Skip to main content
Erschienen in: InFo Hämatologie + Onkologie 12/2022

13.12.2022 | Akute myeloische Leukämie | Schwerpunkt

Schwerpunkt APL

Die akute Promyelozytenleukämie - ein hämatologischer Notfall

verfasst von: Dr. med. Franziska Modemann, Dr. med. Susanne Ghandili, Irina Zhurba, Prof. Dr. med. Florian Langer, Prof. Dr. med. Carsten Bokemeyer, Prof. Dr. med. Walter Fiedler

Erschienen in: InFo Hämatologie + Onkologie | Ausgabe 12/2022

Einloggen, um Zugang zu erhalten

Auszug

Die akute Promyelozytenleukämie (APL) ist eine seltene Form der akuten myeloischen Leukämie (AML), die einer umgehenden Diagnostik und Therapieeinleitung bedarf, da es ohne Einleitung einer entsprechenden (Supportiv-)Therapie zu schweren Gerinnungsstörungen kommen kann. Schwere Blutungen können durch eine Störung der plasmatischen Gerinnung durch die APL-Blasten in Kombination mit einer evtl. bestehenden Thrombopenie auftreten, wodurch die Patient*innen akut lebensbedrohlich gefährdet sind. Wird die APL jedoch früh diagnostiziert und wird rasch eine zielgerichtete Therapie eingeleitet, haben Patient*innen mit dieser speziellen Form der AML ausgezeichnete Heilungschancen. Was die APL zum hämatologischen Notfall macht und wie sie diagnostiziert wird, lesen Sie im folgenden Beitrag. …
Literatur
3.
Zurück zum Zitat Adams J, Nassiri M. Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations. Arch Pathol Lab Med. 2015;139(10):1308-13 Adams J, Nassiri M. Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations. Arch Pathol Lab Med. 2015;139(10):1308-13
4.
Zurück zum Zitat Dinmohamed AG, Visser O. Incidence of acute promyelocytic leukemia across Europe: results of RARECAREnet-a population-based study. Stem Cell Investig. 2019;6:37 Dinmohamed AG, Visser O. Incidence of acute promyelocytic leukemia across Europe: results of RARECAREnet-a population-based study. Stem Cell Investig. 2019;6:37
5.
Zurück zum Zitat Hasan SK et al. Analysis of t(15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: association of DNA breaks with specific DNA motifs at PML and RARA loci. Genes Chromosomes Cancer. 2010;49(8):726-32 Hasan SK et al. Analysis of t(15;17) chromosomal breakpoint sequences in therapy-related versus de novo acute promyelocytic leukemia: association of DNA breaks with specific DNA motifs at PML and RARA loci. Genes Chromosomes Cancer. 2010;49(8):726-32
6.
Zurück zum Zitat Braun T et al. Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group. Cancer. 2015;121(14):2393-9 Braun T et al. Evolving characteristics and outcome of secondary acute promyelocytic leukemia (APL): A prospective analysis by the French-Belgian-Swiss APL group. Cancer. 2015;121(14):2393-9
7.
Zurück zum Zitat Khoury JD et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-19 Khoury JD et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-19
8.
Zurück zum Zitat Arber DA et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405 Arber DA et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405
9.
Zurück zum Zitat Dohner H et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-77 Dohner H et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-77
10.
Zurück zum Zitat Sanz MA et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019;133(15):1630-43 Sanz MA et al. Management of acute promyelocytic leukemia: updated recommendations from an expert panel of the European LeukemiaNet. Blood. 2019;133(15):1630-43
11.
Zurück zum Zitat Ablain J, de The H. Revisiting the differentiation paradigm in acute promyelocytic leukemia. Blood. 2011;117(22):5795-802 Ablain J, de The H. Revisiting the differentiation paradigm in acute promyelocytic leukemia. Blood. 2011;117(22):5795-802
12.
Zurück zum Zitat Madan V et al. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia. Leukemia. 2016;30(12):2430 Madan V et al. Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia. Leukemia. 2016;30(12):2430
13.
Zurück zum Zitat Sanz MA et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96(4):1247-53 Sanz MA et al. Definition of relapse risk and role of nonanthracycline drugs for consolidation in patients with acute promyelocytic leukemia: a joint study of the PETHEMA and GIMEMA cooperative groups. Blood. 2000;96(4):1247-53
14.
