Tom 11, Nr 4 (2020)
Artykuł przeglądowy
Opublikowany online: 2021-03-30
Pobierz cytowanie

Postępowanie terapeutyczne w zespołach mielodysplastycznych niższego ryzyka

Kamil Wiśniewski, Aleksandra Gołos, Joanna Góra-Tybor
DOI: 10.5603/Hem.2020.0042
·
Hematologia 2020;11(4):219-234.

dostęp płatny

Tom 11, Nr 4 (2020)
PRACE POGLĄDOWE
Opublikowany online: 2021-03-30

Streszczenie

Zespoły mielodysplastyczne (MDS) są grupą nabytych klonalnych zaburzeń układu krwiotwórczego spowodowanych mutacją krwiotwórczych komórek macierzystych szpiku. W zależności od parametrów klinicznych i laboratoryjnych MDS dzieli się na grupy niskiego (LR-MDS) i wysokiego (HR-MDS) ryzyka, co determinuje rodzaj postępowania terapeutycznego. W ostatnich latach, w wyniku rejestracji nowych leków oraz coraz nowocześniejszych metod leczenia wspomagającego, obserwuje się wydłużenie życia i poprawę jego jakości u chorych na MDS. W artykule przedstawiono aktualne dane dotyczące postępowania diagnostycznego i terapeutycznego w LR-MDS z uwzględnieniem najnowszych zarejestrowanych metod terapii. Ponadto omówiono leczenie wspomagające i terapie będące w fazie badań klinicznych.

Streszczenie

Zespoły mielodysplastyczne (MDS) są grupą nabytych klonalnych zaburzeń układu krwiotwórczego spowodowanych mutacją krwiotwórczych komórek macierzystych szpiku. W zależności od parametrów klinicznych i laboratoryjnych MDS dzieli się na grupy niskiego (LR-MDS) i wysokiego (HR-MDS) ryzyka, co determinuje rodzaj postępowania terapeutycznego. W ostatnich latach, w wyniku rejestracji nowych leków oraz coraz nowocześniejszych metod leczenia wspomagającego, obserwuje się wydłużenie życia i poprawę jego jakości u chorych na MDS. W artykule przedstawiono aktualne dane dotyczące postępowania diagnostycznego i terapeutycznego w LR-MDS z uwzględnieniem najnowszych zarejestrowanych metod terapii. Ponadto omówiono leczenie wspomagające i terapie będące w fazie badań klinicznych.
Pobierz cytowanie

Słowa kluczowe

MDS niskiego ryzyka, diagnostyka MDS, leczenie MDS niskiego ryzyka

Informacje o artykule
Tytuł

Postępowanie terapeutyczne w zespołach mielodysplastycznych niższego ryzyka

Czasopismo

Hematologia

Numer

Tom 11, Nr 4 (2020)

Typ artykułu

Artykuł przeglądowy

Strony

219-234

Data publikacji on-line

2021-03-30

DOI

10.5603/Hem.2020.0042

Rekord bibliograficzny

Hematologia 2020;11(4):219-234.

