Skip to main content

Advertisement

Log in

Acute lymphoblastic leukemia–like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients

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

Abstract

Mixed phenotype acute leukemia (MPAL) is a rare type of leukemia with a limited number of studies conducted to characterize its clinical spectrum and most importantly the best treatment modality. MPAL blasts show more than one phenotype either myeloid/monocytic with T- or B-lymphoid or extremely rare triple lineage associated phenotypic markers. This study aimed to characterize MPAL cases with special emphasis on comparing adult and pediatric age groups, exploring treatment regimens, and clinical outcome. Among 2571 acute leukemia patients, 102 MPAL cases fulfilling the 2008/2016 WHO diagnostic criteria of MPAL were recruited in the study. The incidence of MPAL was 4% of acute leukemia patients. Pediatric cases were 54 (53%) while adults were 48/102 (47%). Myeloid/B-lymphoid phenotype was found in 86/102 (84%), with BCR-ABL fusion gene transcript detected in 14/102(13.7%) patients. ALL-like treatment showed better response rates as compared with the myeloid based regimen (p = 0.001). MPAL behaves in a manner that resembles in clinical features, their lymphoid progenitor counterpart leukemias both in adults and pediatric patients with superior treatment response to ALL-like regimen, especially in adults.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Shimizu H, Yokohama A, Koya H, Shimizu R, Hatsumi N, Takada S, Saitoh T, Sakura T, Miyawaki S, Handa H (2012) Clinical significance of mixed phenotype in adult patients with Philadelphia chromosome-positive acute leukemia–no prognostic impact in the Imatinib Era. Blood 120:2574–2574

    Article  Google Scholar 

  2. Alexander TB, Gu Z, Iacobucci I, Dickerson K, Choi JK, Xu B, Payne-Turner D, Yoshihara H, Loh ML, Horan J, Buldini B, Basso G, Elitzur S, de Haas V, Zwaan CM, Yeoh A, Reinhardt D, Tomizawa D, Kiyokawa N, Lammens T, de Moerloose B, Catchpoole D, Hori H, Moorman A, Moore AS, Hrusak O, Meshinchi S, Orgel E, Devidas M, Borowitz M, Wood B, Heerema NA, Carrol A, Yang YL, Smith MA, Davidsen TM, Hermida LC, Gesuwan P, Marra MA, Ma Y, Mungall AJ, Moore RA, Jones SJM, Valentine M, Janke LJ, Rubnitz JE, Pui CH, Ding L, Liu Y, Zhang J, Nichols KE, Downing JR, Cao X, Shi L, Pounds S, Newman S, Pei D, Guidry Auvil JM, Gerhard DS, Hunger SP, Inaba H, Mullighan CG (2018) The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature 562:373–379. https://doi.org/10.1038/s41586-018-0436-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, van't Veer M (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786

    CAS  PubMed  Google Scholar 

  4. Swerdlow SH et al (2008) WHO classification of tumours of haematopoietic and lymphoid tissues, 4th edn. Internat. Agency for Research on Cancer, Lyon

    Google Scholar 

  5. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127:2375–2390. https://doi.org/10.1182/blood-2016-01-643569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Porwit A, Béné MC (2019) Multiparameter flow cytometry applications in the diagnosis of mixed phenotype acute leukemia. Cytometry B Clin Cytom 96:183–194. https://doi.org/10.1002/cyto.b.21783

    Article  PubMed  Google Scholar 

  7. van den Ancker W, Terwijn M, Westers TM, Merle PA, van Beckhoven E, Dräger AM, Ossenkoppele GJ, van de Loosdrecht AA (2010) Acute leukemias of ambiguous lineage: diagnostic consequences of the WHO2008 classification. Leukemia 24:1392–1396. https://doi.org/10.1038/leu.2010.119

    Article  PubMed  Google Scholar 

  8. Sabattini E, Bacci F, Sagramoso C, Pileri SA (2010) WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica 102:83–87

    CAS  PubMed  Google Scholar 

  9. Matutes E, Pickl WF, van’t Veer M et al (2011) Mixed-phenotype acute leukemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification. Blood 117:3163–3171. https://doi.org/10.1182/blood-2010-10-314682

    Article  CAS  PubMed  Google Scholar 

  10. Xu X-Q, Wang J-M, Lü S-Q et al (2009) Clinical and biological characteristics of adult biphenotypic acute leukemia in comparison with that of acute myeloid leukemia and acute lymphoblastic leukemia: a case series of a Chinese population. Haematologica 94:919–927. https://doi.org/10.3324/haematol.2008.003202

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yan L, Ping N, Zhu M, Sun A, Xue Y, Ruan C, Drexler HG, MacLeod RAF, Wu D, Chen S (2012) Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008 classification. Haematologica 97:1708–1712. https://doi.org/10.3324/haematol.2012.064485

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wolach O, Stone RM (2015) How I treat mixed-phenotype acute leukemia. Blood 125:2477–2485. https://doi.org/10.1182/blood-2014-10-551465

    Article  CAS  PubMed  Google Scholar 

  13. Kahn J, Barrera S, Davila R, Roberts E, Jin ZZ, Stevenson K, Blonquist TM, Neuberg DS, Athale UH, Clavell LA, Cole P, Laverdiere C, Michon B, Schorin MA, Welch JJG, Sallan SE, Silverman LB, Kelly KM (2015) Higher incidence of treatment-related toxicities in non-Hispanic patients undergoing therapy for newly diagnosed pediatric acute lymphoblastic leukemia on Dana-Farber Cancer Institute ALL Consortium Protocol 05-001. Blood 126:248–248. https://doi.org/10.1182/blood.V126.23.248.248

