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Treatment Protocol of the NHL-BFM and the NOPHO Study Groups for Mature Aggressive B-cell Lymphoma and Leukemia in Children and Adolescents

Registration Number
NCT03206671
Lead Sponsor
University Hospital Muenster
Brief Summary

The trial B-NHL 2013 is a collaborative prospective, multi-national, multi-center, randomized trial with participating centers of the NHL-BFM group (Austria, Switzerland, Czech Republic, Germany) and the Scandinavian NOPHO group (Denmark, Finland, Norway, Sweden). The aim of the trial is to evaluate the role of rituximab in the treatment of mature aggressive B-cell Non-Hodgkin lymphoma and leukemia (B-NHL and B-AL) in children and adolescents.

The following primary study questions are going to be analyzed:

* the effectiveness (event-free survival) in pediatric patients with very limited mature B-NHL (R1 and R2 stage I and II) of substituting anthracyclines by the rituximab window without compromising survival rates.

* the effectiveness (event-free survival) in pediatric patients with limited mature B-NHL (R2 stage III) randomly assigned to receive the rituximab window plus standard chemotherapy or standard chemotherapy without the rituximab window.

* the effectiveness (event-free survival) and the immune reconstitution (recovery of CD19+ B-cells, IR) in pediatric patients with advanced mature B-NHL/B-AL (R3 and R4 incl. R4 CNS+) treated with BFM-type chemotherapy and randomly assigned schedules of one versus seven doses rituximab.

Secondary study questions will address

* additional parameters for immune reconstitution, lymphocyte subpopulations, immunoglobulin levels, vaccination titers and infection rates

* kinetics of immune reconstitution after treatment

* adverse event and severe adverse event profile

* inter-individual variability of rituximab response

* role of different mechanisms of action of rituximab in advanced B-NHL/B-AL

Detailed Description

Risk group stratification:

R1/R2 stage I+II:

* R1: resection status: complete

* R2: resection status: incomplete, stage I and II

R2 III:

- R 2: resection status: incomplete, stage III and LDH \< 2 x ULN (according to local reference value for adults)

R3/R4:

* R3: resection status: incomplete, stage III and LDH ≥ 2 x ULN but \< 4 x ULN or stage IV/B-AL and LDH \< 4 x ULN and CNS negative

* R4: resection status: incomplete, Stage III and LDH ≥ 4 x ULN or stage IV/B-AL and LDH ≥ 4 x ULN and CNS negative

* R4 CNS +: stage IV/B-AL and CNS positive

For patients with very limited disease (R1/R2 stage I/II), the addition of rituximab might allow the omission of anthracyclines without jeopardizing survival rates but reducing acute and long term toxicities. In this treatment arm, it is tested whether the event-free survival is similar to that of the historical control when all patients receive one dose of rituximab as monotherapeutic agent in the rituximab window R five days prior to the start of standard chemotherapy as a substitute for anthracyclines.

For patients with limited disease (R2 stage III) it is tested whether the event-free survival can be improved by adding rituximab to the standard chemotherapy. Two different treatment regimens will be evaluated in a randomized design: Patients in the standard arm will receive the standard chemotherapy. Patients of the rituximab plus arm will receive one dose of rituximab as monotherapeutic agent in the rituximab window R five days prior to the start of standard chemotherapy.

For patients with advanced disease (R3/R4) it is tested whether the event-free survival can be improved by adding rituximab to the standard chemotherapy. Two different rituximab regimens will be evaluated in a randomized design: Patients in the standard arm will receive one dose of rituximab as monotherapeutic agent in the rituximab window R five days prior to the start of standard chemotherapy. Patients of the rituximab plus arm will receive the rituximab window and additional six doses of rituximab added to the first four courses of chemotherapy. In addition the immune reconstitution will be analyzed comparing the effect of the two regimens of rituximab added to standard chemotherapy.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
650
Inclusion Criteria
  • Newly diagnosed, histological or cytological and immunological proven aggressive mature B-cell Non-Hodgkin lymphoma including Burkitt lymphoma (BL), Burkitt leukemia (B-AL), diffuse large B-cell lymphoma (DLBCL), or mature B-cell NHL not further classified according to current WHO classification124. For rare subtypes (e.g. primary mediastinal large B-NHL, PMLBL, double hit lymphoma or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements), consultation of the study center is recommended.

