Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia

Sponsor

St. Anna Kinderkrebsforschung (Other)

Overall Status

Recruiting

CT.gov ID

NCT01949129

Collaborator

ALL SCTped Forum (Other), European Society for Blood and Marrow Transplantation (Other), ALL-BFM Study Group (Other), Assistance Publique - Hôpitaux de Paris (Other), Dutch Childhood Oncology Group (Other), Swiss Pediatric Oncology Group (Other), Australian & New Zealand Children's Haematology/Oncology Group (Other)

1,000

Enrollment

119

Locations

Arms

156

Duration (Months)

8.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The ALL SCTped 2012 FORUM is a multinational, multi-centre, controlled, prospective phase III study for the therapy and therapy optimisation for children and adolescents with ALL in complete morphological remission (CR, less than 5% bone marrow blasts, no blasts in cerebrospinal fluid, no other extramedullary leukemia), who have an indication for HSCT with a myeloablative conditioning regimen.

The stratification of patients in first and following remissions according to the individual transplantation modalities rests upon an indication for allogeneic HSCT and the availability of a suitable donor within the individual transplantation groups.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukaemia	Drug: VP16 Radiation: TBI Drug: Thiotepa Drug: Treosulfan Drug: Fludarabine Drug: Busulfan Drug: ATG Thymoglobulin Drug: Cyclophosphamide Drug: Grafalon	Phase 2/Phase 3

Detailed Description

Acute and late side effects of TBI in combination with other chemotherapeutic are manifold to the growing organism and include severe organ dysfunction/failure due to toxicity. Although transplant associated mortality was reduced after HSCT in the last decade due to better HLA matching, infection prevention and control, the burden of late complications is still a matter of concern. Growth retardation, hormonal dysfunction, sterility and the risk of secondary cancer are the late consequences of TBI in children. However, so far no prospective study has demonstrated similar outcomes in paediatric ALL using chemo-conditioning regimen before HSCT. The reason for that is manifold: only a minority of children with ALL qualifies for allogeneic HSCT as most patients are cured with sole modern chemotherapy approaches. Those with dismal prognosis are treated in HSCT centres offering a care to patients with different diseases. Therefore it is nearly impossible to answer the complex outcome questions in single centres or even in single countries. International cooperation is essential to allow prospective investigation within comparable patient cohorts.

This study aimed to explore the efficacy and efficiency of two different chemo-conditioning regimens (Flu/Thio with Treo or ivBu) in comparison to the standard conditioning regimen (TBI/VP16). All patients with an indication for HSCT, age > 4 years and a matched donor (MD) or matched sibling donor (MSD) underwent a randomisation between these two conditioning regimens. The decision if the irradiation free conditioning is Flu/Thio/Treo or Flu/Thio/ivBu was stratified by country. Patients with age < 4 years received the irradiation free conditioning. Patients with a mismatched donor were stratified according to the donor's stem cell source (cordblood, haploidentical tx or bone marrow/peripheral blood stem cells).

After an interim analysis of the randomized FORUM-trial in December 2018, which showed superior OS for TBI/Etoposide with equal outcomes for Bu or Treo-containing regimen, the randomization was suspended. The reason was less relapse incidence whereas 1-year TRM was comparable in all 3 arms. The randomization was closed in March 2019 based on the results of additional analyses confirming the superiority of TBI/VP16 over chemo-conditioning. Consequently, the TBI conditioning has remained a standard for the patients older than 4 years with a MSD/MD. Use of a conditioning other than TBI/VP16 in this age group is made at the center level based on the assessment of each individual patient.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1000 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Allogeneic Stem Cell Transplantation for Children and Adolescents With Acute Lymphoblastic Leukaemia

Study Start Date :

Apr 1, 2013

Anticipated Primary Completion Date :

Apr 1, 2021

Anticipated Study Completion Date :

