Skip to main content

Advertisement

SpringerLink
Log in

Meta-analysis and meta-regression analysis to compare the outcomes of chemotherapy for T- and B-lineage acute lymphoblastic leukemia (ALL): the use of dexamethasone, l-asparaginase, and/or methotrexate may improve the outcome of T-lineage ALL

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

Abstract

The effects of intensive regimens and the roles of drugs used might differ between T- and B-lineage acute lymphoblastic leukemia (ALL). We performed a literature search for clinical studies published from January 1998 to March 2013. Studies were eligible for inclusion in the analyses if they included more than 80 patients with adult ALL who were treated with a uniform regimen and compared T- and B-lineage ALL. Studies that included only adolescent or elderly patients were excluded. We identified 11 clinical studies, which included a total of 381 and 1366 patients with T- and B-lineage ALL, respectively, and performed meta-analyses using the selected studies. Nine studies included patients with Philadelphia chromosome-positive (Ph+) ALL. A meta-analysis using the random-effect model demonstrated superior survival in patients with T-lineage ALL compared to those with B-lineage ALL (hazard ratio 1.78, 95 % confidence interval 1.50–2.11), though the inclusion of patients with Ph+ ALL in B-lineage ALL must have influenced this result strongly. We performed meta-regression analyses, adjusted according to whether or not patients with Ph+ ALL were included in each study. Use of dexamethasone (Dex), higher dose of methotrexate (MTX), and higher dose of l-asparaginase (l-asp) were associated with a significant trend toward a better outcome in T-lineage ALL. A meta-regression analysis including Dex and the dose of l-asp or MTX together as covariates showed that these factors were independently significant. In conclusion, the use of Dex and high-dose l-asp or MTX may improve the outcome of T-lineage ALL. This hypothesis should be tested in a prospective study including only patients with Ph-negative ALL.

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

Similar content being viewed by others

References

  1. Armstrong SA, Look AT (2005) Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol 23(26):6306–15. doi:10.1200/JCO.2005.05.047

    Article  PubMed  CAS  Google Scholar 

  2. Mullighan CG (2012) The molecular genetic makeup of acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2012:389–96. doi:10.1182/asheducation-2012.1.389

    PubMed  Google Scholar 

  3. Riley RS, Massey D, Jackson-Cook C, Idowu M, Romagnoli G (2002) Immunophenotypic analysis of acute lymphocytic leukemia. Hematol Oncol Clin North Am 16(2):245–99, v

    Article  PubMed  Google Scholar 

  4. Boucheix C, David B, Sebban C, Racadot E, Bene MC, Bernard A, Campos L, Jouault H, Sigaux F, Lepage E et al (1994) Immunophenotype of adult acute lymphoblastic leukemia, clinical parameters, and outcome: an analysis of a prospective trial including 562 tested patients (LALA87). French Group on Therapy for Adult Acute Lymphoblastic Leukemia. Blood 84(5):1603–12

    PubMed  CAS  Google Scholar 

  5. Czuczman MS, Dodge RK, Stewart CC, Frankel SR, Davey FR, Powell BL, Szatrowski TP, Schiffer CA, Larson RA, Bloomfield CD (1999) Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: cancer and leukemia Group B study 8364. Blood 93(11):3931–9

    PubMed  CAS  Google Scholar 

  6. Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH (2005) Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 106(12):3760–7

    Article  PubMed  CAS  Google Scholar 

  7. Larson RA, Dodge RK, Linker CA, Stone RM, Powell BL, Lee EJ, Schulman P, Davey FR, Frankel SR, Bloomfield CD, George SL, Schiffer CA (1998) A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 92(5):1556–64

    PubMed  CAS  Google Scholar 

  8. Stock W, Johnson JL, Stone RM, Kolitz JE, Powell BL, Wetzler M, Westervelt P, Marcucci G, DeAngelo DJ, Vardiman JW, McDonnell D, Mrozek K, Bloomfield CD, Larson RA (2013) Dose intensification of daunorubicin and cytarabine during treatment of adult acute lymphoblastic leukemia: results of Cancer and Leukemia Group B Study 19802. Cancer 119(1):90–8. doi:10.1002/cncr.27617

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  9. Bajel A, George B, Mathews V, Viswabandya A, Kavitha ML, Srivastava A, Chandy M (2007) Adult ALL: treatment outcome and prognostic factors in an Indian population using a modified German ALL (GMALL) protocol. Leukemia 21(10):2230–3. doi:10.1038/sj.leu.2404785

    Article  PubMed  CAS  Google Scholar 

  10. Ribera JM, Ortega JJ, Oriol A, Granada I, Hernandez-Rivas JM, Parody R, Bethencourt C, Rivas C, Bastida P, del Potro E, Gonzalez-Valentin ME, Moreno MJ, Besalduch J, Fernandez-Calvo J, Tormo M, Arias J, Molines A, Sanz MA, Maldonado J, Milla F, Feliu E, San Miguel JF (2002) Prognostic value of karyotypic analysis in children and adults with high-risk acute lymphoblastic leukemia included in the PETHEMA ALL-93 trial. Haematologica 87(2):154–66