  • availability of slides/blocks for reference pathology and international pathology panel (except in cases with immunological and cytomorphological assurance of diagnosis)

  • age at diagnosis < 18 years

  • diagnostics and treatment in one of the participating centers of the trial

  • no previous chemotherapy, no previous lymphoma-directed treatment. No application of steroids for more than two days during the last month

  • adequate hepatic, renal and cardiac function, except if alteration is due to lymphoma infiltration. Please contact the study center in case of unclear cases.

  • signed informed consent of patient and/or parents/guardians for treatment according to the protocol, participation and transfer of data

  • follow-up of at least two years after initial diagnosis is expected

  • Certificate of vaccination against hepatitis B or negative serology, defined as

    • evidence of immunization with HBs-antigen negative, anti-HBs positive and anti-HBc negative or
    • negative hepatitis B serology with HBs-antigen negative, anti-HBs and anti- HBc negative
Read More
Exclusion Criteria
  • patients with insufficient work up not allowing a correct stratification into the risk groups
  • B-cell neoplasia as second malignancy
  • any other medical, psychiatric or social condition prohibiting treatment according to the protocol (e.g. previous malignancy, prior organ transplant, HIV infection or AIDS or severe immunodeficiency, etc.)
  • participation within a different trial for treatment of B-cell malignancies and/or concurrent treatment within any other clinical trial. Exceptions to this are the NHL-BFM Registry 2012 and trials with different endpoints, involving aspects of supportive treatment which can run parallel to B-NHL 2013 without influencing the outcome of this trial e.g. trials on antiemetics, antibiotics, strategies for psychosocial support etc.
  • overt hepatitis B or history of hepatitis B
  • hypersensitivity to rituximab or to murine proteins or to any of the other excipients of the Investigational Medicinal Product rituximab (MabThera®) or to ingredients of other IMPs.
  • lack of CD20 expression of the lymphoma cells
  • pregnancy and lactation
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
R3/R4 standard armRituximab windowRituximab window + standard chemotherapy
R1/R2 stage I+IIRituximab windowRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R3/R4 rituximab plus armVindesine SulfateRituximab window + standard chemotherapy plus six additional doses of rituximab
R2 stage III experimental armRituximab windowRituximab window + Standard chemotherapy
R2 stage III experimental armMethotrexateRituximab window + Standard chemotherapy
R2 stage III standard armCyclophosphamideStandard chemotherapy
R3/R4 rituximab plus armRituximab windowRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armMethotrexateRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armPrednisoloneRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 standard armDexamethasoneRituximab window + standard chemotherapy
R3/R4 rituximab plus armAdditional doses of RituximabRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 standard armVindesine SulfateRituximab window + standard chemotherapy
R3/R4 standard armVincristineRituximab window + standard chemotherapy
R1/R2 stage I+IICyclophosphamideRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IICytarabineRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IIDexamethasoneRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IIEtoposideRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IIIfosfamideRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IIVincristineRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IIMethotrexateRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R1/R2 stage I+IIPrednisoloneRituximab window + standard chemotherapy without anthracyclines (Vincristine not in R1)
R2 stage III experimental armCyclophosphamideRituximab window + Standard chemotherapy
R2 stage III experimental armEtoposideRituximab window + Standard chemotherapy
R2 stage III experimental armDexamethasoneRituximab window + Standard chemotherapy
R2 stage III experimental armDoxorubicin hydrochlorideRituximab window + Standard chemotherapy
R2 stage III experimental armCytarabineRituximab window + Standard chemotherapy
R2 stage III experimental armIfosfamideRituximab window + Standard chemotherapy
R2 stage III standard armCytarabineStandard chemotherapy
R2 stage III experimental armPrednisoloneRituximab window + Standard chemotherapy
R2 stage III experimental armVincristineRituximab window + Standard chemotherapy
R2 stage III standard armDexamethasoneStandard chemotherapy
R2 stage III standard armDoxorubicin hydrochlorideStandard chemotherapy
R2 stage III standard armEtoposideStandard chemotherapy
R2 stage III standard armIfosfamideStandard chemotherapy
R2 stage III standard armPrednisoloneStandard chemotherapy
R2 stage III standard armMethotrexateStandard chemotherapy
R2 stage III standard armVincristineStandard chemotherapy
R3/R4 rituximab plus armCyclophosphamideRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armCytarabineRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armDexamethasoneRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armDoxorubicin hydrochlorideRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armEtoposideRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armIfosfamideRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 rituximab plus armVincristineRituximab window + standard chemotherapy plus six additional doses of rituximab
R3/R4 standard armCytarabineRituximab window + standard chemotherapy
R3/R4 standard armCyclophosphamideRituximab window + standard chemotherapy
R3/R4 standard armDoxorubicin hydrochlorideRituximab window + standard chemotherapy
R3/R4 standard armEtoposideRituximab window + standard chemotherapy
R3/R4 standard armIfosfamideRituximab window + standard chemotherapy
R3/R4 standard armMethotrexateRituximab window + standard chemotherapy
R3/R4 standard armPrednisoloneRituximab window + standard chemotherapy
Primary Outcome Measures
NameTimeMethod
Event-free survival (EFS)through study completion, maximal seven years

