Skip to main content

Advertisement

SpringerLink
Log in

Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia–like or acute lymphoblastic leukemia–like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study

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

Abstract    

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent. Median age was 49 years; 7.6% of cases had a BCR::ABL1 rearrangement. Thirty patients (39%) were treated with an acute myeloid leukemia (AML)–like induction and 47 (61%) with an ALL-like scheme. The complete remission (CR) rate was 67.6% and an ALL-like therapy was associated with a better CR rate (P = 0.048). The median OS was 41.9 months; age ≤ 60 years was associated with a better OS (67 vs 26 months, P = 0.014). An AlloSCT was performed in 50 patients (65%). The 5-year OS of transplanted patients was 54%. The OS post-AlloSCT was better in patients who were minimal residual disease (MRD)-negative prior to transplant (75.8% vs 45.2%, P = 0.06). This study shows that MPAL patients respond better to an ALL-like induction therapy; that consolidation therapy should include, whenever possible, an AlloSCT and that MRD negativity should be a primary endpoint of treatment.

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

Similar content being viewed by others

Data availability

All relevant summary data are provided in the manuscript text and tables. Further inquiries can be directed to the corresponding author.

References

  1. Matutes E, Morilla R, Farahat N et al (1997) Definition of acute biphenotypic leukemia. Haematologica 82:64–66

    CAS  PubMed  Google Scholar 

  2. Weinberg OK, Arber DA (2010) Mixed-phenotype acute leukemia: historical overview and a new definition. Leukemia 24:1844–1851

    Article  CAS  PubMed  Google Scholar 

  3. Aggarwal N, Weinberg OK (2021) Update on acute leukemias of ambiguous lineage. Clin Lab Med 41:453–466

    Article  PubMed  Google Scholar 

  4. Bene MC, Castoldi G, Knapp W et al (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 

  5. Vardiman JW, Thiele J, Arber DA et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951

    Article  CAS  PubMed  Google Scholar 

  6. Arber DA, Orazi A, Hasserjian R et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127:2391–2405

    Article  CAS  PubMed  Google Scholar 

  7. Gerr H, Zimmermann M, Schrappe M et al (2010) Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations. Br J Haematol 149:84–92

    Article  PubMed  Google Scholar 

  8. Weir EG, Ali Ansari-Lari M, Batista DA et al (2007) Acute bilineal leukemia: a rare disease with poor outcome. Leukemia 21:2264–2270

    Article  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

    Article  CAS  PubMed  Google Scholar 

  10. Hrusak O, de Haas V, Stancikova J et al (2018) International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia. Blood 132:264–276

    Article  CAS  PubMed  Google Scholar 

  11. Alexander TB, Gu Z, Iacobucci I et al (2018) The genetic basis and cell of origin of mixed phenotype acute leukaemia. Nature 562:373–379

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Takahashi K, Wang F, Morita K et al (2018) Integrative genomic analysis of adult mixed phenotype acute leukemia delineates lineage associated molecular subtypes. Nat Commun 9:2670

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rasekh EO, Osman R, Ibraheem D et al (2021) 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

    Article  CAS  PubMed  Google Scholar 

  14. Shi R, Munker R (2015) Survival of patients with mixed phenotype acute leukemias: a large population-based study. Leuk Res 39:606–616

    Article  PubMed  Google Scholar 

  15. Qasrawi A, Ramlal R, Munker R, Hildebrandt GC (2020) Prognostic impact of Philadelphia chromosome in mixed phenotype acute leukemia (MPAL): a cancer registry analysis on real-world outcome. Am J Hematol 95:1015–1021

    Article  CAS  PubMed  Google Scholar 

  16. 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

    Article  PubMed  PubMed Central  Google Scholar 

  17. Munker R, Brazauskas R, Wang HL et al (2016) Allogeneic hematopoietic cell transplantation for patients with mixed phenotype acute leukemia. Biol Blood Marrow Transplant 22:1024–1029

    Article  PubMed  PubMed Central  Google Scholar 

  18. Munker R, Labopin M, Esteve J, Schmid C, Mohty M, Nagler A (2017) Mixed phenotype acute leukemia: outcomes with allogeneic stem cell transplantation. A retrospective study from the Acute Leukemia Working Party of the EBMT. Haematologica 102:2134–2140

    Article  PubMed  PubMed Central  Google Scholar 

  19. Tremblay Z, Wong A, Otis AS et al (2022) Use of midostaurin in mixed phenotype acute leukemia with FLT3 mutation: a case series. Eur J Haematol 108:163–165