    PubMed  Google Scholar 

  11. Larson RA, Dodge RK, Burns CP, Lee EJ, Stone RM, Schulman P, Duggan D, Davey FR, Sobol RE, Frankel SR et al (1995) A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811. Blood 85(8):2025–37

    PubMed  CAS  Google Scholar 

  12. 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, Bene MC, Ifrah N (2004) 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 104(10):3028–37

    Article  PubMed  CAS  Google Scholar 

  13. Pui CH, Relling MV, Downing JR (2004) Acute lymphoblastic leukemia. N Engl J Med 350(15):1535–48. doi:10.1056/NEJMra023001

    Article  PubMed  CAS  Google Scholar 

  14. Kantarjian H, Thomas D, O’Brien S, Cortes J, Giles F, Jeha S, Bueso-Ramos CE, Pierce S, Shan J, Koller C, Beran M, Keating M, Freireich EJ (2004) Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101(12):2788–801

    Article  PubMed  CAS  Google Scholar 

  15. Linker C, Damon L, Ries C, Navarro W (2002) Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia. J Clin Oncol 20(10):2464–71

    Article  PubMed  CAS  Google Scholar 

  16. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E, Chevallier P, Buzyn A, Delannoy A, Chalandon Y, Vernant JP, Lafage-Pochitaloff M, Chassevent A, Lheritier V, Macintyre E, Bene MC, Ifrah N, Dombret H (2009) Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol 27(6):911–8

    Article  PubMed  CAS  Google Scholar 

  17. Bostrom BC, Sensel MR, Sather HN, Gaynon PS, La MK, Johnston K, Erdmann GR, Gold S, Heerema NA, Hutchinson RJ, Provisor AJ, Trigg ME (2003) Dexamethasone versus prednisone and daily oral versus weekly intravenous mercaptopurine for patients with standard-risk acute lymphoblastic leukemia: a report from the Children’s Cancer Group. Blood 101(10):3809–17. doi:10.1182/blood-2002-08-2454

    Article  PubMed  CAS  Google Scholar 

  18. Schwartz CL, Thompson EB, Gelber RD, Young ML, Chilton D, Cohen HJ, Sallan SE (2001) Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia. J Clin Oncol 19(4):1040–6

    PubMed  CAS  Google Scholar 

  19. Niemeyer CM, Gelber RD, Tarbell NJ, Donnelly M, Clavell LA, Blattner SR, Donahue K, Cohen HJ, Sallan SE (1991) Low-dose versus high-dose methotrexate during remission induction in childhood acute lymphoblastic leukemia (protocol 81-01 update). Blood 78(10):2514–9

    PubMed  CAS  Google Scholar 

  20. Silverman LB, Gelber RD, Dalton VK, Asselin BL, Barr RD, Clavell LA, Hurwitz CA, Moghrabi A, Samson Y, Schorin MA, Arkin S, Declerck L, Cohen HJ, Sallan SE (2001) Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01. Blood 97(5):1211–8

    Article  PubMed  CAS  Google Scholar 

  21. Reiter A, Schrappe M, Ludwig WD, Hiddemann W, Sauter S, Henze G, Zimmermann M, Lampert F, Havers W, Niethammer D et al (1994) Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Blood 84(9):3122–33

    PubMed  CAS  Google Scholar 

  22. Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M, Katz J, Yu A, Laver J, Ravindranath Y, Kurtzberg J, Desai S, Camitta B, Murphy SB (1999) Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study. Leukemia 13(3):335–42

    Article  PubMed  CAS  Google Scholar 

  23. Parmar MK, Torri V, Stewart L (1998) Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 17(24):2815–34

    Article  PubMed  CAS  Google Scholar 

  24. Kanda Y (2013) Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3):452–8. doi:10.1038/bmt.2012.244

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Huizenga HM, Visser I, Dolan CV (2011) Testing overall and moderator effects in random effects meta-regression. Br J Math Stat Psychol 64(Pt 1):1–19. doi:10.1348/000711010X522687

    Article  PubMed  Google Scholar 

  26. Ueda T, Miyawaki S, Asou N, Kuraishi Y, Hiraoka A, Kuriyama K, Minami S, Ohshima T, Ino T, Tamura J, Kanamaru A, Nishikawa K, Tanimoto M, Oh H, Saito K, Nagata K, Naoe T, Yamada O, Urasaki Y, Sakura T, Ohno R (1998) Response-oriented individualized induction therapy with six drugs followed by four courses of intensive consolidation, 1 year maintenance and intensification therapy: the ALL90 study of the Japan Adult Leukemia Study Group. Int J Hematol 68(3):279–89