Apr 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Flu/Thio/Treo Fludarabine/Thiotepa/Treosulfan is for conditioning before HSCT from MSD or MD. ATG Thymo or Grafalon is used for patients who receive stem cells from unrelated donors. Fludarabine/Thiotepa/Treosulfan with either ATG Thymo or Grafalon is also used for HSCT from MMD with in vitro T-Cell Depletion (TCD) or with CD34+ selection. Fludarabine/Thiotepa/Treosulfan with Post Tx-Cyclophosphamide is used for MMD-graft without in vitro TCD.	Drug: Thiotepa 2x5 mg/kg BW, 1 day Other Names: Thio Drug: Treosulfan 14g/m² BS, 3 days Other Names: Treo Drug: Fludarabine 30 mg/m² BS, 5 days Other Names: Flu Drug: ATG Thymoglobulin MD: ATG Thymo: 2,5mg/kg BW/d 3 days. Other Names: ATG Thymo Drug: Grafalon MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days Other Names: Anti-human T-lymphocyte immunoglobulin
Active Comparator: TBI/VP16 TBI (Total Body Irradiation) / VP16 is used for conditioning for HSCT with MSD or MD graft with patients who are older than 48 months at the time of conditioning. TBI/VP16 is also used with Post TX-Cyclophosphamide for MMD-graft without in vitro T-Cell Depletion. TBI/VP16 with either ATG Thymo or Grafalon is used for MMD-HSCT with in vitro T-Cell Depletion or with CD34+ selection.	Drug: VP16 60 mg/kg BW,1 day Other Names: Etoposide Radiation: TBI 2 x 2Gy/day , 3 days (total 12Gy) Drug: ATG Thymoglobulin MD: ATG Thymo: 2,5mg/kg BW/d 3 days. Other Names: ATG Thymo Drug: Grafalon MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days Other Names: Anti-human T-lymphocyte immunoglobulin
Experimental: Flu/Thio/ivBu Fludarabine/Thiotepa/iV Busulfan is used for conditioning before HSCT from MSD or MD. Fludarabine/Thiotepa/iBu with either ATG Thymo or Grafalon is also used for HSCT from MMD-HSCT with T-Cell Depletion (TCD) or haplo with CD34+ selection. Fludarabine/Thiotepa/iV Busulfan with Post Tx-Cyclophosphamide is used for MMD-graft without in vitro TCD.	Drug: Thiotepa 2x5 mg/kg BW, 1 day Other Names: Thio Drug: Fludarabine 30 mg/m² BS, 5 days Other Names: Flu Drug: Busulfan iV, dosage according therapeutic drug monitoring, 4 days Other Names: Bu Drug: ATG Thymoglobulin MD: ATG Thymo: 2,5mg/kg BW/d 3 days. Other Names: ATG Thymo Drug: Cyclophosphamide 50mg/kg BW/d 2 days with Mesna Other Names: Cy Drug: Grafalon MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days Other Names: Anti-human T-lymphocyte immunoglobulin

Arm

Intervention/Treatment

Experimental: Flu/Thio/Treo

Fludarabine/Thiotepa/Treosulfan is for conditioning before HSCT from MSD or MD. ATG Thymo or Grafalon is used for patients who receive stem cells from unrelated donors. Fludarabine/Thiotepa/Treosulfan with either ATG Thymo or Grafalon is also used for HSCT from MMD with in vitro T-Cell Depletion (TCD) or with CD34+ selection. Fludarabine/Thiotepa/Treosulfan with Post Tx-Cyclophosphamide is used for MMD-graft without in vitro TCD.

Drug: Thiotepa

2x5 mg/kg BW, 1 day

Other Names:

Thio

Drug: Treosulfan

14g/m² BS, 3 days

Other Names:

Treo

Drug: Fludarabine

30 mg/m² BS, 5 days

Other Names:

Flu

Drug: ATG Thymoglobulin

MD: ATG Thymo: 2,5mg/kg BW/d 3 days.

Other Names:

ATG Thymo

Drug: Grafalon

MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days

Other Names:

Anti-human T-lymphocyte immunoglobulin

Active Comparator: TBI/VP16

TBI (Total Body Irradiation) / VP16 is used for conditioning for HSCT with MSD or MD graft with patients who are older than 48 months at the time of conditioning. TBI/VP16 is also used with Post TX-Cyclophosphamide for MMD-graft without in vitro T-Cell Depletion. TBI/VP16 with either ATG Thymo or Grafalon is used for MMD-HSCT with in vitro T-Cell Depletion or with CD34+ selection.

Drug: VP16

60 mg/kg BW,1 day

Other Names:

Etoposide

Radiation: TBI

2 x 2Gy/day , 3 days (total 12Gy)

Drug: ATG Thymoglobulin

MD: ATG Thymo: 2,5mg/kg BW/d 3 days.

