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Akute lymphoblastische Leukämien (ALL) im Kindes- und Jugendalter

Acute lymphoblastic leukemia (ALL) in childhood and adolescence

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Zusammenfassung

Die ALL ist die häufigste maligne Erkrankung im Kindes- und Jugendalter. Derzeit werden 80–85 % aller Patienten im ersten Anlauf geheilt. Die Entwicklung der an das Rezidivrisiko angepassten Polychemotherapie inklusive einer konsequenten prophylaktischen Mitbehandlung des Zentralnervensystems sowie die Durchführung der Protokolle in multizentrischen Therapieoptimierungsstudien stellen eine der bedeutendsten Erfolgsgeschichten in der Onkologie dar. Mittels initialer Laborparameter, biologischer Eigenschaften der leukämischen Zellen und des frühen Therapieansprechens lässt sich das Rezidivrisiko sehr gut vorhersehen, sodass die erwähnten Parameter in nahezu allen Studien zur Therapiestratifizierung herangezogen werden. Trotzdem kommt es bei 20 % der Patienten zu einem Rückfall, sodass die Zukunft darauf abzielt, mit Medikamenten, die molekulare leukämiespezifische Veränderungen zum Angriffsziel haben, die therapeutische Effizienz bei Verringerung der Nebenwirkungen zu steigern.

Abstract

Acute lymphoblastic leukemia (ALL) is the most common malignant disease in childhood and adolescence. Nowadays 80–85 % of patients can be cured from the disease with first-line therapy. The development of a relapse risk adapted polychemotherapy, including simultaneous prophylactic treatment of the central nervous system and implementation of the protocols in multicentre therapy optimization trials represent one of the most distinguished stories of success in the whole field of oncology. By using initial laboratory parameters, biological features of the leukemic cells and initial response to therapy, the patient risk for relapse can be predicted very reliably so that in almost all clinical trials most of the prognostic parameters mentioned are used for treatment stratification. Nevertheless, 20 % of patients relapse so that future research aims at developing a more targeted therapy directed towards molecular alterations of the leukemic cells in order to improve therapeutic efficacy and reduce therapy-associated side effects.

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Abbreviations

ALL:

Akute lymphoblastische Leukämie

AML:

Akute myeloische Leukämie

APCR :

Aktivierte Protein-C-Resistenz

BFM:

Für die Städte Berlin, Frankfurt und Münster als Erstanwender des entsprechenden Protokolls

B-(Vorläufer)-ALL:

ALL mit B-(Vorläufer)-lymphozytärer Differenzierung

CML:

Chronische myeloische Leukämie

CMV:

Zytomegalievirus

CRP:

C-reaktives Protein

EBV:

Epstein-Barr-Virus

EEG:

Elektroenzephalographie

EKG:

Elektrokardiographie

FAB:

„French-American-British“

FISH:

Fluoreszenz-in-situ-Hybridisierung

HIV:

Humanes Immundefizienzvirus

HLA:

Humanes Leukozytenantigen

HSV:

Herpes-simplex-Virus

Ig:

Immunglobulin

JIA:

Juvenile idiopathische Arthritis

LDH :

Laktatdehydrogenase

MRD:

„Minimal residual disease“

MRT:

Magnetresonanztomographie

PCR:

Polymerasekettenreaktion

T-(Vorläufer)-ALL:

ALL mit T-(Vorläufer)-lymphozytärer Differenzierung

TCR:

T-Zell-Rezeptor

TPMT:

Thiopurinmethyltransferase

VZV:

Varizella-Zoster-Virus

ZNS:

Zentralnervensystem

Literatur

  1. Pui CH, Evans WE (2006) Treatment of acute lymphoblastic leukemia. N Engl J Med 354:166–178

    Article  PubMed  CAS  Google Scholar 

  2. Pui CH, Relling MV, Downing JR (2004) Acute lymphoblastic leukemia. N Engl J Med 350:1535–1548

    Article  PubMed  CAS  Google Scholar 

  3. Stanulla M, Bourquin JP (2012) Treatment of acute lymphoblastic leukemia in childhood: state of things and outlook for the future. Pharm Unserer Zeit 41:203–213

    Article  PubMed  Google Scholar 

  4. Pieters R (2009) Infant acute lymphoblastic leukemia: lessons learned and future directions. Curr Hematol Malig Rep 4:167–174

    Article  PubMed  Google Scholar 

  5. Schrappe M, Harbott J, Riehm H (2006) Akute lymphoblastische Leukämien. In: Gadner H, Gaedicke G, Niemeyer C et al (Hrsg) Pädiatrische Hämatologie und Onkologie. Springer, Berlin Heidelberg New York, S 656–679

  6. Does-van den Berg A van der, Bartram CR, Basso G et al (1992) Minimal requirements for the diagnosis, classification, and evaluation of the treatment of childhood acute lymphoblastic leukemia (ALL) in the „BFM Family“ Cooperative Group. Med Pediatr Oncol 20:497–505

    Article  Google Scholar 

  7. Bene MC, Castoldi G, Knapp W et al (1995) Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 9:1783–1786

    PubMed  CAS  Google Scholar 

  8. Campana D (2003) Determination of minimal residual disease in leukaemia patients. Br J Haematol 121:823–838

    Article  PubMed  Google Scholar 

  9. Mullighan CG (2012) The molecular genetic makeup of acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2012:389–396

    PubMed  Google Scholar 

  10. Van Vlierberghe P, Ferrando A (2012) The molecular basis of T cell acute lymphoblastic leukemia. J Clin Invest 122:3398–3406