Słowa kluczowe

MDS niskiego ryzyka
diagnostyka MDS
leczenie MDS niskiego ryzyka

Autorzy

Kamil Wiśniewski
Aleksandra Gołos
Joanna Góra-Tybor

Referencje (87)
  1. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391–2405.
  2. Platzbecker U. Treatment of MDS. Blood. 2019; 133(10): 1096–1107.
  3. Steensma DP. Myelodysplastic syndromes current treatment algorithm 2018. Blood Cancer J. 2018; 8(5): 47.
  4. Valent P, Orazi A, Steensma DP, et al. Proposed minimal diagnostic criteria for myelodysplastic syndromes (MDS) and potential pre-MDS conditions. Oncotarget. 2017; 8(43): 73483–73500.
  5. Solé F, Espinet B, Sanz GF, et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Español de Citogenética Hematológica. Br J Haematol. 2000; 108(2): 346–356.
  6. Visconte V, Tiu RV, Rogers HJ. Pathogenesis of myelodysplastic syndromes: an overview of molecular and non-molecular aspects of the disease. Blood Res. 2014; 49(4): 216–227.
  7. Le Beau MM, Albain KS, Larson RA, et al. Clinical and cytogenetic correlations in 63 patients with therapy-related myelodysplastic syndromes and acute nonlymphocytic leukemia: further evidence for characteristic abnormalities of chromosomes no. 5 and 7. J Clin Oncol. 1986; 4(3): 325–345.
  8. Hosono N. Genetic abnormalities and pathophysiology of MDS. Int J Clin Oncol. 2019; 24(8): 885–892.
  9. Mossner M, Jann JC, Nowak D, et al. Prevalence, clonal dynamics and clinical impact of TP53 mutations in patients with myelodysplastic syndrome with isolated deletion (5q) treated with lenalidomide: results from a prospective multicenter study of the german MDS study group (GMDS). Leukemia. 2016; 30(9): 1956–1959.
  10. DiNardo CD, Watts J, Stein E, et al. Ivosidenib (AG-120) induced durable remissions and transfusion independence in patients with IDH1-mutant relapsed or refractory myelodysplastic syndrome: results from a phase 1 dose escalation and expansion study. Blood. 2018; 132(Suppl 1): 1812–1812.
  11. Richard-Carpentier G, DeZern A, Takahashi K, et al. Preliminary results from the phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS). Blood. 2019; 134(Suppl_1): 678–678.
  12. Greenberg P, Cox C, LeBeau M, et al. International Scoring System for evaluating prognosis in myelodysplastic syndromes. Blood. 1997; 89(6): 2079–2088.
  13. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012; 120(12): 2454–2465.
  14. Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005; 23(30): 7594–7603.
  15. Moreno Berggren D, Folkvaljon Y, Engvall M, et al. Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register. Br J Haematol. 2018; 181(5): 614–627.
  16. Neukirchen J, Schoonen WM, Strupp C, et al. Incidence and prevalence of myelodysplastic syndromes: data from the Düsseldorf MDS-registry. Leuk Res. 2011; 35(12): 1591–1596.
  17. Jaeger M, Aul C, Söhngen D, et al. [Secondary hemochromatosis in polytransfused patients with myelodysplastic syndromes] [Article in German]. Beitr Infusionsther. 1992; 30: 464–468.
  18. Fenaux P, Platzbecker U, Ades L. How we manage adults with myelodysplastic syndrome. Br J Haematol. 2020; 189(6): 1016–1027.
  19. Hellström-Lindberg E, Tobiasson M, Greenberg P. Myelodysplastic syndromes: moving towards personalized management. Haematologica. 2020; 105(7): 1765–1779.
  20. Fenaux P, Santini V, Spiriti MA, et al. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-α in anemic patients with low-risk MDS. Leukemia. 2018; 32(12): 2648–2658.
  21. Platzbecker U, Symeonidis A, Oliva EN, et al. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017; 31(9): 1944–1950.
  22. Park S, Kelaidi C, Meunier M, et al. The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion. Ann Hematol. 2020; 99(1): 7–19.
  23. Santini V, Schemenau J, Levis A, et al. Can the revised IPSS predict response to erythropoietic-stimulating agents in patients with classical IPSS low or intermediate-1 MDS? Blood. 2013; 122(13): 2286–2288.
