International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia
- Conditions
- Leukemia
- Interventions
- Drug: PEG-L-asparaginaseRadiation: Radiation Therapy
- Registration Number
- NCT01117441
- Lead Sponsor
- University Hospital Schleswig-Holstein
- Brief Summary
Rationale/Purpose: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating young patients with acute lymphoblastic leukemia (ALL).
This trial is studying several different combination chemotherapy regimens to compare how well they work in treating young patients with ALL.
Study objectives
Primary study questions:
* Non high-risk (non-HR) precursor-B ALL (pB-ALL) patients with TEL/AML1-negative ALL or unknown TEL/AML1 status and flow cytometry minimal residual disease (MRD) in bone marrow on day 15 \<0.1% or with TEL/AML1-positive ALL (randomized study question R1): Can the daunorubicin dose in Protocol IA be safely reduced by 50 % with a non-inferior EFS and a reduction of toxicity (treatment-related mortality and AE/SAE in Protocol I)?
* Patients with pB-ALL and risk group medium risk (MR) (randomized study question R2): Can the clinical outcome be improved by protracted asparagine depletion achieved through application of intensified PEG-L-asparaginase during reintensification and early maintenance?
* High-risk (HR) patients (as identified by day 33 - randomized study question RHR): Can the clinical outcome be improved by protracted exposure to PEG-L-asparaginase during Protocol IB?
Secondary study questions:
* Standard risk (SR) patients identified by at least one sensitive marker: Is the clinical outcome comparable to that obtained in SR patients (identified with two sensitive markers) in AIEOP-BFM ALL 2000, or can the outcome even be improved with the use of PEG-L-asparaginase instead of native E. coli L-ASP?
* T-ALL non-HR patients: Can the high level of outcome which was obtained for these patients in study AIEOP-BFM ALL 2000 be preserved or even improved with the use of PEG-L-ASP instead of native E. coli L-ASP?
* HR patients with persisting high MRD levels despite the use of the HR blocks in the intensified consolidation phase "MRD Non-Responders": Is it possible to improve the outcome and to achieve a further reduction of leukemic cell burden by administration of an innovative treatment schedule (DNX-FLA)?
* Patients participating in the randomized asparaginase studies (pB-ALL/MR, HR): Are asparaginase activity and asparaginase antibodies associated with development of allergic reactions, and do they have an effect on the outcome of the patients?
* What is the relative value of different methods of MRD monitoring in the definition of alternative stratification systems within a BFM-oriented protocol?
- Detailed Description
Risk Stratification
* T/non-HR: T-ALL in absence of any HR criteria (see below)
* pB/non-HR: pB-ALL in absence of any HR criteria (see below).
* SR (polymerase chain reaction(PCR)-MRD-SR (MRD-negative on day 33 and 78) or, if no PCR-MRD result available, FCM d15 \< 0.1%)
* MR (no SR)
* HR: Prednisone poor-response (≥1000 blast cells/µl in peripheral blood on day 8), blast cells ≥10% in bone marrow on day 15 as measured by FCM, non-remission on day 33, positivity for MLL/AF4 or t(4;11), hypodiploidy (\< 45 chromosomes), PCR-MRD-HR (MRD ≥10E-3 on day 78) or PCR-MRD-MR SER (only in pB-ALL, MRD ≥ 10-3 on day 33 and MRD positive at a level of \< 10E-3 on day 78)
Chemotherapy
According to the risk group, patients receive the following chemotherapy elements:
T/non-HR: Protocol I, Protocol M, Protocol II and Maintenance pB/non-HR: Protocol I, Protocol M, Protocol II and Maintenance HR: Protocol I, HR-1', HR-2', HR-3', 3x Protocol III, Maintenance Patients of the HR group with PCR-MRD ≥10E-3 after element HR-3' are eligible for treatment with element DNX-FLA.
