Skip to main content
Erschienen in: Current Oncology Reports 6/2021

01.06.2021 | Leukemia (A Aguayo, Section Editor)

Erythroleukemia: an Update

verfasst von: Olga K. Weinberg, Daniel A. Arber

Erschienen in: Current Oncology Reports | Ausgabe 6/2021

Einloggen, um Zugang zu erhalten

Abstract

Purpose of the Review

Acute erythroleukemia (AEL) is a rare form of acute myeloid leukemia recognized by erythroblastic proliferation. Many controversies remain around diagnosis influencing prognostic and therapeutic implications relating to this unique leukemia subset.

Recent Findings

The 2016 WHO classification includes more clear and restrictive diagnostic criteria for AEL. Primary acute erythroid leukemia is associated with complex and high-risk karyotypes including chromosomes 5q and 7q abnormalities. Mutational data shows that AEL is characterized by far lower NPM1 and FLT3-ITD mutation rates and higher mutational rates in TP53 compared with other AML subtypes. Hypomethylating agents have shown therapeutic value in AEL.

Summary

In this article, we discuss the evolving diagnostic concepts of erythroleukemia, genomics, clinical outcome, and promising therapeutic targets through an appraisal of the current literature.
Literatur
1.
Zurück zum Zitat Schwartz SO, Critchlow J. Erythremic myelosis (DI Guglielmo’s disease); critical review with report of four cases, and comments on erythroleukemia. Blood. 1952;7(8):765–93.CrossRef Schwartz SO, Critchlow J. Erythremic myelosis (DI Guglielmo’s disease); critical review with report of four cases, and comments on erythroleukemia. Blood. 1952;7(8):765–93.CrossRef
2.
Zurück zum Zitat Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6(4):372–5.CrossRef Dameshek W. Some speculations on the myeloproliferative syndromes. Blood. 1951;6(4):372–5.CrossRef
3.
Zurück zum Zitat Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, et al. Proposals for the classification of the acute leukemias. Br J Haematol. 1976;33:451–8.CrossRef Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, et al. Proposals for the classification of the acute leukemias. Br J Haematol. 1976;33:451–8.CrossRef
4.
Zurück zum Zitat Villeval JL, Cramer P, Lemoine F, Henri A, Bettaieb A, Bernaudin F, et al. Phenotype of early erythroblastic leukemias. Blood. 1986;68(5):1167–74.CrossRef Villeval JL, Cramer P, Lemoine F, Henri A, Bettaieb A, Bernaudin F, et al. Phenotype of early erythroblastic leukemias. Blood. 1986;68(5):1167–74.CrossRef
5.
Zurück zum Zitat Kowal-Vern A, Cotelingam J, Schumacher HR. The prognostic significance of proerythroblasts in acute erythroleukemia. The prognostic significance of proerythroblasts in acute erythroleukemia. Am J Clin Pathol. 1992;98(1):34–40.CrossRef Kowal-Vern A, Cotelingam J, Schumacher HR. The prognostic significance of proerythroblasts in acute erythroleukemia. The prognostic significance of proerythroblasts in acute erythroleukemia. Am J Clin Pathol. 1992;98(1):34–40.CrossRef
6.
Zurück zum Zitat Mazzella FM, Kowal-Vern A, Shrit MA, Wibowo AL, Rector JT, Cotelingam JT. et alR. Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis. Am J Clin Pathol. 1998;110(5):590–8.CrossRef Mazzella FM, Kowal-Vern A, Shrit MA, Wibowo AL, Rector JT, Cotelingam JT. et alR. Acute erythroleukemia: evaluation of 48 cases with reference to classification, cell proliferation, cytogenetics, and prognosis. Am J Clin Pathol. 1998;110(5):590–8.CrossRef
7.
Zurück zum Zitat Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103:626–9.CrossRef Bennett JM, Catovsky D, Daniel MT, et al. Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American-British Cooperative Group. Ann Intern Med. 1985;103:626–9.CrossRef