    Article  CAS  PubMed  Google Scholar 

  20. Brethon B, Lainey E, Caye-Eude A et al (2021) Case Report: targeting 2 antigens as a promising strategy in mixed phenotype acute leukemia: combination of blinatumomab with gemtuzumab ozogamicin in an infant with a KMT2A-rearranged leukemia. Front Oncol 11:637951

    Article  PubMed  PubMed Central  Google Scholar 

  21. Klocke H, Dong ZM, O’Brien C et al (2020) Venetoclax and decitabine for T/myeloid mixed-phenotype acute leukemia not otherwise specified (MPAL NOS). Case Rep Hematol 2020:8811673

    PubMed  PubMed Central  Google Scholar 

  22. Yan L, Ping N, Zhu M et al (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

    Article  PubMed  PubMed Central  Google Scholar 

  23. Weinberg OK, Seetharam M, Ren L, Alizadeh A, Arber DA (2014) Mixed phenotype acute leukemia: a study of 61 cases using World Health Organization and European Group for the Immunological Classification of Leukaemias criteria. Am J Clin Pathol 142:803–808

    Article  PubMed  Google Scholar 

  24. Williams DL, Harris A, Williams KJ, Brosius MJ, Lemonds W (1984) A direct bone marrow chromosome technique for acute lymphoblastic leukemia. Cancer Genet Cytogenet 13:239–225

    Article  CAS  PubMed  Google Scholar 

  25. van Dongen JJ, Macintyre EA, Gabert JA et al (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  PubMed  Google Scholar 

  26. van Dongen JJ, Langerak AW, Brüggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317

    Article  PubMed  Google Scholar 

  27. van der Velden VH, Cazzaniga G, Schrauder A et al (2007) Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia 21:604–611

    Article  PubMed  Google Scholar 

  28. Khan M, Siddiqi R, Naqvi K (2018) An update on classification, genetics, and clinical approach to mixed phenotype acute leukemia (MPAL). Ann Hematol 97:945–953

    Article  CAS  PubMed  Google Scholar 

  29. Alexander TB, Orgel E (2021) Mixed phenotype acute leukemia: Current Approaches to Diagnosis and Treatment. Curr Oncol Rep 23:22

    Article  PubMed  Google Scholar 

  30. Wolach O, Stone RM (2015) How I treat mixed-phenotype acute leukemia. Blood 125:2477–2485

    Article  CAS  PubMed  Google Scholar 

  31. DeFilipp Z, Advani AS, Bachanova V et al (2019) Hematopoietic cell transplantation in the treatment of adult acute lymphoblastic leukemia: updated 2019 evidence-based review from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant 25:2113–2123

    Article  PubMed  Google Scholar 

  32. Cerrano M, Bonifacio M, Olivi M et al (2022) Daratumumab with or without chemotherapy in relapsed and refractory acute lymphoblastic leukemia. A retrospective observational Campus ALL study. Haematologica 107:996–999

    Article  PubMed  PubMed Central  Google Scholar 

  33. Candoni A, Lazzarotto D, Ferrara F et al (2020) Nelarabine as salvage therapy and bridge to allogeneic stem cell transplant in 118 adult patients with relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma. A CAMPUS ALL study. Am J Hematol 95:1466–1472

    Article  CAS  PubMed  Google Scholar 

  34. Foà R, Bassan R, Vitale A et al (2020) Dasatinib-blinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med 383:1613–1623

    Article  PubMed  Google Scholar 

  35. Foà R, Chiaretti S (2022) Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 386:2399–2411

    Article  PubMed  Google Scholar 

  36. El Chaer F, Ali OM, Sausville EA et al (2019) Treatment of CD19-positive mixed phenotype acute leukemia with blinatumomab. Am J Hematol 94:E7–E8

    Article  PubMed  Google Scholar 

  37. Durer S, Durer C, Shafqat M et al (2019) Concomitant use of blinatumomab and donor lymphocyte infusion for mixed-phenotype acute leukemia: a case report with literature review. Immunotherapy 11:373–378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank all the members of the Campus ALL network.

Funding

The work was partly supported by Associazione Italiana Ricerca sul Cancro (AIRC), Special 5 × 1000 Program Metastases (21198), Milan (Italy) to Robin Foà.

