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Annals of Hematology

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22.09.2020 | Original Article

Comparative study on allogeneic with autologous hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia in the era of TKIs: a systematic review and meta-analysis

verfasst von: Haichen Wei, Pu Kuang, Ting Liu

Erschienen in: Annals of Hematology | Ausgabe 11/2020

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Abstract

In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06–1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86–1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22–1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03–24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.

Moorman AV, Harrison CJ, Buck GA et al (2007) Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood 109:3189–3197. https://doi.org/10.1182/blood-2006-10-051912CrossRefPubMed

Burmeister T, Schwartz S, Bartram CR et al (2008) Patients’ age and BCR-ABL frequency in adult B-precursor ALL: a retrospective analysis from the GMALL study group. Blood 112:918–919. https://doi.org/10.1182/blood-2008-04-149286CrossRefPubMed

Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, Kovacsovics T, Delannoy A, Fegueux N, Fenaux P, Stamatoullas A, Vernant JP, Tournilhac O, Buzyn A, Reman O, Charrin C, Boucheix C, Gabert J, Lhéritier V, Fiere D (2004) Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 22:4075–4086. https://doi.org/10.1200/JCO.2004.10.050CrossRefPubMed

Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ, Marks DI, McMillan AK, 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. https://doi.org/10.1182/blood-2009-01-199380CrossRefPubMedPubMedCentral

National Comprehensive Cancer Network. Acute Lymphoblastic Leukemia (Adult and AYA). (Version2.2019). https://www.nccn.org/professionals/physiciangls/pdf/allblocks.pdf

Ribera JM, Oriol A, González M et al (2010) Concurrent intensive chemotherapy and imatinib before and after stem cell transplantation in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia. Final results of the CSTIBES02 trial. Haematologica 95:87–95. https://doi.org/10.3324/haematol.2009.011221CrossRefPubMed

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. https://doi.org/10.1038/leu.2010.228CrossRefPubMed

Chalandon Y, Thomas X, Hayette S, Cayuela JM, Abbal C, Huguet F, Raffoux E, Leguay T, Rousselot P, Lepretre S, Escoffre-Barbe M, Maury S, Berthon C, Tavernier E, Lambert JF, Lafage-Pochitaloff M, Lhéritier V, Chevret S, Ifrah N, Dombret H, Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) (2015) Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia. Blood 125:3711–3719. https://doi.org/10.1182/blood-2015-02-627935CrossRefPubMed

Kanfar SS, Chan SM, Gupta V, Schimmer AD, Schuh AC, Sibai H, Yee KWL, Minden MD (2016) Outcomes of adult Philadelphia positive acute lymphoblastic leukemia patients treated with pediatric multi-agent chemotherapy and imatinib and the impact of residual disease monitoring on survival. Blood 128:3976CrossRef

10.

Giebel S, Labopin M, Gorin NC, Caillot D, Leguay T, Schaap N, Michallet M, Dombret H, Mohty M (2014) Improving results of autologous stem cell transplantation for Philadelphia-positive acute lymphoblastic leukaemia in the era of tyrosine kinase inhibitors: a report from the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation. Eur J Cancer 50:411–417. https://doi.org/10.1016/j.ejca.2013.08.027CrossRefPubMed

11.

Wetzler M, Watson D, Stock W, Koval G, Mulkey FA, Hoke EE, McCarty JM, Blum WG, Powell BL, Marcucci G, Bloomfield CD, Linker CA, Larson RA (2014) Autologous transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation: results of CALGB Study 10001 (Alliance). Haematologica 99:111–115. https://doi.org/10.3324/haematol.2013.085811CrossRefPubMedPubMedCentral

12.

Duarte RF, Labopin M, Bader P et al (2019) Indications for haematopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2019. Bone Marrow Transplant 54:1525–1552. https://doi.org/10.1038/s41409-019-0516-2CrossRefPubMed

13.

Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C (2013) Assessing bias in studies of prognostic factors. Ann Intern Med 158:280–286. https://doi.org/10.7326/0003-4819-158-4-201302190-00009CrossRefPubMed

14.

Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16. https://doi.org/10.1186/1745-6215-8-16CrossRefPubMedPubMedCentral

15.

Bassan R, Rossi G, Pogliani EM, di Bona E, Angelucci E, Cavattoni I, Lambertenghi-Deliliers G, Mannelli F, Levis A, Ciceri F, Mattei D, Borlenghi E, Terruzzi E, Borghero C, Romani C, Spinelli O, Tosi M, Oldani E, Intermesoli T, Rambaldi A (2010) 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 28:3644–3652. https://doi.org/10.1200/JCO.2010.28.1287CrossRefPubMed

16.

