Supplemental data
Supplementary table 1.Conditioning regimens in TBI-based and chemotherapy-based allo-SCTTBI-based allo-SCT / Chemotherapy-based allo-SCT
Number (%) / 523 (87%) / 78 (13%)
Conditioningregimen / 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 TBI-based regimen (n=523) / 6≤TBI<12: 48 (9%) / -
TBI = 12 : 439 (84%)
12<TBI ≤ 14.4: 36 (7%)
TBI Fractioning among TBI-based 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.
Supplementary table 2: outcome according to patients' age
5-year RI / 5year NRM / 5-year LFS / 5-year OS
youngerthan 35 / chemo (n= 54) / 60% [45-72] / 22% [12-34] / 18% [8-28] / 21% [10-33]
TBI (n=351) / 30% [25-35] / 21% [11-32] / 50% [44-55] / 53% [48-59]
p / <10-5 / 0.75 / <10-5 / <10-5
olderthan 35 / chemo (n=24) / 50% [26-70] / 9% [1-24] / 41% [19-63] / 45% [23-67]
TBI (n=172) / 30% [23-37] / 38% [18-57] / 32% [25-40] / 34% [27-42]
p / 0.04 / 0.01 / 0.48 / 0.23
Chemo indicates chemotherapy-only regimens: TBI, total body irradiation regimens.
Supplementary Table 3. T-ALL features at diagnosis and allo-SCT characteristics for patients less than 35TBI-basedregimens / Chemotherapy-onlyregimens / P value / Total
Number of patients / 351 (86.7%) / 54 (13.3%) / 405
Medianage, 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%)
WBC (available data=494)
≥100 G/L (%) / 93 (33%) / 10 (22%) / 0.15 / 103 (31%)
<100 G/L (%) / 189 (67%) / 35 (78%) / 224 (69%)
T-lineageimmunophenotype (available data=273)
Thymic / 45 (19%) / 10 (27%) / 0.26 / Thymic: 55 (20%)
Other / 191 (81%) / 27 (73%) / Other 218 (80%)
Complexkaryotype (available data = 458) / 45 (17%) / 11 (26%) / 0.19 / 56 (18%)
MedianYear of Transplant / 2006 / 2006 / 0.94 / 2006 (range, 2000-2010)
Disease status at allo-SCT:
CR1 / 248 (71%) / 25 (46%) / 273 (68%)
CR2 / 48 (14%) / 18 (33%) / <10-4 / 66 (16%)
CR>2 or advanced / 55 (16%) / 11 (20%) / 66 (16%)
Donor type:
Identical sibling (%) / 189 (54%° / 27 (50%) / 0.6 / 216 (53%)
Unrelateddonor (%) / 162 (46%) / 27 (50%) / 189 (47%)
Stem cell source:
BoneMarrow / 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%)
GVHD prophylaxis (available data=567)
CsA / 41 (12%) / 4 (8%) / 0.01 / CsA: 45 (12%)
CsA + MTX / 266 (80%) / 37 (72%) / CsA + MTX: 303 (79%)
CsA + MMF / 21 (6%) / 10 (20%) / CsA + MMF: 31 (8%)
CsA + MMF + MTX / 3 (1%) / 0 / CsA + MMF + MTX: 3 (1%)
Use of ATG as part of GVHD prophylaxis / 96 (27%) / 17 (32%) / 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, mycophenolatemofetil; ATG, anti-thymocyte globulin; TBI, total body irradiation, WBC, White Blood Cell.
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
TBI vs IV Bu
TBI (n=351) / 30% [25-35] / 21% [11-32] / 50% [44-55] / 53% [48-59]
IV Bu (n=38) / 62% [43-77] / 24% [4-53] / 15% [3-26] / 17% [4-29]
p (global) / 4.10-5 / 0.62 / <10-5 / <10-5
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
Statusat transplantation / 0.5 / 0.48
Complexkaryotype / 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
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 (OspedalediCareggi,Firenze, Italy), JH Bourhis (IGR, Villejuif, France), D. Bron (Institut Jules Bordet, Brussels, Belgium), D. Bunjes (KlinikfuerInnereMedzin IIIUniversitätsklinikum 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 (OspedaleCivile, 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. GarciaLaraña (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 (Elisabethinen-Hospital, 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 (AziendaOspedaliRiunitidiAncona, Ancona-Torrete, Italy), B. Lioure (Service d'OncoHematologie, 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 SudService Hematologie, Lyon, France), A. Nagler (Chaim Sheba Medical Center, Tel-Hashomer, Israel), S. Vigouroux (CHU Bordeaux, Hôpital Haut-leveque, Pessac, France), M. Mohty (Hôpital Saint Antoine, Paris, France), J. Moraleda (Hospital UniversitarioVirgen de la Arrixaca, Murcia, Spain), E. Morra (OspedalediNiguarda Ca` Granda, Milano, Italy), S. Nguyen-Quoc (HôpitalPitie-Salpetriere, Paris, France), D. Niederwieser (University Hospital Leipzig Div.Hematology, Oncology and Hemostasiology, Leipzig, Germany), H. Ozsan (DokuzEylülUniversitesi, Izmir, Turkey), J. Passweg (University HospitalHematology, 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 TriasiPujol, 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 KlinikfürDiagnostik, Wiesbaden, Germany), P. Sedlacek (University Hospital Motol, Prague, Czech Republic), H. Sengeløv (Bone Marrow Transplant Unit L 4043, Copenhagen, Denmark), J. Sierra (Hospital Santa CreuiSant 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 MünsterDept. of Hematol./Oncol., Münster, Germany), F. Suarez (Hôpital Necker, Paris), G. Sucak (GaziUniversitesi Tip FakültesiHastanesiEriskinHematolojiBilim 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), LiisaVolin (Helsinki University Central Hospital, Helsinki, Finland), J. Vorlicek (University Hospital Brno, Brno, Czech Republic), A. Wahlin (Umea University Hospital, Umeå, Sweden), H. Wandt (KlinikumNürnberg, Germany), G. Wulf (UniversitätsklinikumGöttingen, Germany), I. Yakoub-Agha (HôpitalHuriez, CHRU Lille, France), M. Yeshurun (Beilinson Hospital, Petach-Tikva, Israel), T. Zuckerman (Rambam Medical CenterDept. of Hematology & BMT, Haifa, Israel).
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