Supplemental data
Supplementary table 1.Conditioning regimens in TBI-based and chemotherapybased allo-SCT
Number (%)
Conditioning regimen
TBI-based allo-SCT
Chemotherapy-based alloSCT
523 (87%)
78 (13%)
TBI + one drug: 479 (80%)
IV Bu-Cy: 46 (8%)
TBI-Cy: 403 (67%) Oral Bu-Cy: 16 (3%)
TBI-VP16: 57 (10%) Other: 16 (4%)
TBI-AraC: 8 (1%)
TBI-Mel: 4 (1%)
Other: 7 (1%)
TBI + at least 2 drugs: 44 (7%)
TBI-Cy-VP16: 29 (5%)
TBI-Amsa-AraC-Fluda: 7 (1%)
TBI-Cy-Thiotepa: 3
TBI-Mel-VP16: 2
TBI-Cy-AraC: 1
Other: 2
TBI dose (Gy) among TBIbased regimen (n=523)
6≤TBI<12:
TBI = 12 :
48 (9%)
-
439 (84%)
12<TBI ≤ 14.4: 36 (7%)
TBI Fractioning among TBIbased regimen (available data
= 517)
No (one single fraction): 17 (3%)
-
Yes: 500 (97%)
Median of 6 fractions (range, 2-11)
Median
dose/fraction
(available data = 500)
2 Gy (range, 1-6)
-
Cy indicates cyclophosphamide; Bu, Busulfan; VP16, etoposide; Amsa, amsacrine; AraC, aracytine;
Fluda, fludarabine; Mel, Melphalan; TBI, total body irradiation.
1
Supplementary table 2: outcome according to patients' age
younger than 35 chemo (n= 54)
TBI (n=351)
5-year RI
60% [45-72]
30% [25-35]
5year NRM
22% [12-34]
21% [11-32]
5-year LFS
18% [8-28]
50% [44-55]
5-year OS
21% [10-33]
53% [48-59]
p
chemo (n=24)
TBI (n=172)
p
<10-5
50% [26-70]
30% [23-37]
0.04
0.75
9% [1-24]
38% [18-57]
0.01
<10-5
41% [19-63]
32% [25-40]
0.48
<10-5
45% [23-67]
34% [27-42]
0.23
older than 35
Chemo indicates chemotherapy-only regimens: TBI, total body irradiation regimens.
2
Supplementary Table 3. T-ALL features at diagnosis and allo-SCT characteristics for
patients less than 35
TBI-based
regimens
Chemotherapy-only
regimens
Number of patients
351 (86.7%)
54 (13.3%)
Median age, years
27 (18-34.9)
25 (18-35)
0.02
25 (18-35)
Male gender (%)
273 (78%)
38 (70%)
0.23
311 (77%)
CNS involvement
(available data=590)
52 (15%)
10 (18%)
0.52
62 (16%)
93 (33%)
10 (22%)
0.15
103 (31%)
<100 G/L (%)
T-lineage
immunophenotype
(available data=273)
189 (67%)
35 (78%)
Thymic
45 (19%)
10 (27%)
Other
Complex karyotype
(available data = 458)
191 (81%)
45 (17%)
WBC (available
data=494)
≥100 G/L (%)
Median
Year
of
Transplant
Disease status at alloSCT:
CR1
P value
Total
405
224 (69%)
0.26
Thymic: 55 (20%)
27 (73%)
11 (26%)
0.19
Other 218 (80%)
56 (18%)
2006
2006
0.94
248 (71%)
25 (46%)
2006 (range, 20002010)
273 (68%)
<10
-4
CR2
48 (14%)
18 (33%)
66 (16%)
CR>2 or advanced
Donor type:
55 (16%)
11 (20%)
Identical sibling (%)
189 (54%°
27 (50%)
Unrelated donor (%)
162 (46%)
27 (50%)
189 (47%)
Bone Marrow
126 (36%)
14 (26%)
140 (35%)
GCSF-mobilized PBSC
225 (64%)
40 (74%)
0.15
265 (65%)
Female donor to male
receipt
81 (24%)
14 (26%)
0.72
95 (24%)
CsA
41 (12%)
4 (8%)
0.01
CsA: 45 (12%)
CsA + MTX
266 (80%)
37 (72%)
CsA + MMF
21 (6%)
10 (20%)
CsA + MMF + MTX
3 (1%)
0
96 (27%)
17 (32%)
66 (16%)
0.6
216 (53%)
Stem cell source:
GVHD
prophylaxis
(available data=567)
Use of ATG as part of
GVHD prophylaxis
CsA + MTX: 303
(79%)
CsA + MMF: 31 (8%)
CsA + MMF + MTX: 3
(1%)
0.55
113 (28%)
CR indicates Complete Remission; CNS, central nervous system; GCSF, Granulocyte-colony stimulating
factor; PBSC, peripheral blood stem cells; GVHD, graft versus host disease; CsA, cyclosporin A; MTX,
methotrexate; MMF, mycophenolate mofetil; ATG, anti-thymocyte globulin; TBI, total body irradiation,
WBC, White Blood Cell.
