La prise en charge de la leucémie aigue lymphoblastique B avec chromosome Philadelphie positif en Tunisie
DOI :
https://doi.org/10.62438/tunismed.v104i02.6158Mots-clés :
Leucémie aigüe lymphoblastique, Chromsome Philadelphie, inhibiteurs de tyrosine kinase, pronostic, Profil clinique, chimiothérapieRésumé
Introduction : La prise en charge de la leucémie aiguë lymphoblastique B avec chromosome Philadelphie positif (LAL B Ph+) est en progression. Les données tunisiennes sur ce sujet restent limitées.
Objectif : Notre objectif était de décrire le profil clinique et pronostique ainsi que les résultats thérapeutiques de la LAL B Ph+.
Méthodes : Il s’agissait d’une étude rétrospective et descriptive menée au service d’hématologie clinique adulte de l’hôpital Aziza Othmana sur
12 ans. Nous avons inclus les patients âgés entre 18 et 60 ans, diagnostiqués LAL B Ph+ de novo ou secondaire, et traités par une association
chimiothérapie et inhibiteur de tyrosine kinase (ITK).
Résultats : Nous avons colligé 36 patients avec une atteinte initiale du système nerveux central dans un cas. Le GRAAPH-2005 était le protocole
le plus utilisé (n=29). Trente-quatre patients ont reçu un ITK : imatinib (n=28) et dasatinib (n=6). Après l’induction, tous étaient en rémission
cytologique. Une réponse moléculaire était obtenue chez 52 % des 21 patients évalués. Après consolidation, 17 avaient une évaluation de la
réponse moléculaire, avec 13 en rémissions moléculaires. Sept étaient allogreffés et deux autogreffés. Quatorze ont rechuté, avec un délai médian de 18 mois [4-42] de début de l’ITK. La survie globale, la survie sans rechute et la survie sans événements à 5 ans étaient respectivement de 25 %, ,22% et 22%.
Conclusion : Notre étude a souligné les obstacles rencontrés dans la prise en charge de la LAL B Ph+ en Tunisie. Leur résolution pourrait améliorer
les résultats thérapeutiques.
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Foà R, Chiaretti S. Philadelphia chromosome positive acute lymphoblastic leukemia. N Engl J Med. 2022 Jun;386(25):2399-411.
Abou Dalle I, Jabbour E, Short NJ, Ravandi F. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Curr Treat Options Oncol. 2019 Jan;20(1):1-13.
Haddad FG, Sawyers J, Short NJ. Treatment de-escalation in Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia: the emerging role of chemotherapy-free regimens. Ther Adv Hematol. 2023 Feb;14:1-10.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the world health organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May;127(20):2391-405.
Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European group for the immunological characterization of leukemias (EGIL). Leukemia. 1995 Oct;9(10):1783-6.
Chalandon Y, Thomas X, Hayette S, Cayuela JM, Abbal C, Huguet F, et al. Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood. 2015 Jun;125(24):3711-9.
Rousselot P, Chalandon Y, Chevret S, Cayuela JM, Huguet F, Chevallier P, et al. The omission of high-dose cytarabine during consolidation therapy of ph-positive all patients treated with nilotinib and low-intensity chemotherapy results in an increased risk of relapses despite non-inferior levels of late BCR-ABL1 MRD response. First results of the randomized graaph-2014 study. Blood. 2021 Nov;138 Suppl 1:1-9.
Rousselot P, Coudé MM, Gokbuget N, Gambacorti Passerini C, Hayette S, Cayuela JM, et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome– positive ALL. Blood. 2016 Aug;128(6):774-82.
Daver N, Thomas D, Ravandi F, Cortes J, Garris R, Jabbour E, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015 May;100(5):653-61.
Ribera JM, García Calduch O, Ribera J, Montesinos P, Cano Ferri I, Martínez P, et al. Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood Adv. 2022 Sep;6(18):5395-402.
