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  • 1 HCEMM-SE Molekuláris Onkohematológia Kutatócsoport, , Budapest
  • | 2 I. Sz. Patológiai és Kísérleti Rákkutató Intézet, Semmelweis Egyetem, , 1085 Budapest, Üllői út 26.
  • | 3 Belgyógyászati és Onkológiai Klinika, Semmelweis Egyetem, , Budapest
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Összefoglaló. A hajas sejtes leukémia (HCL) egy indolens lefolyású ritka B-sejtes lymphoma. Diagnosztikájában jellegzetes morfológiai képén túlmenően a sejtek felszínén megtalálható markerek azonosítása áramlási citometriával, valamint a betegségben előforduló specifikus fehérjék immunhisztokémiai detektálása jelenti a rutineljárást. Kiemelt szerepet tölt be a differenciáldiagnosztikában a BRAF V600E mutációjának a kimutatása, melyre ma már számos módszer áll rendelkezésre, mint például az immunhisztokémia, pyroszekvenálás, allélspecifikus PCR vagy a droplet digitalis PCR. A tumorsejtek jelátviteli rendszerében és szabályozásában azonban a BRAF mutációjának következtében kialakuló folyamatos aktivitása mellett egyéb mechanizmusok is szerepet játszhatnak, többek között növekedési faktorok, interleukinek, adhéziós fehérjék vagy éppen mikro-RNS-ek. A patomechanizmus egyre részletesebb megismerése érdekében egyéb daganatokhoz hasonlóan a HCL-ben is aktív kutatások folynak a genetikai háttér feltérképezésére új generációs szekvenálás segítségével. Leírtak már nagy százalékban előforduló mutációkat a CDKN1B-, KLF2- és KMT2C-gének esetében, továbbá egyéb génekben is alacsonyabb előfordulási aránnyal. Genetikailag, sőt klinikai manifesztáció és terápiás válasz alapján is jelentős eltérések láthatóak a klasszikus és variáns HCL-es betegek között, elkülönítésük épp ezért rendkívül fontos. Míg a klasszikus esetben első vonalban alkalmazott purin nukleozid analógok kiemelkedő válaszreakciót képesek kiváltani, a variáns HCL-es betegek gyakran refrakterek a kezelésre, és esetükben a célzott BRAF-gátlók szintén hatástalanok. Számos klinikai kutatás zajlik a jelenleg is alkalmazott terápiás szerek optimalizálása, kombinációban történő alkalmazása, valamint egyéb lymphoid daganatokban alkalmazott gyógyszerek és új támadáspontok ellen tervezett molekuláknak a HCL kezelésébe történő bevonása céljából.

Summary. Hairy cell leukemia (HCL) is a rare indolent B-cell malignancy. In addition to characteristic morphology of HCL cells, the identification of the cellular surface markers and the expression of specific proteins by flow cytometry and immunohistochemistry are routine procedure in HCL diagnosis. Detection of BRAF V600E mutation plays key role in differential diagnosis of HCL which can be detected by several novel methods, such as immunohistochemistry, pyrosequencing, allele specific PCR or droplet digital PCR. Beside the BRAF mutation there can be other mechanisms causing constitutive activity in the signaling pathway and regulating the tumor cells such as growth factors, interleukins, adhesion proteins and micro-RNAs as well. Like in other malignancies, in order to clarify the pathomechanism, the genetic background of HCL is also actively investigated by next-generation sequencing. Frequent mutations were described in CDKN1B, KLF2 and KMT2C genes, moreover in other genes with lower incidence rate, as well. Genetically, and even in clinical manifestation and therapeutic response, significant differences can be found between patients with classical and variant HCL. While classical type has outstanding response for the first-line treatment with purine analogues, patients with variant HCL are often refractory to the treatment, and the BRAF inhibitors prove to be ineffective. Therefore, it is really important to distinguish these two entities. Several clinical studies are still in progress for the optimization and application of combining the currently applied therapeutic agents, furthermore other drugs that used in lymphoid malignancies are under investigation. New target molecules are also designed as novel therapeutic opportunity in HCL treatment.

  • 1

    Teras LR, DeSantis CE, Cerhan JR, et al. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016; 66: 443–459.

  • 2

    Bouroncle BA, Wiseman BK, Doan CA. Leukemic reticuloendotheliosis. Blood 1958; 13: 609–630.

  • 3

    Burns GF, Cawley JC. A re-examination of the alleged monocytic features of hairy-cell leukaemia. Scand J Haematol. 1979; 22: 386–396.

