Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta-analysis of studies over the last ten years.
chronic myeloid leukemia
first and second attempt
meta-analysis
tyrosine kinase inhibitors discontinuation
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
09
10
2019
accepted:
25
11
2019
pubmed:
20
2
2020
medline:
2
2
2021
entrez:
20
2
2020
Statut:
ppublish
Résumé
More than 10 years ago, the first pilot observational study of imatinib discontinuation was reported in chronic myeloid leukaemia (CML) patients in deep molecular response (DMR). Several studies have been published since then, in patients treated with frontline imatinib, or second-generation tyrosine kinase inhibitors (TKI) in first or second line but also on second attempt of TKI discontinuation. Our objective was to estimate, through meta-analyses of the literature data, the probability of molecular recurrence (MolRec) in the time periods of 0-6, 6-12, 12-18 and 18-24 months after a first and second TKI discontinuation and the probability of re-acquisition of DMR after MolRec. The Medline and Scopus databases were searched up to April 2019. The studies were selected by three independent reviewers. Random-effect meta-analyses were conducted using the MetaXL software. The probability of MolRec in the time periods 0-6, 6-12, 12-18 and 18-24 months after the first attempt was respectively 35%, 8%, 3% and 3%, whereas the probability of MolRec in the time periods 0-6, 6-12 and 12-18 after the second attempt was 48%, 27% and 12% respectively. Re-acquisition of a DMR was observed in 90% of patients. Most of the MolRec occur during the first six months in case of a first attempt, whereas the second MolRec occurs over a larger window of time.
Substances chimiques
Protein Kinase Inhibitors
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
452-468Informations de copyright
© 2020 British Society for Haematology and John Wiley & Sons Ltd.
Références
Campiotti, L., Suter, M.B., Guasti, L., Piazza, R., Gambacorti-Passerini, C., Grandi, A.M. & Squizzato, A. (2017) Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: a systematic review and a meta-analysis. European Journal of Cancer (Oxford, England: 1990), 77, 48-56.
Cerveira, N., Loureiro, B., Bizarro, S., Correia, C., Torres, L., Lisboa, S., Vieira, J., Santos, R., Pereira, D., Moreira, C., Chacim, S., Domingues, N., Espírito-Santo, A., Oliveira, I., Moreira, I., Viterbo, L., Martins, Â., Teixeira, M.R. & Mariz, J.M. (2018) Discontinuation of tyrosine kinase inhibitors in CML patients in real-world clinical practice at a single institution. BMC Cancer, 18, 1245.
Chamoun, K., Kantarjian, H., Atallah, R., Gonzalez, G.N., Issa, G.C., Rios, M.B., Garcia-Manero, G., Borthakur, G., Ravandi, F., Jain, N., Daver, N., Konopleva, M., DiNardo, C.D., Kadia, T., Pemmaraju, N., Jabbour, E. & Cortes, J. (2019) Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience. Journal of Hematology & Oncology, 12, 1.
Chen, K.-K., Du, T.-F., Xiong, P.-S., Fan, G.-H. & Yang, W. (2019) Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia with losing major molecular response as a definition for molecular relapse: a systematic review and meta-analysis. Frontiers in Oncology, 9, 372.
Clark, R.E., Polydoros, F., Apperley, J.F., Milojkovic, D., Rothwell, K., Pocock, C., Byrne, J., de Lavallade, H., Osborne, W., Robinson, L., O’Brien, S.G., Read, L., Foroni, L. & Copland, M. (2019) De-escalation of tyrosine kinase inhibitor therapy before complete treatment discontinuation in patients with chronic myeloid leukaemia (DESTINY): a non-randomised, phase 2 trial. The Lancet Haematology, 6, e375-e383.
Devos, T., Verhoef, G., Steel, E., Mazure, D., Lewalle, P., Bron, D., Berneman, Z., Benghiat, F.S., Mineur, P., Theunissen, K., Zachée, P., Doyen, C., Put, N., Lejeune, M., Van Eygen, K., Havelange, V., Reusens, M., Pluymers, W. & Peeters, K. (2019) Interruption or discontinuation of tyrosine kinase inhibitor treatment in chronic myeloid leukaemia: a retrospective cohort study (SPARKLE) in Belgium. Acta Haematologica, 142, 197-207.