Protocol I Cytoreductive prephase: Prednisone (PDN) on days 1-7 and one dose of methotrexate (MTX) intrathecal (IT) on day 1 Protocol IA: Prednisone (PDN) on days 8 to 28 (21 days); vincristine (VCR) on days 8, 15, 22, 29 (4 doses); daunorubicin (DNR) on days 8, 15, 22 and 29 (4 doses); pegylated L-asparaginase (PEG-L-ASP) on days 12 and 26; MTX IT on days 12 and 33 and in case of blast cells in cerebrospinal fluid at diagnosis additional IT MTX is given on days 19 and 26.
Protocol IA': Only two doses of DNR on days 8 and 15 given to patients eligible for randomization R1 and randomized into the experimental arm Protocol IA-CPM: additional cyclophosphamide (CPM) on day 10 only in T-ALL patients with prednisone poor-response Protocol IA-Dexa (IAD): Dexamethasone (DXM) instead of PDN is given to all patients with T-ALL without any high-risk criteria as identified by day 8.
Protocol IB: CPM on days 36 and 64; cytarabine (ARA-C) on days 38-41, 45-48, 52-55 and 59-62; 6-mercaptopurine (6-MP) on days 36 to 63 (28 days); MTX IT on day 45 and 59 Protocol IB-ASP+: additional PEG-L-ASP on days 40, 47, 54, and 61 (4 doses) are given to the patients eligible for randomization RHR and randomized into the experimental arm.
Protocol M 6-MP on days 1- 56, high-dose MTX (HD-MTX) on days 8, 22, 36, 50 and MTX IT on days 8, 22, 36 and 50 Protocol II Protocol IIA: DXM on days 1 to 21 (21 days); VCR on days 8, 15, 22, 29 (4 doses); doxorubicine (DOX) on days 8, 15, 22 and 29 (4 doses); PEG-L-ASP on day 8 (1 dose); MTX IT on days 1 and 18 only in patients with initial CNS involvement.
Protocol IIA-ASP+: additional PEG-L-ASP on day 22 for patients eligible for randomization R2 and randomized into the experimental arm.
Protocol IIB: CPM on day 36; ARA-C on days 38-41 and 45-48; thioguanine (TG) on days 36 to 49 (14 days) and MTX IT on days 38 and 45.
Protocol IIB-ASP+: additional PEG-L-ASP on days 36 and 50 for eligible for randomization R2 and randomized into the experimental arm.
Protocol III DXM on days 1-15; VCR on days 1 and 8; DOX on days 1 and 8; PEG-L-ASP on day 1; CPM on day 15; ARA-C on days 17-20 and 24-27; TG on days 15 - 28 and MTX IT on days 17 and 24, also on day 1 in patients with initial CNS involvement HR-1' DXM on days 1-5; VCR on days 1 and 6; HD-MTX on day 1; CPM every 12 hours on days 2-4 (5 doses); HD-ARA-C every 12 hours on day 5 (2 doses); PEG-L-ASP on day 6, MTX IT on day 1 HR-2' DXM on days 1 to 5; VDS on days 1 and 6; HD-MTX on day 1; IFO every 12 hours on days 2-4 (5 doses); DNR on day 5; PEG-L-ASP on day 6; MTX IT on day 1 and 1 in patients with initial CNS involvement also day 5 HR-3' DXM on days 1-5; ARA-C 4 x on days 1-2 in 12 h intervals; etoposide (VP-16) every 12 hours on days 3-5 (5 doses); PEG-L-ASP on day 6; MTX IT on day 1 DNX-FLA Flucytosine (FLU) on days 1-5 (5 doses); HD-ARA-C on days 1 to 5 (5 doses); liposomal daunorubicin (DNX) on days 1, 3 and 5 (3 doses); MTX IT on day 1
Interim/Maintenance (until week 104):
6-MP p.o. daily; MTX p.o. once a week, doses adjusted to white blood cell count; PEG-L-ASP: every second week (6 doses), only for patients eligible for randomization R2 and randomized into the experimental arm; MTX IT every 6 weeks up to a total of 6 doses for the following subgroups (all CNS-negative):