  • 4

    Saxon A, Stevens RH, Golde DW. T-lymphocyte variant of hairy-cell leukemia. Ann Intern Med. 1978; 88: 323–326.

  • 5

    Schrek R, Donnelly WJ. “Hairy” cells in blood in lymphoreticular neoplastic disease and “flagellated” cells of normal lymph nodes. Blood 1966; 27: 199–211.

  • 6

    Kontrogianni-Konstantopoulos A, Frye CS, Benz EJ, Jr., et al. The prototypical 4.1R-10-kDa domain and the 4.1g-10-kDa paralog mediate fodrin-actin complex formation. J Biol Chem. 2001; 276: 20679–20687.

  • 7

    Basso K, Liso A, Tiacci E, et al. Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors. J Exp Med. 2004; 199: 59–68.

  • 8

    Forconi F, Sahota SS, Raspadori D, et al.: Hairy cell leukemia: at the crossroad of somatic mutation and isotype switch. Blood 2004; 104: 3312–3317.

  • 9

    Seifert M, Kuppers R. Human memory B cells. Leukemia 2016; 30: 2283–2292.

  • 10

    Anderson KC, Boyd AW, Fisher DC, et al. Hairy cell leukemia: a tumor of pre-plasma cells. Blood 1985; 65: 620–629.

  • 11

    Thorselius M, Walsh SH, Thunberg U, et al. Heterogeneous somatic hypermutation status confounds the cell of origin in hairy cell leukemia. Leuk Res. 2005; 29: 153–158.

  • 12

    Forconi F, Raspadori D, Lenoci M, et al.: Absence of surface CD27 distinguishes hairy cell leukemia from other leukemic B-cell malignancies. Haematologica 2005; 90: 266–268.

  • 13

    Shao H, Calvo KR, Gronborg M, et al. Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria. Leuk Res. 2013; 37: 401–409.

  • 14

    Catovsky D, Pettit JE, Galton DA, et al. Leukaemic reticuloendotheliosis (‘Hairy’ cell leukaemia): a distinct clinico-pathological entity. Br J Haematol. 1974; 26: 9–27.

  • 15

    Wang XJ, Kim A, Li S. Immunohistochemical analysis using a BRAF V600E mutation specific antibody is highly sensitive and specific for the diagnosis of hairy cell leukemia. Int J Clin Exp Pathol. 2014; 7: 4323–4328.

  • 16

    Andrulis M, Penzel R, Weichert W, et al. Application of a BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia. Am J Surg Pathol. 2012; 36: 1796–1800.

  • 17

    Turakhia S, Lanigan C, Hamadeh F, et al. Immunohistochemistry for BRAF V600E in the differential diagnosis of hairy cell leukemia vs other splenic B-cell lymphomas. Am J Clin Pathol. 2015; 144: 87–93.

  • 18

    Davies H, Bignell GR, Cox C, et al.: Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949–954.

  • 19

    Arcaini L, Zibellini S, Boveri E, et al. The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms. Blood 2012; 119: 188–191.

  • 20

    Tiacci E, Trifonov V, Schiavoni G, et al. BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011; 364: 2305–2315.

  • 21

    Ahmadzadeh A, Shahrabi S, Jaseb K, et al. BRAF mutation in hairy cell leukemia. Oncol Rev. 2014; 8: 253.

  • 22

    Chung SS, Kim E, Park JH, et al. Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia. Sci Transl Med. 2014; 6: 238ra271.

  • 23

    Jebaraj BM, Kienle D, Buhler A, et al. BRAF mutations in chronic lymphocytic leukemia. Leuk Lymphoma 2013; 54: 1177–1182.

  • 24

    Verma S, Greaves WO, Ravandi F, et al. Rapid detection and quantitation of BRAF mutations in hairy cell leukemia using a sensitive pyrosequencing assay. Am J Clin Pathol. 2012; 138: 153–156.

  • 25

    Guerrini F, Paolicchi M, Ghio F, et al. The droplet digital PCR: A new valid molecular approach for the assessment of B-RAF V600E mutation in hairy cell leukemia. Front Pharmacol. 2016; 7: 363.

  • 26

    Tiacci E, Schiavoni G, Forconi F, et al. Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation. Blood 2012; 119: 192–195.

  • 27

    Brennan P, Babbage JW, Burgering BM, et al. Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F. Immunity 1997; 7: 679–689.

  • 28

    Gruber G, Schwarzmeier JD, Shehata M, et al. Basic fibroblast growth factor is expressed by CD19/CD11c-positive cells in hairy cell leukemia. Blood 1999; 94: 1077–1085.

