (DEGRO) (2)
German Society for Ultrasound in Medicine (DEGUM) (3)
German Radiological Society (DRG) (4)
German Society of Gerontology and Geriatrics (5)
German Society for Clinical Chemistry and Laboratory Medicine (DGKL) (6)
German Society for Endoscopy and Imaging Procedures DGE BV (7)
German Society of Internal Medicine DGIM (8)
German Society of Nuclear Medicine (DGN) (9)
German Association for Palliative Medicine (10)
German Society of Pathology (11)
German Society of Andrology (12)
German Society of Reproductive Medicine (13)
German Association for Medical Informatics, Biometry and Epidemiology (GMDS) (14)
Professional Association of Hematologists and Oncologists in Private Practice in Germany (BNHO) (15)
Working Group for Internal Oncology of the German Cancer Society (AOI) (16)
German Working Group for Blood and Marrow Transplantation (DAG KBT) (17)
Conference on Oncological Nursing and Pediatric Nursing (KOK) (18)
Working Group for Oncological Pathology (19)
Worging Group Prevention and Integrated Oncology (AG PRiO) (20)
Working Group for Psycho-Oncology (PSO) (21)
Working Group on Radiation Oncology (22)
German Working Group for Supportive Care in Cancer ASORS (23)
German Leukemia and Lymphoma Aid (DLH) (24)
East German Study Group of Hematology and Oncology (OSHO) (25)
Scientific Institute of Hematologists and Oncologists in Private Practice (WINHO) (26)
Drug Commission of the German Medical Association (AkdÄ) (27)
Competence Center Oncology, MDK North Rhine (28)
Competence Network Malignant Lymphomas (KML) (29)
German Low Grade Lymphoma Study Group (GLSG) (30)
German Urology Society (31)
Evidence-Based Oncology, Department of Medicine I, University Hospital of Cologne (32)
Guideline Program for Oncology (OL) (33)
Prof. Dr. med. Wolfgang Hiddemann (1)
Prof. Dr. med. Michael Herold (1)
Prof. Dr. med. Martin Dreyling (1)
Prof. Dr. med. Wolfram Klapper (1)
Dr. med. Michael Unterhalt (1)
Prof. Dr. med. Christian Buske (1)
PD Dr. med. Christian Scholz (1)
PD Dr. med. Andreas Viardot (1)
Prof. Dr. med. Klaus Herfarth (2)
Prof. Dr. med. Christian Görg (3)
Dr. med. Corinna Trenker (3)
Prof. Dr. med. Ulrich Dührsen (3)
Prof. Dr. med. Ernst Rummeny (4)
PD Dr. med. Valentin Goede (5)
Dr. med. Manfred Wick (6)
Prof. Dr. med. Christoph Frank Dietrich (7)
Prof. Dr. med. Ulrich Dührsen (7)
Prof. Dr. med. Lorenz Trümper (8)
Prof. Dr. med. Wolfgang Hiddemann (8)
Prof. Dr. med. Thomas Pfluger (9)
Prof. Dr. med. Andreas Buck (9)
Prof. Dr. med., Dipl.-Phys. Dirk Hellwig (9)
Dr. med. Johannes Rosenbruch (10)
Prof. Dr. med. Falko Fend (11)
Prof. Dr. med. Peter Möller (11)
Prof. Dr. med. Frank-Michael Köhn (12)
Prof. Dr. med. Andreas Schüring (13)
Prof. Dr. med. Frank-Michael Köhn (13)
Prof. Dr. rer. biol. hum., Dipl.-Math. Eva Hoster (14)
Prof. Dr. rer. nat. Ulrich Mansmann (14)
PD Dr. med. Michael Sandherr (15)
Dr. med. Lars H. Nipken (16)
Prof. Dr. med. Peter Dreger (17)
Prof. Dr. med. Nicolaus Kröger (17)
Prof. Dr. med. Kai Hübel (17)
Kerstin Paradies (18)
Prof. Dr. med. Peter Möller (19)
Prof. Dr. med. Falko Fend (19)
Prof. Dr. med. Oliver Micke (20)
Dr. med. Christoph Stoll (20)
