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Frequency of Paroxysmal Nocturnal Hemoglobinuria in Patients with Lymphoma

Year 2022, Volume: 8 Issue: 1, 130 - 138, 25.02.2022
https://doi.org/10.19127/mbsjohs.1029549

Abstract

Objective: To investigate the frequency of paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal hematopoietic stem cell disease resulting in complement-mediated hemolysis, in patients with lymphoma by flow cytometry.
Methods: Fifty patients with lymphoma who were admitted to the hematology clinic, newly diagnosed and not yet treated were included in this study conducted in 2014. The presence of PNH clones was checked by FLAER flow cytometry method in peripheral blood samples. FLAER is a non-hemolytic fluorescently labeled inactive toxin aerolysin method that can detect up to 0.5% of PNH cells instead of bacterial toxin aerolysin, which binds to RBCs via the GPI anchor and initiates hemolysis for PNH screening or PNH clone detection. With this technique, PNH clones in all hematopoietic cell lines can be detected in an assay.
Results: PNH clone was observed over 10% in two patients, one male and the other female. However, no hemolysis was found in patients with PNH clones. The lymphoma subtypes of the patients with positive PNH clone were B-cell small-cell lymphocytic lymphoma in the male patient and primary splenic lymphoma in the female patient.
Conclusion: PNH or PNH-like disorders accompanying hematological malignancies, especially lymphomas, are not very common in the literature. There is a need to elucidate the relationship between hematological malignancies and PNH with the help of more advanced molecular techniques.

References

  • 1. Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: role of the complement system, pathogenesis, and pathophysiology. J Manag Care Spec Pharm. Aralık 2020;26(12-b Suppl):3-8.
  • 2. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.
  • 3. Hillmen P, Muus P, Röth A, Elebute MO, Risitano AM, Schrezenmeier H, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162(1):62-73.
  • 4. Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-709.
  • 5. Socie G, Mary JY, Gramont A, Rio B, Leporrier M, Rose C. et al. Paroxysmal nocturnal hemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996;348(9027):573-7.
  • 6. Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR, vd. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom. 2010;78(4):211-30.
  • 7. Guc D, Canpinar H, Kucukaksu C, Kansu E. Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. Eur J Haematol. 2000;64(1):3-9.
  • 8. Meletis J, Terpos E, Samaekos M, Meletis C, Apostolidou E, Komninaka V. et. al. Red Cells with Paroxysmal Nocturnal Hemoglobinuria-phenotype in Patients with Acute Leukemia. Hematology. 2002; 7(2):69-74.
  • 9. Kirito K. Expansion of paroxysmal nocturnal hemoglobinuria clones in MPLW515L mutation harboring primary myelofibrosis. Ann Hematol. Kasım 2020;99(11):2707-9.
  • 10. Van Voolen GA, Hellstrom HR, Nelson DA. Paroxysmal nocturnal hemoglobinuria and the myeloproliferative syndrome. Ann Intern Med. 1982;96(6 Pt 1):792.
  • 11. Vyrides N, Douka V, Gavriilaki E, Papaioannou G, Athanasiadou A, Neofytou S, et al. Paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome: Disappearance of cytogenetic abnormalities. Cancer Genet. 2021;250-251:1-5.
  • 12. Dunn DE, Tanawattanacharoen P, Boccuni P, Nagakura S, Green SW, Kirby MR, et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med. 1999;131(6):401-8.
  • 13. Meletis J, Terpos E, Samarkos M, Meletis C, Konstantopoulos K, Komninaka V, vd. Detection of CD55 and/or CD59 deficient red cell populations in patients with aplastic anaemia, myelodysplastic syndromes and myeloproliferative disorders. Haematologia (Budap). 2001;31(1):7-16.
  • 14. Iwanaga M, Furukawa K, Amenomori T, Mori H, Nakamura H, Fuchigami K, vd. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102(2):465-74.
  • 15. Christou T, Subramanian S, Fung C. Paroxysmal nocturnal hemoglobinuria preceding malignant lymphoma. Arch Intern Med. 1987;147(2):377-8.
  • 16. Ligorsky RD, Schaffner S, Oliver J, Oliver D, Lavine D. Unusual association between non-Hodgkin’s malignant lymphoma and a PNH-like defect in the red cell. Am J Med. 1994;96(4):395-6.
  • 17. Lanza F, Lazzari MC, Brambilla P, Di Martino G, Spedini P. An unusual association of paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, and diffuse large B-cell non-Hodgkin lymphoma in a Caucasian man. Ann Hematol. 2016;95(9):1555-7.
  • 18. Hertenstein B, Wagner B, Bunjes D, Duncker C, Raghavachar A, Arnold R. et al. Emergence of CD52-, Phosphatidylinositolglycan-Anchor-Deficient T Lymphocytes After In Vivo Application of Campath-1H for Refractory B-Cell Non-Hodgkin Lymphoma. Blood. 1995;86(4):1487-1492.
  • 19. Taylor VC, Sims M, Brett S, Field MC. Antibody selection against CD52 produces a paroxysmal nocturnal haemoglobinuria phenotype in human lymphocytes by a novel mechanism. Biochem J. 15 Mart 1997;322 (Pt 3):919-25.
  • 20. Fukuda H, Seya T, Hara T, Matsumoto M, Kinoshita T, Masaoka T. Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin’s lymphoma. Immunol Lett. Ağustos 1991;29(3):205-9.
  • 21. Seya T, Matsumoto M, Hara T, Hatanaka M, Masaoka T, Akedo H. Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1), CD46 (MCP), and CD55 (DAF), in hematological malignancies. Leuk Lymphoma. Şubat 1994;12(5-6):395-400. 22. Sun X, Funk CD, Deng C, Sahu A, Lambris JD, Song WC. Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targeting. Proc Natl Acad Sci U S A. 19 Ocak 1999;96(2):628-33.
  • 23. Rowan W, Tite J, Topley P, Brett SJ. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology. Kasım 1998;95(3):427-36