    Article  PubMed  CAS  Google Scholar 

  27. Tobinai K, Takeyama K, Arima F, Aikawa K, Kobayashi T, Hanada S, Kasai M, Ogura M, Sueoka E, Mukai K, Tajima K, Fukuda H, Shirakawa S, Hotta T, Masanori S (2007) Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group Study 9004. Cancer Sci 98(9):1350–7. doi:10.1111/j.1349-7006.2007.00556.x

    Article  PubMed  CAS  Google Scholar 

  28. Wetzler M, Sanford BL, Kurtzberg J, DeOliveira D, Frankel SR, Powell BL, Kolitz JE, Bloomfield CD, Larson RA (2007) Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Blood 109(10):4164–7. doi:10.1182/blood-2006-09-045351

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  29. Jinnai I, Sakura T, Tsuzuki M, Maeda Y, Usui N, Kato M, Okumura H, Kyo T, Ueda Y, Kishimoto Y, Yagasaki F, Tsuboi K, Horiike S, Takeuchi J, Iwanaga M, Miyazaki Y, Miyawaki S, Ohnishi K, Naoe T, Ohno R (2010) Intensified consolidation therapy with dose-escalated doxorubicin did not improve the prognosis of adults with acute lymphoblastic leukemia: the JALSG-ALL97 study. Int J Hematol 92(3):490–502

    Article  PubMed  CAS  Google Scholar 

  30. Azuma T, Tobinai K, Takeyama K, Shibata T, Hidaka M, Kurosawa M, Kasai M, Chou T, Fukushima N, Mukai K, Tsukasaki K, Shimoyama M (2012) Phase II study of intensive post-remission chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia and lymphoblastic lymphoma: Japan Clinical Oncology Group Study, JCOG9402. Jpn J Clin Oncol 42(5):394–404. doi:10.1093/jjco/hys029

    Article  PubMed  Google Scholar 

  31. Fielding AK (2011) Current treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2011:231–7. doi:10.1182/asheducation-2011.1.231

    Article  PubMed  Google Scholar 

  32. Stock W (2010) Adolescents and young adults with acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2010:21–9. doi:10.1182/asheducation-2010.1.21

    Article  PubMed  Google Scholar 

Download references

Compliance with ethical standards

ᅟ

Conflict of interest

Kako S. reports grants and/or honoraria from MSD K.K., Kyowa Hakko Kirin Co., Ltd., and Nippon Shinyaku Co., Ltd. with regard to this study. Harada N. reports honoraria from Kyowa Hakko Kirin Co., Ltd. to this study. Kimura S. reports honoraria from Pfizer K.K. and Kyowa Hakko Kirin Co., Ltd. to this study. Misato Kikuchi reports grant from MSD K.K. to this study. Kanda J. reports grants and/or honoraria from Kyowa Hakko Kirin Co., Ltd., and Nippon Shinyaku Co., Ltd. with regard to this study. Kanda Y. reports grants and/or honoraria from MSD K.K., Pfizer K.K., Kyowa Hakko Kirin Co., Ltd., and Nippon Shinyaku Co., Ltd. with regard to this study.

Ethical approval

Since this study was meta-analyses using published articles, an approval by an ethics committee and statement of informed consent were not applicable.

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya-ku, Saitama-city, Saitama, 330-8503, Japan

    Shinichi Kako, Yu Akahoshi, Naonori Harada, Hirofumi Nakano, Kazuaki Kameda, Tomotaka Ugai, Hidenori Wada, Ryoko Yamasaki, Yuko Ishihara, Koji Kawamura, Kana Sakamoto, Miki Sato, Masahiro Ashizawa, Kiriko Terasako-Saito, Shun-ichi Kimura, Misato Kikuchi, Hideki Nakasone, Rie Yamazaki, Junya Kanda, Junji Nishida & Yoshinobu Kanda

Authors
  1. Shinichi Kako
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Akahoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naonori Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hirofumi Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kazuaki Kameda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomotaka Ugai
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hidenori Wada
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ryoko Yamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yuko Ishihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Koji Kawamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kana Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Miki Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masahiro Ashizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Kiriko Terasako-Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shun-ichi Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Misato Kikuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Hideki Nakasone
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Rie Yamazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Junya Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Junji Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Yoshinobu Kanda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshinobu Kanda.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kako, S., Akahoshi, Y., Harada, N. et al. Meta-analysis and meta-regression analysis to compare the outcomes of chemotherapy for T- and B-lineage acute lymphoblastic leukemia (ALL): the use of dexamethasone, l-asparaginase, and/or methotrexate may improve the outcome of T-lineage ALL. Ann Hematol 95, 87–92 (2016). https://doi.org/10.1007/s00277-015-2510-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2510-0

Keywords

Search

Navigation