  24. Houston BL, Jayakar J, Wells RA, et al. A predictive model of response to erythropoietin stimulating agents in myelodysplastic syndrome: from the Canadian MDS patient registry. Ann Hematol. 2017; 96(12): 2025–2029.
  25. Malcovati L, Hellström-Lindberg E, Bowen D, et al. European Leukemia Net. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013; 122(17): 2943–2964.
  26. Garcia-Manero G, Chien KS, Montalban-Bravo G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020; 95(11): 1399–1420.
  27. Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood. 2009; 114(12): 2393–2400.
  28. Hellström-Lindberg E, Birgegård G, Carlsson M, et al. A combination of granulocyte colony-stimulating factor and erythropoietin may synergistically improve the anaemia in patients with myelodysplastic syndromes. Leuk Lymphoma. 1993; 11(3-4): 221–228.
  29. Jädersten M, Malcovati L, Dybedal I, et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008; 26(21): 3607–3613.
  30. List A, Dewald G, Bennett J, et al. Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006; 355(14): 1456–1465.
  31. Santini V, Almeida A, Giagounidis A, et al. Randomized phase III study of lenalidomide versus placebo in RBC transfusion-dependent patients with lower-risk non-del(5q) myelodysplastic syndromes and ineligible for or refractory to erythropoiesis-stimulating agents. J Clin Oncol. 2016; 34(25): 2988–2996.
  32. Sibon D, Cannas G, Baracco F, et al. Groupe Francophone des Myélodysplasies. Lenalidomide in lower-risk myelodysplastic syndromes with karyotypes other than deletion 5q and refractory to erythropoiesis-stimulating agents. Br J Haematol. 2012; 156(5): 619–625.
  33. Narla A, Dutt S, McAuley JR, et al. Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis. Blood. 2011; 118(8): 2296–2304.
  34. McGraw KL, Basiorka AA, Johnson JO, et al. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors. PLoS One. 2014; 9(12): e114249.
  35. Adema V, Palomo L, Toma A, et al. Groupe Francophone des Myélodysplasies. A G polymorphism in the CRBN gene acts as a biomarker of response to treatment with lenalidomide in low/int-1 risk MDS without del(5q). Leukemia. 2013; 27(7): 1610–1613.
  36. Komrokji RS. Activin receptor II ligand traps: new treatment paradigm for low-risk MDS. Curr Hematol Malig Rep. 2019; 14(4): 346–351.
  37. Komrokji RS. Luspatercept in myelodysplastic syndromes: who and when? Hematol Oncol Clin North Am. 2020; 34(2): 393–400.
  38. Platzbecker U, Germing U, Götze KS, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017; 18(10): 1338–1347.
  39. Fenaux P, Platzbecker U, Mufti GJ, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020; 382(2): 140–151.
  40. Kantarjian H, Issa JPJ, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006; 106(8): 1794–1803.
  41. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009; 10(3): 223–232.
  42. Musto P, Maurillo L, Spagnoli A, et al. Ad Hoc Italian Cooperative Study Group on Azacitidine in Myelodysplastic Syndromes Acute Leukemias. Azacitidine for the treatment of lower risk myelodysplastic syndromes: a retrospective study of 74 patients enrolled in an Italian named patient program. Cancer. 2010; 116(6): 1485–1494.
  43. Sanchez-Garcia J, Falantes J, Medina Perez A, et al. Grupo Andaluz SMD. Prospective randomized trial of 5 days azacitidine versus supportive care in patients with lower-risk myelodysplastic syndromes without 5q deletion and transfusion-dependent anemia. Leuk Lymphoma. 2018; 59(5): 1095–1104.
  44. Garcia-Manero G, Jabbour E, Borthakur G, et al. Randomized open-label phase II study of decitabine in patients with low- or intermediate-risk myelodysplastic syndromes. J Clin Oncol. 2013; 31(20): 2548–2553.
  45. Jabbour E, Short NJ, Montalban-Bravo G, et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood. 2017; 130(13): 1514–1522.
  46. Grinblatt DL, Sekeres MA, Komrokji RS, et al. Patients with myelodysplastic syndromes treated with azacitidine in clinical practice: the AVIDA registry. Leuk Lymphoma. 2015; 56(4): 887–895.
  47. Tobiasson M, Dybedahl I, Holm MS, et al. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial. Blood Cancer J. 2014; 4: e189.