    Article  Google Scholar 

  11. Biondi A, Schrappe M, De Lorenzo P et al (2012) Imatinib after induction for treatment of children and adolescents with Philadelphia-chromosome-positive acute lymphoblastic leukaemia (EsPhALL): a randomised, open-label, intergroup study. Lancet Oncol 13:936–945

    Article  PubMed  CAS  Google Scholar 

  12. Mann G, Cazzaniga G, Velden VH van der et al (2007) Acute lymphoblastic leukemia with t(4;11) in children 1 year and older: the ‚big sister‘ of the infant disease? Leukemia 21:642–646

    PubMed  CAS  Google Scholar 

  13. Mullighan CG (2012) Molecular genetics of B-precursor acute lymphoblastic leukemia. J Clin Invest 122:3407–3415

    Article  PubMed  CAS  Google Scholar 

  14. Moorman AV, Richards SM, Martineau M et al (2003) Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia. Blood 102:2756–2762

    Article  PubMed  CAS  Google Scholar 

  15. Nachman JB, Heerema NA, Sather H et al (2007) Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 110:1112–1115

    Article  PubMed  CAS  Google Scholar 

  16. Gaynon PS (2000) Prognostic factors in acute lymphoblastic leukemia. J Pediatr Hematol Oncol 22:403–404

    Article  PubMed  CAS  Google Scholar 

  17. Conter V, Bartram CR, Valsecchi MG et al (2010) Molecular response to treatment redefines all prognostic factors in children and adolescents with B-cell precursor acute lymphoblastic leukemia: results in 3184 patients of the AIEOP-BFM ALL 2000 study. Blood 115:3206–3214

    Article  PubMed  CAS  Google Scholar 

  18. Schrappe M, Valsecchi MG, Bartram CR et al (2011) Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study. Blood 118:2077–2084

    Article  PubMed  CAS  Google Scholar 

  19. Moricke A, Reiter A, Zimmermann M et al (2008) Risk-adjusted therapy of acute lymphoblastic leukemia can decrease treatment burden and improve survival: treatment results of 2169 unselected pediatric and adolescent patients enrolled in the trial ALL-BFM 95. Blood 111:4477–4489

    Article  PubMed  Google Scholar 

  20. Pieters R, Schrappe M, De Lorenzo P et al (2007) A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet 370:240–250

    Article  PubMed  CAS  Google Scholar 

  21. Burger B, Beier R, Zimmermann M et al (2005) Osteonecrosis: a treatment related toxicity in childhood acute lymphoblastic leukemia (ALL) – experiences from trial ALL-BFM 95. Pediatr Blood Cancer 44:220–225

    Article  PubMed  Google Scholar 

  22. Schrappe M, Camitta B, Pui CH et al (2000) Long-term results of large prospective trials in childhood acute lymphoblastic leukemia. Leukemia 14:2193–2194

    Article  PubMed  CAS  Google Scholar 

  23. Schrappe M, Reiter A, Ludwig WD et al (2000) Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 95:3310–3322

    PubMed  CAS  Google Scholar 

  24. Schrauder A, Reiter A, Gadner H et al (2006) Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95. J Clin Oncol 24:5742–5749

    Article  PubMed  Google Scholar 

  25. Peters C, Schrauder A, Schrappe M et al (2005) Allogeneic haematopoietic stem cell transplantation in children with acute lymphoblastic leukaemia: the BFM/IBFM/EBMT concepts. Bone Marrow Transplant [Suppl 1] 35:S9–S11

  26. Reiter A, Schrappe M, Ludwig WD et al (1994) Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Blood 84:3122–3133

    PubMed  CAS  Google Scholar 

  27. Riehm H, Reiter A, Schrappe M et al (1987) Corticosteroid-dependent reduction of leukocyte count in blood as a prognostic factor in acute lymphoblastic leukemia in childhood (therapy study ALL-BFM 83). Klin Padiatr 199:151–160

    Article  PubMed  CAS  Google Scholar 

  28. Schrappe M, Hunger SP, Pui CH et al (2012) Outcomes after induction failure in childhood acute lymphoblastic leukemia. N Engl J Med 366:1371–1381

    Article  PubMed  CAS  Google Scholar 

  29. Moricke A, Zimmermann M, Reiter A et al (2010) Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia 24:265–284

    Article  PubMed  CAS  Google Scholar 

  30. Dordelmann M, Schrappe M, Reiter A et al (1998) Down’s syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Munster Group. Leukemia 12:645–651

    Article  PubMed  CAS  Google Scholar 

  31. Moricke A, Zimmermann M, Reiter A et al (2005) Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95. Klin Padiatr 217:310–320

    Article  PubMed  CAS  Google Scholar 

  32. Locatelli F, Schrappe M, Bernardo ME et al (2012) How I treat relapsed childhood acute lymphoblastic leukemia. Blood 120:2807–2816

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. ALL-BFM Studienzentrale Österreich, St. Anna Kinderspital, Universitätsklinik für Kinder- und Jugendheilkunde, Medizinische Universität Wien (MUW), Kinderspitalgasse 6, A-1090, Wien, Österreich

    A. Attarbaschi

  2. ALL-BFM Studienzentrale Deutschland, Haus 9, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105, Kiel, Deutschland

    A. Möricke

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  1. A. Attarbaschi
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Attarbaschi, A., Möricke, A. Akute lymphoblastische Leukämien (ALL) im Kindes- und Jugendalter. Monatsschr Kinderheilkd 161, 559–574 (2013). https://doi.org/10.1007/s00112-013-2911-x

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