* T-ALL (HR or non-HR) with \< 2 years of age at start of maintenance,
* T-ALL, non-HR and initial WBC \< 100 000/μl
* pB-ALL with PPR and/or FCM-MRD day 15 ≥ 10 % and/or PCR-MRDMR SER as only HR criteria
Radiotherapy Patients without CNS involvement and
* T-ALL/non-HR, WBC ≥ 100 000/μl, and age ≥ 2 years at start of pCRT or
* with risk group HR and age ≥ 2 years at start of pCRT except pB-ALL with PPR and/or FCM-MRD day 15 ≥ 10 % and/or PCR-MRD-MR SER as only HR criteria receive preventive cranial radiotherapy with 12 Gy
Patients with CNS involvement receive therapeutic cranial radiotherapy with 18 Gy (age 1 to \<2 years 12 Gy).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6136
- newly diagnosed acute lymphoblastic leukemia
- age ≥ 1 year (> 365 days) and < 18 years old (up to 17 years old and 365 days)
- no Ph+ (BCR/ABL or t(9;22)-positive) ALL
- no evidence of pregnancy or lactation period
- no participation in another clinical study
- patient enrolled in a participating center
- written informed consent
- pre-treatment with cytostatic drugs
- pre-treatment with cytostatic drugs
- steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis
- treatment started according to another protocol
- underlying diseases that prohibit treatment according to the protocol
- ALL diagnosed as second malignancy steroid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description R1 control arm PEG-L-asparaginase see detailed protocol description R1 control arm cytarabine see detailed protocol description R1 control arm daunorubicin hydrochloride see detailed protocol description R1 control arm dexamethasone see detailed protocol description R1 control arm vincristine sulfate see detailed protocol description R1 control arm Radiation Therapy see detailed protocol description R1 experimental arm PEG-L-asparaginase see detailed protocol description R1 experimental arm daunorubicin hydrochloride see detailed protocol description R1 experimental arm vincristine sulfate see detailed protocol description R1 experimental arm Radiation Therapy see detailed protocol description R-HR control arm etoposide see detailed protocol description R2 control arm PEG-L-asparaginase see detailed protocol description R2 control arm cytarabine see detailed protocol description R2 control arm daunorubicin hydrochloride see detailed protocol description R2 control arm vincristine sulfate see detailed protocol description R2 control arm Radiation Therapy see detailed protocol description R2 experimental arm PEG-L-asparaginase see detailed protocol description R2 experimental arm daunorubicin hydrochloride see detailed protocol description R2 experimental arm vincristine sulfate see detailed protocol description R2 experimental arm mercaptopurine see detailed protocol description R2 experimental arm Radiation Therapy see detailed protocol description R-HR control arm PEG-L-asparaginase see detailed protocol description R-HR control arm cyclophosphamide see detailed protocol description R-HR control arm cytarabine see detailed protocol description R-HR control arm daunorubicin hydrochloride see detailed protocol description R-HR control arm dexamethasone see detailed protocol description R-HR control arm doxorubicin hydrochloride see detailed protocol description R-HR control arm ifosfamide see detailed protocol