Frequency of Paroxysmal Nocturnal Hemoglobinuria in Patients with Lymphoma

Year 2022, Volume: 8 Issue: 1, 130 - 138, 25.02.2022
https://doi.org/10.19127/mbsjohs.1029549

Abstract

Objective: To investigate the frequency of paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal hematopoietic stem cell disease resulting in complement-mediated hemolysis, in patients with lymphoma by flow cytometry.
Methods: Fifty patients with lymphoma who were admitted to the hematology clinic, newly diagnosed and not yet treated were included in this study conducted in 2014. The presence of PNH clones was checked by FLAER flow cytometry method in peripheral blood samples. FLAER is a non-hemolytic fluorescently labeled inactive toxin aerolysin method that can detect up to 0.5% of PNH cells instead of bacterial toxin aerolysin, which binds to RBCs via the GPI anchor and initiates hemolysis for PNH screening or PNH clone detection. With this technique, PNH clones in all hematopoietic cell lines can be detected in an assay.
Results: PNH clone was observed over 10% in two patients, one male and the other female. However, no hemolysis was found in patients with PNH clones. The lymphoma subtypes of the patients with positive PNH clone were B-cell small-cell lymphocytic lymphoma in the male patient and primary splenic lymphoma in the female patient.
Conclusion: PNH or PNH-like disorders accompanying hematological malignancies, especially lymphomas, are not very common in the literature. There is a need to elucidate the relationship between hematological malignancies and PNH with the help of more advanced molecular techniques.