Other Names:

ATG Thymo

Drug: Grafalon

MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days

Other Names:

Anti-human T-lymphocyte immunoglobulin

Experimental: Flu/Thio/ivBu

Fludarabine/Thiotepa/iV Busulfan is used for conditioning before HSCT from MSD or MD. Fludarabine/Thiotepa/iBu with either ATG Thymo or Grafalon is also used for HSCT from MMD-HSCT with T-Cell Depletion (TCD) or haplo with CD34+ selection. Fludarabine/Thiotepa/iV Busulfan with Post Tx-Cyclophosphamide is used for MMD-graft without in vitro TCD.

Drug: Thiotepa

2x5 mg/kg BW, 1 day

Other Names:

Thio

Drug: Fludarabine

30 mg/m² BS, 5 days

Other Names:

Flu

Drug: Busulfan

iV, dosage according therapeutic drug monitoring, 4 days

Other Names:

Drug: ATG Thymoglobulin

MD: ATG Thymo: 2,5mg/kg BW/d 3 days.

Other Names:

ATG Thymo

Drug: Cyclophosphamide

50mg/kg BW/d 2 days with Mesna

Other Names:

Drug: Grafalon

MD: 15mg/kg BW/d 3 days MMD: 10mg/kg BW/d 3 days

Other Names:

Anti-human T-lymphocyte immunoglobulin

Outcome Measures

Primary Outcome Measures

Overall Survival (OS) Stratum 1a (randomisation TBI+ chemo-conditioning vs. chemo-conditioning only) [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
Stratum 1 - randomisation related question was closed in December 2018; patients are in active follow-up: To show that a non total body irradiation (TBI) containing conditioning (Flu/Thio/ivBu or Flu/Thio/Treo) results in a non-inferior survival as compared to conditioning with TBI/Etoposide in children older than 4 years after HSCT from a Human leucocyte antigen (HLA) identical sibling donor (MSD) or a HLA matched donor (MD). The primary endpoint is the OS calculated from the date of the randomisation. Death from any cause will be considered an event.
Event free survival (EFS) Stratum 2 (mismatched donor transplantation) [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
EFS after allogeneic HSCT. EFS calculated from date of recruitment to disease progression or relapse, secondary neoplasm and death from any cause.
Overall Survival (OS), Stratum 1b: MSD/MD without randomisation [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
To explore the impact of risk factors on the incidence of adverse events of special interest (AESIs) and on overall survival and event free survival in the entire MSD/MD cohort

Secondary Outcome Measures

EFS (Stratum 1a and 1b) [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
EFS calculated from date of randomization (1a) or recruitment (1b) to disease progression or relapse, secondary neoplasm and death from any cause. Patients lost to follow-up without event will be censored at the date of their last follow-up evaluation.
TRM [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
Cumulative Incidence of Treatment-related mortality (TRM) for Stratum 1 and 2.
Relapse/progression [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
Cumulative Incidence of Relapse for Stratum 1a, 1b and 2.
Acute and late toxicity for Stratum 1a, 1b and 2 [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
according a preselection out of CTC3
OS (Stratum 2) [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
The primary endpoint is the OS calculated from the date of the recruitment . Death from any cause will be considered an event.

Other Outcome Measures

Acute Graft versus Host Disease (aGVHD) [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
According to the modified Seattle Glucksberg criteria
Secondary malignancies [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
Incidence, type and timepoint of occurence
Chronic Graft-versus-host disease (cGvHD) [first: 18 months after inclusion of first patient, afterwards annually up to 10 years]
Chronic GVHD is diagnosed using criteria created through the NIH consensus development project

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with ALL (except for patients with B-ALL) who fulfil the following criteria:

age at diagnosis ≤ 18 years. Age at HSCT ≤ 21 years
indication for allogeneic HSCT
complete remission (CR) before HSCT
written consent of the parents (legal guardian) and, if necessary, the minor patient via "Informed Consent Form"
no pregnancy
no secondary malignancy
no previous HSCT
HSCT is performed in a study participating centre

Exclusion Criteria:

patients who do not fulfil the inclusion criteria
Non Hodgkin-Lymphoma
the whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
no consent is given for saving and propagation of anonymous medical data for study reasons
severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
Karnofsky / Lansky score < 50%
subjects unwilling or unable to comply with the study procedures