description R-HR control arm mercaptopurine see detailed protocol description R-HR control arm methotrexate see detailed protocol description R-HR control arm prednisone see detailed protocol description R-HR control arm vincristine sulfate see detailed protocol description R-HR control arm daunoxome see detailed protocol description R-HR control arm fludarabine see detailed protocol description R-HR control arm Radiation Therapy see detailed protocol description R-HR experimental arm PEG-L-asparaginase see detailed protocol description R-HR experimental arm cyclophosphamide see detailed protocol description R-HR experimental arm cytarabine see detailed protocol description R-HR experimental arm daunorubicin hydrochloride see detailed protocol description R-HR experimental arm doxorubicin hydrochloride see detailed protocol description R-HR experimental arm etoposide see detailed protocol description R-HR experimental arm ifosfamide see detailed protocol description R-HR experimental arm mercaptopurine see detailed protocol description R-HR experimental arm methotrexate see detailed protocol description R-HR experimental arm prednisone see detailed protocol description R-HR experimental arm thioguanine see detailed protocol description R-HR experimental arm vincristine sulfate see detailed protocol description R-HR experimental arm vindesine see detailed protocol description R-HR experimental arm daunoxome see detailed protocol description R-HR experimental arm Radiation Therapy see detailed protocol description R1 control arm cyclophosphamide see detailed protocol description R1 control arm doxorubicin hydrochloride see detailed protocol description R2 control arm cyclophosphamide see detailed protocol description R2 experimental arm prednisone see detailed protocol description R2 control arm thioguanine see detailed protocol description R2 experimental arm cyclophosphamide see detailed protocol description R1 control arm mercaptopurine see detailed protocol description R1 control arm prednisone see detailed protocol description R1 control arm methotrexate see detailed protocol description R1 control arm thioguanine see detailed protocol description R1 experimental arm cytarabine see detailed protocol description R1 experimental arm cyclophosphamide see detailed protocol description R1 experimental arm dexamethasone see detailed protocol description R1 experimental arm mercaptopurine see detailed protocol description R1 experimental arm doxorubicin hydrochloride see detailed protocol description R1 experimental arm methotrexate see detailed protocol description R1 experimental arm prednisone see detailed protocol description R1 experimental arm thioguanine see detailed protocol description R2 control arm doxorubicin hydrochloride see detailed protocol description R2 control arm mercaptopurine see detailed protocol description R2 control arm dexamethasone see detailed protocol description R2 control arm prednisone see detailed protocol description R2 control arm methotrexate see detailed protocol description R2 experimental arm dexamethasone see detailed protocol description R2 experimental arm cytarabine see detailed protocol description R2 experimental arm doxorubicin hydrochloride see detailed protocol description R2 experimental arm methotrexate see detailed protocol description R2 experimental arm thioguanine see detailed protocol description R-HR control arm vindesine see detailed protocol description R-HR control arm thioguanine see detailed protocol description R-HR experimental arm dexamethasone see detailed protocol description R-HR experimental arm fludarabine see detailed protocol description
