The impacts of BCR-ABL1 mutations in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia who underwent allogeneic hematopoietic cell transplantation.
Adolescent
Adult
Aged
Allografts
Antineoplastic Agents
/ therapeutic use
Combined Modality Therapy
Disease-Free Survival
Female
Follow-Up Studies
Fusion Proteins, bcr-abl
/ genetics
Hematopoietic Stem Cell Transplantation
Humans
Japan
/ epidemiology
Kaplan-Meier Estimate
Male
Middle Aged
Mutation, Missense
Philadelphia Chromosome
Point Mutation
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Prognosis
Protein Kinase Inhibitors
/ therapeutic use
Recurrence
Registries
Retrospective Studies
Treatment Outcome
Young Adult
Allogeneic hematopoietic cell transplantation
BCR-ABL1
Mutation
Ph + ALL
Prognosis
T315I
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Oct 2020
Oct 2020
Historique:
received:
03
06
2020
accepted:
01
08
2020
pubmed:
18
8
2020
medline:
2
10
2020
entrez:
18
8
2020
Statut:
ppublish
Résumé
The prognostic impacts of BCR-ABL1 fusion gene mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remain unknown. Using data from a nationwide Japanese registry, we have evaluated the prognostic impact of BCR-ABL1 mutations prior to the first allogeneic hematopoietic cell transplantation (HCT). The cohort included 289 patients with a median of 48 years of age (range: 16-70). Point mutations were detected in 110 patients. Of these, 90 (82%) harbored T315I mutations, while 20 had other mutations. With a median follow-up period of 29 months (range: 1-125), outcomes after 2 years were worse with mutations than without (overall survival [OS]: 34% vs 68%, p < 0.001; relapse rate [RR]: 48% vs 18%, p < 0.001), particularly with the presence of the T315I mutation (OS: 29% vs 68%, p < 0.001; RR: 54% vs 18%, p < 0.001). OS was significantly worse in the T315I group even among the cohort with hematological (p < 0.001) or molecular complete remission (p = 0.025) as compared to the no mutation group. Multivariate analysis determined the prognostic impact of the T315I mutation (OS: hazard ratio [HR] = 2.19, 95% confidence interval [CI]: 1.5-3.3, p < 0.001; RR: HR = 2.51, 95% CI: 1.5-4.2, p < 0.001). This study is the first to report on the prognostic significance of BCR-ABL1 mutations in Ph + ALL.
Identifiants
pubmed: 32803312
doi: 10.1007/s00277-020-04212-1
pii: 10.1007/s00277-020-04212-1
doi:
Substances chimiques
Antineoplastic Agents
0
BCR-ABL1 fusion protein, human
0
Protein Kinase Inhibitors
0
Fusion Proteins, bcr-abl
EC 2.7.10.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2393-2404Références
Takeuchi J, Kyo T, Naito K, Sao H, Takahashi M, Miyawaki S, Kuriyama K, Ohtake S, Yagasaki F, Murakami H, Asou N, Ino T, Okamoto T, Usui N, Nishimura M, Shinagawa K, Fukushima T, Taguchi H, Morii T, Mizuta S, Akiyama H, Nakamura Y, Ohshima T, Ohno R (2002) Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 16:1259–1266
pubmed: 12094249
Gleißner B, Gokbuget N, Bartram CR et al (2002) Leading prognostic relevance of the BCR-ABL translocation in adult acute B-lineage lymphoblastic leukemia: a prospective study of the German Multicenter Trial Group and confirmed polymerase chain reaction analysis. Blood 99:1536–1543
pubmed: 11861265
Dombret H, Gabert J, Boiron J-M, Rigal-Huguet F, Blaise D, Thomas X, Delannoy A, Buzyn A, Bilhou-Nabera C, Cayuela JM, Fenaux P, Bourhis JH, Fegueux N, Charrin C, Boucheix C, Lhéritier V, Espérou H, MacIntyre E, Vernant JP, Fière D, Groupe d'Etude et de Traitement de la Leucémie Aiguë Lymphoblastique de l'Adulte (GET-LALA Group) (2002) Outcome of treatment in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia—results of the prospective multicenter LALA-94 trial. Blood 100:2357–2366
