Myeloablative conditioning with thiotepa-busulfan-fludarabine does not improve the outcome of patients transplanted with active leukemia: final results of the GITMO prospective trial GANDALF-01

被引：8

作者：

Bonifazi, Francesca ^{[1
]}

Pavoni, Chiara ^{[2
]}

Peccatori, Jacopo ^{[3
,4
]}

Giglio, Fabio ^{[3
,4
]}

Arpinati, Mario ^{[1
]}

Busca, Alessandro ^{[5
]}

Bernasconi, Paolo ^{[6
]}

Grassi, Anna ^{[2
]}

Iori, Anna Paola ^{[7
]}

Patriarca, Francesca ^{[8
,9
]}

Brunello, Lucia ^{[10
]}

Di Grazia, Carmen ^{[11
]}

Carella, Angelo Michele ^{[12
]}

Cilloni, Daniela ^{[13
]}

Picardi, Alessandra ^{[14
,15
]}

Proia, Anna ^{[16
]}

Santarone, Stella ^{[17
]}

Sorasio, Roberto ^{[18
]}

Carluccio, Paola ^{[19
]}

Chiusolo, Patrizia ^{[20
,21
]}

Cupri, Alessandra ^{[22
]}

Luppi, Mario ^{[23
]}

Nozzoli, Chiara ^{[24
]}

Baronciani, Donatella ^{[25
]}

Casini, Marco ^{[26
]}

Grillo, Giovanni ^{[27
]}

Musso, Maurizio ^{[28
]}

Onida, Francesco ^{[29
]}

Palazzo, Giulia ^{[30
]}

Parma, Matteo ^{[31
]}

Tringali, Stefania ^{[32
]}

Vacca, Adriana ^{[33
]}

Vallisa, Daniele ^{[34
]}

Sacchi, Nicoletta ^{[35
]}

Oldani, Elena ^{[2
]}

Masciulli, Arianna ^{[36
]}

Gheorghiu, Angela ^{[37
]}

Girmenia, Corrado ^{[7
]}

Martino, Massimo ^{[38
]}

Bruno, Benedetto ^{[39
]}

Rambaldi, Alessandro ^{[2
,40
]}

Ciceri, Fabio ^{[3
,4
]}

机构：

[1] Univ Bologna, Azienda Osped, IRCCS, Bologna, Italy

[2] Azienda Socio Sanitaria Terr Papa Giovanni XXIII, Dept Oncol & Hematol, Bergamo, Italy

[3] Ist Sci San Raffaele, IRCCS, Dept OncoHematol Hematol & Bone Marrow Transplant, Milan, Italy

[4] Univ Vita Salute San Raffaele, Milan, Italy

[5] AOU Citta Salute & Sci, SSD Trapianto Cellule Staminali, Turin, Italy

[6] Fdn IRCCS Policlin San Matteo, UOC Ematol, Ctr Trapianti Cellule Staminali Ematopoietiche, Pavia, Italy

[7] Sapienza Univ Roma, AOU Policlin Umberto 1, Ematol, Rome, Italy

[8] ASUFC, Clin Ematol & Ctr Trapianti, Udine, Italy

[9] Univ Udine, DAME, Udine, Italy

[10] Azienda Osped SS Antonio & Biagio & Cesare Arrigo, Ematol, Alessandria, Italy

[11] Osped Policlin San Martino, IRCCS, Ematol & Ctr Trapianti, Genoa, Italy

[12] Fdn Casa Sollievo Sofferenza, Dipartimento Sci Med, SSD UTIE & Terapie Cellulari, San Giovanni Rotondo, FG, Italy

[13] Univ Turin, Dept Clin & Biol Sci, Turin, Italy

[14] Tor Vergata Univ, Dept Biotecnol & Prevent, Rome Transplant Network, Rome, Italy

[15] Stem Cell Transplant Program AORN Cardarelli, Naples, Italy

[16] AO San Camillo Forlanini, Ematol & Trapianto CSE, Rome, Italy

[17] Osped Civile, Terapia Intens Ematol, Pescara, Italy

[18] AO S Croce & Carle, SC Ematol, Cuneo, Italy

[19] Univ Bari, Hematol Sect, Dept Emergency & Organ Transplantat DETO, Bari, Italy

