Research Article
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Efficacy of Induction Treatments in Patients with Biphenotypic Acute Leukemia

Year 2023, Volume: 6 Issue: 4, 713 - 718, 15.10.2023
https://doi.org/10.19127/bshealthscience.1276568

Abstract

Despite advances in leukemia diagnosis and treatment, BAL management remains challenging. The aim of this study is to contribute to the literature by analyzing the clino-pathological characteristics and treatment outcome of 13 patients diagnosed as BAL. Medical charts of 13 patients who were diagnosed as BAL according to EGIL or WHO 2016 criteria in our center between 2017- 2022 were retrospectively reviewed. Of the 13 BAL patients with a mean age of 36, 6 (46%) were female and 7 (54%) were male. Eleven (84.6%) of the cases showed B/myeloid, 2 (15.6%) T/myeloid cell expression patterns. In cytogenetic examination, 3 (23.1%) of the cases had t(v; 11q23) MLL, 1 (7.7%) t(9;22) BCR-ABL1 and 1 (7.7%) FLT- ITD abnormality. Eight of the cases (61.5%) received ALL induction therapy and 5 (38.5%) of them received AML induction therapy, and 8 (61.5%) of them responded to the treatment. The treatment protocols with the highest rate of response to treatment were ALLOLD07 (100%), S-HAM (75%) and HYPER-CVAD (66%), respectively. Median follow-up from the time of diagnosis was 32 months (range: 2-71), median OS 9 months (95%CI: 2.71-15.94) and the median PFS 4.5 months (95%CI: 3.32-5.67). Allo-Hematopoietic stem cell transplantation (HSCT) was performed in 8 of the cases. After HSCT, 1 patient developed relapsed disease and died from disease progression. Four of the cases died due to BAL progression, 2 died due to infection, and the overall survival rate was 53.8%. Since BAL is a rare disease, there is no consensus on which treatment is optimal. Although ALL-based induction regimens seem to be superior in the treatment of BAL, multicenter clinical studies with more cases are needed to better understand the heterogeneous nature of this rare disease.

Project Number

YOK

References

  • Arber DA, Orazi A, Hasserjian R. 2016. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood J, 127(20): 2391–2405.
  • Bene MC, Bernier M, Casasnovas RO. 1998. The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood J, 92(2): 596-9.
  • Bene MC, Castoldi G, Knapp W. 1995. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia J, 9: 1783–1786.
  • Béné MC, Porwit A. 2012. Acute leukemias of ambiguous lineage. Seminars Diagnostic Pathol J, 29(1): 12-18.
  • Berry DA, Zhou S, Higley H. 2017. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: A meta-analysis. JAMA Oncology J. 3(7):e170580.
  • Dohner H, Estey E, Grimwade D. 2017. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood J, 129(4): 424–447.
  • Huang J, Zhou J, Xiao M. 2021. The association of complex genetic background with the prognosis of acute leukemia with ambiguous lineage. Sci Report, 11(1): 24290.
  • Killick S, Matutes E, Powles RL. 1999. Outcome of biphenotypic acute leukemia. Haematologica J, 84: 699-706.
  • Maruffi M, Sposto R, Oberley MJ, Kysh L, Etan Orge. 2018. Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis. Leukemia J, 32(7): 1515–1528.
  • Mikulic M, Batinic D, Sucic M. 2008. Biological features and outcome of biphenotypic acute leukemia: a case series. Hematology Oncol Stem Cell Therapy J, 1: 225–230.
  • Munker R, Brazauskas R, Wang HL. 2016. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia. Biol Blood Marrow Transplant J, 22(6): 1024-1029
  • Munker R, Labopin M, Esteve J, Schmid C, Mohty M, Nagler A. 2017 Dec. Mixed phenotype acute leukemia: outcomes with allogeneic stem cell transplantation. A retrospective study from the Acute Leukemia Working Party of the EBMT. Haematologica J, 102(12): 2134-2140.
  • Oskarsson T, Söderhäll S, Arvidson J. 2016. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome. Haematologica J, 101: 68–76.
  • Owaidah TM, Al Beihany A, Iqbal MA, Roberts GT. 2006. Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia J, 20: 620-626.
  • Rubnitz JE, Onciu M, Pounds S. 2009. Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital. Blood J, 113: 5083-5089.
  • Shi R, Munker R. 2015. Survival of patients with mixed phenotype acute leukemias: A large population-based study. Leukemia Res, 39: 606-616.
  • Tong H, Liu Z, Lu C, Wang Q. 2013. Clinical and laboratory features of adult biphenotypic acute leukemia. Asia-Pacific J Clini Oncol, 9(2): 146-154.
  • Weir EG, Ali Ansari-Lari M, Batista DA. 2007. Acute bi-lineal leukemia: a rare disease with poor outcome. Leukemia J, 21: 2264–2270.
  • Wolach O, Stone RM. 2015. How I treat mixed-phenotype acute leukemia. Blood J, 125: 2477–2485.
  • Xu XQ, Wang JM, Lü SQ. 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 J, 94(7): 919–927.
  • Yan L, Ping N, Zhu M. 2012. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008. Haematologica J, 97(11): 1708-1712.
  • Yu J, Li Y, Xing H. 2019. Clinical Characteristics And Outcome Of Biphenotypic Acute Leukemia: 10 Case Reports And Literature Review. Cancer Manage Res, 11: 9297-9306.

Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği

Year 2023, Volume: 6 Issue: 4, 713 - 718, 15.10.2023
https://doi.org/10.19127/bshealthscience.1276568

Abstract

Lösemi tanı ve tedavisindeki ilerlemelere rağmen BAL yönetimi zorlu kalmaya devam etmektedir. Bu çalışmanın amacı BAL tanısı alan 13 hastanın klinokopatolojik özelliklerini ve tedavi sonuçlarını analiz edip literatüre katkıda bulunmaktır. Merkezimizde 2017-2022 yılları arasında EGIL veya WHO 2016 kriterlerine göre BAL tanısı alan 13 hastanın tıbbi kayıtları geriye dönük olarak incelendi. Ortalama yaşları 36 olan 13 BAL hastasının 6’sı (%46) kadın 7’si (%54) erkekti. Olguların 11’i (%84,6) myeloid/B, 2’si (%15,6) myeloid/T hücre ekspresyon paterni sergiliyordu. Sitogenetik incelemede olguların 3’ünde (%23,1) t(v;11q23) MLL, 1’inde (%7,7) t(9;22) BCR-ABL1 ve 1’inde (%7,7) FLT-ITD anomalisi mevcuttu. Olguların 7’si (%53) ALL ve 6’sı (%47) AML indüksiyon tedavisi aldı ve 8’inde (%61,5) tedaviye yanıt vardı. Tedaviye yanıt oranının en fazla olduğu protokoller sırasıyla ALLOLD07 (%100), S-HAM (%75) ve HYPER-CVAD (%66) idi. Tanı anından itibaren medyan takip süresi 32 ay (aralık: 2-71), medyan OS 9 ay (%95 CI: 2,71-15,94) ve medyan PFS ise 4.5 ay (%95 CI: 3,32-5,67) idi. Olguların 8’ine allojenik hematopoietik kök hücre transplantasyonu (AKİT) yapıldı. AKİT sonrası 1 hastada relaps hastalık gelişti ve hastalık progresyonundan öldü. Olguların 4’ü BAL progresyonu, 2’si enfeksiyon sebebiyle öldü ve genel sağkalım oranı %53.8 idi. BAL nadir görülen bir hastalık olduğundan optimal tedavinin ne olduğu konusunda ortak bir görüş yoktur. BAL tedavisinde ALL tabanlı indüksiyon rejimleri daha üstün gibi görünmekle beraber, bu nadir hastalığın heterojen doğasını anlamak için daha fazla olguyla yapılacak çok merkezli klinik çalışmalara ihtiyaç vardır.

Supporting Institution

YOK

Project Number

YOK

Thanks

Çukurova Üniversitesi Tıp Fakültesi Hematoloji Kliniği Çalışanlarına ve Patoloji bölümüne teşekkür ederiz.