Etienne, G., Guilhot, J., Rea, D., Rigal-Huguet, F., Nicolini, F., Charbonnier, A., Guerci-Bresler, A., Legros, L., Varet, B., Gardembas, M., Dubruille, V., Tulliez, M., Noel, M.-P., Ianotto, J.-C., Villemagne, B., Carré, M., Guilhot, F., Rousselot, P. & Mahon, F.-X. (2017) Long-term follow-up of the french stop imatinib (STIM1) study in patients with chronic myeloid leukemia. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 35, 298-305.
Fava, C., Rege-Cambrin, G., Dogliotti, I., Cerrano, M., Berchialla, P., Dragani, M., Rosti, G., Castagnetti, F., Gugliotta, G., Martino, B., Gambacorti-Passerini, C., Abruzzese, E., Elena, C., Pregno, P., Gozzini, A., Capodanno, I., Bergamaschi, M., Crugnola, M., Bocchia, M., Galimberti, S., Rapezzi, D., Iurlo, A., Cattaneo, D., Latagliata, R., Breccia, M., Cedrone, M., Santoro, M., Annunziata, M., Levato, L., Stagno, F., Cavazzini, F., Sgherza, N., Giai, V., Luciano, L., Russo, S., Musto, P., Caocci, G., Sorà, F., Iuliano, F., Lunghi, F., Specchia, G., Pane, F., Ferrero, D., Baccarani, M. & Saglio, G. (2019) Observational study of chronic myeloid leukemia Italian patients who discontinued tyrosine kinase inhibitors in clinical practice. Haematologica, 104, 1589-1596.
Ferrero, D., Cerrano, M., Crisà, E., Aguzzi, C., Giai, V. & Boccadoro, M. (2017) How many patients can proceed from chronic myeloid leukaemia diagnosis to deep molecular response and long-lasting imatinib discontinuation? A real life experience. British Journal of Haematology, 176, 669-671.
Fujisawa, S., Ueda, Y., Usuki, K., Kobayashi, H., Kondo, E., Doki, N., Nakao, T., Kanda, Y., Kosugi, N., Kosugi, H., Kumagai, T., Harada, H., Shikami, M., Maeda, Y., Sakura, T., Inokuchi, K., Saito, A., Nawa, Y., Ogasawara, M., Nishida, J., Kondo, T., Yoshida, C., Kuroda, H., Tabe, Y., Maeda, Y., Imajo, K., Kojima, K., Morita, S., Komukai, S., Kawaguchi, A., Sakamoto, J. & Kimura, S. (2019) Feasibility of the imatinib stop study in the Japanese clinical setting: delightedly overcome CML expert stop TKI trial (DOMEST Trial). International Journal of Clinical Oncology, 24, 445-453.
Gunnarsson, N., Sandin, F., Höglund, M., Stenke, L., Björkholm, M., Lambe, M., Olsson-Strömberg, U., Richter, J. & Själander, A. (2016) Population-based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence. European Journal of Haematology, 97, 387-392.
Hernández-Boluda, J.C., Pereira, A., Pastor-Galán, I., Alvarez-Larrán, A., Savchuk, A., Puerta, J.M., Sánchez-Pina, J.M., Collado, R., Díaz-González, A., Angona, A., Sagüés, M., García-Gutiérrez, V., Boqué, C., Osorio, S., Vallansot, R., Palomera, L., Mendizábal, A., Casado, L.F., Pérez-Encinas, M., Pérez-López, R., Ferrer-Marín, F., Sánchez-Guijo, F., García, C., de Las, N., Heras, J.L., López-Lorenzo, F.C., Steegmann, J.L. & Grupo Español de Leucemia Mieloide Crónica (GELMC) (2018) Feasibility of treatment discontinuation in chronic myeloid leukemia in clinical practice: results from a nationwide series of 236 patients. Blood Cancer Journal, 8, 91.