Tanguy-Schmidt A, Rousselot P, Chalandon Y, Cayuela JM, Hayette S, Vekemans MC, Escoffre M, Huguet F, Réa D, Delannoy A, Cahn JY, Vernant JP, Ifrah N, Dombret H, Thomas X (2013) 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 19:150–155. https://doi.org/10.1016/j.bbmt.2012.08.021CrossRefPubMed

17.

Giebel S, Labopin M, Potter M, Poiré X, Sengeloev H, Socié G, Huynh A, Afanasyev BV, Schanz U, Ringden O, Kalhs P, Beelen DW, Campos AM, Masszi T, Canaani J, Mohty M, Nagler A (2018) 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 96:73–81. https://doi.org/10.1016/j.ejca.2018.03.018CrossRefPubMed

18.

Oliansky DM, Larson RA, Weisdorf D et al (2012) The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 evidence-based review. Biol Blood Marrow Transplant 18:18–36.e6. https://doi.org/10.1016/j.bbmt.2011.07.019CrossRefPubMed

19.

Ravandi F, Jorgensen JL, Thomas DA, O’Brien S, Garris R, Faderl S, Huang X, Wen S, Burger JA, Ferrajoli A, Kebriaei P, Champlin RE, Estrov Z, Challagundla P, Wang SA, Luthra R, Cortes JE, Kantarjian HM (2013) Detection of MRD may predict the outcome of patients with Philadelphia chromosome-positive ALL treated with tyrosine kinase inhibitors plus chemotherapy. Blood 122:1214–1221. https://doi.org/10.1182/blood-2012-11-466482CrossRefPubMedPubMedCentral

20.

Short NJ, Jabbour E, Sasaki K et al (2016) Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood 128:504–507. https://doi.org/10.1182/blood-2016-03-707562CrossRefPubMedPubMedCentral

21.

Yoon JH, Yhim HY, Kwak JY, Ahn JS, Yang DH, Lee JJ, Kim SJ, Kim JS, Park SJ, Choi CW, Eom HS, Park SK, Choi SY, Kim SH, Kim DW, Lee S (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. https://doi.org/10.1093/annonc/mdw123CrossRefPubMed

22.

Yoon JH, Min GJ, Park SS, Jeon YW, Lee SE, Cho BS, Eom KS, Kim YJ, Kim HJ, Min CK, Cho SG, Kim DW, Lee JW, Lee S (2019) Minimal residual disease-based long-term efficacy of reduced-intensity conditioning versus myeloablative conditioning for adult Philadelphia-positive acute lymphoblastic leukemia. Cancer 125:873–883. https://doi.org/10.1002/cncr.31874CrossRefPubMed

23.

Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, Baccarani M, Cortes J, Cross NC, Druker BJ, Gabert J, Grimwade D, Hehlmann R, Kamel-Reid S, Lipton JH, Longtine J, Martinelli G, Saglio G, Soverini S, Stock W, Goldman JM (2006) Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 108:28–37. https://doi.org/10.1182/blood-2006-01-0092CrossRefPubMedPubMedCentral

24.

Pfeifer H, Cazzaniga G, van der Velden V et al (2019) Standardisation and consensus guidelines for minimal residual disease assessment in Philadelphia-positive acute lymphoblastic leukemia (Ph + ALL) by real-time quantitative reverse transcriptase PCR of e1a2 BCR-ABL1. Leukemia 33:1910–1922. https://doi.org/10.1038/s41375-019-0413-0CrossRefPubMed

25.

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. https://doi.org/10.1002/cncr.28522CrossRefPubMed

26.

Soverini S, Bassan R, Lion T (2019) Treatment and monitoring of Philadelphia chromosome-positive leukemia patients: recent advances and remaining challenges. J Hematol Oncol 12:39. https://doi.org/10.1186/s13045-019-0729-2CrossRefPubMedPubMedCentral

27.

O'Hare T, Shakespeare WC, Zhu X, Eide CA, Rivera VM, Wang F, Adrian LT, Zhou T, Huang WS, Xu Q, Metcalf CA III, Tyner JW, Loriaux MM, Corbin AS, Wardwell S, Ning Y, Keats JA, Wang Y, Sundaramoorthi R, Thomas M, Zhou D, Snodgrass J, Commodore L, Sawyer TK, Dalgarno DC, Deininger MWN, Druker BJ, Clackson T (2009) AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell 16:401–412. https://doi.org/10.1016/j.ccr.2009.09.028CrossRefPubMedPubMedCentral

28.

Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, O'Hare T, Hu S, Narasimhan NI, Rivera VM, Clackson T, Turner CD, Haluska FG, Druker BJ, Deininger MWN, Talpaz M (2012) Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med 367:2075–2088. https://doi.org/10.1056/NEJMoa1205127CrossRefPubMedPubMedCentral

29.

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. https://doi.org/10.1056/NEJMoa1306494CrossRefPubMed

30.

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 122:3650–3656CrossRefPubMed

31.