- Primary Outcome Measures
Name Time Method Event-free survival 10 years from the start of recruitment * Randomization R1: Event-free survival from time of randomization
* Historical comparison non-HR T-ALL: Event-free survival from diagnosis
* Historical comparison "MRD Non-Responders": Event-free survival from start of DNX-FLA (morphological non-response after HR-3' is no event for this study question)Disease-free survival 10 years from the start of recruitment * Randomization R2: Disease-free survival from time of randomization
* Historical comparison SR: Disease-free survival from start of Protocol Mminimal residual disease (MRD) week 12 of treatment Randomization RHR: rate of MRD highly positive patients (MRD ≥ 10-3) at TP2 (week 12)
- Secondary Outcome Measures
Name Time Method minimal residual disease after 24 weeks of treatment "MRD Non-Responders": MRD levels after DNX-FLA
survival 10 years from the start of recruitment All randomized and historical comparisons: Survival
treatment-related mortality up to 25 months from the diagnosis All randomized and historical comparisons: treatment-related mortality in induction or CCR (overall and by chemotherapy/SCT)
adverse events up to 25 months from the diagnosis All randomized and historical comparisons: incidence and frequency of adverse events of interest and serious adverse events
event-free survival 10 years from the start of recruitment Randomization R-HR: Event-free survival from time of randomization
Trial Locations
- Locations (137)
A.oe. Landeskrankenhaus Klagenfurt, Abt. für Kinder- und Jugendheilkunde
🇦🇹Klagenfurt, Austria
University Hospital Brno, Department of Pediatric Oncology
🇨🇿Brno, Czechia
Klinikum Berlin-Buch II. Kinderklinik, Bereich Onkologie/Allg. Pädiatrie
🇩🇪Berlin, Germany
University Hospital Motol, Department of Pediatric Hematology and Oncology
🇨🇿Praha 5, Czechia
Kinderklinik der Charité, Campus Virchow Klinikum (CVK), Abt.: Kinderhämatologie
🇩🇪Berlin, Germany
HELIOS Kliniken Schwerin, Klinik f. Kinder-u. Jugendmedizin
🇩🇪Schwerin, Germany
Soroka Medical Center
🇮🇱Beer-Sheva, Israel
Rambam Medical Center
🇮🇱Haifa, Israel
Cnopf'sche Kinderklinik, Onkologie
🇩🇪Nürnberg, Germany
University Hospital Plzeň, Department of Pediatrics
🇨🇿Plzeň, Czechia
Gemeinschaftskrankenhaus Herdecke, Kinderabteilung
🇩🇪Herdecke, Germany
Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abt. Hämatologie/Onkologie
🇩🇪Gießen, Germany
Regional Hospital České Budějovice, Department of Pediatrics
🇨🇿České Budějovice, Czechia
Klinikum Bayreuth, Kinderklinik
🇩🇪Bayreuth, Germany
Oncologia ed Ematologia "Lalla Seràgnoli" Clinica Pediatrica Policlinico Sant'Orsola Malpighi
🇮🇹Bologna, Italy
Klinikum Lippe-Detmold, Kinder- und Jugendmedizin
🇩🇪Detmold, Germany
Uni.Klinik Carl Gustav Carus, Klinik f. Kinderheilkunde
🇩🇪Dresden, Germany
Klinikum Kassel, Kinderklinik
🇩🇪Kassel, Germany
Dana children hospital
🇮🇱Tel-Aviv, Israel
Bnai-Zion Medical Center
🇮🇱Haifa, Israel
Johannes Wesling Klinikum Minden