pubmed: 12239143
Pullarkat V, Slovak ML, Kopecky KJ, Forman SJ, Appelbaum FR (2008) Impact of cytogenetics on the outcome of adult acute lymphoblastic leukemia: results of Southwest Oncology Group 9400 study. Blood 111:2563–2572
pubmed: 18156492
pmcid: 2254550
Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan A, Litzow MR, Lazarus HM, Foroni L, Dewald G, Franklin IM, Luger SM, Paietta E, Wiernik PH, Tallman MS, Goldstone AH (2009) Prospective outcome data on 267 unselected adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia confirms superiority of allogeneic transplantation over chemotherapy in the pre-imatinib era: results from the International ALL Trial MRC UKALLXII/ECOG2993. Blood 113:4489–4496
pubmed: 19244158
pmcid: 4188540
Yanada M, Takeuchi J, Sugiura I, Akiyama H, Usui N, Yagasaki F, Kobayashi T, Ueda Y, Takeuchi M, Miyawaki S, Maruta A, Emi N, Miyazaki Y, Ohtake S, Jinnai I, Matsuo K, Naoe T, Ohno R, Japan Adult Leukemia Study Group (2006) High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol 24:460–466
pubmed: 16344315
Mizuta S, Matsuo K, Yagasaki F, Yujiri T, Hatta Y, Kimura Y, Ueda Y, Kanamori H, Usui N, Akiyama H, Miyazaki Y, Ohtake S, Atsuta Y, Sakamaki H, Kawa K, Morishima Y, Ohnishi K, Naoe T, Ohno R (2011) Pre-transplant imatinib-based therapy improves the outcome of allogeneic hematopoietic stem cell transplantation for BCR–ABL-positive acute lymphoblastic leukemia. Leukemia 25:41–47
pubmed: 20944676
Thomas DA, Faderl S, Cortes J, O'Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, Beran M, Verstovsek S, Pierce S, Letvak L, Salvado A, Champlin R, Talpaz M, Kantarjian H (2004) Treatment of Philadelphia chromosome–positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103:4396–4407
pubmed: 14551133
Wassmann B, Pfeifer H, Goekbuget N, Beelen DW, Beck J, Stelljes M, Bornhäuser M, Reichle A, Perz J, Haas R, Ganser A, Schmid M, Kanz L, Lenz G, Kaufmann M, Binckebanck A, Brück P, Reutzel R, Gschaidmeier H, Schwartz S, Hoelzer D, Ottmann OG (2006) Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood 108:1469–1477
pubmed: 16638934
de Labarthe A, Rousselot P, Huguet-Rigal F et al (2007) Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study. Blood 109:1408–1413
pubmed: 17062730
Ottmann OG, Wassmann B, Pfeifer H, Giagounidis A, Stelljes M, Dührsen U, Schmalzing M, Wunderle L, Binckebanck A, Hoelzer D, for the GMALL Study Group (2007) Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Cancer 109:2068–2076
pubmed: 17429836
Vignetti M, Fazi P, Cimino G, Martinelli G, di Raimondo F, Ferrara F, Meloni G, Ambrosetti A, Quarta G, Pagano L, Rege-Cambrin G, Elia L, Bertieri R, Annino L, Foà R, Baccarani M, Mandelli F (2007) Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive acute lymphoblastic leukemia patients without additional chemotherapy: results of the GIMEMA LAL0201-B protocol. Blood 109:3676–3678
pubmed: 17213285
Foà R, Vitale A, Vignetti M, Meloni G, Guarini A, de Propris MS, Elia L, Paoloni F, Fazi P, Cimino G, Nobile F, Ferrara F, Castagnola C, Sica S, Leoni P, Zuffa E, Fozza C, Luppi M, Candoni A, Iacobucci I, Soverini S, Mandelli F, Martinelli G, Baccarani M, on behalf of the GIMEMA Acute Leukemia Working Party (2011) Dasatinib as first-line treatment for adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood 118:6521–6528
pubmed: 21931113