References

  • 1. Bektas M, Copley-Merriman C, Khan S, Sarda SP, Shammo JM. Paroxysmal nocturnal hemoglobinuria: role of the complement system, pathogenesis, and pathophysiology. J Manag Care Spec Pharm. Aralık 2020;26(12-b Suppl):3-8.
  • 2. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.
  • 3. Hillmen P, Muus P, Röth A, Elebute MO, Risitano AM, Schrezenmeier H, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162(1):62-73.
  • 4. Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106(12):3699-709.
  • 5. Socie G, Mary JY, Gramont A, Rio B, Leporrier M, Rose C. et al. Paroxysmal nocturnal hemoglobinuria: long-term follow-up and prognostic factors. French Society of Haematology. Lancet. 1996;348(9027):573-7.
  • 6. Borowitz MJ, Craig FE, Digiuseppe JA, Illingworth AJ, Rosse W, Sutherland DR, vd. Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry. Cytometry B Clin Cytom. 2010;78(4):211-30.
  • 7. Guc D, Canpinar H, Kucukaksu C, Kansu E. Expression of complement regulatory proteins CR1, DAF, MCP and CD59 in haematological malignancies. Eur J Haematol. 2000;64(1):3-9.
  • 8. Meletis J, Terpos E, Samaekos M, Meletis C, Apostolidou E, Komninaka V. et. al. Red Cells with Paroxysmal Nocturnal Hemoglobinuria-phenotype in Patients with Acute Leukemia. Hematology. 2002; 7(2):69-74.
  • 9. Kirito K. Expansion of paroxysmal nocturnal hemoglobinuria clones in MPLW515L mutation harboring primary myelofibrosis. Ann Hematol. Kasım 2020;99(11):2707-9.
  • 10. Van Voolen GA, Hellstrom HR, Nelson DA. Paroxysmal nocturnal hemoglobinuria and the myeloproliferative syndrome. Ann Intern Med. 1982;96(6 Pt 1):792.
  • 11. Vyrides N, Douka V, Gavriilaki E, Papaioannou G, Athanasiadou A, Neofytou S, et al. Paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome: Disappearance of cytogenetic abnormalities. Cancer Genet. 2021;250-251:1-5.
  • 12. Dunn DE, Tanawattanacharoen P, Boccuni P, Nagakura S, Green SW, Kirby MR, et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med. 1999;131(6):401-8.
  • 13. Meletis J, Terpos E, Samarkos M, Meletis C, Konstantopoulos K, Komninaka V, vd. Detection of CD55 and/or CD59 deficient red cell populations in patients with aplastic anaemia, myelodysplastic syndromes and myeloproliferative disorders. Haematologia (Budap). 2001;31(1):7-16.
  • 14. Iwanaga M, Furukawa K, Amenomori T, Mori H, Nakamura H, Fuchigami K, vd. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102(2):465-74.
  • 15. Christou T, Subramanian S, Fung C. Paroxysmal nocturnal hemoglobinuria preceding malignant lymphoma. Arch Intern Med. 1987;147(2):377-8.
  • 16. Ligorsky RD, Schaffner S, Oliver J, Oliver D, Lavine D. Unusual association between non-Hodgkin’s malignant lymphoma and a PNH-like defect in the red cell. Am J Med. 1994;96(4):395-6.
  • 17. Lanza F, Lazzari MC, Brambilla P, Di Martino G, Spedini P. An unusual association of paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, and diffuse large B-cell non-Hodgkin lymphoma in a Caucasian man. Ann Hematol. 2016;95(9):1555-7.
  • 18. Hertenstein B, Wagner B, Bunjes D, Duncker C, Raghavachar A, Arnold R. et al. Emergence of CD52-, Phosphatidylinositolglycan-Anchor-Deficient T Lymphocytes After In Vivo Application of Campath-1H for Refractory B-Cell Non-Hodgkin Lymphoma. Blood. 1995;86(4):1487-1492.
  • 19. Taylor VC, Sims M, Brett S, Field MC. Antibody selection against CD52 produces a paroxysmal nocturnal haemoglobinuria phenotype in human lymphocytes by a novel mechanism. Biochem J. 15 Mart 1997;322 (Pt 3):919-25.
  • 20. Fukuda H, Seya T, Hara T, Matsumoto M, Kinoshita T, Masaoka T. Deficiency of complement decay-accelerating factor (DAF, CD55) in non-Hodgkin’s lymphoma. Immunol Lett. Ağustos 1991;29(3):205-9.
  • 21. Seya T, Matsumoto M, Hara T, Hatanaka M, Masaoka T, Akedo H. Distribution of C3-step regulatory proteins of the complement system, CD35 (CR1), CD46 (MCP), and CD55 (DAF), in hematological malignancies. Leuk Lymphoma. Şubat 1994;12(5-6):395-400. 22. Sun X, Funk CD, Deng C, Sahu A, Lambris JD, Song WC. Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targeting. Proc Natl Acad Sci U S A. 19 Ocak 1999;96(2):628-33.
  • 23. Rowan W, Tite J, Topley P, Brett SJ. Cross-linking of the CAMPATH-1 antigen (CD52) mediates growth inhibition in human B- and T-lymphoma cell lines, and subsequent emergence of CD52-deficient cells. Immunology. Kasım 1998;95(3):427-36
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research articles
Authors

Muhammet Özbilen 0000-0001-6052-7486

Aysın Tulunay Virlan This is me 0000-0003-4735-9902

Abdullah Hacıhanefioğlu 0000-0001-5164-6301

Publication Date February 25, 2022
Published in Issue Year 2022 Volume: 8 Issue: 1

Cite

Vancouver Özbilen M, Tulunay Virlan A, Hacıhanefioğlu A. Frequency of Paroxysmal Nocturnal Hemoglobinuria in Patients with Lymphoma. Mid Blac Sea J Health Sci. 2022;8(1):130-8.

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