3
Supplementary table 4: study of TBI versus IV Bu in younger patients (<35)
5-year Relapse
incidence
5-year NRM
5-year LFS
5-year OS
30% [25-35]
62% [43-77]
21% [11-32]
24% [4-53]
50% [44-55]
15% [3-26]
53% [48-59]
17% [4-29]
4.10-5
0.62
<10-5
<10-5
TBI vs IV Bu
TBI (n=351)
IV Bu (n=38)
p (global)
4
Supplementary table 5: Grambsch-Therneau tests in the multivariate
analysis in patients younger than 35.
LFS
OS
TBI
0.51
0.45
Year
0.42
0.22
WBC > 100
0.97
0.15
0.5
0.48
Complex karyotype
0.59
0.95
Unrelated donor versus
sibling donor
0.79
0.87
PB versus BM
0.09
0.0508
Centre
0.81
0.6
Global
0.69
0.27
Status at transplantation
5
Participating EBMT centers
F. Abdelrahman (King Hussein Cancer Centre, Amman, Jordan), B. Afanasyev (SPb State I.
Pavlov Medical University, St. Petersburg, Russia), M. Aljurf (King Faisal Specialist Hospital
& Research Centre Oncology (Section of Adult Haematolgy/BMT), Riyadh, Saudi Arabia), F.
Altuntas (Ankara Oncology Research & Education Hospital, Ankara, Turkey), F. Bonifazi
(Bologna University, S.Orsola-Malpighi Hospital Institute of Hematology & Medical Oncology
L & A Seràgnoli, Bologna, Italy), A. Bazarbachi (American University, Beirut, Lebanon), Yves
Beguin (Université, Liège, Belgium), M. Bentz (Klinikum Karlsruhe gGmbH, Karlsruhe,
Germany), C. Berthou (CHU Morvan, Brest, France), P. Bordigoni (Vandoeuvre-Les-Nancy,
France), A. Bosi (Ospedale di Careggi, Firenze, Italy), JH Bourhis (IGR, Villejuif, France), D.
Bron (Institut Jules Bordet, Brussels, Belgium), D. Bunjes (Klinik fuer Innere Medzin III
Universitätsklinikum Ulm, Germany), D. Caballero (Hospital Clínico, Salamanca, Spain), P.
Cannell (RP Group Royal Perth Hospital, Perth, Australia), P. Chevallier (CHU Nantes,
France), J. Cornelissen (Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam,
Netherlands), C. Craddock (Centre For Clinical Haematology, Queen Elizabeth, Birmingham,
United Kingdom), C. De Souza (Univ. Est. de Campinas/TMO/UNICAMP, Brazil), P. Di
Bartolomeo (Ospedale Civile, Pescara, Italy), P. Dreger (University of Heidelberg, Germany),
N. Fegueux (CHU Lapeyronie, Montpellier, France), J. Finke (University of Freiburg, Dept. of
Medicine -Hematology, Oncology, Germany), M. Eder (Hannover Medical School, Department
of Haematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany),
J. Garcia Laraña (Hospital Ramon y Cajal, Madrid, Spain), H. Goker (Hacettepe University,
Ankara, Turkey), J. Gribben (St. Bartholomew`s and The Royal London Hospital, London,
United Kingdom), B. Gruhn (University of Jena, Germany), R. Haas (Heinrich Heine
Universität, Düsseldorf, Germany), M. Hallek (University of Cologne, Cologne, Germany), R.
Hamladji (Centre Pierre et Marie Curie, Alger, Algeria), M. Hamon (Plymouth Hospitals NHS
Trust, Plymouth, United Kingdom), R. Handgretinger (University Hospital, Tübingen,
Germany), A. Huynh (Hôpital de Purpan, CHU Toulouse, France), N. Ifrah (CHRU, Service
des Maladies du Sang, Angers, France), K. Indrák (University Hospital, Olomouc, Czech
Republic), G. Jackson (Royal Victoria Infirmary, Newcastle-Upon-Tyne, United Kingdom), P.