Dr. med. Pia Heußner (21)
Dr. med. Friederike Mumm (21)
Prof. Dr. med. Heinz Schmidberger (22)
Dr. med. Markus Horneber (23)
Dr. med. Ulrike Holtkamp (24)
Rainer Göbel (24)
PD Dr. med. Christian Scholz (25)
Dr. rer. med. Walter Baumann (26)
Prof. Dr. med. Georg Maschmeyer (27)
PD Dr. med. Sebastian Fetscher (27)
Prof. Dr. med. Axel Heyll (28)
Dr. med. Ulrich Hackenberg (28)
Dr. med. Eva Hilgenfeld (28)
Prof. Dr. med. Kai Hübel (29)
PD Dr. med. Bastian von Tresckow (29)
Dr. med. Christian Schmidt (30)
Prof. Dr. med. Sabine Kliesch (31)
Prof. Dr. med. Frank-Michael Köhn (31)
PD Dr. med. Nicole Skoetz (32)
Tina Jakob (32)
Marius Goldkuhle (32)
Ina Monsef (32)
Acknowledgments
Translated from the original German by Birte Twisselmann, PhD.
Footnotes
Conflict of interest statement Dr Zoellner received consultancy fees from Abbvie und Hexal. She was reimbursed for travel expenses by Abbvie. She has been an employee of Janssen-Cilag since August 2019.
Prof Herfahrt has received funding from Roche Pharma for a research project he initiated.
Prof Herold has received third party funding from Roche Pharma for conducting commissioned clinical studies.
Prof Klapper received third party funding from Roche and Bayer for conducting commissioned clinical studies.
Prof Hiddeman received consultancy fees from Roche Pharma, Janssen-Cilag, and Gilead. He was reimbursed for travel expenses from Roche Pharma. He received speaker honoraria from Janssen-Cilag and Roche Pharma. He received third party funding from Roche Pharma, Janssen-Cilag, and Gilead for conducting commissioned clinical studies.
Dr Skoetz declares that no conflict of interest exists.
Clinical guidelines published in Deutsches Ärzteblatt are not subject to peer review—just as in many other specialist journals—because S3 clinical practice guidelines are texts that have in many cases been assessed, discussed, and broadly consented by experts (peers).
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Associated Data
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Supplementary Materials
eMethods
Participating scientific medical societies, organizations, experts and others*
* The numbers in parentheses indicate the affiliation of the experts and others to the respective scientific medical societies and organizations
Organizations with a mandate
Organizations without mandate
Participants and experts
German Society of Hematology and Medical Oncology (DGHO) (in charge) (1)
German Society of Radiation Oncology (DEGRO) (2)
German Society for Ultrasound in Medicine (DEGUM) (3)
German Radiological Society (DRG) (4)
German Society of Gerontology and Geriatrics (5)
German Society for Clinical Chemistry and Laboratory Medicine (DGKL) (6)
German Society for Endoscopy and Imaging Procedures DGE BV (7)
German Society of Internal Medicine DGIM (8)
German Society of Nuclear Medicine (DGN) (9)
German Association for Palliative Medicine (10)
German Society of Pathology (11)
German Society of Andrology (12)
German Society of Reproductive Medicine (13)
German Association for Medical Informatics, Biometry and Epidemiology (GMDS) (14)