References

  • Arber DA, Orazi A, Hasserjian R. 2016. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood J, 127(20): 2391–2405.
  • Bene MC, Bernier M, Casasnovas RO. 1998. The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL). Blood J, 92(2): 596-9.
  • Bene MC, Castoldi G, Knapp W. 1995. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia J, 9: 1783–1786.
  • Béné MC, Porwit A. 2012. Acute leukemias of ambiguous lineage. Seminars Diagnostic Pathol J, 29(1): 12-18.
  • Berry DA, Zhou S, Higley H. 2017. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: A meta-analysis. JAMA Oncology J. 3(7):e170580.
  • Dohner H, Estey E, Grimwade D. 2017. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood J, 129(4): 424–447.
  • Huang J, Zhou J, Xiao M. 2021. The association of complex genetic background with the prognosis of acute leukemia with ambiguous lineage. Sci Report, 11(1): 24290.
  • Killick S, Matutes E, Powles RL. 1999. Outcome of biphenotypic acute leukemia. Haematologica J, 84: 699-706.
  • Maruffi M, Sposto R, Oberley MJ, Kysh L, Etan Orge. 2018. Therapy for children and adults with mixed phenotype acute leukemia: a systematic review and meta-analysis. Leukemia J, 32(7): 1515–1528.
  • Mikulic M, Batinic D, Sucic M. 2008. Biological features and outcome of biphenotypic acute leukemia: a case series. Hematology Oncol Stem Cell Therapy J, 1: 225–230.
  • Munker R, Brazauskas R, Wang HL. 2016. Allogeneic Hematopoietic Cell Transplantation for Patients with Mixed Phenotype Acute Leukemia. Biol Blood Marrow Transplant J, 22(6): 1024-1029
  • Munker R, Labopin M, Esteve J, Schmid C, Mohty M, Nagler A. 2017 Dec. Mixed phenotype acute leukemia: outcomes with allogeneic stem cell transplantation. A retrospective study from the Acute Leukemia Working Party of the EBMT. Haematologica J, 102(12): 2134-2140.
  • Oskarsson T, Söderhäll S, Arvidson J. 2016. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome. Haematologica J, 101: 68–76.
  • Owaidah TM, Al Beihany A, Iqbal MA, Roberts GT. 2006. Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system. Leukemia J, 20: 620-626.
  • Rubnitz JE, Onciu M, Pounds S. 2009. Acute mixed lineage leukemia in children: the experience of St Jude Children's Research Hospital. Blood J, 113: 5083-5089.
  • Shi R, Munker R. 2015. Survival of patients with mixed phenotype acute leukemias: A large population-based study. Leukemia Res, 39: 606-616.
  • Tong H, Liu Z, Lu C, Wang Q. 2013. Clinical and laboratory features of adult biphenotypic acute leukemia. Asia-Pacific J Clini Oncol, 9(2): 146-154.
  • Weir EG, Ali Ansari-Lari M, Batista DA. 2007. Acute bi-lineal leukemia: a rare disease with poor outcome. Leukemia J, 21: 2264–2270.
  • Wolach O, Stone RM. 2015. How I treat mixed-phenotype acute leukemia. Blood J, 125: 2477–2485.
  • Xu XQ, Wang JM, Lü SQ. 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 J, 94(7): 919–927.
  • Yan L, Ping N, Zhu M. 2012. Clinical, immunophenotypic, cytogenetic, and molecular genetic features in 117 adult patients with mixed-phenotype acute leukemia defined by WHO-2008. Haematologica J, 97(11): 1708-1712.
  • Yu J, Li Y, Xing H. 2019. Clinical Characteristics And Outcome Of Biphenotypic Acute Leukemia: 10 Case Reports And Literature Review. Cancer Manage Res, 11: 9297-9306.
There are 22 citations in total.

Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section Research Article
Authors

İbrahim Halil Açar 0000-0002-8657-1407

Birol Güvenç 0000-0001-7641-5673

Project Number YOK
Early Pub Date October 5, 2023
Publication Date October 15, 2023
Submission Date April 4, 2023
Acceptance Date September 30, 2023
Published in Issue Year 2023 Volume: 6 Issue: 4

Cite

APA Açar, İ. H., & Güvenç, B. (2023). Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği. Black Sea Journal of Health Science, 6(4), 713-718. https://doi.org/10.19127/bshealthscience.1276568
AMA Açar İH, Güvenç B. Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği. BSJ Health Sci. October 2023;6(4):713-718. doi:10.19127/bshealthscience.1276568
Chicago Açar, İbrahim Halil, and Birol Güvenç. “Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği”. Black Sea Journal of Health Science 6, no. 4 (October 2023): 713-18. https://doi.org/10.19127/bshealthscience.1276568.
EndNote Açar İH, Güvenç B (October 1, 2023) Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği. Black Sea Journal of Health Science 6 4 713–718.
IEEE İ. H. Açar and B. Güvenç, “Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği”, BSJ Health Sci., vol. 6, no. 4, pp. 713–718, 2023, doi: 10.19127/bshealthscience.1276568.
ISNAD Açar, İbrahim Halil - Güvenç, Birol. “Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği”. Black Sea Journal of Health Science 6/4 (October 2023), 713-718. https://doi.org/10.19127/bshealthscience.1276568.
JAMA Açar İH, Güvenç B. Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği. BSJ Health Sci. 2023;6:713–718.
MLA Açar, İbrahim Halil and Birol Güvenç. “Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği”. Black Sea Journal of Health Science, vol. 6, no. 4, 2023, pp. 713-8, doi:10.19127/bshealthscience.1276568.
Vancouver Açar İH, Güvenç B. Bifenotipik Akut Lösemili Hastalarda Uygulanan İndüksiyon Tedavilerinin Etkinliği. BSJ Health Sci. 2023;6(4):713-8.