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital de Pediatria "Juan P. Garrahan" Combate de Los Pozos N°1800 CABA	Buenos Aires	Argentina
2	Hospital Sor Maria Ludovica, Department Hematology Stem Cell Transplant Unit	La Plata	Argentina	1651
3	Children's Cancer Centre The Royal Children's Hospital	Melbourne	Australia	3052
4	Princess Margaret Hospital for Children	Perth	Australia	6008
5	Sydney Children's Hospital	Randwick	Australia	2031
6	Lady Cilento Children's Hospital	South Brisbane	Australia	4101
7	The Children's Hospital at Westmead Oncology Unit	Sydney	Australia	2145
8	Universitätsklinik für Kinder- und Jugendheilkunde, Abt. f. Hämato-Onkologie	Graz	Austria	8036
9	Universitätsklinik für Kinder- und Jugendheilkunde	Innsbruck	Austria	6020
10	St. Anna Children's Hospital, Vienna, Austria	Vienna	Austria	1090
11	Belarusian Research Center for Pediatric Oncology, Hematology and Immunology	Minsk	Belarus
12	Hôpital Universitaire des Enfants Reine Fabiola (HUDERF)	Brussels	Belgium	1020
13	Cliniques Universitaires Saint-Luc (UCL) Hématologie et oncologie pédiatrique	Brussels	Belgium	1200
14	University Hospital Gent Pediatrische hemato-oncologie	Gent	Belgium	9000
15	University Hospitals Leuven Kinderhemato-oncologie	Leuven	Belgium	3000
16	Centre Hospitalier Universitaire de Liège Domaine Universitaire du Sart Tilman	Liège	Belgium
17	Alberta Children's Hospital Division of Pediatric Oncology	Calgary	Canada
18	Montreal Children's Hospital	Montral	Canada
19	CHU Sainte-Justine Hematology-Oncology Division	Montreal	Canada
20	Hospital for Sick Children University of Toronto Division of Haematology/Oncology	Toronto	Canada
21	BC Children's Hospital	Vancouver	Canada
22	CancerCare Manitoba/University of Manitoba	Winnipeg	Canada
23	Hospital Dr Luis Calvo Mackenna	Santiago	Chile
24	Department of Pediatrics, UHC Zagreb	Zagreb	Croatia
25	Department of Pediatric Hematology and Oncology Teaching Hospital Motol, 2nd Medical School, Charles University	Prague	Czechia	150 06
26	Paediatric Stem Cell Transplant and Immune Deficiency, Dept. for children and adolescents 4072, Rigshospitalet	Copenhagen	Denmark	2100
27	Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Univ. of Helsinki	Helsinki	Finland	00029 HUS
28	CHU Bordeaux	Bordeaux	France	33076
29	CHU Clermont-Ferrand	Clermont-Ferrand	France	63003
30	CHU Grenoble - Clinique Universitaire de Pédiatrie, Hôpital Couple Enfant	Grenoble	France	38043
31	CHRU Lille, Service d'Hématologie Pédiatrique	Lille	France	59037
32	IHOP / Lyon, Service Hématologie et d'Oncologie pédiatrique	Lyon	France	69372
33	Hopital la Timone Adulte	Marseille	France	13385
34	Hopital Arnaud de Villeneuve	Montpellier	France	34295
35	CHU Nancy - Hopital d'Enfants	Nancy	France	54500
36	CHU Nantes, Service d'onco hémato pédiatrie	Nantes	France	44093
37	Hôpital Robert Debré	Paris	France	75019
38	CHU de Rennes, Serive d'Onco-Pédiatrie	Rennes	France	35203
39	CHU de Rouen, Hopital des Enfants, Service d' Immuno-Hématologie Oncologie Pédiatrique	Rouen	France	76031
40	CHU Strasbourg, Service d'hématologie et d'oncologie pédiatrique	Strasbourg	France	67098
41	Uniklinik RWTH Aachen, Kinder- und Jugendmedizin	Aachen	Germany	52074
42	Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum	Berlin	Germany	13353
43	Universitätsklinikum Bonn, Abteilung für Pädiatrische Hämatologie und Onkologie	Bonn	Germany	53113
44	Universitätsklinikum Düsseldorf, Klinik für Kinder-Onkologie, -Hämatologie und Klinische Immunologie	Düsseldorf	Germany	40225
45	Universitätsklinikum Erlangen, Kinder- und Jugendklinik	Erlangen	Germany	1054