EFS is defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

Immune reconstitution rate (only in R3/R4 patients)12 months after start of treatment

Immune reconstitution rate is defined as percentage of patients achieving age adjusted normal B-cell counts (CD19 positive subpopulations) 12 months after start of treatment.

Secondary Outcome Measures
NameTimeMethod
Relapse-free survival (RFS)through study completion, maximal seven years

RFS is defined as time from start of treatment/randomization up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease, or relapse.

Adverse event ratefrom the first day of protocol defined treatment until two years after start of protocol defined treatment

Rate of patients with acute toxicity defined as grade III/IV/V AE

Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood.through study completion, maximal seven years
Overall survival (OS)through study completion, maximal seven years

OS is defined as time from start of treatment/randomization up to death of any cause or to date of last contact for patients alive.

Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment12 months after start of treatment
Interval to normal lymphocyte subpopulations in the peripheral blood.through study completion, maximal seven years
Rate of infections (defined by CTCAE V4) in the time interval from start of treatment until 24 months after start of treatment24 months after start of treatment
Rate of infections (defined by CTCAE V4) in the time interval from start of treatment until immune reconstitution (achievement of age adjusted normal B-cell counts)through study completion, maximal seven years
Rate of patients with sufficient titers after vaccination one year after start of treatment1 year after start of treatment
Response rate (RR)after rituximab window on day 5, after prephase (patients with rituximab window on day 10, patients without rituximab window on day 6) and after second course (on an average 5 to 6 weeks after start of treatment)

Complete response, partial remission, objective effect, stable disease or progressive disease

Rate of patients achieving normal immunoglobulin level 12 months after start of treatment12 months after start of treatment
Time interval to normal immunoglobulin levelthrough study completion, maximal seven years
Immune reconstitution rate (only in R1/R2 patients)12 months after start of treatment

Immune reconstitution rate is defined as percentage of patients achieving age adjusted normal B-cell counts (CD19 positive subpopulations) 12 months after start of treatment.

Trial Locations

Locations (92)

Turku University Hospital, Paediatric and Adolescent Haematology and Oncology

🇫🇮

Turku, Finland

Universitäts-Kinderspital, Pädiatrische Onkologie

🇨🇭

Zürich, Switzerland

Kinderspital Pädiatrische Hämatologie/ Onkologie

🇨🇭

Luzern, Switzerland

Oslo University Hospital, Rikshospitalet

🇳🇴

Oslo, Norway

Ospedale San Giovanni, Reparto die Pediatria

🇨🇭

Bellinzona, Switzerland

Centre hospitalier universitaire vaudois, Unité d'hémato-oncologie pédiatrique

🇨🇭

Lausanne, Switzerland

Universitäts - Kinderspital beider Basel

🇨🇭

Basel, Switzerland

Universitätsklinik für Kinderheilkunde, Pädiatrische Hämatologie/ Onkologie, Inselspital