  48. Houwerzijl EJ, Blom NR, van der Want JJL, et al. Increased peripheral platelet destruction and caspase-3-independent programmed cell death of bone marrow megakaryocytes in myelodysplastic patients. Blood. 2005; 105(9): 3472–3479.
  49. Tamura H, Ogata K, Luo S, et al. Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes. Br J Haematol. 1998; 103(3): 778–784.
  50. Fenaux P, Muus P, Kantarjian H, et al. Romiplostim monotherapy in thrombocytopenic patients with myelodysplastic syndromes: long-term safety and efficacy. Br J Haematol. 2017; 178(6): 906–913.
  51. Kantarjian H, Fenaux P, Sekeres MA, et al. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol. 2010; 28(3): 437–444.
  52. Kantarjian HM, Sekeres MA, Ribrag V, et al. Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes. Cancer. 2011; 117(5): 992–1000.
  53. Sekeres MA, Giagounidis A, Kantarjian H, et al. Development and validation of a model to predict platelet response to romiplostim in patients with lower-risk myelodysplastic syndromes. Br J Haematol. 2014; 167(3): 337–345.
  54. Oliva EN, Alati C, Santini V, et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol. 2017; 4(3): e127–e136.
  55. Corazza F, Hermans C, D'Hondt S, et al. Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia. Blood. 2006; 107(6): 2525–2530.
  56. Kantarjian HM, Fenaux P, Sekeres MA, et al. Long-term follow-up for up to 5 years on the risk of leukaemic progression in thrombocytopenic patients with lower-risk myelodysplastic syndromes treated with romiplostim or placebo in a randomised double-blind trial. Lancet Haematol. 2018; 5(3): e117–e126.
  57. Prica A, Sholzberg M, Buckstein R. Safety and efficacy of thrombopoietin-receptor agonists in myelodysplastic syndromes: a systematic review and meta-analysis of randomized controlled trials. Br J Haematol. 2014; 167(5): 626–638.
  58. Kantarjian HM, Giles FJ, Greenberg PL, et al. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010; 116(17): 3163–3170.
  59. Greenberg PL, Garcia-Manero G, Moore M, et al. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood. 2010; 116(17): 3163–3170.
  60. Girmenia C, Candoni A, Delia M, et al. Infection control in patients with myelodysplastic syndromes who are candidates for active treatment: Expert panel consensus-based recommendations. Blood Rev. 2019; 34: 16–25.
  61. Nachtkamp K, Stark R, Strupp C, et al. Causes of death in 2877 patients with myelodysplastic syndromes. Ann Hematol. 2016; 95(6): 937–944.
  62. Greenberg PL, Stone RM, Al-Kali A, et al. Myelodysplastic syndromes, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017; 15(1): 60–87.
  63. Biesma DH, van den Tweel JG, Verdonck LF. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer. 1997; 79(8): 1548–1551, doi: 10.1002/(sici)1097-0142(19970415)79:8<1548::aid-cncr16>3.0.co;2-y.
  64. Saunthararajah Y, Nakamura R, Wesley R, et al. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood. 2003; 102(8): 3025–3027.
  65. Haider M, Al Ali N, Padron E, et al. Immunosuppressive therapy: exploring an underutilized treatment option for myelodysplastic syndrome. Clin Lymphoma Myeloma Leuk. 2016; 16 Suppl: S44–S48.
  66. Passweg JR, Giagounidis AAN, Simcock M, et al. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care--SAKK 33/99. J Clin Oncol. 2011; 29(3): 303–309.
  67. Sloand EM, Wu CO, Greenberg P, et al. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008; 26(15): 2505–2511.
  68. Stahl M, DeVeaux M, de Witte T, et al. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort. Blood Adv. 2018; 2(14): 1765–1772.
  69. Shenoy N, Vallumsetla N, Rachmilewitz E, et al. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome. Blood. 2014; 124(6): 873–881.
  70. Zeidan AM, Griffiths EA. To chelate or not to chelate in MDS: that is the question! Blood Rev. 2018; 32(5): 368–377.
  71. Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007; 25(23): 3503–3510.