Zurück zum Zitat Brissot E et al. Management of patients with acute leukemia during the COVID-19 outbreak: practical guidelines from the acute leukemia working party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2021;56(3):532-5 Brissot E et al. Management of patients with acute leukemia during the COVID-19 outbreak: practical guidelines from the acute leukemia working party of the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2021;56(3):532-5
15.
Zurück zum Zitat Lengfelder E et al. High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG. Leukemia. 2009;23(12):2248-58 Lengfelder E et al. High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG. Leukemia. 2009;23(12):2248-58
16.
Zurück zum Zitat Abaza Y et al. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017;129(10):1275-83 Abaza Y et al. Long-term outcome of acute promyelocytic leukemia treated with all-trans-retinoic acid, arsenic trioxide, and gemtuzumab. Blood. 2017;129(10):1275-83
17.
Zurück zum Zitat Iland HJ et al. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial. Lancet Haematol. 2015;2(9):e357-66 Iland HJ et al. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial. Lancet Haematol. 2015;2(9):e357-66
18.
Zurück zum Zitat Stahl M, Tallman MS. Acute promyelocytic leukemia (APL): remaining challenges towards a cure for all. Leuk Lymphoma. 2019;60(13):3107-15 Stahl M, Tallman MS. Acute promyelocytic leukemia (APL): remaining challenges towards a cure for all. Leuk Lymphoma. 2019;60(13):3107-15
19.
Zurück zum Zitat Lehmann S et al. Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-2013. Leukemia. 2017;31(6):1457-9 Lehmann S et al. Early death rates remain high in high-risk APL: update from the Swedish Acute Leukemia Registry 1997-2013. Leukemia. 2017;31(6):1457-9
20.
Zurück zum Zitat Altman JK et al. Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res. 2013;37(9):1004-9 Altman JK et al. Administration of ATRA to newly diagnosed patients with acute promyelocytic leukemia is delayed contributing to early hemorrhagic death. Leuk Res. 2013;37(9):1004-9
21.
Zurück zum Zitat Park JH et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118(5):1248-54 Park JH et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood. 2011;118(5):1248-54
22.
Zurück zum Zitat McClellan JS et al. Treatment advances have not improved the early death rate in acute promyelocytic leukemia. Haematologica. 2012;97(1):133-6 McClellan JS et al. Treatment advances have not improved the early death rate in acute promyelocytic leukemia. Haematologica. 2012;97(1):133-6
23.
Zurück zum Zitat Hambley BC et al. Coagulopathy in Acute Promyelocytic Leukemia: Can We Go Beyond Supportive Care? Front Med (Lausanne). 2021;8:722614 Hambley BC et al. Coagulopathy in Acute Promyelocytic Leukemia: Can We Go Beyond Supportive Care? Front Med (Lausanne). 2021;8:722614
24.
Zurück zum Zitat Avvisati G et al. Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia. Br J Haematol. 1988;70(1):43-8 Avvisati G et al. Acquired alpha-2-antiplasmin deficiency in acute promyelocytic leukaemia. Br J Haematol. 1988;70(1):43-8
25.
Zurück zum Zitat Menell JS et al. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. 1999;340(13):994-1004 Menell JS et al. Annexin II and bleeding in acute promyelocytic leukemia. N Engl J Med. 1999;340(13):994-1004
26.
Zurück zum Zitat Kwaan HC et al. Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin. J Thromb Haemost. 2004;2(2):306-12 Kwaan HC et al. Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin. J Thromb Haemost. 2004;2(2):306-12
27.
Zurück zum Zitat Sakata Y et al. The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia. Blood. 1991;77(9):1949-57 Sakata Y et al. The specific activity of plasminogen activator inhibitor-1 in disseminated intravascular coagulation with acute promyelocytic leukemia. Blood. 1991;77(9):1949-57
28.
Zurück zum Zitat Egbring R et al. Demonstration of granulocytic proteases in plasma of patients with acute leukemia and septicemia with coagulation defects. Blood. 1977;49(2):219-31 Egbring R et al. Demonstration of granulocytic proteases in plasma of patients with acute leukemia and septicemia with coagulation defects. Blood. 1977;49(2):219-31
29.