Higgins, J.P.T., Thompson, S.G., Deeks, J.J. & Altman, D.G. (2003) Measuring inconsistency in meta-analyses. BMJ (Clinical research ed.), 327, 557-560.
Hughes, T.P. & Ross, D.M. (2016) Moving treatment-free remission into mainstream clinical practice in CML. Blood, 128, 17-23.
Iino, M., Yamamoto, T. & Sakamoto, Y. (2019) Outcomes of unplanned tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: retrospective analysis of real-world experience in a single institution. Hematology (Amsterdam, Netherlands), 24, 355-361.
Imagawa, J., Tanaka, H., Okada, M., Nakamae, H., Hino, M., Murai, K., Ishida, Y., Kumagai, T., Sato, S., Ohashi, K., Sakamaki, H., Wakita, H., Uoshima, N., Nakagawa, Y., Minami, Y., Ogasawara, M., Takeoka, T., Akasaka, H., Utsumi, T., Uike, N., Sato, T., Ando, S., Usuki, K., Morita, S., Sakamoto, J., Kimura, S. &DADI Trial Group (2015) Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. The Lancet Haematology, 2, e528-535.
Kadowaki, N., Kawaguchi, T., Kuroda, J., Nakamae, H., Matsumura, I., Miyamoto, T., Ishikawa, J., Nagafuji, K., Imamura, Y., Yamazaki, H., Shimokawa, M., Akashi, K. & Kanakura, Y. (2016) Discontinuation of nilotinib in patients with chronic myeloid leukemia who have maintained deep molecular responses for at least 2 years: a multicenter Phase 2 Stop Nilotinib (Nilst) Trial. Blood, 128, 790-790.
Kim, D.D.H., Busque, L., Forrest, D.L., Savoie, L., Bence-Bruckler, I., Couban, S., Delage, R., Xenocostas, A., Liew, E., Laneuville, P., Paulson, K., Lipton, J.H., Kamel-Reid, S. & Leber, B. (2018) Second attempt of TKI discontinuation with dasatinib for treatment-free remission after failing first attempt with imatinib: treatment-free remission accomplished by dasatinib (TRAD) Trial. Blood, 132, 787-787.
Kumagai, T., Nakaseko, C., Nishiwaki, K., Yoshida, C., Ohashi, K., Takezako, N., Takano, H., Kouzai, Y., Murase, T., Matsue, K., Morita, S., Sakamoto, J., Wakita, H., Sakamaki, H., Inokuchi, K. & Kanto CML and Shimousa Hematology Study Groups (2018) Dasatinib cessation after deep molecular response exceeding 2 years and natural killer cell transition during dasatinib consolidation. Cancer Science, 109, 182-192.
Lee, S.-E., Choi, S.Y., Song, H.-Y., Kim, S.-H., Choi, M.-Y., Park, J.S., Kim, H.-J., Kim, S.-H., Zang, D.Y., Oh, S., Kim, H., Do, Y.R., Kwak, J.-Y., Kim, J.-A., Kim, D.-Y., Mun, Y.-C., Lee, W.S., Chang, M.H., Park, J., Kwon, J.H. & Kim, D.-W. (2016) Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study. Haematologica, 101, 717-723.
Legros, L., Rousselot, P., Giraudier, S., Tulliez, M., Huguet, F., Nicolini, F.-E. & Mahon, F.-X. (2012) Second attempt to discontinue imatinib in CP-CML patients with a second sustained complete molecular response. Blood, 120, 1959-1960.
Legros, L., Nicolini, F.E., Etienne, G., Rousselot, P., Rea, D., Giraudier, S., Guerci-Bresler, A., Huguet, F., Gardembas, M., Escoffre, M., Ianotto, J.-C., Noël, M.-P., Varet, B.R., Pagliardini, T., Touitou, I., Morisset, S., Mahon, F.-X. & French Intergroup for Chronic Myeloid Leukemias (2017) Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer, 123, 4403-4410.
Liberati, A., Altman, D.G., Tetzlaff, J., Mulrow, C., Gøtzsche, P.C., Ioannidis, J.P.A., Clarke, M., Devereaux, P.J., Kleijnen, J. & Moher, D. (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of Clinical Epidemiology, 62, e1-34.
Mahon, F.-X. (2016) Discontinuation of TKI therapy and ‘functional’ cure for CML. Best Practice & Research. Clinical Haematology, 29, 308-313.
Mahon, F.-X., Réa, D., Guilhot, J., Guilhot, F., Huguet, F., Nicolini, F., Legros, L., Charbonnier, A., Guerci, A., Varet, B., Etienne, G., Reiffers, J., Rousselot, P. & Intergroupe Français des Leucémies Myéloïdes Chroniques (2010) Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. The Lancet Oncology, 11, 1029-1035.
Mahon, F.X., Nicolini, F.E., Noël, M.-P., Escoffre, M., Charbonnier, A., Rea, D., Dubruille, V., Varet, B.R., Legros, L., Guerci, A., Etienne, G., Guilhot, F., Dulucq, S., Rousselot, P. & Guilhot, J. (2013) Preliminary report of the STIM2 study: a multicenter stop imatinib trial for chronic phase chronic myeloid leukemia de novo patients on imatinib. Blood, 122, 654-654.
Mahon, F.-X., Boquimpani, C., Kim, D.-W., Benyamini, N., Clementino, N.C.D., Shuvaev, V., Ailawadhi, S., Lipton, J.H., Turkina, A.G., De Paz, R., Moiraghi, B., Nicolini, F.E., Dengler, J., Sacha, T., Takahashi, N., Fellague-Chebra, R., Acharya, S., Wong, S., Jin, Y. & Hughes, T.P. (2018) Treatment-free remission after second-line nilotinib treatment in patients with chronic myeloid leukemia in chronic phase: results from a single-group, phase 2, open-label study. Annals of Internal Medicine, 168, 461-470.
Matsuki, E., Sakurai, M., Karigane, D., Kasahara, H., Kikuchi, T., Shimizu, T., Yokoyama, K., Mori, T. & Okamoto, S. (2016) Second attempt to discontinue TKI in CML patients who have sustained CMR for over 2 years is rarely successful even with the use of second generation TKIs. Blood, 128, 1887-1887.
Mori, S., Vagge, E., le Coutre, P., Abruzzese, E., Martino, B., Pungolino, E., Elena, C., Pierri, I., Assouline, S., D’Emilio, A., Gozzini, A., Giraldo, P., Stagno, F., Iurlo, A., Luciani, M., De Riso, G., Redaelli, S., Kim, D.-W., Pirola, A., Mezzatesta, C., Petroccione, A., D'Oria, A. L., Crivori, P., Piazza, R. & Gambacorti-Passerini, C. (2015) Age and dPCR can predict relapse in CML patients who discontinued imatinib: the ISAV study. American Journal of Hematology, 90, 910-914.
Nicolini, F.E., Dulucq, S., Boureau, L., Cony-Makhoul, P., Charbonnier, A., Escoffre-Barbe, M., Huguet-Rigal, F., Coiteux, V., Varet, B., Dubruille, V., Lenain, P. & Rousselot, P. (2019) The evaluation of residual disease by droplet digital PCR and TKI duration are critical predictive factors for molecular recurrence after stopping Imatinib first-line in chronic phase CML Patients: Results of the STIM2 study. Clinical Cancer Research, 25, 6606-6613.
Okada, M., Imagawa, J., Tanaka, H., Nakamae, H., Hino, M., Murai, K., Ishida, Y., Kumagai, T., Sato, S., Ohashi, K., Sakamaki, H., Wakita, H., Uoshima, N., Nakagawa, Y., Minami, Y., Ogasawara, M., Takeoka, T., Akasaka, H., Utsumi, T., Uike, N., Sato, T., Ando, S., Usuki, K., Mizuta, S., Hashino, S., Nomura, T., Shikami, M., Fukutani, H., Ohe, Y., Kosugi, H., Maeda, Y., Fukushima, T., Yamazaki, H., Tsubaki, K., Kukita, T., Adachi, Y., Nataduka, T., Sakoda, H., Yokoyama, H., Okamoto, T., Shirasugi, Y., Onishi, Y., Nohgawa, M., Yoshihara, S., Morita, S., Sakamoto, J., Kimura, S. & DADI Trial Group, Japan (2018) Final 3-year results of the dasatinib discontinuation trial in patients with chronic myeloid leukemia who received dasatinib as a second-line treatment. Clinical Lymphoma, Myeloma & Leukemia, 18, 353-360.e1.
Rea, D., Nicolini, F.E., Tulliez, M., Guilhot, F., Guilhot, J., Guerci-Bresler, A., Gardembas, M., Coiteux, V., Guillerm, G., Legros, L., Etienne, G., Pignon, J.-M., Villemagne, B., Escoffre-Barbe, M., Ianotto, J.-C., Charbonnier, A., Johnson-Ansah, H., Noel, M.-P., Rousselot, P., Mahon, F.-X. & France Intergroupe des Leucémies Myéloïdes Chroniques (2017) Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood, 129, 846-854.
Rea, D., Ame, S., Berger, M., Cayuela, J.-M., Charbonnier, A., Coiteux, V., Cony-Makhoul, P., Dubruille, V., Dulucq, S., Etienne, G., Legros, L., Nicolini, F., Roche-Lestienne, C., Escoffre-Barbe, M., Gardembas, M., Guerci-Bresler, A., Johnson-Ansah, H., Rigal-Huguet, F., Rousselot, P., Mahon, F.-X. & French Chronic Myeloid Leukemia Study Group (2018) Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: recommendations for clinical practice from the French Chronic Myeloid Leukemia Study Group. Cancer, 124, 2956-2963.
Ross, D.M., Branford, S., Seymour, J.F., Schwarer, A.P., Arthur, C., Yeung, D.T., Dang, P., Goyne, J.M., Slader, C., Filshie, R.J., Mills, A.K., Melo, J.V., White, D.L., Grigg, A.P. & Hughes, T.P. (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood, 122, 515-522.
Ross, D.M., Masszi, T., Gómez Casares, M.T., Hellmann, A., Stentoft, J., Conneally, E., Garcia-Gutierrez, V., Gattermann, N., le Coutre, P.D., Martino, B., Saussele, S., Giles, F.J., Radich, J.P., Saglio, G., Deng, W., Krunic, N., Bédoucha, V., Gopalakrishna, P. & Hochhaus, A. (2018a) Durable treatment-free remission in patients with chronic myeloid leukemia in chronic phase following frontline nilotinib: 96-week update of the ENESTfreedom study. Journal of Cancer Research and Clinical Oncology, 144, 945-954.
Ross, D.M., Pagani, I.S., Shanmuganathan, N., Kok, C.H., Seymour, J.F., Mills, A.K., Filshie, R.J., Arthur, C.K., Dang, P., Saunders, V.A., Braley, J., Yong, A.S., Yeung, D.T., White, D.L., Grigg, A.P., Schwarer, A.P., Branford, S., Hughes, T.P. & Australasian Leukaemia and Lymphoma Group (ALLG) (2018b) Long-term treatment-free remission of chronic myeloid leukemia with falling levels of residual leukemic cells. Leukemia, 32, 2572-2579.
Rousselot, P., Huguet, F., Rea, D., Legros, L., Cayuela, J.M., Maarek, O., Blanchet, O., Marit, G., Gluckman, E., Reiffers, J., Gardembas, M. & Mahon, F.-X. (2007) Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood, 109, 58-60.
Rousselot, P., Charbonnier, A., Cony-Makhoul, P., Agape, P., Nicolini, F.E., Varet, B., Gardembas, M., Etienne, G., Réa, D., Roy, L., Escoffre-Barbe, M., Guerci-Bresler, A., Tulliez, M., Prost, S., Spentchian, M., Cayuela, J.M., Reiffers, J., Chomel, J.C., Turhan, A., Guilhot, J. et al (2014) Loss of major molecular response as a trigger for restarting tyrosine kinase inhibitor therapy in patients with chronic-phase chronic myelogenous leukemia who have stopped imatinib after durable undetectable disease. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 32, 424-430.
Saussele, S., Richter, J., Guilhot, J., Gruber, F.X., Hjorth-Hansen, H., Almeida, A., Janssen, J.J.W.M., Mayer, J., Koskenvesa, P., Panayiotidis, P., Olsson-Strömberg, U., Martinez-Lopez, J., Rousselot, P., Vestergaard, H., Ehrencrona, H., Kairisto, V., Machová Poláková, K., Müller, M.C., Mustjoki, S., Berger, M.G., Fabarius, A., Hofmann, W.-K., Hochhaus, A., Pfirrmann, M., Francois-Xavier, M. &EURO-SKI Investigators (2018) Discontinuation of tyrosine kinase inhibitor therapy in chronic myeloid leukaemia (EURO-SKI): a prespecified interim analysis of a prospective, multicentre, non-randomised, trial. The Lancet Oncology, 19, 747-757.
Shah, N.P., Paquette, R., Müller, M.C., Saussele, S., Garcìa-Gutiérrez, V., Jiménez-Velasco, A., Nicolini, F.-E., Mauro, M.J., Mahon, F.-X., Rea, D., Martin-Regueira, P., Subar, M., Li, L. & Lipton, J.H. (2016) Treatment-free remission (TFR) in patients with chronic phase chronic myeloid leukemia (CML-CP) and in stable deep molecular response (DMR) to Dasatinib - the dasfree study. Blood, 128, 1895-1895.
Shah, N.P., Gutiérrez, J.V.G., Jiménez-Velasco, A., Larson, S., Saussele, S., Rea, D., Mahon, F.-X., Levy, M.Y., Gómez-Casares, M.T., Pane, F., Nicolini, F.-E., Mauro, M.J., Sy, O., Regueira, P.M. & Lipton, J.H. (2018) Updated 18-month results from dasfree: a study evaluating dasatinib discontinuation in patients (Pts) with chronic myeloid leukemia in chronic phase (CML-CP) and deep molecular response (DMR). Blood, 132, 4253-4253.
Takahashi, N., Kyo, T., Maeda, Y., Sugihara, T., Usuki, K., Kawaguchi, T., Usui, N., Okamoto, S., Ohe, Y., Ohtake, S., Kitamura, K., Yamamoto, M., Teshima, H., Motoji, T., Tamaki, T., Sawada, K. & Ohyashiki, K. (2012) Discontinuation of imatinib in Japanese patients with chronic myeloid leukemia. Haematologica, 97, 903-906.
Takahashi, N., Nishiwaki, K., Nakaseko, C., Aotsuka, N., Sano, K., Ohwada, C., Kuroki, J., Kimura, H., Tokuhira, M., Mitani, K., Fujikawa, K., Iwase, O., Ohishi, K., Kimura, F., Fukuda, T., Tanosaki, S., Takahashi, S., Kameoka, Y., Nishikawa, H., Wakita, H. et al (2018a) Treatment-free remission after two-year consolidation therapy with nilotinib in patients with chronic myeloid leukemia: STAT2 trial in Japan. Haematologica, 103, 1835-1842.
Takahashi, N., Tauchi, T., Kitamura, K., Miyamura, K., Saburi, Y., Hatta, Y., Miyata, Y., Kobayashi, S., Usuki, K., Matsumura, I., Minami, Y., Usui, N., Fukuda, T., Takada, S., Ishikawa, M., Fujimaki, K., Gomyo, H., Sasaki, O., Ohishi, K., Miyake, T. Naoe, T. & Japan Adult Leukemia Study Group (2018b) Deeper molecular response is a predictive factor for treatment-free remission after imatinib discontinuation in patients with chronic phase chronic myeloid leukemia: the JALSG-STIM213 study. International Journal of Hematology, 107, 185-193.