  72. Jin X, He X, Cao X, et al. Iron overload impairs normal hematopoietic stem and progenitor cells through reactive oxygen species and shortens survival in myelodysplastic syndrome mice. Haematologica. 2018; 103(10): 1627–1634.
  73. Chacko J, Pennell DJ, Tanner MA, et al. Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions. Br J Haematol. 2007; 138(5): 587–593.
  74. Jensen PD, Jensen FT, Christensen T, et al. Relationship between hepatocellular injury and transfusional iron overload prior to and during iron chelation with desferrioxamine: a study in adult patients with acquired anemias. Blood. 2003; 101(1): 91–96.
  75. Gattermann N, Finelli C, Della Porta M, et al. Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes. Haematologica. 2012; 97(9): 1364–1371.
  76. Jensen PD, Heickendorff L, Pedersen B, et al. The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br J Haematol. 1996; 94(2): 288–299.
  77. Improta S, Villa MR, Volpe A, et al. Transfusion-dependent low-risk myelodysplastic patients receiving deferasirox: Long-term follow-up. Oncol Lett. 2013; 6(6): 1774–1778.
  78. Leitch HA, Parmar A, Wells RA, et al. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient-related factors and measuring from time of first red blood cell transfusion dependence: an MDS-CAN analysis. Br J Haematol. 2017 Oct. ; 179(1): 83–97.
  79. Remacha ÁF, Arrizabalaga B, Villegas A, et al. IRON-2 Study Group. Evolution of iron overload in patients with low-risk myelodysplastic syndrome: iron chelation therapy and organ complications. Ann Hematol. 2015; 94(5): 779–787.
  80. Rose C, Brechignac S, Vassilief D, et al. GFM (Groupe Francophone des Myélodysplasies). Does iron chelation therapy improve survival in regularly transfused lower risk MDS patients? A multicenter study by the GFM (Groupe Francophone des Myélodysplasies). Leuk Res. 2010; 34(7): 864–870.
  81. Mainous AG, Tanner RJ, Hulihan MM, et al. The impact of chelation therapy on survival in transfusional iron overload: a meta-analysis of myelodysplastic syndrome. Br J Haematol. 2014; 167(5): 720–723.
  82. Angelucci E, Li J, Greenberg P, et al. TELESTO Study Investigators. Iron chelation in transfusion-dependent patients with low- to intermediate-1-risk myelodysplastic syndromes: a randomized trial. Ann Intern Med. 2020; 172(8): 513–522.
  83. Komrokji R, Garcia-Manero G, Ades L, et al. Sotatercept with long-term extension for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes: a phase 2, dose-ranging trial. Lancet Haematol. 2018; 5(2): e63–e72.
  84. Steensma DP, Fenaux P, Van Eygen K, et al. Imetelstat achieves meaningful and durable transfusion independence in high transfusion-burden patients with lower-risk myelodysplastic syndromes in a phase II study. J Clin Oncol. 2021; 39(1): 48–56.
  85. Garcia-Manero G, Gore SD, Kambhampati S, et al. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016; 30(4): 889–896.
  86. Garcia-Manero G, Scott BL, Cogle CR, et al. CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with pretreatment thrombocytopenia. Leuk Res. 2018; 72: 79–85.
  87. Garcia-Manero G, McCloskey J, Griffiths E, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized cross over phase 3 study (ASCERTAIN study) of an oral hypomethylating agent ASTX727 (cedazuridine/decitabine) compared to IV decitabine. Blood. 2019; 134(Suppl_1): 846–846.

Ważne: serwis https://journals.viamedica.pl/ wykorzystuje pliki cookies. Więcej >>

Używamy informacji zapisanych za pomocą plików cookies m.in. w celach statystycznych, dostosowania serwisu do potrzeb użytkownika (np. język interfejsu) i do obsługi logowania użytkowników. W ustawieniach przeglądarki internetowej można zmienić opcje dotyczące cookies. Korzystanie z serwisu bez zmiany ustawień dotyczących cookies oznacza, że będą one zapisane w pamięci komputera. Więcej informacji można znaleźć w naszej Polityce prywatności.

Czym są i do czego służą pliki cookie możesz dowiedzieć się na stronie wszystkoociasteczkach.pl.

 

Wydawcą serwisu jest  "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl