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Erschienen in: Der Onkologe 12/2012

01.12.2012 | Leitthema

Aktuelle Therapie der akuten lymphatischen Leukämie des Erwachsenen

verfasst von: N. Gökbuget, M.D., O. Ottmann

Erschienen in: Die Onkologie | Ausgabe 12/2012

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Zusammenfassung

Die akute lymphatische Leukämie (ALL) ist die häufigste maligne Erkrankung im Kindesalter mit einem Anteil von etwa 20% an den akuten Leukämien des Erwachsenenalters. Sie ist eine der wenigen disseminierten malignen Krankheiten, die allein mit Chemotherapie geheilt werden können. In den vergangenen Jahrzehnten wurden in der Charakterisierung und Behandlung der Erkrankung wesentliche Fortschritte gemacht. Es konnten biologische Subgruppen und Risikogruppen mit unterschiedlichem klinischem Verlauf charakterisiert werden. Darauf basieren aktuelle, individualisierte risikoadaptierte Therapieprotokolle. Etwa 90% der erwachsenen ALL-Patienten erreichen eine komplette Remission. Die Heilungschancen konnten in den vergangenen 30 Jahren von unter 10% auf über 50% erhöht werden. Wesentlich für die Verbesserung der Therapieergebnisse war eine Optimierung der Chemotherapie und Supportivbehandlung, die Integration der Stammzelltransplantation in die Erstlinienbehandlung sowie eine verbesserte Risikostratifikation. Dazu kamen in jüngster Zeit individualisierte Therapiemodifikationen unter Berücksichtigung der minimalen Resterkrankung und zielgerichtete Therapie wie der Einsatz von Tyrosinkinaseinhibitoren bei der Ph/BCR-ABL-positiven ALL.
Literatur
1.
Zurück zum Zitat Annino L, Vegna ML, Camera A et al (2002) Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow- up of the GIMEMA ALL 0288 randomized study. Blood 99:863–871PubMedCrossRef Annino L, Vegna ML, Camera A et al (2002) Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow- up of the GIMEMA ALL 0288 randomized study. Blood 99:863–871PubMedCrossRef
2.
Zurück zum Zitat Bassan R, Hoelzer D (2011) Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 29:532–543PubMedCrossRef Bassan R, Hoelzer D (2011) Modern therapy of acute lymphoblastic leukemia. J Clin Oncol 29:532–543PubMedCrossRef
3.
Zurück zum Zitat Bassan R, Spinelli O, Oldani E et al (2009) Improved risk classification for risk-specific therapy based on the molecular study of MRD in adult ALL. Blood Bassan R, Spinelli O, Oldani E et al (2009) Improved risk classification for risk-specific therapy based on the molecular study of MRD in adult ALL. Blood
4.
Zurück zum Zitat Brüggemann M, Gökbuget N, Kneba M (2012) Acute lymphoblastic leukemia: monitoring minimal residual disease as a therapeutic principle. Semin Oncol 39:47–57PubMedCrossRef Brüggemann M, Gökbuget N, Kneba M (2012) Acute lymphoblastic leukemia: monitoring minimal residual disease as a therapeutic principle. Semin Oncol 39:47–57PubMedCrossRef
5.
Zurück zum Zitat Brüggemann M, Schrauder A, Raff T et al (2010) Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia 24:521–535PubMedCrossRef Brüggemann M, Schrauder A, Raff T et al (2010) Standardized MRD quantification in European ALL trials: proceedings of the Second International Symposium on MRD assessment in Kiel, Germany, 18–20 September 2008. Leukemia 24:521–535PubMedCrossRef
6.
Zurück zum Zitat Chen IM, Harvey RC, Mullighan CG et al (2012) Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children’s Oncology Group study. Blood 119:3512–3522PubMedCrossRef Chen IM, Harvey RC, Mullighan CG et al (2012) Outcome modeling with CRLF2, IKZF1, JAK, and minimal residual disease in pediatric acute lymphoblastic leukemia: a Children’s Oncology Group study. Blood 119:3512–3522PubMedCrossRef
7.
Zurück zum Zitat Cornelissen JJ, Holt B van der, Verhoef GE et al (2009) Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 113:1375–1382PubMedCrossRef Cornelissen JJ, Holt B van der, Verhoef GE et al (2009) Myeloablative allogeneic versus autologous stem cell transplantation in adult patients with acute lymphoblastic leukemia in first remission: a prospective sibling donor versus no-donor comparison. Blood 113:1375–1382PubMedCrossRef
8.
Zurück zum Zitat Diller L (2011) Clinical practice. Adult primary care after childhood acute lymphoblastic leukemia. N Engl J Med 365:1417–1424PubMedCrossRef Diller L (2011) Clinical practice. Adult primary care after childhood acute lymphoblastic leukemia. N Engl J Med 365:1417–1424PubMedCrossRef
9.