8.
Zurück zum Zitat Brunning RD, Matutes E, Flandrin G, Jaffe ES, Harris NL, Stein H, Vardiman JW. et al. Acute myeloid leukaemia not otherwise categorised., World Health Organization Classification of Tumours, 2001 Lyon, FranceI ARC Press(pg. 91-105) Brunning RD, Matutes E, Flandrin G, Jaffe ES, Harris NL, Stein H, Vardiman JW. et al. Acute myeloid leukaemia not otherwise categorised., World Health Organization Classification of Tumours, 2001 Lyon, FranceI ARC Press(pg. 91-105)
9.
Zurück zum Zitat Arber DA, Brunning RD, Orazi A, Porwit A, Peterson L, Thiele J, et al. Acute myeloid leukemia, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classifiction of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 134–6. Arber DA, Brunning RD, Orazi A, Porwit A, Peterson L, Thiele J, et al. Acute myeloid leukemia, not otherwise specified. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al., editors. WHO Classifiction of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC; 2008. p. 134–6.
10.
Zurück zum Zitat Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRef Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.CrossRef
11.
Zurück zum Zitat Santos FPS, Bueso-Ramos CE, Ravandi F. Acute erythroleukemia: diagnosis and management. Expert Rev Hematol. 2010;3(6):705–18.CrossRef Santos FPS, Bueso-Ramos CE, Ravandi F. Acute erythroleukemia: diagnosis and management. Expert Rev Hematol. 2010;3(6):705–18.CrossRef
12.
Zurück zum Zitat Barnard DR, Alonzo TA, Gerbing RB, Lange R, Woods WG. Children’s Oncology Group Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group. Pediatr Blood Cancer. 2007;49(1):17–22.CrossRef Barnard DR, Alonzo TA, Gerbing RB, Lange R, Woods WG. Children’s Oncology Group Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group. Pediatr Blood Cancer. 2007;49(1):17–22.CrossRef
13.
Zurück zum Zitat Hasserjian RB, Zuo Z, Garcia C, Tang G, Kasyan A, Luthra R, et al. Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood. 2010;115(10):1985–92.CrossRef Hasserjian RB, Zuo Z, Garcia C, Tang G, Kasyan A, Luthra R, et al. Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood. 2010;115(10):1985–92.CrossRef
14.
Zurück zum Zitat Olopade OI, Thangavelu M, Larson RA, Mick R, Kowal-Vern A, Schumacher HR, et al. Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Blood. 1992;80:2873–82.CrossRef Olopade OI, Thangavelu M, Larson RA, Mick R, Kowal-Vern A, Schumacher HR, et al. Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia. Blood. 1992;80:2873–82.CrossRef
15.
Zurück zum Zitat Li H, Hasserjian RP, Kroft SH, Harrington AM, Wheaton SE, Pildain A, et al. Pure Erythroid Leukemia and Erythroblastic Sarcoma Evolving From Chronic Myeloid Neoplasms. Am J Clin Pathol. 2016;145(4):538–51.CrossRef Li H, Hasserjian RP, Kroft SH, Harrington AM, Wheaton SE, Pildain A, et al. Pure Erythroid Leukemia and Erythroblastic Sarcoma Evolving From Chronic Myeloid Neoplasms. Am J Clin Pathol. 2016;145(4):538–51.CrossRef
16.
Zurück zum Zitat Domingo-Claros A, Larriba I, Rozman M, Irriguible D, Vallespí T, Aventin A, et al. Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Haematologica. 2002;87(2):148–53.PubMed Domingo-Claros A, Larriba I, Rozman M, Irriguible D, Vallespí T, Aventin A, et al. Acute erythroid neoplastic proliferations. A biological study based on 62 patients. Haematologica. 2002;87(2):148–53.PubMed
17.