  • 29

    Aziz KA, Till KJ, Chen H, et al. The role of autocrine FGF-2 in the distinctive bone marrow fibrosis of hairy-cell leukemia (HCL). Blood 2003; 102: 1051–1056.

  • 30

    Pettirossi V, Santi A, Imperi E, et al. BRAF inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia and exert potent antileukemic activity. Blood 2015; 125: 1207–1216.

  • 31

    Burthem J, Baker PK, Hunt JA, et al. Hairy cell interactions with extracellular matrix: expression of specific integrin receptors and their role in the cell’s response to specific adhesive proteins. Blood 1994; 84: 873–882.

  • 32

    Vincent AM, Burthem J, Brew R, et al. Endothelial interactions of hairy cells: the importance of alpha 4 beta 1 in the unusual tissue distribution of the disorder. Blood 1996; 88: 3945–3952.

  • 33

    le Sage C, Nagel R, Egan DA, et al. Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007; 26: 3699–3708.

  • 34

    Kitagawa Y, Brahmachary M, Tiacci E, et al. A microRNA signature specific for hairy cell leukemia and associated with modulation of the MAPK-JNK pathways. Leukemia 2012; 26: 2564–2567.

  • 35

    Durham BH, Getta B, Dietrich S, et al. Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations. Blood 2017; 130: 1644–1648.

  • 36

    Maitre E, Bertrand P, Maingonnat C, et al. New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes. Oncotarget 2018; 9: 28866–28876.

  • 37

    Chu IM, Hengst L, Slingerland JM. The Cdk inhibitor p27 in human cancer: prognostic potential and relevance to anticancer therapy. Nat Rev Cancer 2008; 8: 253–267.

  • 38

    Tiacci E, Pettirossi V, Schiavoni G, et al. Genomics of hairy cell leukemia. J Clin Oncol. 2017; 35: 1002–1010.

  • 39

    Dietrich S, Hullein J, Lee SC, et al. Recurrent CDKN1B (p27) mutations in hairy cell leukemia. Blood 2015; 126: 1005–1008.

  • 40

    Vallianatos CN, Iwase S. Disrupted intricacy of histone H3K4 methylation in neurodevelopmental disorders. Epigenomics 2015; 7: 503–519.

  • 41

    Arons E, Suntum T, Stetler-Stevenson M, et al. VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy. Blood 2009; 114: 4687–4695.

  • 42

    Waterfall JJ, Arons E, Walker RL, et al. High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias. Nat Genet. 2014; 46: 8–10.

  • 43

    Bernstein L, Newton P, Ross RK. Epidemiology of hairy cell leukemia in Los Angeles County. Cancer Res 1990; 50: 3605–3609.

  • 44

    Tadmor T, Polliack A. Epidemiology and environmental risk in hairy cell leukemia. Best Pract Res Clin Haematol. 2015; 28: 175–179.

  • 45

    Frassoldati A, Lamparelli T, Federico M, et al. Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia. Leuk Lymphoma 1994; 13: 307–316.

  • 46

    Jansen J, Hermans J. Splenectomy in hairy cell leukemia: a retrospective multicenter analysis. Cancer 1981; 47: 2066–2076.

  • 47

    Van Norman AS, Nagorney DM, Martin JK, et al. Splenectomy for hairy cell leukemia. A clinical review of 63 patients. Cancer 1986; 57: 644–648.

  • 48

    Paganelli KA, Evans SS, Han T, et al.: B cell growth factor-induced proliferation of hairy cell lymphocytes and inhibition by type I interferon in vitro. Blood 1986; 67: 937–942.

  • 49

    Lehn P, Sigaux F, Grausz D, et al. c-myc and c-fos expression during interferon-alpha therapy for hairy cell leukemia. Blood 1986; 68: 967–970.

  • 50

    Heslop HE, Bianchi AC, Cordingley FT, et al. Effects of interferon alpha on autocrine growth factor loops in B lymphoproliferative disorders. J Exp Med. 1990; 172: 1729–1734.

  • 51

    Sigaux F, Castaigne S, Lehn P, et al. Alpha-interferon in hairy cell leukaemia: direct effects on hairy cells or indirect cytotoxicity? Int J Cancer Suppl. 1987; 1: 2–8.

  • 52

    Vedantham S, Gamliel H, Golomb HM. Mechanism of interferon action in hairy cell leukemia: a model of effective cancer biotherapy. Cancer Res. 1992; 52: 1056–1066.