Professional Association of Hematologists and Oncologists in Private Practice in Germany (BNHO) (15)
Working Group for Internal Oncology of the German Cancer Society (AOI) (16)
German Working Group for Blood and Marrow Transplantation (DAG KBT) (17)
Conference on Oncological Nursing and Pediatric Nursing (KOK) (18)
Working Group for Oncological Pathology (19)
Worging Group Prevention and Integrated Oncology (AG PRiO) (20)
Working Group for Psycho-Oncology (PSO) (21)
Working Group on Radiation Oncology (22)
German Working Group for Supportive Care in Cancer ASORS (23)
German Leukemia and Lymphoma Aid (DLH) (24)
East German Study Group of Hematology and Oncology (OSHO) (25)
Scientific Institute of Hematologists and Oncologists in Private Practice (WINHO) (26)
Drug Commission of the German Medical Association (AkdÄ) (27)
Competence Center Oncology, MDK North Rhine (28)
Competence Network Malignant Lymphomas (KML) (29)
German Low Grade Lymphoma Study Group (GLSG) (30)
German Urology Society (31)
Evidence-Based Oncology, Department of Medicine I, University Hospital of Cologne (32)
Guideline Program for Oncology (OL) (33)
Prof. Dr. med. Wolfgang Hiddemann (1)
Prof. Dr. med. Michael Herold (1)
Prof. Dr. med. Martin Dreyling (1)
Prof. Dr. med. Wolfram Klapper (1)
Dr. med. Michael Unterhalt (1)
Prof. Dr. med. Christian Buske (1)
PD Dr. med. Christian Scholz (1)
PD Dr. med. Andreas Viardot (1)
Prof. Dr. med. Klaus Herfarth (2)
Prof. Dr. med. Christian Görg (3)
Dr. med. Corinna Trenker (3)
Prof. Dr. med. Ulrich Dührsen (3)
Prof. Dr. med. Ernst Rummeny (4)
PD Dr. med. Valentin Goede (5)
Dr. med. Manfred Wick (6)
Prof. Dr. med. Christoph Frank Dietrich (7)
Prof. Dr. med. Ulrich Dührsen (7)
Prof. Dr. med. Lorenz Trümper (8)
Prof. Dr. med. Wolfgang Hiddemann (8)
Prof. Dr. med. Thomas Pfluger (9)
Prof. Dr. med. Andreas Buck (9)
Prof. Dr. med., Dipl.-Phys. Dirk Hellwig (9)
Dr. med. Johannes Rosenbruch (10)
Prof. Dr. med. Falko Fend (11)
Prof. Dr. med. Peter Möller (11)
Prof. Dr. med. Frank-Michael Köhn (12)
Prof. Dr. med. Andreas Schüring (13)
Prof. Dr. med. Frank-Michael Köhn (13)
Prof. Dr. rer. biol. hum., Dipl.-Math. Eva Hoster (14)
Prof. Dr. rer. nat. Ulrich Mansmann (14)
PD Dr. med. Michael Sandherr (15)
Dr. med. Lars H. Nipken (16)
Prof. Dr. med. Peter Dreger (17)
Prof. Dr. med. Nicolaus Kröger (17)
Prof. Dr. med. Kai Hübel (17)
Kerstin Paradies (18)
Prof. Dr. med. Peter Möller (19)
Prof. Dr. med. Falko Fend (19)
Prof. Dr. med. Oliver Micke (20)
Dr. med. Christoph Stoll (20)
Dr. med. Pia Heußner (21)
Dr. med. Friederike Mumm (21)
Prof. Dr. med. Heinz Schmidberger (22)
Dr. med. Markus Horneber (23)
Dr. med. Ulrike Holtkamp (24)
Rainer Göbel (24)
PD Dr. med. Christian Scholz (25)
Dr. rer. med. Walter Baumann (26)
Prof. Dr. med. Georg Maschmeyer (27)
PD Dr. med. Sebastian Fetscher (27)
Prof. Dr. med. Axel Heyll (28)
Dr. med. Ulrich Hackenberg (28)
Dr. med. Eva Hilgenfeld (28)
Prof. Dr. med. Kai Hübel (29)
PD Dr. med. Bastian von Tresckow (29)
Dr. med. Christian Schmidt (30)
Prof. Dr. med. Sabine Kliesch (31)
Prof. Dr. med. Frank-Michael Köhn (31)
PD Dr. med. Nicole Skoetz (32)
Tina Jakob (32)
Marius Goldkuhle (32)
Ina Monsef (32)