Zurück zum Zitat Gökbuget N (2011) Acute lymphoblastic leukemia in older patients. Hematology Education (Education Programme for the 16th Congress of the EHA). 20–26 Gökbuget N (2011) Acute lymphoblastic leukemia in older patients. Hematology Education (Education Programme for the 16th Congress of the EHA). 20–26
10.
Zurück zum Zitat Gökbuget N (2011) Recommendations of the European Working Group for Adult ALL. UNI-MED, Bremen Gökbuget N (2011) Recommendations of the European Working Group for Adult ALL. UNI-MED, Bremen
11.
Zurück zum Zitat Gökbuget N, Arnold R, Böhme A et al (2007) Improved outcome in high risk and very high risk ALL by risk adapted SCT and in Standard Risk ALL by intensive chemotherapy in 713 adult all patients treated according to the Prospective GMALL Study 07/2003. Blood 110:abstract #12 Gökbuget N, Arnold R, Böhme A et al (2007) Improved outcome in high risk and very high risk ALL by risk adapted SCT and in Standard Risk ALL by intensive chemotherapy in 713 adult all patients treated according to the Prospective GMALL Study 07/2003. Blood 110:abstract #12
12.
Zurück zum Zitat Gökbuget N, Basara N, Baurmann H et al (2011) High single drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood Gökbuget N, Basara N, Baurmann H et al (2011) High single drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation. Blood
13.
Zurück zum Zitat Gökbuget N, Hoelzer D (2009) Treatment of adult acute lymphoblastic leukemia. Semin Hematol 46:64–75PubMedCrossRef Gökbuget N, Hoelzer D (2009) Treatment of adult acute lymphoblastic leukemia. Semin Hematol 46:64–75PubMedCrossRef
14.
Zurück zum Zitat Gökbuget N, Hoelzer D, Arnold R et al (2001) Subtypes and treatment outcome in adult acute lymphoblastic leukemia (ALL) < > 55 years. Hematol J 1:694a Gökbuget N, Hoelzer D, Arnold R et al (2001) Subtypes and treatment outcome in adult acute lymphoblastic leukemia (ALL) < > 55 years. Hematol J 1:694a
15.
Zurück zum Zitat Gokbuget N, Kneba M, Raff T et al (2012) Adults with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood Gokbuget N, Kneba M, Raff T et al (2012) Adults with acute lymphoblastic leukemia and molecular failure display a poor prognosis and are candidates for stem cell transplantation and targeted therapies. Blood
16.
Zurück zum Zitat Gökbuget N, Leguay T, Hunault M et al (2008) First European chemotherapy schedule for elderly patients with acute lymphoblastic leukemia: promising remission rate and feasible moderate dose intensity consolidation. ASH Annual Meeting Abstracts 112:304 Gökbuget N, Leguay T, Hunault M et al (2008) First European chemotherapy schedule for elderly patients with acute lymphoblastic leukemia: promising remission rate and feasible moderate dose intensity consolidation. ASH Annual Meeting Abstracts 112:304
17.
Zurück zum Zitat Gökbuget N, Stanze D, Beck J et al (2012) Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors and realization of stem cell transplantation. Blood Gökbuget N, Stanze D, Beck J et al (2012) Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors and realization of stem cell transplantation. Blood
18.
Zurück zum Zitat Hoelzer D, Gökbuget N (2012) Chemoimmunotherapy in acute lymphoblastic leukemia. Blood Rev 26:25–32PubMedCrossRef Hoelzer D, Gökbuget N (2012) Chemoimmunotherapy in acute lymphoblastic leukemia. Blood Rev 26:25–32PubMedCrossRef
19.
Zurück zum Zitat Hoelzer D, Ludwig WD, Thiel E et al (1996) Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87:495–508PubMed Hoelzer D, Ludwig WD, Thiel E et al (1996) Improved outcome in adult B-cell acute lymphoblastic leukemia. Blood 87:495–508PubMed
20.
Zurück zum Zitat Juliusson G, Karlsson K, Hallbook H (2010) Population-based analyses in adult acute lymphoblastic leukemia. Blood 116:1011 (author reply 1012)PubMedCrossRef Juliusson G, Karlsson K, Hallbook H (2010) Population-based analyses in adult acute lymphoblastic leukemia. Blood 116:1011 (author reply 1012)PubMedCrossRef
21.
Zurück zum Zitat Kantarjian H, Thomas D, O’Brien S et al (2004) Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101:2788–2801PubMedCrossRef Kantarjian H, Thomas D, O’Brien S et al (2004) Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer 101:2788–2801PubMedCrossRef
22.
Zurück zum Zitat Labar B, Suciu S, Zittoun R et al (2004) Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin’s lymphoma for patients < or = 50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica 89:809–817PubMed Labar B, Suciu S, Zittoun R et al (2004) Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin’s lymphoma for patients < or = 50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica 89:809–817PubMed