Zurück zum Zitat • Reinig EF, Greipp PT, Chiu A, Howard MT, Reichard KK. De novo pure erythroid leukemia: refining the clinicopathologic and cytogenetic characteristics of a rare entity. Mod Pathol. 2018;31:705–17 This series of pure erythroid leukemia illustrates high rate of very complex karyotype in this disease.CrossRef • Reinig EF, Greipp PT, Chiu A, Howard MT, Reichard KK. De novo pure erythroid leukemia: refining the clinicopathologic and cytogenetic characteristics of a rare entity. Mod Pathol. 2018;31:705–17 This series of pure erythroid leukemia illustrates high rate of very complex karyotype in this disease.CrossRef
18.
Zurück zum Zitat Sondergaard-Petersen H Erythrophagocytosis by pathological erythroblasts in the Di Guglielmo syndrome. A study of 18 cases. Scand J Haematol. 1974;13(4):260-5. (19). Histopathology 2017, 71, 316-321 Sondergaard-Petersen H Erythrophagocytosis by pathological erythroblasts in the Di Guglielmo syndrome. A study of 18 cases. Scand J Haematol. 1974;13(4):260-5. (19). Histopathology 2017, 71, 316-321
19.
Zurück zum Zitat Hasserjian RP. Erythroleukemia and Its Differential Diagnosis. Surg Path Clin. 2013;6:641–59.CrossRef Hasserjian RP. Erythroleukemia and Its Differential Diagnosis. Surg Path Clin. 2013;6:641–59.CrossRef
20.
Zurück zum Zitat Greaves MF, Sieff C, Edwards PA. Monoclonal antiglycophorin as a probe for erythroleukemias. Blood. 1983;61(4):645–51.CrossRef Greaves MF, Sieff C, Edwards PA. Monoclonal antiglycophorin as a probe for erythroleukemias. Blood. 1983;61(4):645–51.CrossRef
21.
Zurück zum Zitat Gupta AD, Dhond SR. Phenotypic heterogeneity of erythroblasts in erythroblastic leukemia revealed by monoclonal antibodies. Am J Hematol. 1988;29(1):12–7.CrossRef Gupta AD, Dhond SR. Phenotypic heterogeneity of erythroblasts in erythroblastic leukemia revealed by monoclonal antibodies. Am J Hematol. 1988;29(1):12–7.CrossRef
22.
Zurück zum Zitat Garand R, Duchayne E, Blanchard D, Robillard N, Kuhlein E, Fenneteau O, et al. Minimally differentiated erythroleukaemia (AML M6 ‘variant’): a rare subset of AML distinct from AML M6. Groupe Français d'Hématologie Cellulaire. Br J Haematol. 1995;90(4):868–75.CrossRef Garand R, Duchayne E, Blanchard D, Robillard N, Kuhlein E, Fenneteau O, et al. Minimally differentiated erythroleukaemia (AML M6 ‘variant’): a rare subset of AML distinct from AML M6. Groupe Français d'Hématologie Cellulaire. Br J Haematol. 1995;90(4):868–75.CrossRef
23.
Zurück zum Zitat • Lee WY, Weinberg OW, Pinkus GS. GATA1 Is a sensitive and specific Nuclear marker for erythroid and megakaryocytic lineages. Am J Clin Pathol. 2017;147(4):420–6 This study shows that blasts in acute erythroleukemia exhibit intense nuclear GATA1 positivity.CrossRef • Lee WY, Weinberg OW, Pinkus GS. GATA1 Is a sensitive and specific Nuclear marker for erythroid and megakaryocytic lineages. Am J Clin Pathol. 2017;147(4):420–6 This study shows that blasts in acute erythroleukemia exhibit intense nuclear GATA1 positivity.CrossRef
24.
Zurück zum Zitat Wong E, Ling V, Westerman D, Morgan S, Juneja S. How unique is pure erythroid leukaemia? A retrospective analysis of seven cases and review of the literature. JCP. 2015;68:301–5.PubMed Wong E, Ling V, Westerman D, Morgan S, Juneja S. How unique is pure erythroid leukaemia? A retrospective analysis of seven cases and review of the literature. JCP. 2015;68:301–5.PubMed
25.
Zurück zum Zitat • Wang SA, Patel KP, Pozdnyakova O, Peng J, Zuo Z, Dal Cin P, et al. Acute erythroid leukemia with <20% bone marrow blasts is clinically and biologically similar to myelodysplastic syndrome with excess blasts. Mod Pathol. 2016;29:1221–31 The results of this study supports WHO change in definition of acute erythroid leukemia.CrossRef • Wang SA, Patel KP, Pozdnyakova O, Peng J, Zuo Z, Dal Cin P, et al. Acute erythroid leukemia with <20% bone marrow blasts is clinically and biologically similar to myelodysplastic syndrome with excess blasts. Mod Pathol. 2016;29:1221–31 The results of this study supports WHO change in definition of acute erythroid leukemia.CrossRef
26.
Zurück zum Zitat Lessard M, Struski S, Leymarie V, Flandrin G, Lafage-Pochitaloff M, Mozziconacci MJ, et al. Cytogenetic study of 75 erythroleukemias. Cancer Genet Cytogenet. 2005;163:113–22.CrossRef Lessard M, Struski S, Leymarie V, Flandrin G, Lafage-Pochitaloff M, Mozziconacci MJ, et al. Cytogenetic study of 75 erythroleukemias. Cancer Genet Cytogenet. 2005;163:113–22.CrossRef
27.
Zurück zum Zitat Grossmann V, Bacher U, Haferlach C, Schnittger S, Pötzinger F, Weissmann S, et al. Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics. Leukemia. 2013;27(9):1940–3.CrossRef Grossmann V, Bacher U, Haferlach C, Schnittger S, Pötzinger F, Weissmann S, et al. Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics. Leukemia. 2013;27(9):1940–3.CrossRef
28.
Zurück zum Zitat Cervera N, Carbuccia N, Garnier S, Guille A, Adélaïde J, Murati A, et al. Molecular characterization of acute erythroid leukemia (M6-AML) using targeted next-generation sequencing. Leukemia. 2016;30:966–70.CrossRef Cervera N, Carbuccia N, Garnier S, Guille A, Adélaïde J, Murati A, et al. Molecular characterization of acute erythroid leukemia (M6-AML) using targeted next-generation sequencing. Leukemia. 2016;30:966–70.CrossRef
29.
Zurück zum Zitat Ko PS, Liu YC, Yeh CM, Gau JP, Yu YB, Hsiao LT, et al. The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification. PLoS One. 2017;12(2):e0172029.CrossRef Ko PS, Liu YC, Yeh CM, Gau JP, Yu YB, Hsiao LT, et al. The uniqueness of morphological features of pure erythroid leukemia in myeloid neoplasm with erythroid predominance: A reassessment using criteria revised in the 2016 World Health Organization classification. PLoS One. 2017;12(2):e0172029.CrossRef
30.
Zurück zum Zitat • Rose D, Haferlach T, Schnittger S, Perglerová K, Kern W, Haferlach C. Subtype-specific patterns of molecular mutations in acute myeloid leukemia. Leukemia. 2017;31(1):11–7 This study illustrates mutation profile in acute erythroleukemia.CrossRef • Rose D, Haferlach T, Schnittger S, Perglerová K, Kern W, Haferlach C. Subtype-specific patterns of molecular mutations in acute myeloid leukemia. Leukemia. 2017;31(1):11–7 This study illustrates mutation profile in acute erythroleukemia.CrossRef
31.
Zurück zum Zitat •• Montalban-Bravo G, Benton CB, Wang SA, Ravandi F, Kadia T, Cortes J, et al. More than 1 TP53 abnormality is a dominant characteristic of pure erythroid leukemia. Blood. 2017;129(18):2584–7 This study illustrates high rate of TP53 mutations in acute erythroleukemia.CrossRef •• Montalban-Bravo G, Benton CB, Wang SA, Ravandi F, Kadia T, Cortes J, et al. More than 1 TP53 abnormality is a dominant characteristic of pure erythroid leukemia. Blood. 2017;129(18):2584–7 This study illustrates high rate of TP53 mutations in acute erythroleukemia.CrossRef
32.
Zurück zum Zitat •• Iacobucci I, Wen J, Meggendorfer M, Choi JK, et al. Genomic subtyping and therapeutic targeting of acute erythroleukemia. Nat Genet. 2019;51:694–704 This large study compares genomic features of pediatric and adult acute erythroleukemia.CrossRef •• Iacobucci I, Wen J, Meggendorfer M, Choi JK, et al. Genomic subtyping and therapeutic targeting of acute erythroleukemia. Nat Genet. 2019;51:694–704 This large study compares genomic features of pediatric and adult acute erythroleukemia.CrossRef
