AUTOIMMUNE HEMOLITYC ANEMIA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: SINGLE CENTER EXPERIENCE

  • Sanja Trajkova University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Svetlana Krstevska-Balkanov University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Aleksandra Pivkova-Veljanovska University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Zlate Stojanovski University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, Skopje, North Macedonia
  • Marija Popova-Labacevska University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Nevenka Ridova University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Simona Stojanovska-Jakimovska University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Milce Cvetanovski University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Tara Risteska University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Bozidar Kocoski University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Arita Fazliu University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Irina Panovska-Stavridis University Clinic for Hematology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia

Abstract

Autoimmune phenomena are a well-known complication of lymphoproliferative diseases, particular in chronic lymphocytic leukemia (CLL). Autoimmune hemolytic anemia(AIHA) is the most frequent autoimmune disorder described in CLL. AIHA is more frequently found in patients with unfavorable biological risk factors for CLL.   Aim of the study: Evaluation of AIHA in chronic lymphocytic leukemia patients from Republic of North Macedonia in correlation with genetic structure of pathologic B lymphocyte. Material and methods: This is a retrospective study of 100 patients with CLL, diagnosed and followed in the period between January 2012 and January 2022. Traditional laboratory, clinical prognostic, and biological prognostic factors were evaluated at first patient visit to University Clinic of Hematology -Skopje Macedonia. Immunohematology workup was performed Institute for Transfusion, Skopje, North Macedonia.  Mutational status and configuration of IGHV-IGHD-IGHJ rearrangements and genetics were analyzed using reverse transcriptase– polymerase chain reaction (RT-PCR) and sequencing methodology. Results: A diagnosis of AIHA was made in 10% of the new diagnosed treatment naïve CLL patients observed at our institution. Seventy percent of the patients have unmutated IGHV gene. The genetic results presented most frequent unfavorable cytogenetics with 11q deletions and NOTHCH mutation. TTF was 11,3 months and OS of CLL/AIHA was 35,9months. Conclusion: This study indicates that AIHA is a rare event in CLL with a significantly higher incidence in patients with   unmuteted  IGHV genes  subgroup IGHV1-69 and adverse genetic profile with 11q deletions  and NOTHCH mutation. The results of our study are consistent with published studies with specific molecular signature.


 Keywords: CLL, AIHA, unmutated IGHV, del11q.

References

1. Foon KA, Rai KR, Gale RP. Chronic lymphocytic leukemia: new insight into biology and therapy. Ann Intern Med. 1990;113:525.
2. Diehl LF, Ketchum LH. Autoimmune disease and chronic lymphocytic leukemia: autoimmune hemolytic anemia, pure red cell aplasia and autoimmune thrombocytopenia. Semin Oncol. 1998;25:80.
3. De Rossi G, Granati L, Girelli G, et al. Incidence and prognostic significance of autoantibodies against erythrocytes and platelets in chronic lymphocytic leukemia (CLL). Nouv Rev Fr Hematol. 1988;30:403.
4. Robak T, Blasinska-Morawiec M, Krykowski E, Hellmann A, Konopka L. Autoimmune haemolytic anaemia in patients with chronic lymphocytic leukaemia treated with 2-chlorodeoxyadenosine (cladribine). Eur J Haematol. 1997;58:109.
5. Pritsch O, Maloum K, Dighiero G. Basic biology of autoimmune phenomena in chronic lymphocytic leukemia. Semin Oncol. 1998;25:34.
6. Hodgson K, Ferrer G, Montserrat E, Moreno C. Chronic lymphocytic leukemia and autoimmunity: a systematic review. Haematologica. 2011 May;96(5):752-61. doi: 10.3324/haematol.2010.036152. Epub 2011 Jan 17. PMID: 21242190; PMCID: PMC3084923.
7.Efremov DG, Ivanovski M, Siljanovski N, et al. Restricted immunoglobulin VH region repertoire in chronic lymphocytic leukemia patients with autoimmune hemolytic anemia. Blood. 1996;87:3869.
8. Michael Hallek, Bruce D. Cheson, Daniel Catovsky, Federico Caligaris-Cappio, Guillermo Dighiero, Hartmut Döhner, Peter Hillmen, Michael Keating, Emili Montserrat, Nicholas Chiorazzi, Stephan Stilgenbauer, Kanti R. Rai, John C. Byrd, Barbara Eichhorst, Susan O’Brien, Tadeusz Robak, John F. Seymour, Thomas J. Kipps; iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood 2018; 131 (25): 2745–2760.
9. https://escca.eu/images/ERIC-ESCCA-CLL-Dx-consensus-submitted-to-cytometry.pdf.
10. Hamblin TJ, Oscier DG, Young BJ. Autoimmunity in chronic lymphocytic leukaemia. J Clin Pathol. 1986;39:713.
11. Weinberg K, Parkman R. Age, the thymus and T lymphocytes. N Engl J Med. 1995;332:182.
12. Francesco Forconi, Kathleen N. Potter, Isla Wheatley, Nikos Darzentas, Elisa Sozzi, Kostas Stamatopoulos, C. Ian Mockridge, Graham Packham, Freda K. Stevenson; The normal IGHV1-69–derived B-cell repertoire contains stereotypic patterns characteristic of unmutated CLL. Blood 2010; 115 (1): 71–77. doi: https://doi.org/10.1182/blood-2009-06-225813.
Published
2024-04-30
How to Cite
TRAJKOVA, Sanja et al. AUTOIMMUNE HEMOLITYC ANEMIA IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA: SINGLE CENTER EXPERIENCE. Journal of Morphological Sciences, [S.l.], v. 7, n. 1, p. 6-16, apr. 2024. ISSN 2545-4706. Available at: <https://jms.mk/jms/article/view/vol7no1-2>. Date accessed: 20 june 2024.
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Articles