  • 53

    Rai KR, Davey F, Peterson B, et al. Recombinant alpha-2b-interferon in therapy of previously untreated hairy cell leukemia: long-term follow-up results of study by Cancer and Leukemia Group B. Leukemia 1995; 9: 1116–1120.

  • 54

    Quesada JR, Reuben J, Manning JT, et al. Alpha interferon for induction of remission in hairy-cell leukemia. N Engl J Med. 1984; 310: 15–18.

  • 55

    Berman E, Heller G, Kempin S, et al. Incidence of response and long-term follow-up in patients with hairy cell leukemia treated with recombinant interferon alfa-2a. Blood 1990; 75: 839–845.

  • 56

    Ratain MJ, Golomb HM, Vardiman JW, et al. Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables. J Clin Oncol. 1988; 6: 1714–1721.

  • 57

    Golomb HM, Ratain MJ, Fefer A, et al. Randomized study of the duration of treatment with interferon alfa-2B in patients with hairy cell leukemia. J Natl Cancer Inst. 1988; 80: 369–373.

  • 58

    Grever MR, Abdel-Wahab O, Andritsos LA, et al. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood 2017; 129: 553–560.

  • 59

    Yazdani Brojeni P, Matok I, Garcia Bournissen F, et al. A systematic review of the fetal safety of interferon alpha. Reprod Toxicol. 2012; 33: 265–268.

  • 60

    Goodman GR, Burian C, Koziol JA, et al. Extended follow-up of patients with hairy cell leukemia after treatment with cladribine. J Clin Oncol. 2003; 21: 891–896.

  • 61

    Tallman MS, Hakimian D, Variakojis D, et al. A single cycle of 2-chlorodeoxyadenosine results in complete remission in the majority of patients with hairy cell leukemia. Blood 1992; 80: 2203–2209.

  • 62

    Hoffman MA, Janson D, Rose E, et al. Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up. J Clin Oncol. 1997; 15: 1138–1142.

  • 63

    Khorshid O, Namour AE, El-Gammal MM, et al. Efficacy and Safety of Cladribine: Subcutaneous versus Intravenous Administration in Hairy Cell Leukemia Patients. Mediterr J Hematol Infect Dis. 2015; 7: e2015058.

  • 64

    Lopez Rubio M, Da Silva C, Loscertales J, et al. Hairy cell leukemia treated initially with purine analogs: a retrospective study of 107 patients from the Spanish Cooperative Group on Chronic Lymphocytic Leukemia (GELLC). Leuk Lymphoma 2014; 55: 1007–1012.

  • 65

    Forconi FEC, Zaja F, Intermesoli T, et al. Analysis of toxicity and efficacy of subcutaneous cladribine at reduced or standard doses (five versus seven consecutive days) in patients with hairy cell leukemia (HCL) in the ICGHCL2004 protocol by the Italian Cooperative Group on HCL. Blood 2010; 116: 701.

  • 66

    Piro LD, Carrera CJ, Carson DA, et al. Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med. 1990; 322: 1117–1121.

  • 67

    Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47: 8–32.

  • 68

    Spiers AS. Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases. Haematologia (Budap) 1996; 27: 55–84.

  • 69

    Dearden CE, Matutes E, Hilditch BL, et al. Long-term follow-up of patients with hairy cell leukaemia after treatment with pentostatin or cladribine. Br J Haematol. 1999; 106: 515–519.

  • 70

    Else M, Dearden CE, Matutes E, et al. Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis. Br J Haematol. 2009; 145: 733–740.

  • 71

    Sadeghi N, Li HC. MRD-negative complete remission in relapsed refractory hairy cell leukemia with bendamustine and obinutuzumab. Ann Hematol. 2018; 97: 723–724.

  • 72

    Thomas DA, O’Brien S, Bueso-Ramos C, et al. Rituximab in relapsed or refractory hairy cell leukemia. Blood 2003; 102: 3906–3911.

  • 73

    Leclerc M, Suarez F, Noel MP, et al.: Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases. Ann Hematol. 2015; 94: 89–95.

  • 74

    Chihara D, Kantarjian H, O’Brien S, et al. Long-term durable remission by cladribine followed by rituximab in patients with hairy cell leukaemia: update of a phase II trial. Br J Haematol. 2016; 174: 760–766.

  • 75

    Tiacci E, Park JH, De Carolis L, et al. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia. N Engl J Med. 2015; 373: 1733–1747.

  • 76

    Dietrich S, Pircher A, Endris V, et al. BRAF inhibition in hairy cell leukemia with low-dose vemurafenib. Blood 2016; 127: 2847–2855.