🇩🇪Minden, Germany
Universitätsklinikum Essen, Kinderklinik, Hämatologie/Onkologie
🇩🇪Essen, Germany
HaEmek Medical Center
🇮🇱Afula, Israel
Pediatria Ospedale Regionale
🇮🇹Bolzano, Italy
Dipartimento di Medicina Clinica e Sperimentale Sezione di Pediatria Università di Ferrara
🇮🇹Ferrara, Italy
Dipartimento di Ematologia e Oncologia Pediatrica Instituto " G. Gaslini"
🇮🇹Genova, Italy
Stadtkrankenhaus, Kinderklinik
🇩🇪Wolfsburg, Germany
Hadassah University Medical Center
🇮🇱Jerusalem, Israel
Krankenanstalt Trier, Mutterhaus der Borromaeerinnen, Pädiatrische Abteilung
🇩🇪Trier, Germany
Universitäts-Kinderklinik, Abt. Kinderheilkunde II, Hämatologie/Onkologie
🇩🇪Tübingen, Germany
Unità Operativa Pediatria Azienda Ospedaliera Annuziata
🇮🇹Cosenza, Italy
Ospedale "Vito Fazzi" U.O. di Pediatria
🇮🇹Lecce, Italy
Clinica Pediatrica dell'Università Milano - Bicocca A.O. San Gerardo - Fondazione MBBM
🇮🇹Monza, Italy
S.C. di Oncoematologia Pediatrica con Trapianto di CSE, Ospedale "S.M. della Misericordia" A.O. Perugia
🇮🇹Perugia, Italy
U.O Pediatria Ospedale Infermi Azienda USL Rimini
🇮🇹Rimini, Italy
Kinderspital Zürich, Universitäts-Kinderklinik
🇨🇭Zürich, Switzerland
U.O. di Ematologia, oncologia e trapianto Azienda Policlinico di Modena
🇮🇹Modena, Italy
Baseler Kinderspital, Hämatologische Poliklinik
🇨🇭Basel, Switzerland
Kinderklinik, Hämatologie/Onkologie
🇨🇭Aarau, Switzerland
Centro Regionale Oncoematologia Pediatrica Ospedale dei Bambini "G. Salesi" Clinica Pediatrica
🇮🇹Ancona, Italy
Dipartimento Biomedicina Età Evolutiva U.O Pediatrica I Policlinico
🇮🇹Bari, Italy
Clinica Pediatrica Oncoematologia pediatrica e TMO Ospedale dei Bambini
🇮🇹Brescia, Italy
Istituto di Clinica Pediatrica Ospedale Regionale per le Microcitemie
🇮🇹Cagliari, Italy
Divisione Ematologia - Oncologia Pediatrica Clinica Pediatrica
🇮🇹Catania, Italy
Unità Operativa di Ematologia ed Oncologia Pediatrica Az. Osp. "Pugliese-Ciaccio"
🇮🇹Catanzaro, Italy
Dipartimento A.I. Oncoematologia Pediatrica e Cure Domiciliari U.O. Oncoematologia Pediatrica Azienda Ospedaliero-Universitaria Meyer
🇮🇹Firenze, Italy
Unità di Ricerca Clinica Pediatrica HSR TIGET - Istituto Scientifico San Raffaele
🇮🇹Milano, Italy
Divisione di Oncologia Pediatrica Ist. Nazionale Studio e Cura Tumori
🇮🇹Milano, Italy
Dipartimento di Oncologia A.O. Santobono - Pausilipon
🇮🇹Napoli, Italy
A.O. "A. Cardarelli", U.O.S. Talassemia pediatrica ed emoglobinopatie pediatriche
🇮🇹Napoli, Italy
U.O.C. Pediatria - TIN, Ospedale "Umberto Primo" ASL SA - 1
🇮🇹Nocera Inferiore, Italy
Oncoematologia Pediatrica Ospedale dei Bambini G. di Cristina
🇮🇹Palermo, Italy
Oncoematologia Pediatrica IRCCS, Policlinico San Matteo
🇮🇹Pavia, Italy
Ematologia, Ospedale di Muraglia
🇮🇹Pesaro, Italy
U.O. Pediatrica Azienda Ospedaliera San Salvatore
🇮🇹Pesaro, Italy
Dipartimento di Ematologia Ospedale Civile
🇮🇹Pescara, Italy
Centro di Oncoematologia Pediatrica e Trapianto Midollo Osseo Azienda Ospedaliero Universitaria Pisana Ospedale S. Chiara
🇮🇹Pisa, Italy
Centro Integrato di Emato-oncologia e dell'adolescenza A.O. S. Maria degli Angeli - Pordenone e IRCCS Centro di Riferimento Oncologico - Aviano
🇮🇹Pordenone, Italy
Divisione Ematologia Ospedali Riuniti
🇮🇹Reggio Calabria, Italy
Oncoematologia pediatrica Università "La Sapienza" Roma
🇮🇹Roma, Italy