Tanguy Schmidt A, Rousselot P, Chalandon Y, Cayuela JM, Hayette S, Vekemans MC, et al. Long-term follow-up of the imatinib GRAAPH-2003 study in newly diagnosed patients with de novo philadelphia chromosome-positive acute lymphoblastic leukemia: a GRAALL study. Biol Blood Marrow Transplant. 2013 Jan;19(1):150-5.
Schultz KR, Bowman WP, Aledo A, Slayton WB, Sather H, Devidas M, et al. Improved early event-free survival with imatinib in philadelphia chromosome–positive acute lymphoblastic leukemia: a children’s oncology group study. J Clin Oncol. 2009 Nov;27(31):5175-81.
Ottmann OG, Wassmann B, Pfeifer H, Giagounidis A, Stelljes M, Dührsen U, et al. Imatinib compared with chemotherapy as front- line treatment of elderly patients with Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph+ALL). Cancer. 2007 Feb;109(10):2068-76.
Hatta Y, Mizuta S, Matsuo K, Ohtake S, Iwanaga M, Sugiura I, et al. Final analysis of the JALSG Ph+ALL202 study: tyrosine kinase inhibitor-combined chemotherapy for Ph+ALL. Ann Hematol. 2018 Sep;97(9):1535-45.
Kano Y, Akutsu M, Tsunoda S, Mano H, Sato Y, Honma Y, et al. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood. 2001 Apr;97(7):1999-2007.
Topaly J, Zeller WJ, Fruehauf S. Combination therapy with imatinib mesylate (sti571): synopsis of in vitro studies. Br J Haematol. 2002 Oct;119(1):3-14.
Bassan R, Rossi G, Pogliani EM, Di Bona E, Angelucci E, Cavattoni I, et al. Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: northern italy leukemia group protocol 09/00. J Clin Oncol. 2010 Aug;28(22):3644-52.
Ottmann O, Dombret H, Martinelli G, Simonsson B, Guilhot F, Larson RA, et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome– positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007 Oct;110(7):2309-15.
Ravandi F, O’Brien S, Cortes J, Thomas D, Garris R, Faderl S, et al. Long-term follow-up of phase II study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia- chromosome positive acute lymphoblastic leukemia. Cancer. 2015 Dec;121(23):4158-64.
Soverini S, De Benedittis C, Papayannidis C, Paolini S, Venturi C, Iacobucci I, et al. 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. 2014 Apr;120(7):1002-9.
O’Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, et al. AP24534, a Pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell. 2009 Nov;16(5):401-12.
Jabbour E, Kantarjian H, Ravandi F, Thomas D, Huang X, Faderl S, et al. First report of a phase II prospective study of combination of hyper-CVAD with ponatinib in frontline therapy of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.Lancet Oncol. 2015 Nov;16(15):1547-55.
Jabbour E, Der Sarkissian M, Duh MS, McCormick N, Cheng WY, McGarry LJ, et al. Efficacy of ponatinib versus earlier generation tyrosine kinase inhibitors for front-line treatment of newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Clin Lymphoma Myeloma Leuk. 2018 Apr;18(4):257-65.
Aldoss I, Stiller T, Cao TM, Palmer JM, Thomas SH, Forman SJ, et al. The impact of additional cytogenetic abnormalities in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015 Jul;21(7):1326-9.
Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, et al. 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. 2009 May;113(19):4489-96.
Saleh K, Fernandez A, Pasquier F. Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia in adults. Cancers. 2022 Apr;14(7):1-24.
Ponvilawan B, Kungwankiattichai S, Charoenngam N, Owattanapanich W. Is stem cell transplantation still needed for
adult Philadelphia chromosome-positive acute lymphoblastic leukemia receiving tyrosine kinase inhibitors therapy?: a systematic review and meta-analysis. PLoS One. 2021 Jun;16(6):1-21.
Ravandi F. How I treat Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood. 2019 Jan;133(2):130-6.