[20] Fdn Policlin Univ A Gemelli IRCCS, Dipartimento Diagnost Immagini Radioterapia Oncol, Rome, Italy

[21] Univ Cattolica Sacro Cuore, Dipartimento Sci Radiol & Ematol, Sez Ematol, Rome, Italy

[22] Azienda Osped Policlin Catania, Div Ematol, Unita Trapianto Midollo, Catania, Italy

[23] Univ Modena, Unimore Azienda Osped, Dept Med & Surg Sci, Modena, Italy

[24] Careggi Hosp, Dept Cellular Therapies & Transfus Med, Florence, Italy

[25] Ematol & TMO Osped Oncol A Businco, Cagliari, Italy

[26] Ematol & TMO, Bolzano, Italy

[27] GOM Niguarda Milano, Milan, Italy

[28] UOC Oncoematol & TMO Dipartimento Oncol La Maddal, Palermo, Italy

[29] Univ Milan, IRCCS Ca Granda Osped Maggiore Policlinico Ctr Tr, UOC Ematol, Dipartimento Oncol & Ematooncol, Milan, Italy

[30] Ematol Taranto, Taranto, Italy

[31] Osped San Gerardo, Div Ematol & Ctr Trapianti Midollo, Monza, Italy

[32] UOSD Unita Trapianti Midollo Osseo, Dipartimento Oncol, AOR Villa Sofia Cervello, Palermo, Italy

[33] UO Ctr Trapianti Midollo Osseo Presidio Osped R B, Cagliari, Italy

[34] UO Ematol & CTMO, Piacenza, Italy

[35] Osped Galliera, IBMDR EO, Genoa, Italy

[36] FROM Fdn Ric Osped Bergamo, Bergamo, Italy

[37] GITMO Grp Italiano Trapianto Midollo Osseo Cellul, Trials Off, Genoa, Italy

[38] Grande Osped Metropolitano BMM, Stem Cell Transplant & Cellular Therapies Unit, Reggio Di Calabria, Italy

[39] Univ Torino, Dipartimento Biotecnol Mol & Scienze Salute, Turin, Italy

[40] Univ Milan, Milan, Italy

来源：

BONE MARROW TRANSPLANTATION | 2022年 / 57卷 / 06期

关键词：

ACUTE MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; UNRELATED DONORS; HEMATOLOGIC MALIGNANCIES; RETROSPECTIVE ANALYSIS; CHEMOTHERAPY; DISEASE; REGIMEN; ADULTS;

D O I：

10.1038/s41409-022-01626-5

中图分类号：

Q6 [生物物理学];

学科分类号：

071011 ;

摘要：

The outcome of refractory/relapsed (R/R) acute leukemias is still dismal and their treatment represents an unmet clinical need. However, allogeneic transplantation (allo-HSCT) remains the only potentially curative approach in this setting. A prospective study (GANDALF-01, NCT01814488; EUDRACT:2012-004008-37) on transplantation with alternative donors had been run by GITMO using a homogeneous myeloablative conditioning regimen with busulfan, thiotepa and fludarabine while GVHD prophylaxis was stratified by donor type. The study enrolled 101 patients; 90 found an alternative donor and 87 ultimately underwent allo-HSCT. Two-year overall survival of the entire and of the transplant population (primary endpoint) were 19% and 22%, without significant differences according to disease, donor type and disease history (relapsed vs refractory patients). Two-year progression-free survival was 19% and 17% respectively. The cumulative incidences of relapse and non-relapse mortality were 49% and 33% at two years. Acute grade II-IV and chronic GVHD occurred in 23 and 10 patients. Dose intensification with a myeloablative two-alkylating regimen as sole strategy for transplanting R/R acute leukemia does seem neither to improve the outcome nor to control disease relapse. A pre-planned relapse prevention should be included in the transplant strategy in this patient population.

引用

页码：949 / 958

页数：10

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