Rousselot P, Coudé MM, Gokbuget N, Gambacorti Passerini C, Hayette S, Cayuela JM, Huguet F, Leguay T, Chevallier P, Salanoubat C, Bonmati C, Alexis M, Hunault M, Glaisner S, Agape P, Berthou C, Jourdan E, Fernandes J, Sutton L, Banos A, Reman O, Lioure B, Thomas X, Ifrah N, Lafage-Pochitaloff M, Bornand A, Morisset L, Robin V, Pfeifer H, Delannoy A, Ribera J, Bassan R, Delord M, Hoelzer D, Dombret H, Ottmann OG, European Working Group on Adult ALL (EWALL) group (2016) Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL. Blood 128:774–782
pubmed: 27121472
pmcid: 5085255
Ravandi F, O'Brien S, Thomas D, Faderl S, Jones D, Garris R, Dara S, Jorgensen J, Kebriaei P, Champlin R, Borthakur G, Burger J, Ferrajoli A, Garcia-Manero G, Wierda W, Cortes J, Kantarjian H (2010) First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia. Blood 116:2070–2077
pubmed: 20466853
pmcid: 4081177
Yoon JH, Yhim HY, Kwak et al (2016) Minimal residual disease-based effect and long-term outcome of first-line dasatinib combined with chemotherapy for adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Ann Oncol 27:1081–1088
pubmed: 26951627
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DeAngelo DJ, Abruzzese E, Rea D, Baccarani M, Müller MC, Gambacorti-Passerini C, Lustgarten S, Rivera VM, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes TP, Shah NP, Kantarjian HM (2018) Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood 132:393–404
pubmed: 29567798
pmcid: 6071555
Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre P, Paquette R, Chuah C, Nicolini FE, Apperley JF, Khoury HJ, Talpaz M, DiPersio J, DeAngelo D, Abruzzese E, Rea D, Baccarani M, Müller MC, Gambacorti-Passerini C, Wong S, Lustgarten S, Rivera VM, Clackson T, Turner CD, Haluska FG, Guilhot F, Deininger MW, Hochhaus A, Hughes T, Goldman JM, Shah NP, Kantarjian H, PACE Investigators (2013) A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 369:1783–1796
pubmed: 24180494
Jabbour E, Short NJ, Ravandi F, Huang X, Daver N, DiNardo CD, Konopleva M, Pemmaraju N, Wierda W, Garcia-Manero G, Sasaki K, Cortes J, Garris R, Khoury JD, Jorgensen J, Jain N, Alvarez J, O'Brien S, Kantarjian H (2018) Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol 5:e618–e627
pubmed: 30501869
Sasaki K, Jabbour EJ, Ravandi F, Short NJ, Thomas DA, Garcia-Manero G, Daver NG, Kadia TM, Konopleva MY, Jain N, Issa GC, Jeanis V, Moore HG, Garris RS, Pemmaraju N, Cortes JE, O'Brien SM, Kantarjian HM (2016) Hyper-CVAD plus ponatinib versus hyper-CVAD plus dasatinib as frontline therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a propensity score analysis. Cancer 122:3650–3656
pubmed: 27479888
pmcid: 5321539
Hematopoietic Cell Transplantation in Japan. Annual Report of Nationwide Survey 2018 (2018) The Japanese Data Center for Hematopoietic Cell Transplantation/The Japan Society for Hematopoietic Cell Transplantation
Soverini S, De Benedittis C, Papayannidis C et al (2014) Drug resistance and BCR-ABL kinase domain mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia from the imatinib to the second-generation tyrosine kinase inhibitor era: the main changes are in the type of mutations, but not in the frequency of mutation involvement. Cancer 120:1002–1009
pubmed: 24382642
DeBoer R, Koval G, Mulkey F, Wetzler M, Devine S, Marcucci G, Stone RM, Larson RA, Bloomfield CD, Geyer S, Mullighan CG, Stock W (2016) Clinical impact of ABL1 kinase domain mutations and IKZF1 deletion in adults under age 60 with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL): molecular analysis of CALGB (Alliance) 10001 and 9665. Leuk Lymphoma 57:2298–2306
pubmed: 26892479
pmcid: 5008253
