Skip to main content
SpringerLink
Log in

Acute lymphoblastic leukemia in first complete remission: temporal trend of outcomes in studies comparing allogeneic transplant with autologous transplant or chemotherapy

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

In patients with acute lymphoblastic leukemia in first complete remission, several studies have compared allogeneic transplant with autologous transplant or chemotherapy. This material can be the basis for analyzing the temporal trend of outcomes. Our study was designed as a meta-regression focused on temporal trends and based on the endpoint of 5-year leukemia-free survival (5yLFS). Studies in which 5yLFS was determined in a patient group subjected to allogeneic transplant and in a control group (treated with autologous transplant and/or chemotherapy) were eligible for our meta-analysis. A standard literature search was carried out to identify pertinent studies. The results of included studies were submitted to an observational meta-analysis and to a meta-regression focused on two covariates (calendar year in which the study was conducted; percentage of high-risk patients). The endpoint of 5yLFS was separately assessed between allogeneic transplant and autologous transplant or chemotherapy. Our analysis included 14 studies that covered a period (1983 to 1999) in which patients were conditioned only with myeloablative conditioning and not with non-myeloablative ones. In the risk ratio (RR) analysis, the pooled outcome showed a significantly better profile for allogeneic transplantation (RR = 1.42; 95 % confidence interval (CI), 1.22 to 1.65). Separate analysis of the two treatment options found a pooled 5yLFS of 45 % (95 % CI, 38 to 51 %) for allogeneic transplant vs 30 % (95 % CI, 23 to 37 %) for the controls. In meta-regression, the temporal trend analysis revealed that, in patients subjected to allogeneic transplant, the values of 5yLFS showed no significant change over the 16-year interval (p = 0.720); the same stability over time was found in the control group (p = 0.489). On the other hand, the percentage of high-risk patients influenced outcomes in both patient groups at levels of statistical significance (p = 0.014 and p = 0.045 in the allotransplant group and in the controls, respectively). Our results can represent a reference point for future analyses focused on patients treated in more recent years.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Biondi-Zoccai GG, Abbate A, Agostoni P et al (2005) Long-term benefits of an early invasive management in acute coronary syndromes significantly depend on intracoronary stenting and aggressive antiplatelet treatment: a metaregression. Am Heart J 149:504–511

    Article  PubMed  Google Scholar 

  2. Bishop MR, Logan BR, Gandham S, Bolwell BJ, Cahn JY, Lazarus HM, Litzow MR, Marks DI, Wiernik PH, McCarthy PL, Russell JA, Miller CB, Sierra J, Milone G, Keating A, Loberiza FR Jr, Giralt S, Horowitz MM, Weisdorf DJ (2008) Long-term outcomes of adults with acute lymphoblastic leukemia after autologous or unrelated donor bone marrow transplantation: a comparative analysis by the National Marrow Donor Program and Center for International Blood and Marrow Transplant Research. Bone Marrow Transplant 41(7):635–642, Epub 2007 Dec 17

    Article  PubMed  CAS  Google Scholar 

  3. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR (2009) Introduction to meta-analysis. Wiley Chichester. doi:10.1002/9780470743386.ch20

    Google Scholar 

  4. Cornelissen JJ, van der Holt B, Verhoef GE, van't Veer MB, van Oers MH, Schouten HC, Ossenkoppele G, Sonneveld P, Maertens J, van Marwijk Kooy M, Schaafsma MR, Wijermans PW, Biesma DH, Wittebol S, Voogt PJ, Baars JW, Zachée P, Verdonck LF, Löwenberg B, Dekker AW, Dutch-Belgian HOVON Cooperative Group (2009) Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 113(6):1375–1382, Epub 2008 Nov 6

    Article  PubMed  CAS  Google Scholar 

  5. 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(19):4489–4496

    Article  PubMed  CAS  Google Scholar 

  6. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, Burnett AK, Chopra R, Wiernik PH, Foroni L, Paietta E, Litzow MR, Marks DI, Durrant J, McMillan A, Franklin IM, Luger S, Ciobanu N, Rowe JM (2008) In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 111(4):1827–1833

    Article  PubMed  CAS  Google Scholar 

  7. Hahn T, Wall D, Camitta B, Davies S, Dillon H, Gaynon P, Larson RA, Parsons S, Seidenfeld J, Weisdorf D, McCarthy PL Jr (2006) The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant 12(1):1–30

    Article  PubMed  CAS  Google Scholar 

  8. Hunault M, Harousseau JL, Delain M, Truchan-Graczyk M, Cahn JY, Witz F, Lamy T, Pignon B, Jouet JP, Garidi R, Caillot D, Berthou C, Guyotat D, Sadoun A, Sotto JJ, Lioure B, Casassus P, Solal-Celigny P, Stalnikiewicz L, Audhuy B, Blanchet O, Baranger L, Béné MC, Ifrah N; GOELAMS (Groupe Ouest-Est des Leucémies Airguës et Maladies du Sang) Group. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 200415;104(10):3028–37.