  • 77

    Falini B, Tiacci E. New treatment options in hairy cell leukemia with focus on BRAF inhibitors. Hematol Oncol. 2019; 37 Suppl 1: 30–37.

  • 78

    Sari E, Nagy ZG, Baghy K, et al. Treatment of refractory hairy cell leukemia with a BRAF-inhibitor: lessons to be learnt. Pathol Oncol Res. 2014; 20: 973–980.

  • 79

    Grever M, Andritsos L, Banerji V, et al. Hairy cell leukemia and COVID-19 adaptation of treatment guidelines. Leukemia 2021.

  • 80

    Tiacci E, De Carolis L, Zaja F, et al. The chemotherapy-free combination of vemurafenib and rituximab produces deep and durable responses in relapsed or refractory hairy cell leukemia (HCL) patients. Blood 2017; 130: 409.

  • 81

    Kreitman RJ, Pastan I. Antibody fusion proteins: anti-CD22 recombinant immunotoxin moxetumomab pasudotox. Clin Cancer Res. 2011; 17: 6398–6405.

  • 82

    Kreitman RJ, Dearden C, Zinzani PL, et al. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia. Leukemia 2018; 32: 1768–1777.

  • 83

    Kreitman RJ, Tallman MS, Robak T, et al. Phase I trial of anti-CD22 recombinant immunotoxin moxetumomab pasudotox (CAT-8015 or HA22) in patients with hairy cell leukemia. J Clin Oncol. 2012; 30: 1822–1828.

  • 84

    King AC, Kabel CC, Pappacena JJ, et al. No loose ends: A review of the pharmacotherapy of hairy cell and hairy cell leukemia variant. Ann Pharmacother. 2019; 53: 922–932.

  • 85

    Andritsos LA, Grieselhuber NR, Anghelina M, et al. Trametinib for the treatment of IGHV4-34, MAP2K1-mutant variant hairy cell leukemia. Leuk Lymphoma 2018; 59: 1008–1011.

  • 86

    Falini B, Martelli MP, Tiacci E. BRAF V600E mutation in hairy cell leukemia: from bench to bedside. Blood 2016; 128: 1918–1927.

  • 87

    Maitre E, Cornet E, Troussard X. Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019; 94: 1413–1422.

  • 88

    Andrasiak I, Rybka J, Wrobel T. Response to the therapy in hairy cell leukemia: Systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2018; 18: 392–399 e393.

 

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  • Árpád ILLÉS (Debreceni Egyetem, főszerkesztő)
  • Csaba BÖDÖR (Semmelweis Egyetem, főszerkesztő-helyettes)
  • Judit DEMETER (Semmelweis Egyetem, főszerkesztő-helyettes)
  • Lajos GERGELY (Debreceni Egyetem, főszerkesztő-helyettes)
  • Imelda MARTON (Szegedi Tudományegyetem, főszerkesztő-helyettes)
  • Gábor MIKALA (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, főszerkesztő-helyettes)
  • Dezső LEHOCZKY (Semmelweis Egyetem, emeritus főszerkesztő)
  • Sándor FEKETE (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, emeritus főszerkesztő)
  • Hajnalka ANDRIKOVICS (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • Zita BORBÉNYI (Szegedi Tudományegyetem, szerkesztő)
  • Miklós EGYED (Somogy Megyei Kaposi Mór Oktató Kórház, szerkesztő)
  • Alizadeh HUSSAIN (Pécsi Tudományegyetem, szerkesztő)
  • Judit JAKAB (Országos Vérellátó Szolgálat, szerkesztő)
  • Béla KAJTÁR (Pécsi Tudományegyetem, szerkesztő)
  • Tamás MASSZI (Semmelweis Egyetem, szerkesztő)
  • Zsolt György NAGY (Semmelweis Egyetem, szerkesztő)
  • György PFLIEGLER (Debreceni Egyetem, szerkesztő)
  • Péter REMÉNYI (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • Marienn RÉTI (Dél-Pesti Centrumkórház, Országos Hematológiai és Infektológiai Intézet, szerkesztő)
  • Tamás SCHNEIDER (Országos Onkológiai Intézet, szerkesztő)
  • László SZERAFIN (Szabolcs-Szatmár-Bereg Megyei Jósa András Oktatókórház, Nyíregyháza, szerkesztő)
  • Attila TORDAI (Semmelweis Egyetem, szerkesztő)

Hematológia-Transzfuziológia Szerkesztőség
Dr. Illés Árpád
Debreceni Egyetem Klinikai Központ
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