46	Universitätsklinikum Essen, Klinik für Kinderheilkunde III	Essen	Germany	45122
47	Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Kinder- und Jugendmedizin (KKJM)	Frankfurt am Main	Germany	60590
48	Universitätsklinikum Freiburg, Zentrum für Kinder- und Jugendmedizin	Freiburg	Germany	79106
49	Universitätsklinikum Gießen, Zentrum für Kinder- und Jugendmedizin	Gießen	Germany	35392
50	Universitätsmedizin Greifswald, Klinik und Poliklinik für Kinder- und Jugendmedizin	Greifswald	Germany	17475
51	Universitätsklinikum Halle (Saale), Universitätsklinik und Poliklinik für Kinder- und Jugendmedizin	Halle	Germany	06120
52	Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Pädiatrische Hämatologie und Onkologie	Hamburg	Germany	20246
53	Medizinische Hochschule Hannover, Zentrum Kinderheilkunde und Jugendmedizin	Hannover	Germany	30625
54	Universitätsklinikum Heidelberg, Zentrum für Kinder- und Jugendmedizin	Heidelberg	Germany	69120
55	Universitätsklinikum Jena, Sektion für Stammzelltransplantation	Jena	Germany	07745
56	UKSH - Universitätsklinikum Schleswig-Holstein, Klinik für Allgemeine Pädiatrie	Kiel	Germany	24105
57	Universitätsmedizin Leipzig, Abteilung für Pädiatrische Onkologie, Hämatologie und Hämostaseologie	Leipzig	Germany	04103
58	Klinikum der Universität München, Dr. von Haunersches Kinderspital	München	Germany	80337
59	Städt. Krankenhaus München Schwabing, Universitätskinderklinik der TU München	München	Germany	80804
60	Universitätsklinikum Münster, Klinik für Kinder- und Jugendmedizin	Münster	Germany	48149
61	Universitätsklinikum Regensburg, Klinik und Poliklinik für Kinder- und Jugendmedizin	Regensburg	Germany	93053
62	Universitätsklinik für Kinder- und Jugendmedizin Tübingen	Tübingen	Germany	72076
63	Universitätsklinikum Ulm, Klinik für Kinder- und Jugendmedizin	Ulm	Germany	89075
64	Universitäts-Kinderklinik Würzburg	Würzburg	Germany	97080
65	Saint Sophia Children's Hospital BMT Unit	Athens	Greece	11527
66	Hospital of Southern Pest, National Insitute of Hematology and Infectious DiseaseHospital of Southern Pest, National Insitute of Hematology and Infectious Disease Pediatric Bone Marrow Transplantation Unit at Central	Budapest	Hungary	1097
67	Rambam Medical Center	Haifa	Israel	31096
68	Schneider Children's Medical Center of Israel	Petach-Tikva	Israel	49202
69	Dana Children's Hospital	Tel Aviv	Israel	64239
70	Azienda Ospedaliero-Universitaria Policlinico S. Orsola-Malpighi di Bologna	Bologna	Italy	40138
71	Ospedale Mayer di Firenze SODc Tumori Pediatrici e TMO	Florence	Italy	50139
72	Istituto Gaslini Genova Oncoematologia Pediatrica-	Genoa	Italy	16147
73	A.O. San Gerardo di Monza Clinica Pediatrica	Monza	Italy	20900
74	A.O.R.N. Santobono Pausilipon, Dipartimento di Oncoematologia	Napoli	Italy	80123
75	Azienda Ospedaliera di Padova Oncoematologia Pediatrica	Padova	Italy	35128
76	Fondazione IRCCS Policlinico San Matteo	Pavia	Italy	27100
77	Azienda Ospedaliero Universitaria Pisana U.O. di Oncoematologia Pediatrica A.O.	Pisa	Italy	56126
78	Ospedale Pediatrico Bambino Gesù, Sapienza, University of Rome	Rome	Italy	00165
79	Ospedale Infantile Regina Margherita SC Oncoematologia e Centro Trapianti	Torino	Italy	10126
80	University of Malaya, Department of Paediatrics	Kuala Lumpur	Malaysia
81	Instituto Nacional de Peditria	Ciudad de México	Mexico
82	Leiden University Medical Center Department of Pediatrics/BMT unit	Leiden	Netherlands	2300
83	Princess Máxima Center for Pediatric Oncology	Utrecht	Netherlands	3584
84	Starship Children's Hospital	Auckland	New Zealand	1142