Jindra (Charles University Hospital, Pilsen, Czech Republic), H. Kasparu (ElisabethinenHospital, Linz, Austria), S. Kyrcz-Krzemien (Medical University of Silesia Univ. Dept. of
Haematology and BMT, Katowice, Poland), B. Labar (University Hospital Center Rebro,
Zagreb, Croatia), T. Lamy (CHU Rennes, France), S. Lenhoff (University Hospital, Lund,
Sweden), P. Leoni (Azienda Ospedali Riuniti di Ancona, Ancona-Torrete, Italy), B. Lioure
(Service d'Onco Hematologie, Strasbourg, France), P. Ljungman (Huddinge University
Hospital, Sweden), C. Malm (University Hospital, Linköping, Sweden), E. Meijer (VU
University Medical Center, Amsterdam, The Netherlands), M. Michallet (Centre Hospitalier
Lyon Sud Service Hematologie, Lyon, France), A. Nagler (Chaim Sheba Medical Center, TelHashomer, Israel), S. Vigouroux (CHU Bordeaux, Hôpital Haut-leveque, Pessac, France), M.
Mohty (Hôpital Saint Antoine, Paris, France), J. Moraleda (Hospital Universitario Virgen de la
Arrixaca, Murcia, Spain), E. Morra (Ospedale di Niguarda Ca` Granda, Milano, Italy), S.
Nguyen-Quoc (Hôpital Pitie-Salpetriere, Paris, France), D. Niederwieser (University Hospital
Leipzig Div.Hematology, Oncology and Hemostasiology, Leipzig, Germany), H. Ozsan
(Dokuz Eylül Universitesi, Izmir, Turkey), J. Passweg (University Hospital Hematology, Basel,
Switzerland), E. Pogliani (Ospedale San Gerardo, Monza, Italy), M. Potter (Royal Marsden
Hospital, London, United Kingdom), J. Pretnar (University Med. Center, Ljubljana, Slovenia),
K. Remes (Turku University, Turku, Finland), J. Ribera Santasusana (Hospital Universitari
Germans Trias i Pujol, Barcelona, Spain), N. Schaap (University Medical Center St. Radboud,
Nijmegen, The Netherlands), H. Schouten (University Hospital Maastricht, The Netherlands),
W. Schroyens (Antwerp University Hospital (UZA), Antwerp Edegem, Belgium), R.
Schwerdtfeger (Deutsche Klinik für Diagnostik, Wiesbaden, Germany), P. Sedlacek
(University Hospital Motol, Prague, Czech Republic), H. Sengeløv (Bone Marrow Transplant
6
Unit L 4043, Copenhagen, Denmark), J. Sierra (Hospital Santa Creu i Sant Pau, Barcelona,
Spain), M. Sjo (Haukeland University Hospital, Bergen, Norway), J. Snowden (North Trent
BMT Programme (Adults), North Trent BMT Programme (Adults), Sheffield, United
Kingdom), G. Socie (Hopital St. Louis Dept.of Hematology - BMT, Paris, France), M. Stelljes
(University of Münster Dept. of Hematol./Oncol., Münster, Germany), F. Suarez (Hôpital
Necker, Paris), G. Sucak (Gazi Universitesi Tip Fakültesi Hastanesi Eriskin Hematoloji Bilim
Dali, Ankara, Turkey), K. Thomson (University College London Hospital, London, United
Kingdom), J. Thomson (Albert Albert´s Stem Cell Transplantation Centre- Haematology
Pretoria East Hospital, Pretoria Gauteng, South Africa), G.W. van Imhoff (University Medical
Center Groningen (UMCG), Groningen, The Netherlands), J.H. Veelken (Leiden University
Hospital, Leiden, The Netherlands), Liisa Volin (Helsinki University Central Hospital,
Helsinki, Finland), J. Vorlicek (University Hospital Brno, Brno, Czech Republic), A. Wahlin
(Umea University Hospital, Umeå, Sweden), H. Wandt (Klinikum Nürnberg, Germany), G.
Wulf (Universitätsklinikum Göttingen, Germany), I. Yakoub-Agha (Hôpital Huriez, CHRU
Lille, France), M. Yeshurun (Beilinson Hospital, Petach-Tikva, Israel), T. Zuckerman
(Rambam Medical Center Dept. of Hematology & BMT, Haifa, Israel).
7