Ono T, Miyawaki S, Kimura F, Kanamori H, Ohtake S, Kitamura K, Fujita H, Sugiura I, Usuki K, Emi N, Tamaki S, Aoyama Y, Kaya H, Naoe T, Tadokoro K, Yamaguchi T, Ohno R, Ohnishi K, Japan Adult Leukemia Study Group (2011) BCR-ABL1 mutations in patients with imatinib-resistant Philadelphia chromosome-positive leukemia by use of the PCR-Invader assay. Leuk Res 35:598–603
pubmed: 21239056
Nicolini FE, Basak GW, Soverini S, Martinelli G, Mauro MJ, Müller MC, Hochhaus A, Chuah C, Dufva IH, Rege-Cambrin G, Saglio G, Michallet M, Labussière H, Morisset S, Hayette S, Etienne G, Olavarria E, Zhou W, Peter S, Apperley JF, Cortes J (2011) Allogeneic stem cell transplantation for patients harboring T315I BCR-ABL mutated leukemias. Blood 118:5697–5700
pubmed: 21926354
pmcid: 4916555
Nicolini FE, Basak GW, Kim DW, Olavarria E, Pinilla-Ibarz J, Apperley JF, Hughes T, Niederwieser D, Mauro MJ, Chuah C, Hochhaus A, Martinelli G, DerSarkissian M, Duh MS, McGarry LJ, Kantarjian HM, Cortes JE (2017) Overall survival with ponatinib versus allogeneic stem cell transplantation in Philadelphia chromosome-positive leukemias with the T315I mutation. Cancer 123:2875–2880
pubmed: 28387926
pmcid: 5573914
Ray A, Cowan-Jacob SW, Manley PW, Mestan J, Griffin JD (2007) Identification of BCR-ABL point mutations conferring resistance to the Abl kinase inhibitor AMN107 (nilotinib) by a random mutagenesis study. Blood 109:5011–5015
pubmed: 17303698
Deininger M, Buchdunger E, Druker BJ (2005) The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 105:2640–2653
pubmed: 15618470
Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15:1628–1633
pubmed: 19896087
pmcid: 2861656
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 15:825–828
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi MS, Storb R, Donnall Thomas E (1980) Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 69:204–217
pubmed: 6996481
Kanda Y (2013) Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 48:452–458
Alikian M, Gerrard G, Subramanian PG, Mudge K, Foskett P, Khorashad JS, Lim AC, Marin D, Milojkovic D, Reid A, Rezvani K, Goldman J, Apperley J, Foroni L (2012) BCR-ABL1 kinase domain mutations: methodology and clinical evaluation. Am J Hematol 87:298–304
pubmed: 22231203
Soverini S, Bavaro L, Martelli M, de Benedittis C, Iurlo A, Orofino N, Pagano L, Criscuolo M, Bonifacio M, Scaffidi L, Sica S, Sorà F, Maino E, Rondoni M, Laginestra MA, Lunghi F, Ermacora A, D'adda M, Gugliotta G, Castagnetti F, Rosti G, Papayannidis C, Marconi G, Curti A, Miggiano MC, Galimberti S, Percesepe A, Stagno F, Sancetta R, Annunziata M, Falzetti F, Capodanno I, Pregno P, Maffioli M, Intermesoli T, di Bona E, Caocci G, Attolico I, Binotto G, Bocchia M, Angelucci E, Sgherza N, Luciano L, Mignone F, Pileri SA, Martinelli G, Cavo M (2018) Compound BCR-ABL1 kinase domain mutants: prevalence, spectrum and correlation with tyrosine kinase inhibitor resistance in a prospective series of Philadelphia chromosome-positive leukemia patients analyzed by next generation sequencing. Blood 132:789
Watanabe K, Minami Y, Ozawa Y, Miyamura K, Naoe T (2012) T315I mutation in Ph-positive acute lymphoblastic leukemia is associated with a highly aggressive disease phenotype: three case reports. Anticancer Res 32:1779–1783
pubmed: 22593461
Tachibana T, Koyama S, Andou T, Ishiyama Y, Tanaka M, Nakajima H, Kanamori H (2019) Salvage and bridging to allogeneic hematopoietic cell transplantation with ponatinib in patients with relapsed or refractory Philadelphia chromosome-positive leukemia. Int J Hematol 109:162–168
pubmed: 30511314
Kantarjian HM, DeAngelo DJ, Stelljes M et al (2016) Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med 375:740–753
pubmed: 27292104
pmcid: 5594743