Author information

Author notes

  1. Davide Lazzarotto and Ilaria Tanasi contributed equally.

Authors and Affiliations

  1. Clinica Ematologica-Centro Trapianti e Terapie Cellulari, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy

    Davide Lazzarotto & Anna Candoni

  2. Dipartimento Di Medicina, Sezione Di Ematologia, Università Di Verona, Verona, Italy

    Ilaria Tanasi, Massimiliano Bonifacio & Giovanni Pizzolo

  3. Dipartimento Di Medicina Traslazionale E Di Precisione, “Sapienza” Università Di Roma, Rome, Italy

    Antonella Vitale & Robin Foà

  4. SODc Ematologia, Azienda Ospedaliera Universitaria Careggi, Florence, Italy

    Matteo Piccini

  5. S.C. Ematologia, Ospedale Vito Fazzi, Lecce, Italy

    Michelina Dargenio

  6. Unità Di Ematologia E Trapianto Di Midollo Osseo, IRCCS Ospedale San Raffaele Di Milano, Milan, Italy

    Fabio Giglio

  7. S.C. Ematologia, Azienda Ospedaliero Universitaria Di Modena, Modena, Italy

    Fabio Forghieri

  8. U.O. Ematologia, IRCCS Ca’ Granda Ospedale Maggiore Policlinico Di Milano, Milan, Italy

    Nicola Fracchiolla

  9. S.C. Ematologia, AOU Città Della Salute E Della Scienza, Turin, Italy

    Marco Cerrano

  10. Onco-Hematology Division, IEO, European Institute of Oncology IRCCS, Milan, Italy

    Elisabetta Todisco

  11. Ospedale Di Busto Arsizio, ASST Valle Olona, Busto Arsizio, Italy

    Elisabetta Todisco

  12. IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Istituto Di Ematologia “Seràgnoli”, Bologna, Italy

    Cristina Papayannidis

  13. UOC Ematologia, Azienda ULSS 3 Serenissima, Ospedale Dell’Angelo, Venice-Mestre, Italy

    Matteo Leoncin

  14. UOC Ematologia, Azienda Ospedaliero Universitaria Senese, Siena, Italy

    Marzia Defina

  15. Clinica Ematologica, Dipartimento Di Medicina Interna (DiMI), Università Degli Studi Di Genova, Genoa, Italy

    Fabio Guolo

  16. IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Fabio Guolo

  17. U.O. Di Ematologia, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy

    Crescenza Pasciolla

  18. U.O. Ematologia Con Trapianto, Azienda Ospedaliero-Universitaria Consorziale, Policlinico Di Bari, Bari, Italy

    Mario Delia

  19. Dipartimento Di Diagnostica Per Immagini, Radioterapia Oncologica Ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy

    Patrizia Chiusolo

  20. Sezione Di Ematologia, Dipartimento Di Scienze Radiologiche Ed Ematologiche, Università Cattolica del Sacro Cuore, Rome, Italy

    Patrizia Chiusolo

  21. Divisione Di Ematologia Ad Indirizzo Oncologico, Riuniti Villa Sofia-Cervello, A.O. Ospedali, Palermo, Italy

    Antonino Mulè

Authors
  1. Davide Lazzarotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ilaria Tanasi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Antonella Vitale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matteo Piccini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michelina Dargenio
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fabio Giglio
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fabio Forghieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nicola Fracchiolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Marco Cerrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Elisabetta Todisco
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cristina Papayannidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Matteo Leoncin
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Marzia Defina
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Fabio Guolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Crescenza Pasciolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mario Delia
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Patrizia Chiusolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Antonino Mulè
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Anna Candoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Massimiliano Bonifacio
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Giovanni Pizzolo
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Robin Foà
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Davide Lazzarotto, Ilaria Tanasi, and Antonella Vitale: study design, data analysis, and manuscript writing. Matteo Piccini, Michelina Dargenio, Fabio Giglio, Fabio Forghieri, Nicola Fracchiolla, Marco Cerrano, Elisabetta Todisco, Cristina Papayannidis, Matteo Leoncin, Marzia Defina, Fabio Guolo, Crescenza Pasciolla, Mario Delia, Patrizia Chiusolo, Antonino Mulè, and Anna Candoni: data collection and manuscript revision. Massimiliano Bonifacio, Giovanni Pizzolo, and Robin Foà: data discussion and manuscript revision.

Corresponding author

Correspondence to Davide Lazzarotto.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lazzarotto, D., Tanasi, I., Vitale, A. et al. Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia–like or acute lymphoblastic leukemia–like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study. Ann Hematol 102, 1099–1109 (2023). https://doi.org/10.1007/s00277-023-05162-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-023-05162-0

Keywords

Search

Navigation