  9. King NB, Harper S, Young ME (2012) Use of relative and absolute effect measures in reporting health inequalities: structured review. BMJ 345:e5774

    Article  PubMed  Google Scholar 

  10. Labar B, Suciu S, Zittoun R, Muus P, Marie JP, Fillet G, Peetermans M, Stryckmans P, Willemze R, Feremans W, Jaksic B, Bourhis JH, Burghouts JP, de Witte T, EORTC Leukemia Group (2004) Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients < or = 50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica 89(7):809–817

    PubMed  Google Scholar 

  11. Leucht S, Hierl S, Dold M, Kissling W, Davis JM (2012) Putting the efficacy of psychiatric and general medicine medication in perspective: a review of meta-analyses. Br J Psychiatry 200:97–106

    Article  PubMed  Google Scholar 

  12. Messori A, Maratea D, Fadda V, Trippoli S (2012) Antipsychotic drugs for relapse prevention in schizophrenia. Lancet 380(9847):1055–1056

    Article  PubMed  Google Scholar 

  13. Messori A, Maratea D, Fadda V, Trippoli S (2012) Temporal trend of overall survival in patients with advanced non-small cell lung cancer given first-line cytotoxic treatments. Lung 190(6):591–592

    Article  PubMed  Google Scholar 

  14. Messori A, Maratea D, Fadda V, Trippoli S (2012) Biologic agents in rheumatoid arthritis: temporal trend of incremental benefits. Ther Adv Musculoskelet Dis 4(6):423–424

    Article  PubMed  Google Scholar 

  15. Oh H, Gale RP, Zhang MJ, Passweg JR, Ino T, Murakami H, Ohno R, Rowlings PA, Sobocinski KA, Tanimoto M, Tomonaga M, Weisdorf DJ, Horowitz MM (1998) Chemotherapy vs HLA-identical sibling bone marrow transplants for adults with acute lymphoblastic leukemia in first remission. Bone Marrow Transplant 22(3):253–257

    Article  PubMed  CAS  Google Scholar 

  16. Oliansky DM, Larson RA, Weisdorf D, Dillon H, Ratko TA, Wall D, McCarthy PL Jr, Hahn T (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(1):18.e6–36.e6

    Article  Google Scholar 

  17. Orsi C, Bartolozzi B, Messori A, Bosi A (2007) Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation. Bone Marrow Transplant 40(7):643–649

    Article  PubMed  CAS  Google Scholar 

  18. Pidala J, Djulbegovic B, Anasetti C, Kharfan-Dabaja M, Kumar A. Allogeneic hematopoietic cell transplantation for adult acute lymphoblastic leukemia (ALL) in first complete remission. Cochrane Database Syst Rev. 2011;(10):CD008818.

  19. Ram R, Gafter-Gvili A, Vidal L, Paul M, Ben-Bassat I, Shpilberg O, Raanani P (2010) Management of adult patients with acute lymphoblastic leukemia in first complete remission. Systematic review and meta-analysis. Cancer 116:3447–3457

    Article  PubMed  Google Scholar 

  20. Ribera JM, Oriol A, Bethencourt C, Parody R, Hernández-Rivas JM, Moreno MJ, del Potro E, Torm M, Rivas C, Besalduch J, Sanz MA, Ortega JJ, PETHEMA Group, Spain (2005) Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 90(10):1346–1356

    PubMed  CAS  Google Scholar 

  21. Sebban C, Lepage E, Vernant JP, Gluckman E, Attal M, Reiffers J, Sutton L, Racadot E, Michallet M, Maraninchi D et al (1994) Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia. J Clin Oncol 12(12):2580–2587

    PubMed  CAS  Google Scholar 

  22. 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(20):4075–4086

    Article  PubMed  CAS  Google Scholar 

  23. Vasques F, Messori A, Lucenteforte E, Biancari F (2012) Immediate and late outcome of patients aged 80 years and older undergoing isolated aortic valve replacement: a systematic review and meta-analysis of 48 studies. Am Heart J 163:477–485

    Article  PubMed  Google Scholar 

  24. Yanada M, Matsuo K, Suzuki T, Naoe T. Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis. Cancer. 200615;106(12):2657–63.

  25. Zhang MJ, Hoelzer D, Horowitz MM, Gale RP, Messerer D, Klein JP, Löffler H, Sobocinski KA, Thiel E, Weisdorf DJ (1995) Long-term follow-up of adults with acute lymphoblastic leukemia in first remission treated with chemotherapy or bone marrow transplantation. The Acute Lymphoblastic Leukemia Working Committee. Ann Intern Med 123(6):428–431

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of Interest

The authors declare that they had no conflict of interests.

Author information

Authors and Affiliations

  1. HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Firenze, Italy

    Andrea Messori, Valeria Fadda, Dario Maratea & Sabrina Trippoli

  2. HTA Unit, Area Vasta Centro Toscana, Regional Health System, Via Guimaraes 9-11, 59100, Prato, Italy

    Andrea Messori

Authors
  1. Andrea Messori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valeria Fadda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dario Maratea
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sabrina Trippoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrea Messori.

Appendix 1. Approximations

Appendix 1. Approximations

Since not all of the individual studies had either a design or a presentation of the results in perfect agreement with the design of our analysis, the following approximations were employed to include some patient groups in our overall analysis:

  1. 1.

    In handling the patients groups enrolled in the study by Oh and coworkers, the definition of standard or high risk was based only on the criterion of age less or more than 30 years.

  2. 2.

    Since the study by Fielding and coworkers included a comparison between three groups (two receiving allogeneic transplant and one receiving chemotherapy), for the purposes of our analysis, we managed the control group as common comparator for both groups receiving transplant; this control group was therefore introduced twice in our analysis.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Messori, A., Fadda, V., Maratea, D. et al. Acute lymphoblastic leukemia in first complete remission: temporal trend of outcomes in studies comparing allogeneic transplant with autologous transplant or chemotherapy. Ann Hematol 92, 1221–1228 (2013). https://doi.org/10.1007/s00277-013-1766-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-013-1766-5

Keywords

Search

Navigation