Martinelli G, Boissel N, Chevallier P, Ottmann O, Gökbuget N, Topp MS, Fielding AK, Rambaldi A, Ritchie EK, Papayannidis C, Sterling LR, Benjamin J, Stein A (2017) Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol 35:1795–1802
pubmed: 28355115
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH (2013) Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med 368:1509–1518
pubmed: 23527958
pmcid: 4058440
Krishna Chandran R, Geetha N, Sakthivel KM, Suresh Kumar R, Jagathnath Krishna KMN, Sreedharan H (2019) Impact of Additional chromosomal aberrations on the disease progression of chronic myelogenous leukemia. Front Oncol 9:88
pubmed: 30891424
pmcid: 6411713
Wang W, Cortes JE, Tang G et al (2016) Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. Blood 27:2742–2750
Akahoshi Y, Mizuta S, Shimizu H, Uchida N, Fukuda T, Kanamori H, Onizuka M, Ozawa Y, Ohashi K, Ohta S, Eto T, Tanaka J, Atsuta Y, Kako S, Adult Acute Lymphoblastic Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation (2018) Additional cytogenetic abnormalities with Philadelphia chromosome-positive acute lymphoblastic leukemia on allogeneic stem cell transplantation in the tyrosine kinase inhibitor era. Biol Blood Marrow Transplant 24:2009–2016
pubmed: 29908230
Ottmann OG, Pfeifer H (2009) Management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Hematology Am Soc Hematol Educ Program:371–381
Lussana F, Intermesoli T, Gianni F, Boschini C, Masciulli A, Spinelli O, Oldani E, Tosi M, Grassi A, Parolini M, Audisio E, Cattaneo C, Raimondi R, Angelucci E, Cavattoni IM, Scattolin AM, Cortelezzi A, Mannelli F, Ciceri F, Mattei D, Borlenghi E, Terruzzi E, Romani C, Bassan R, Rambaldi A (2016) Achieving molecular remission before allogeneic stem cell transplantation in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: impact on relapse and long-term outcome. Biol Blood Marrow Transplant 22:1983–1987
pubmed: 27492792
Nishiwaki S, Imai K, Mizuta S et al (2016) Impact of MRD and TKI on allogeneic hematopoietic cell transplantation for Ph+ALL: a study from the adult ALL WG of the JSHCT. Bone Marrow Transplant 51:43–50
pubmed: 26389833
Tucunduva L, Ruggeri A, Sanz G, Furst S, Cornelissen J, Linkesch W, Mannone L, Ribera JM, Veelken H, Yakoub-Agha I, González Valentín ME, Schots R, Arcese W, Montesinos P, Labopin M, Gluckman E, Mohty M, Rocha V (2014) Impact of minimal residual disease on outcomes after umbilical cord blood transplantation for adults with Philadelphia-positive acute lymphoblastic leukaemia: an analysis on behalf of Eurocord, Cord Blood Committee and the Acute Leukaemia working party of the European group for Blood and Marrow Transplantation. Br J Haematol 166:749–757
pubmed: 24961645
Giebel S, Czyz A, Ottmann O, Baron F, Brissot E, Ciceri F, Cornelissen JJ, Esteve J, Gorin NC, Savani B, Schmid C, Mohty M, Nagler A (2016) Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a position statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Cancer 122:2941–2951
pubmed: 27309127
DeFilipp Z, Langston AA, Chen Z, Zhang C, Arellano ML, el Rassi F, Flowers CR, Kota VK, al-Kadhimi Z, Veldman R, Jillella AP, Lonial S, Waller EK, Khoury HJ (2016) Does post-transplant maintenance therapy with tyrosine kinase inhibitors improve outcomes of patients with high-risk Philadelphia chromosome-positive leukemia? Clin Lymphoma Myeloma Leuk 16:466–471
pubmed: 27297665
Pfeifer H, Wassmann B, Bethge W et al (2013) Randomized comparison of prophylactic and minimal residual disease-triggered imatinib after allogeneic stem cell transplantation for BCR-ABL1-positive acute lymphoblastic leukemia. Leukemia 27:1254–1262
pubmed: 23212150