33.
Zurück zum Zitat Panagopoulos I, Micci F, Thorsen J, Haugom L, Buechner J, Kerndrup G, et al. Fusion of ZMYND8 and RELA genes in acute erythroid leukemia. PLoS One. 2013;8(5):e63663.CrossRef Panagopoulos I, Micci F, Thorsen J, Haugom L, Buechner J, Kerndrup G, et al. Fusion of ZMYND8 and RELA genes in acute erythroid leukemia. PLoS One. 2013;8(5):e63663.CrossRef
34.
Zurück zum Zitat Colita A, Belhabri A, Chelghoum Y, Charrin C, Fiere D, Thomas X. Prognostic factors and treatment effects on survival in acute myeloid leukemia of M6 subtype: a retrospective study of 54 cases. Ann Oncol. 2001;12(4):451–5.CrossRef Colita A, Belhabri A, Chelghoum Y, Charrin C, Fiere D, Thomas X. Prognostic factors and treatment effects on survival in acute myeloid leukemia of M6 subtype: a retrospective study of 54 cases. Ann Oncol. 2001;12(4):451–5.CrossRef
35.
Zurück zum Zitat Santos F, Faderl S, Garcia-Manero G, Koller C, Beran M, O'Brien S, et al. Adult Acute Erythroleukemia: An Analysis of 108 patients treated at a single institution. Leukemia. 2009;23(12):227–80.CrossRef Santos F, Faderl S, Garcia-Manero G, Koller C, Beran M, O'Brien S, et al. Adult Acute Erythroleukemia: An Analysis of 108 patients treated at a single institution. Leukemia. 2009;23(12):227–80.CrossRef
36.
Zurück zum Zitat Greco R, Petrungaro A, Recchia AG, De Stefano L, Bossio S, Palummo A, et al. Treatment Acute Myeloid Leukemia Using Cytoreductive Chemotherapy Cytarabine (Ara-C) Followed Azacitidine (AZA) Maintenance: A Real Life Single Center Experience. Blood. 2016;128(22):5204.CrossRef Greco R, Petrungaro A, Recchia AG, De Stefano L, Bossio S, Palummo A, et al. Treatment Acute Myeloid Leukemia Using Cytoreductive Chemotherapy Cytarabine (Ara-C) Followed Azacitidine (AZA) Maintenance: A Real Life Single Center Experience. Blood. 2016;128(22):5204.CrossRef
37.
Zurück zum Zitat Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. NEJM. 2016;375(21):2023–36.CrossRef Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. NEJM. 2016;375(21):2023–36.CrossRef
38.
Zurück zum Zitat •• Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, et al. Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study. Int J Mol Sci. 2017;18(4):837 This study supports use of HMAs in acute erythroleukemia.CrossRef •• Almeida AM, Prebet T, Itzykson R, Ramos F, Al-Ali H, Shammo J, et al. Clinical Outcomes of 217 Patients with Acute Erythroleukemia According to Treatment Type and Line: A Retrospective Multinational Study. Int J Mol Sci. 2017;18(4):837 This study supports use of HMAs in acute erythroleukemia.CrossRef
39.
Zurück zum Zitat Peng J, Hasserjian RP, Tang G, Patel KP, Goswami M, Jabbour EJ, et al. Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response. Leuk Lymphoma. 2016;57(4):812–9.CrossRef Peng J, Hasserjian RP, Tang G, Patel KP, Goswami M, Jabbour EJ, et al. Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response. Leuk Lymphoma. 2016;57(4):812–9.CrossRef
Metadaten
Titel
Erythroleukemia: an Update
verfasst von
Olga K. Weinberg
Daniel A. Arber
Publikationsdatum
01.06.2021
Verlag
Springer US
Erschienen in
Current Oncology Reports / Ausgabe 6/2021
Print ISSN: 1523-3790
Elektronische ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-021-01060-8

Weitere Artikel der Ausgabe 6/2021

Current Oncology Reports 6/2021 Zur Ausgabe

Orthopedic Oncology (JA Abraham, Section Editor)

Update on Osteosarcoma

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.