Zeng Q, Xiang B, Liu Z. Comparison of allogeneic hematopoietic stem cell transplantation and TKI combined with chemotherapy for adult philadelphia chromosome positive acute lymphoblastic leukemia: a systematic review and meta-analysis. Cancer Med. 2021 Dec;10(24):8741-53.
Fujisawa S, Mizuta S, Akiyama H, Ueda Y, Aoyama Y, Hatta Y, et al. Phase II study of imatinib-based chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Am J Hematol. 2017 Apr;92(4):367-74.
Candoni A, Rambaldi A, Fanin R, Velardi A, Arcese W, Ciceri F, et al. Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with philadelphia chromosome-positive acute lymphoblastic leukemia in the era of tyrosine kinase inhibitors: a registry-based study of the italian blood and marrow transplantation society (GITMO). Biol Blood Marrow Transplant. 2019 Dec;25(12):2388-97.
Giebel S, Labopin M, Potter M, Poiré X, Sengeloev H, Socié G, et al. Comparable results of autologous and allogeneic haematopoietic stem cell transplantation for adults with philadelphia-positive acute lymphoblastic leukaemia in first complete molecular remission: an analysis by the acute leukemia working party of the EBMT. Eur J Cancer. 2018 Jun;96:73-81.
Shin HJ, Chung JS, Cho GJ. Imatinib interim therapy between chemotherapeutic cycles and in vivo purging prior to autologous stem cell transplantation, followed by maintenance therapy is a feasible treatment strategy in philadelphia chromosome-positive acute lymphoblastic leukemia. Bone Marrow Transplant. 2005 Nov;36(10):917-8.
Wetzler M, Watson D, Stock W, Koval G, Mulkey FA, Hoke EE, et al. Autologous transplantation for philadelphia chromosome-positive acute lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation: results of CALGB study 10001 (alliance). Haematologica. 2014 Jan;99(1):111-5.
Leo C, Mathieu L, Emmanuel J, Ivan S, Orianne W, Alexis C, et al. Long-term outcomeafter autologous BCR::ABL1-negative peripheral blood stem cell transplantation in adults with Philadelphia-positive acute lymphoblastic leukemia: a comparative study. Haematologica. 2024 Apr;109(4): 1264-68.
Short NJ, Jabbour E, Sasaki K, Patel K, O’Brien SM, Cortes JE, et al. Impact of complete molecular response on survival in patients with philadelphia chromosome–positive acute lymphoblastic leukemia. Blood. 2016 Jul;128(4):504-7.
Ravandi F, Jorgensen JL, Thomas DA, O’Brien S, Garris R, Faderl S, et al. Detection of MRD may predict the outcome of patientswith philadelphia chromosome–positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood. 2013 Aug;122(7):1214-21.
Kim DY, Joo YD, Lim SN, Kim SD, Lee JH, Lee JH, et al. Nilotinib combined with multiagent chemotherapy for newly diagnosed philadelphia-positive acute lymphoblastic leukemia. Blood. 2015 Aug;126(6):746-56.
Short NJ, Jabbour E, Sasaki K, Patel K, O’Brien SM, Cortes JE, et al. Impact of complete molecular response on survival in patients with philadelphia chromosome–positive acute lymphoblastic leukemia. Blood. 2016 Jul;128(4):504-7.
Xiangyu ZH, Xiaosu ZH, Huan CH, Yazhen QI, Lanping XU, Xiaohui ZH, et al.Comparative analysis of flow cytometry and RQ-PCR for the detection of minimal residual disease in Philadelphia chromosome– positive acute lymphoblastic leukemia after hematopoietic stem cell transplantation. Biology Of Blood And Marrow Transplantation.
Sept; 24(9):1936-44.
Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al. Dasatinib–blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020 Oct;383(17):1613-23
Jabbour E, Short NJ, Jain N, Huang X, Montalban Bravo G, Banerjee P, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023 Jan;10(1):24-34.
Giovanni M, Nicolas B, Patrice C, Oliver O, Nicola G, Max S T, et al. 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. 2017 Jun; 35(16):1795-02
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