U.O. Oncoematologia Pediatrica Ospedale "Casa Sollievo della Sofferenza"
🇮🇹San Giovanni Rotondo, Italy
Clinica Pediatrica Università
🇮🇹Sassari, Italy
Ospedale Sant'Eugenio clinica pediatrica Univ. Tor Vergata
🇮🇹Roma, Italy
Sezione Ematologia Dipart. di biotecnologie Cellulari ed Ematologia Università "La Sapienza"
🇮🇹Roma, Italy
Divisione di Ematologia Pediatrica Ospedale "Bambin Gesù"Istituto di Ricerca Scientifica
🇮🇹Roma, Italy
Dipartimento di Pediatria Ostetricia e Medicina della Riproduzione Università degli Studi di Siena
🇮🇹Siena, Italy
Unità Operativa di Pediatria - U.T.I.N. Az.Osp. "Card. G. Panico"
🇮🇹Tricase, Italy
U.O. Emato-Oncologia Pediatrica Università degli studi di Trieste Ospedale Infantile Burlo Garofolo
🇮🇹Trieste, Italy
SOS Oncologia Pediatrica Policlinico Universitario
🇮🇹Udine, Italy
Clinica Pediatrica Università degli Studi dell'Insubria di Varese Ospedale "Filippo del Ponte"
🇮🇹Varese, Italy
U.O.C Oncoematologia Pediatrica Policlinico "G.B: Rossi"
🇮🇹Verona, Italy
Ospedale San Bortolo, U.O. di Pediatria e patologia Neonatale
🇮🇹Vicenza, Italy
St. Anna Kinderspital, Zentrum für Kinder- und Jugendheilkunde
🇦🇹Wien, Austria
Repartio di Pediatria
🇨🇭Bellinzona, Switzerland
Department f. Kinder- u. Jugendheilkunde, Universitätsklinik f. Pädiatrie II
🇦🇹Innsbruck, Austria
St. Johanns Spital / Landeskrankenhaus, Salzburg, Kinderspital Abt. Kinder u. Jugendheilkunde
🇦🇹Salzburg, Austria
Landes-Kinderklinik Linz, Haematologie/Onkologie
🇦🇹Linz, Austria
Städtisches Krankenhaus, Kinderklinik
🇩🇪Braunschweig, Germany
Vestische Kinder- u. Jugendklinik, Universitätsklinik Witten/Herdecke
🇩🇪Datteln, Germany
Klinikum Dortmund, Klinik f. Kinder- und Jugendmedizin
🇩🇪Dortmund, Germany
Universitäts-Kinderklinik, Klinik für Kinderheilkunde III, Pädiatrische Hämatologie/Onkologie
🇩🇪Frankfurt, Germany
Universitäts-Kinderklinik, Haematologie/ Onkologie
🇩🇪Freiburg, Germany
Universitäts-Kinderklinik Päd. I, Hämatologie/Onkologie
🇩🇪Göttingen, Germany
Universitätsklinik für, Kinder- und Jugendmedizin, Päd. Hämatologie/ Onkologie
🇩🇪Homburg / Saar, Germany
Klinikum Heilbronn GmbH, Klinik für Kinderheilkunde und Jugendmedizin/Perinatalzentrum
🇩🇪Heilbronn, Germany
Städtisches Klinikum Karlsruhe, Kinderklinik
🇩🇪Karlsruhe, Germany
Klinikum, der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin
🇩🇪Jena, Germany
Klinik für Allgemeine Paediatrie, Univ.-Klinikum Schleswig-Holstein, Campus Kiel
🇩🇪Kiel, Germany
Kliniken der Stadt Köln GmbH, Kinderkrankenhaus Riehl
🇩🇪Köln, Germany
Städt. Krankenhaus München GmbH, Krankenhaus München-Schwabingen, Kinderklinik d. TU
🇩🇪München, Germany
Universitäts-Kinderklinik
🇩🇪Würzburg, Germany
Olga-Hospital, Kinderklinik, Pädiatrisches Zentrum, Abt. Hämatologie/Onkologie
🇩🇪Stuttgart, Germany
Klinikum Mannheim gGmbH, Kinderklinik, Abt. Hämatologie/Onkologie
🇩🇪Mannheim, Germany
Sheba Medical Center
🇮🇱Tel-Hashomer, Israel
The Children's Hospital at Westmead, Department of Oncology
🇦🇺Westmead, Australia
Divisione Oncologia Pediatrica Ospedale "Bambin Gesù"
🇮🇹Roma, Italy
Divisione Oncologia Pediatrica Università Cattolica di Roma
🇮🇹Roma, Italy
Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde
🇩🇪Erfurt, Germany
Städtisches Krankenhaus Kemperhof, Kinderklinik
🇩🇪Koblenz, Germany
University Hospital Olomouc, Department of Pediatrics
🇨🇿Olomouc, Czechia