Zurück zum Zitat Oudijk EJ et al. Elastase mediated fibrinolysis in acute promyelocytic leukemia. Thromb Haemost. 2000;83(6):906-8 Oudijk EJ et al. Elastase mediated fibrinolysis in acute promyelocytic leukemia. Thromb Haemost. 2000;83(6):906-8
30.
Zurück zum Zitat Yang R et al. Neutrophil elastase enhances the proliferation and decreases apoptosis of leukemia cells via activation of PI3K/Akt signaling. Mol Med Rep. 2016;13(5):4175-82 Yang R et al. Neutrophil elastase enhances the proliferation and decreases apoptosis of leukemia cells via activation of PI3K/Akt signaling. Mol Med Rep. 2016;13(5):4175-82
31.
Zurück zum Zitat Yu L et al. Neutrophil elastase-mediated proteolysis of the tumor suppressor p200 CUX1 promotes cell proliferation and inhibits cell differentiation in APL. Life Sci. 2020;242:117229 Yu L et al. Neutrophil elastase-mediated proteolysis of the tumor suppressor p200 CUX1 promotes cell proliferation and inhibits cell differentiation in APL. Life Sci. 2020;242:117229
32.
Zurück zum Zitat Ma G et al. Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia. Ann Hematol. 2013;92(5):645-52 Ma G et al. Increased promyelocytic-derived microparticles: a novel potential factor for coagulopathy in acute promyelocytic leukemia. Ann Hematol. 2013;92(5):645-52
33.
Zurück zum Zitat Langer F et al. Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation. Ann Hematol. 2008;87(6):451-7 Langer F et al. Tissue factor procoagulant activity of plasma microparticles in patients with cancer-associated disseminated intravascular coagulation. Ann Hematol. 2008;87(6):451-7
34.
Zurück zum Zitat Falanga A et al. Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells. Blood. 1998;92(1):143-51 Falanga A et al. Cancer procoagulant and tissue factor are differently modulated by all-trans-retinoic acid in acute promyelocytic leukemia cells. Blood. 1998;92(1):143-51
35.
Zurück zum Zitat Dubois C et al. Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells. Blood. 1994;83(11):3264-70 Dubois C et al. Hematopoietic growth factor expression and ATRA sensitivity in acute promyelocytic blast cells. Blood. 1994;83(11):3264-70
36.
Zurück zum Zitat Schorer AE et al. Interleukin 1 stimulates endothelial cell tissue factor production and expression by a prostaglandin-independent mechanism. Thromb Haemost. 1986;56(3):256-9 Schorer AE et al. Interleukin 1 stimulates endothelial cell tissue factor production and expression by a prostaglandin-independent mechanism. Thromb Haemost. 1986;56(3):256-9
37.
Zurück zum Zitat Schleef RR et al. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem. 1988;263(12):5797-803 Schleef RR et al. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem. 1988;263(12):5797-803
38.
Zurück zum Zitat Lentz SR et al. Regulation of thrombomodulin by tumor necrosis factor-alpha: comparison of transcriptional and posttranscriptional mechanisms. Blood. 1991;77(3):542-50 Lentz SR et al. Regulation of thrombomodulin by tumor necrosis factor-alpha: comparison of transcriptional and posttranscriptional mechanisms. Blood. 1991;77(3):542-50
39.
Zurück zum Zitat Nan B et al. Effects of TNF-alpha and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells. Thromb Res. 2005;115(5):417-26 Nan B et al. Effects of TNF-alpha and curcumin on the expression of thrombomodulin and endothelial protein C receptor in human endothelial cells. Thromb Res. 2005;115(5):417-26
40.
Zurück zum Zitat Tan et al. A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia Blood. 2021;137(11):1503-16 Tan et al. A PML/RARα direct target atlas redefines transcriptional deregulation in acute promyelocytic leukemia Blood. 2021;137(11):1503-16
Metadaten
Titel
Schwerpunkt APL
Die akute Promyelozytenleukämie - ein hämatologischer Notfall
verfasst von
Dr. med. Franziska Modemann
Dr. med. Susanne Ghandili
Irina Zhurba
Prof. Dr. med. Florian Langer
Prof. Dr. med. Carsten Bokemeyer
Prof. Dr. med. Walter Fiedler
Publikationsdatum
13.12.2022
Verlag
Springer Medizin
Erschienen in
InFo Hämatologie + Onkologie / Ausgabe 12/2022
Print ISSN: 2662-1754
Elektronische ISSN: 2662-1762
DOI
https://doi.org/10.1007/s15004-022-9772-1

Weitere Artikel der Ausgabe 12/2022

InFo Hämatologie + Onkologie 12/2022 Zur Ausgabe

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.