    Article  Google Scholar 

  14. van Dongen JJ, Macintyre EA, Gabert JA, Delabesse E, Rossi V, Saglio G, Gottardi E, Rambaldi A, Dotti G, Griesinger F, Parreira A, Gameiro P, Diáz MG, Malec M, Langerak AW, San Miguel JF, Biondi A (1999) Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia. Leukemia 13:1901–1928

    Article  Google Scholar 

  15. Shi R, Munker R (2015) Survival of patients with mixed phenotype acute leukemias: a large population-based study. Leuk Res 39:606–616. https://doi.org/10.1016/j.leukres.2015.03.012

    Article  PubMed  Google Scholar 

  16. Moorman AV, Chilton L, Wilkinson J, Ensor HM, Bown N, Proctor SJ (2010) A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood 115:206–214. https://doi.org/10.1182/blood-2009-07-232124

    Article  CAS  PubMed  Google Scholar 

  17. Harrison CJ (2001) The detection and significance of chromosomal abnormalities in childhood acute lymphoblastic leukaemia. Blood Rev 15:49–59. https://doi.org/10.1054/blre.2001.0150

    Article  CAS  PubMed  Google Scholar 

  18. Gerr H, Zimmermann M, Schrappe M, Dworzak M, Ludwig WD, Bradtke J, Moericke A, Schabath R, Creutzig U, Reinhardt D (2010) Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. Br J Haematol 149:84–92. https://doi.org/10.1111/j.1365-2141.2009.08058.x

    Article  PubMed  Google Scholar 

  19. Wolach O, Stone RM (2017) Mixed-phenotype acute leukemia: current challenges in diagnosis and therapy. Curr Opin Hematol 24:139–145. https://doi.org/10.1097/MOH.0000000000000322

    Article  PubMed  Google Scholar 

  20. Kim H-J (2016) Mixed-phenotype acute leukemia (MPAL) and beyond. Blood Res 51:215–216. https://doi.org/10.5045/br.2016.51.4.215

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lee HG, Baek HJ, Kim HS, Park SM, Hwang TJ, Kook H (2019) Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome. Blood Res 54:63–73. https://doi.org/10.5045/br.2019.54.1.63

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Tian H, Xu Y, Liu L, Yan L, Jin Z, Tang X, Han Y, Fu Z, Qiu H, Sun A, Wu D (2016) Comparison of outcomes in mixed phenotype acute leukemia patients treated with chemotherapy and stem cell transplantation versus chemotherapy alone. Leuk Res 45:40–46. https://doi.org/10.1016/j.leukres.2016.04.002

    Article  CAS  PubMed  Google Scholar 

  23. Duong VH, Begna KH, Kashanian S, Sweet K, Wang ES, Caddell R, Shafer DA, Singh ZN, Baer MR, al-Kali A (2020) Favorable outcomes of acute leukemias of ambiguous lineage treated with hyperCVAD: a multi-center retrospective study. Ann Hematol 99:2119–2124. https://doi.org/10.1007/s00277-020-04179-z

    Article  CAS  PubMed  Google Scholar 

  24. Wang Y, Gu M, Mi Y, Qiu L, Bian S, Wang J (2011) Clinical characteristics and outcomes of mixed phenotype acute leukemia with Philadelphia chromosome positive and/or bcr-abl positive in adult. Int J Hematol 94:552–555. https://doi.org/10.1007/s12185-011-0953-1

    Article  CAS  PubMed  Google Scholar 

  25. Shimizu H, Yokohama A, Hatsumi N, Takada S, Handa H, Sakura T, Nojima Y (2014) Philadelphia chromosome-positive mixed phenotype acute leukemia in the imatinib era. Eur J Haematol 93:297–301. https://doi.org/10.1111/ejh.12343

    Article  CAS  PubMed  Google Scholar 

  26. Zheng C, Wu J, Liu X, Ding K, Cai X, Zhu W (2009) What is the optimal treatment for biphenotypic acute leukemia? Haematologica 94:1778–1780; author reply 1780. https://doi.org/10.3324/haematol.2009.014829

    Article  PubMed  PubMed Central  Google Scholar 

  27. Maruffi M, Sposto R, Oberley MJ, Kysh L, Orgel E (2018) Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis. Leukemia 32:1515–1528. https://doi.org/10.1038/s41375-018-0058-4

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sally Elfishawi.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

Figure (1a): Dot plots of a Myeloid /T case; R1: Gating on CD45 dim population (blasts), R2: co-expression of MPO/cytoplasmic CD3, R3: co-expression of cytoplasmic CD13/cytoplasmic CD3, R4: co-expression of CD33/cytoplasmic CD3 (JPG 353 kb)

ESM 2

Figure (1b): Dot plots of a Myeloid /B case; R1: Gating on CD45 dim population (blasts), R2: co-expression of CD19/ CD33, R3: co-expression of MPO/CD19 (JPG 664 kb)

ESM 3

Figure (1c): 3D plot for cCD3 PE (Z axis) / CD33 PC5.5 (Y axis) / CD19 PC7 (X axis) expression in a case with T/B/Myeloid antigens expression (JPG 37 kb)

ESM 4

Figure (1d): Dot plots for using residual normal lymphocytes as an internal negative control for MPO; R1: CD45 bright lymphocytes, R2: CD45 dim blasts, R3: negative MPO expression in lymphocytes, R4: MPO expression in blasts population. (JPG 379 kb)

ESM 5

(DOCX 18 kb)

ESM 6

(DOCX 12 kb)

ESM 7

(DOCX 18 kb)

ESM 8

(DOCX 25 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rasekh, E.O., Osman, R., Ibraheem, D. et al. Acute lymphoblastic leukemia–like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients. Ann Hematol 100, 699–707 (2021). https://doi.org/10.1007/s00277-020-04354-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-020-04354-2

Keywords

Navigation