🇨🇭

Bern, Switzerland

LKH Salzburg, Universitätsklinik für Kinder- und Jugendheilkunde, Kinderonkologie

🇦🇹

Salzburg, Austria

University Hospital of Oulu, Paediatric Haematology and Oncology

🇫🇮

Oulu, Finland

Tampere University Hospital, Paediatric Haematology and Oncology

🇫🇮

Tampere, Finland

Universitätsklinikum Aachen, Klinik für Kinder - und Jugendmedizin, Hämatologie / Onkologie

🇩🇪

Aachen, Germany

Klinikum Augsburg, Schwäbisches Kinderkrebszentrum, I. Klinik für Kinder und Jugendliche, Hämatologie / Onkologie

🇩🇪

Augsburg, Germany

Vestische Kinderklinik, Universität Witten / Herdecke

🇩🇪

Datteln, Germany

Städtisches Klinikum Braunschweig gGmbH, Klinik für Kinder- und Jugendmedizin, Station K5 / Päd. Hämato- und Onkologie

🇩🇪

Braunschweig, Germany

HELIOS Klinikum Erfurt GmbH, Klinik für Kinder- und Jugendmedizin, Päd. Onkologie / Hämatologie

🇩🇪

Erfurt, Germany

Universitätsklinikum Essen, Zentrum für Kinder- und Jugendmedizin, Hämatologie / Onkologie

🇩🇪

Essen, Germany

Universitätskliniken für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie, Geb. 9

🇩🇪

Homburg, Germany

Georg-August-Universität Universitäts-Kinderklinik, Pädiatrie I

🇩🇪

Göttingen, Germany

Universitätsklinikum Schleswig Holstein Campus Kiel, Klinik für Allgemeine Pädiatrie, Päd. Onkologie / Hämatologie

🇩🇪

Kiel, Germany

Universitätsklinikum Leipzig, Klinik für Kinder und Jugendliche, Abt. Päd. Hämatologie / Onkologie

🇩🇪

Leipzig, Germany

Klinikum Kassel Gesundheit Nordhessen Holding AG, Klinik für pädiatrische Hämatologie und Onkologie

🇩🇪

Kassel, Germany

University Hospital Northern Norway

🇳🇴

Tromsø, Norway

Universitätsklinikum Regensburg, Klinik für Kinder- und Jugendmedizin, Abt. Päd. Hämatologie, Onkologie, SZT

🇩🇪

Regensburg, Germany

Asklepios Klinik St. Augustin GmbH, Kinder- und Jugendmedizin, Kinder-Hämatologie und Onkologie

🇩🇪

Sankt Augustin, Germany

Universitätsklinikum Schleswig Holstein Campus Lübeck, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie

🇩🇪

Lübeck, Germany

Universitätsklinikum Magdeburg A. ö. R., Kinderklinik, Päd. Hämatologie / Onkologie

🇩🇪

Magdeburg, Germany

Johannes Wesling Klinikum Minden, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie, Station E 22

🇩🇪

Minden, Germany

Haukeland University Hospital, National Study Center Norway

🇳🇴

Bergen, Norway

St Olavs Hospital

🇳🇴

Trondheim, Norway

Universitätskinderklinik Würzburg, Päd. Onkologie und Hämatologie

🇩🇪

Würzburg, Germany

Sahlgrenska Universitetssjukhuset, Drottning Silvias Barn och Ungdomssjukhus, Barncancercentrum

🇸🇪

Göteborg, Sweden

Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie

🇩🇪

Ulm, Germany

Kantonsspital Aarau, Kinderklinik

🇨🇭

Aarau, Switzerland

Skåne Universitetssjukhus, Barnonkologi

🇸🇪

Lund, Sweden

Karolinska Universitetssjukhuset, Astrid Lindgrens Barnsjukhus, Barnonkologen

🇸🇪

Stockholm, Sweden

Charité Campus Virchow-Klinikum, Zentrum für Kinder- und Jugendmedizin, Abt. Hämatologie / Onkologie