The Sydney Children's Hospital, Centre for Children's Cancer and Blood Disorders
🇦🇺Randwick, Australia
Univ.-Kinderklinik Graz, Abt. Pädiatrische Hämato-Onkologie
🇦🇹Graz, Austria
Krankenhaus Dornbirn, Abt. für Kinder- und Jugendheilkunde
🇦🇹Dornbirn, Austria
A.oe. Landeskrankenhaus Leoben, Abt. für Kinder und Jugendliche
🇦🇹Leoben, Austria
University Hospital Hradec Králové, Department of Pediatrics
🇨🇿Hradec Králové, Czechia
Teaching Hospital Ostrava-Poruba, Department of Pediatrics
🇨🇿Ostrava-Poruba, Czechia
Kinderklinik der med. Fakultät der RWTH, Bereich Hämatologie/Onkologie
🇩🇪Aachen, Germany
Masaryk´s Hospital Ústí nad Labem, Department of Pediatrics
🇨🇿Ústí nad Labem, Czechia
I. Klinik für Kinder u. Jugendliche, Klinikum Augsburg, Hämatologie/ Onkologie
🇩🇪Augsburg, Germany
Carl-Thiem-Klinikum, Kinderklinik, Abt. Hämatologie/Onkologie
🇩🇪Cottbus, Germany
Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Hämatologie / Onkologie
🇩🇪Chemnitz, Germany
Universitätskinderklinik
🇩🇪Düsseldorf, Germany
Universitätsklinikum Erlangen, Kinder- und Jugendmedizin, Abt. für Onkologie/ Hämatologie/Immunologie
🇩🇪Erlangen, Germany
Klinik und Poliklinik für Kinder und Jugendmedizin, Allgemeine Pädiatrie mit Poliklinik/Pädiatrische Onkologie und Hämatologie
🇩🇪Greifswald, Germany
Medizinische Hochschule Hannover, Zentrum Kinderheilkunde u. Jugendmedizin
🇩🇪Hannover, Germany
Universitäts-Kinderklinik, Päd. Onkologie, Hämatologie, und Immunologie
🇩🇪Heidelberg, Germany
Uniklinikum d. Martin Luther Universität, Halle Wittenberg, Univ.-und Poliklinik für Kinder- und Jugendmedizin
🇩🇪Halle, Germany
Department für Frauen- und Kindermedizin, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie
🇩🇪Leipzig, Germany
Universitätsklinikum Magdeburg, Klinik für Päd. Hämatologie/Onkologie
🇩🇪Magdeburg, Germany
Med. Einrichtungen der Universität zu Köln, Klinik für Allg. Kinderheilkunde, Onkologisch-hämatologische Station
🇩🇪Köln, Germany
Universität zu Lübeck, Klinik für Kinder- u. Jugendmedizin, Abt. Hämatologie/ Onkologie/Immunologie
🇩🇪Lübeck, Germany
Klinikum Oldenburg gGmbH, Zentrum für Kinder- u. Jugendmedizin, (Elisabeth Kinderkrankenhaus)
🇩🇪Oldenburg, Germany
Universitäts-Kinderklinik, Päd. Hämatologie und Onkologie
🇩🇪Münster, Germany
Schneider Children Medical Center of Israel
🇮🇱Petach Tikva, Israel
Asklepios-Klinik, Sankt Augustin GmbH
🇩🇪Sankt Augustin, Germany
U.O.C. Pediatria e Patologia Neonatale Ospedale San Martino
🇮🇹Belluno, Italy
U.O. Pediatrica - OO.RR Bergamo
🇮🇹Bergamo, Italy
Istituto Ortopedico Rizzoli Sez. di chemioterapia dei tumori dell'apparato locomotore
🇮🇹Bologna, Italy
Clinica Pediatrica II De Marchi
🇮🇹Milano, Italy
Divisione Pediatria "Mariani" Ospedale "Niguarda Ca' Granda"
🇮🇹Milano, Italy
Servizio di Oncologia Pediatrica Dipartimento di Pediatria Seconda Università degli Studi di Napoli
🇮🇹Napoli, Italy
S.C.D.U. Azienda Ospedaliera "Maggiore della carità"
🇮🇹Novara, Italy
Dipartimento di Pediatria Università di Padova Cattedra Di Oncoematologia Pediatrica
🇮🇹Padova, Italy
U.O. di Pediatria e Oncoematologia Pediatrica Az. Osp. Di Parma Ospedali Riuniti
🇮🇹Parma, Italy
Ospedale Infantile Regina Margherita
🇮🇹Torino, Italy
Pädiatrische Klinik, Kinderspital Luzern, Kinderonkologie
🇨🇭Luzern, Switzerland
Hämatologie/Onkologie, Ostschweizer Kinderspital, FMH Pädiatrie, Hämatologie
🇨🇭St. Gallen, Switzerland