Brissot E, Labopin M, Beckers MM, Socié G, Rambaldi A, Volin L, Finke J, Lenhoff S, Kröger N, Ossenkoppele GJ, Craddock CF, Yakoub-Agha I, Gürman G, Russell NH, Aljurf M, Potter MN, Nagler A, Ottmann O, Cornelissen JJ, Esteve J, Mohty M (2015) Tyrosine kinase inhibitors improve long-term outcome of allogeneic hematopoietic stem cell transplantation for adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia. Haematologica 100:392–399. https://doi.org/10.3324/haematol.2014.116954CrossRefPubMedPubMedCentral

32.

Saini NY, Marin D, Ledesma C, Delgado R, Rondon G, Popat U, Bashir Q, Hosing C, Nieto Y, Alousi A, Qazilbash MH, Ciurea SO, Shpall EJ, Khouri IF, Kantarjian HM, Jabbour E, Ravandi F, Champlin R, Kebriaei P (2020) Impact of TKI maintenance post-allogeneic transplant in Philadelphia positive acute lymphoblastic leukemia. Blood. https://doi.org/10.1182/blood.2019004685

33.

Martinelli G, Iacobucci I, Storlazzi CT, Vignetti M, Paoloni F, Cilloni D, Soverini S, Vitale A, Chiaretti S, Cimino G, Papayannidis C, Paolini S, Elia L, Fazi P, Meloni G, Amadori S, Saglio G, Pane F, Baccarani M, Foà R (2009) IKZF1 (Ikaros) deletions in BCR-ABL1-positive acute lymphoblastic leukemia are associated with short disease-free survival and high rate of cumulative incidence of relapse: a GIMEMA AL WP report. J Clin Oncol 27:5202–5207. https://doi.org/10.1200/JCO.2008.21.6408CrossRefPubMed

34.

Kim M, Park J, Kim DW, Kim YJ, Jeon YW, Yoon JH, Shin SH, Yahng SA, Lee SE, Cho BS, Eom KS, Kim HJ, Min CK, Cho SG, Kim Y, Lee JW, Han K, Min WS, Lee S (2015) Impact of IKZF1 deletions on long-term outcomes of allo-SCT following imatinib-based chemotherapy in adult Philadelphia chromosome-positive ALL. Bone Marrow Transplant 50:354–362. https://doi.org/10.1038/bmt.2014.281CrossRefPubMed

35.

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. https://doi.org/10.3109/10428194.2016.1144881CrossRefPubMedPubMedCentral

36.

Li H, Zhang W, Kuang P, Ye Y, Yang J, Dai Y, Lu X, Zheng Y, Liu T (2018) Combination of IKZF1 deletion and early molecular response show significant roles on prognostic stratification in Philadelphia chromosome-positive acute lymphoblastic leukemia patients. Leuk Lymphoma 59:1890–1898. https://doi.org/10.1080/10428194.2017.1406933CrossRefPubMed

37.

Xu N, Li YL, Li X, Zhou X, Cao R, Li H, Li L, Lu ZY, Huang JX, Fan ZP, Huang F, Zhou HS, Zhang S, Liu Z, Zhu HQ, Liu QF, Liu XL (2016) Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia. J Hematol Oncol 9:40. https://doi.org/10.1186/s13045-016-0270-5CrossRefPubMedPubMedCentral

38.

Pfeifer H, Raum K, Markovic S, Nowak V, Fey S, Obländer J, Pressler J, Böhm V, Brüggemann M, Wunderle L, Hüttmann A, Wäsch R, Beck J, Stelljes M, Viardot A, Lang F, Hoelzer D, Hofmann WK, Serve H, Weiss C, Goekbuget N, Ottmann OG, Nowak D (2018) Genomic CDKN2A/2B deletions in adult Ph+ ALL are adverse despite allogeneic stem cell transplantation. Blood 131:1464–1475. https://doi.org/10.1182/blood-2017-07-796862CrossRefPubMed

39.

Fedullo AL, Messina M, Elia L, Piciocchi A, Gianfelici V, Lauretti A, Soddu S, Puzzolo MC, Minotti C, Ferrara F, Martino B, Chiusolo P, Calafiore V, Paolini S, Vignetti M, Vitale A, Guarini A, Foà R, Chiaretti S (2019) Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica 104:312–318. https://doi.org/10.3324/haematol.2018.196055CrossRefPubMedPubMedCentral

40.

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. https://doi.org/10.1002/cncr.30130CrossRefPubMed

Titel: Comparative study on allogeneic with autologous hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia in the era of TKIs: a systematic review and meta-analysis
verfasst von: Haichen Wei
Pu Kuang
Ting Liu
Publikationsdatum: 22.09.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 11/2020
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-04258-1

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Comparative study on allogeneic with autologous hematopoietic stem cell transplantation in adult patients with Philadelphia chromosome–positive acute lymphoblastic leukemia in the era of TKIs: a systematic review and meta-analysis

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