🇩🇪

Berg, Germany

Universitätsklinik Carl Gustav Carus der TU Dresden, Klinik für Kinder- und Jugendmedizin

🇩🇪

Dresden, Germany

Universitätsklinikum Düsseldorf, Zentrum für Kinder- und Jugendmedizin, Klinik für Päd. Hämatologie und Onkologie

🇩🇪

Düsseldorf, Germany

Universitätsklinikum Erlangen, Klinik für Kinder- und Jugendmedizin, Pädiatrische Onkologie / Hämatologie

🇩🇪

Erlangen, Germany

Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin, Klinik IV: Päd. Hämatologie und Onkologie

🇩🇪

Freiburg, Germany

Universitätsklinikum Frankfurt, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie

🇩🇪

Frankfurt am Main, Germany

Universitätsklinikum Gießen und Marburg, Standort Gießen, Zentrum für Kinderhämatologie und -onkologie

🇩🇪

Gießen, Germany

Klinikum Schwabing, Kinderklinik der TU Päd. Hämatologie / Onkologie, Station 24d

🇩🇪

München, Germany

Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie

🇩🇪

Münster, Germany

Klinikum Mannheim gGmbH, Universitäts-Kinderklinik, Päd. Onkologie /Hämatologie

🇩🇪

Mannheim, Germany

Universitätsklinikum Rostock, Kinder- und Jugendklinik, Päd. Hämatologie und Onkologie

🇩🇪

Rostock, Germany

HELIOS Klinikum Berlin-Buch, Kinderklinik, Pädiatrische Hämatologie und Onkologie

🇩🇪

Berlin, Germany

Univ.Klinik für Kinder- und Jugendheilkunde Innsbruck, Universitätsklinik für Pädiatrie I

🇦🇹

Innsbruck, Austria

Klinikum Klagenfurt am Wörthersee, Abteilung für Kinder- und Jugendheilkunde

🇦🇹

Klagenfurt, Austria

Kepler Universitätsklinikum, Med Campus IV / Onkologie

🇦🇹

Linz, Austria

St. Anna Kinderspital

🇦🇹

Wien, Austria

LKH Leoben, Abteilung für Kinder- und Jugendheilkunde

🇦🇹

Leoben, Austria

Børneonkologisk afsnit 303B, Børneafdelingen, Aalborg Universitetshospital Nord

🇩🇰

Aalborg, Denmark

Department of Pediatric Oncology, University Hospital Brno

🇨🇿

Brno, Czechia

Department of Pediatric Hematology and Oncology, University Hospital Motol

🇨🇿

Prague, Czechia

Børn og Unge afsnit 4, Børneafdelingen, Aarhus Universitetshospital Skejby

🇩🇰

Aarhus, Denmark

Børneonkologisk afsnit 5054, BørneUngeKlinikken, Juliane Marie Centret, Rigshospitalet

🇩🇰

Kobenhavn, Denmark

Børneonkologisk afsnit H2, H. C. Andersen Børnehospital, Odense Universitetshospital

🇩🇰

Odense, Denmark

Helsinki University Hospital, Children´s Hospital, Dept of Pediatric Hematology and Oncology

🇫🇮

Helsinki, Finland

Kuopio University Hospital, Paediatric Haematology and Oncology

🇫🇮

Kuopio, Finland

Evangelisches Krankenhaus Bielefeld GmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie und Onkologie

🇩🇪

Bielefeld, Germany

Univ.Klinik für Kinder- und Jugendheilkunde Graz, Klin. Abteilung für pädiatrische Hämato-Onkologie

🇦🇹

Graz, Austria

Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Päd. Hämatologie und Onkologie

🇩🇪

Chemnitz, Germany

Carl-Thieme-Klinikum Cottbus gGmbH, Klinik für Kinder- und Jugendmedizin

🇩🇪

Cottbus, Germany

Zentrum für Kinderheilkunde der Universität Bonn, Abt. Päd. Hämatologie / Onkologie

🇩🇪

Bonn, Germany

Klinikum Dortmund gGmbH, Klinik für Kinder- und Jugendmedizin, Station K1, Abt. Päd. Onkologie / Hämatologie