23.
Zurück zum Zitat Mancini M, Scappaticci D, Cimino G et al (2005) A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood 105:3434–3441PubMedCrossRef Mancini M, Scappaticci D, Cimino G et al (2005) A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood 105:3434–3441PubMedCrossRef
24.
Zurück zum Zitat Oliansky DM, Larson RA, Weisdorf D et al (2011) The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 Evidence-Based Review. Biol Blood Marrow Transplant Oliansky DM, Larson RA, Weisdorf D et al (2011) The role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of adult acute lymphoblastic leukemia: update of the 2006 Evidence-Based Review. Biol Blood Marrow Transplant
25.
Zurück zum Zitat Ottmann OG, Pfeifer H (2009) Management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Hematology. Am Soc Hematol Educ Program 371–381 Ottmann OG, Pfeifer H (2009) Management of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Hematology. Am Soc Hematol Educ Program 371–381
26.
Zurück zum Zitat Ottmann OG, Wassmann B, Pfeifer H et al (2007) Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Cancer 109:2068–2076PubMedCrossRef Ottmann OG, Wassmann B, Pfeifer H et al (2007) Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Cancer 109:2068–2076PubMedCrossRef
27.
Zurück zum Zitat Pieters R, Hunger SP, Boos J et al (2010) L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer Pieters R, Hunger SP, Boos J et al (2010) L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase. Cancer
28.
Zurück zum Zitat Raff T, Gökbuget N, Luschen S et al (2007) Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood 109:910–915PubMedCrossRef Raff T, Gökbuget N, Luschen S et al (2007) Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood 109:910–915PubMedCrossRef
29.
Zurück zum Zitat Ribera JM, Oriol A, Bethencourt C et al (2005) Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 90:1346–1356PubMed Ribera JM, Oriol A, Bethencourt C et al (2005) Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia. Results of the PETHEMA ALL-93 trial. Haematologica 90:1346–1356PubMed
30.
Zurück zum Zitat Ribera JM, Oriol A, Sanz MA et al (2008) Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol 26:1843–1849PubMedCrossRef Ribera JM, Oriol A, Sanz MA et al (2008) Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol 26:1843–1849PubMedCrossRef
31.
Zurück zum Zitat Rowe JM, Buck G, Burnett AK et al (2005) Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 106:3760–3767PubMedCrossRef Rowe JM, Buck G, Burnett AK et al (2005) Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood 106:3760–3767PubMedCrossRef
32.
Zurück zum Zitat Stock W (2010) Adolescents and young adults with acute lymphoblastic leukemia. Hematology. Am Soc Hematol Educ Program 21–29 Stock W (2010) Adolescents and young adults with acute lymphoblastic leukemia. Hematology. Am Soc Hematol Educ Program 21–29
33.
Zurück zum Zitat Stock W, La M, Sanford B et al (2008) What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of children’s cancer group and cancer and leukemia group b studies. Blood 112:1646–1654PubMedCrossRef Stock W, La M, Sanford B et al (2008) What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of children’s cancer group and cancer and leukemia group b studies. Blood 112:1646–1654PubMedCrossRef
34.
Zurück zum Zitat Takeuchi J, Kyo T, Naito K et al (2002) Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 16:1259–1266PubMedCrossRef Takeuchi J, Kyo T, Naito K et al (2002) Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia 16:1259–1266PubMedCrossRef
35.
Zurück zum Zitat Thomas X, Boiron JM, Huguet F et al (2004) Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 22:4075–4086PubMedCrossRef Thomas X, Boiron JM, Huguet F et al (2004) Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol 22:4075–4086PubMedCrossRef
36.
Zurück zum Zitat Topp MS, Kufer P, Gökbuget N et al (2011) Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 29:2493–2498PubMedCrossRef Topp MS, Kufer P, Gökbuget N et al (2011) Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol 29:2493–2498PubMedCrossRef
Metadaten
Titel
Aktuelle Therapie der akuten lymphatischen Leukämie des Erwachsenen
verfasst von
N. Gökbuget, M.D.
O. Ottmann
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
Die Onkologie / Ausgabe 12/2012
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI
https://doi.org/10.1007/s00761-012-2351-6

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