85	Oslo University Hospital Rikshospitalet	Oslo	Norway	0424
86	University Hospital No.1, Collegium Medicum UMK, department of Paediatrics, Oncology, Hematology and Paediatric Transplantology	Bydgoszcz	Poland
87	University Children's Hospital in Krakow, Department of Transplantation	Kraków	Poland
88	Children's University Hospital, Dept. Pediatric Hematology, Oncology, and Transplantology	Lublin	Poland
89	Poznan University of Medical Sciences, Department of Pediatric Onology, Hematology & HSCT	Poznań	Poland
90	Cape of Hope, Wroclaw Medical University	Wrocław	Poland
91	IInsitutul Clinic Fundeni, Sectia de Transplant Medular	Bukarest	Romania
92	University of Medicine and Pharmacy V. BABES, Emergency Children's Hospital LOUIS TURCANU, III. Clinic of Pediatrics , Department of Onco-hematology and Bone Marrow Transplantation	Timişoara	Romania
93	King Abdullah specialists children hospital	Riyadh	Saudi Arabia
94	University Children's Hospital	Bratislava	Slovakia	83340
95	University childrens' hospital, UMCL	Ljubljana	Slovenia
96	Hospital Santa Creu i Sant Pau	Barcelona	Spain
97	Hospital Vall d'Hebron	Barcelona	Spain
98	Hospital Virgen de la Arrixaca	El Palmar	Spain
99	Hospital Materno Infantil de Málaga	Málaga	Spain
100	Hospital Universitario Central de Asturias	Oviedo	Spain
101	Queen Silvia Children's Hospital, Department of Pediatric Oncology (Avdelnig 321-322)	Göteborg	Sweden	41685
102	Skane University Hospital, Dept. of Pediatrics, Section for Hematology and Oncology	Lund	Sweden	22185
103	Karolinska University Hospital, Department of Pediatrics	Stockholm	Sweden	14186
104	University Children's Hospital, Dept. of Women's & Children's Health Section for Pediatrics	Uppsala	Sweden	75185
105	Universitäts-Kinderspital beider Basel (UKBB)	Basel	Switzerland	4056
106	HUG Hôpitaux Universitaire de Genève	Geneva	Switzerland	1211
107	Universitäts-Kinderspital Zurich	Zurich	Switzerland	8032
108	Ankara University School of Medicine Pediatric Stem Cell Transplantation Unit	Ankara	Turkey	06100
109	Gazi University School of Medicine Pediatric Stem Cell Transplantation Unit	Ankara	Turkey
110	Gülhane Training and Research Hospital	Ankara	Turkey
111	Akdeniz University School of Medicine Pediatric Stem Cell Transplantation Unit	Antalya	Turkey
112	Bahcesehir University School of Medicine Pediatric Stem Cell Transplantation Unit	Antalya	Turkey
113	Acibadem University Atakent Hospital Pediatric Stem Cell Transplantation Unit	Istanbul	Turkey
114	Bahcelievler Medicalpark Hospital Pediatric Stem Cell Transplantation Unit	Istanbul	Turkey
115	Bahcesehir University School of Medicine Pediatric Stem Cell Transplantation Unit	Istanbul	Turkey
116	Medipol Mega Üniversite Hastanesi	Istanbul	Turkey
117	Dokuzeylul University School of Medicine Pediatric Stem Cell Transplantation Unit	Izmir	Turkey
118	Ege University School of Medicine Pediatric Stem Cell Transplantation Unit	Izmir	Turkey
119	Erciyes University School of Medicine Pediatric Stem Cell Transplantation Unit	Kayseri	Turkey

Sponsors and Collaborators

St. Anna Kinderkrebsforschung
ALL SCTped Forum
European Society for Blood and Marrow Transplantation
ALL-BFM Study Group
Assistance Publique - Hôpitaux de Paris
Dutch Childhood Oncology Group
Swiss Pediatric Oncology Group
Australian & New Zealand Children's Haematology/Oncology Group

Investigators

Study Chair: Christina Peters, Prof. MD PhD, St. Anna Kinderspital, Vienna, Austria
Study Chair: Peter Bader, Prof. MD PhD, Goethe University
Study Chair: Franco Locatelli, Prof. MD PhD, Ospedale Pediatrico Bambino Gesù, Rome, Italy