🇩🇪

Dortmund, Germany

Klinikum Bremen-Mitte gGmbH, Prof.-Hess-Kinderklinik,Pädiatrische Onkologie und Hämatologie

🇩🇪

Bremen, Germany

Universitäts-Kinderklinik Heidelberg, Abt. Hämatologie / Onkologie

🇩🇪

Heidelberg, Germany

Universitätsklinikum Halle (Saale), Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie

🇩🇪

Halle (Saale), Germany

Universitätsklinikum Greifswald KdöR, Klinik und Poliklinik für Kinder- und Jugendmedizin, Abt. Pädiatrische Onkologie und Hämatologie

🇩🇪

Greifswald, Germany

Medizinische Hochschule Hannover, Kinderheilkunde, Päd. Hämatologie / Onkologie

🇩🇪

Hannover, Germany

Gemeinschaftskrankenhaus Herdecke, Kinder- und Jugendmedizin, Päd. Hämatologie / Onkologie

🇩🇪

Herdecke, Germany

Universitätsklinikum Jena, Klinik für Kinder- und Jugendmedizin

🇩🇪

Jena, Germany

Universitätsklinikum Hamburg Eppendorf, Zentrum für Kinder- und Jugendmedizin, Abt. Pädiatrische Hämatologie und Onkologie

🇩🇪

Hamburg, Germany

Städtisches Klinikum Karlsruhe gGmbH, Kinderklinik, Station S 24

🇩🇪

Karlsruhe, Germany

Gemeinschaftsklinikum Mittelrhein Kemperhof, Klinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie

🇩🇪

Koblenz, Germany

HELIOS Klinikum Krefeld, Zentrum für Kinder- und Jugendmedizin, Päd. Hämatologie/Onkologie

🇩🇪

Krefeld, Germany

Klinikum der Universität zu Köln, Klinik für Kinder- und Jugendmedizin, Abt. Kinderonkologie und -hämatologie

🇩🇪

Köln, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Zentrum für Kinder- und Jugendmedizin, Pädiatrische Hämatologie / Onkologie

🇩🇪

Mainz, Germany

Klinikum Oldenburg AöR, Zentrum für Kinder- und Jugendmedizin, Abt. Hämatologie / Onkologie

🇩🇪

Oldenburg, Germany

Diakonie Neuendettelsau, Kliniken Hallerwiese / Cnopf'sche Kinderklinik, Pädiatrische Hämatologie /Onkologie

🇩🇪

Nürnberg, Germany

Klinikum der LMU, Dr. von Haunersches Kinderspital, Pädiatrische Hämatologie / Onkologie

🇩🇪

München, Germany

HELIOS Kliniken Schwerin GmbH, Klinik für Kinder- und Jugendmedizin, Station A1

🇩🇪

Schwerin, Germany

Universitätsklinik Tübingen Klinik für Kinderheilkunde und Jugendmedizin, Päd. Hämatologie / Onkologie

🇩🇪

Tübingen, Germany

Klinikum Stuttgart, Olgahospital Zentrum für Kinder- und Jugendmedizin Pädiatrie 5 (Onkologie, Hämatologie, Immunologie)

🇩🇪

Stuttgart, Germany

Klinikum Mutterhaus der Borromäerinnen gGmbH, Pädiatrische Abteilung

🇩🇪

Trier, Germany

Universitetssjukhus Umeå, Barnonkologiska avdelningen, Barn 3 Norrlands

🇸🇪

Umeå, Sweden

Akademiska sjukhuset, Barnavdelningen för blod- och tumörsjukdomar

🇸🇪

Uppsala, Sweden

Universitetssjukhuset i Linköping, Barn och Ungdomsmedicinska kliniken, Barnonkologiska enheten

🇸🇪

Linköping, Sweden

Ostschweizer Kinderspital, Hämatologie/ Onkologie

🇨🇭

Saint Gallen, Switzerland

Hôpital des Enfants, Unité d'Oncologie Hématologie

🇨🇭

Geneva, Switzerland

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