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Erschienen in: Annals of Hematology 10/2013

01.10.2013 | Original Article

Allogeneic hematopoietic cell transplantation with reduced-intensity conditioning following FLAMSA for primary refractory or relapsed acute myeloid leukemia

verfasst von: Dominik Schneidawind, Birgit Federmann, Christoph Faul, Wichard Vogel, Lothar Kanz, Wolfgang Andreas Bethge

Erschienen in: Annals of Hematology | Ausgabe 10/2013

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Abstract

Patients with primary refractory or relapsed acute myeloid leukemia (AML) have a dismal prognosis. We report a retrospective single center analysis of aplasia-inducing chemotherapy using fludarabine, cytarabine, and amsacrine (FLAMSA) followed by reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (HCT) in 62 consecutive primary refractory or relapsed AML patients. Two-year event-free survival and overall survival (OS) were 26 and 39 %, respectively. Risk stratification according to cytogenetic and molecular genetic markers showed superior survival in patients in the intermediate-1 risk group (2-year OS 70 %) compared to the intermediate-2 risk (2-year OS 34 %, p = 0.03) and adverse risk (2-year OS 38 %, p = 0.06) group. The use of HLA-matched versus HLA-mismatched donors had no significant influence on survival (p = 0.98). Two-year OS in the elderly subgroup defined by age ≥60 years was 31 % compared to 46 % in the group of younger patients <60 years (p = 0.19). Cumulative incidence of non-relapse mortality at 2 years adjusted for relapse as competing risk was 20 % for patients <60 years and 26 % for older patients (p = 0.55). Chronic graft-versus-host disease was associated with a statistically significant superior survival (p < 0.01). FLAMSA-RIC followed by allogeneic HCT enables long-term disease-free survival in primary refractory or relapsed AML even in the elderly patient population.
Literatur
1.
Zurück zum Zitat Lowenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341:1051–1062PubMedCrossRef Lowenberg B, Downing JR, Burnett A (1999) Acute myeloid leukemia. N Engl J Med 341:1051–1062PubMedCrossRef
2.
Zurück zum Zitat Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF et al (2005) Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 23:1969–1978PubMedCrossRef Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF et al (2005) Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 23:1969–1978PubMedCrossRef
3.
Zurück zum Zitat Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D et al (2006) Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 108:1092–1099PubMedCrossRef Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D et al (2006) Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 108:1092–1099PubMedCrossRef
4.
Zurück zum Zitat Detrait MY, Chevallier P, Sobh M, Guillaume T, Thomas X, Morissetet S et al (2011) Outcome of high-risk and refractory AML/MDS patients receiving a FLAMSA sequential chemotherapy regimen followed by reduced-intensity conditioning (RIC) and allogeneic hematopoeitic stem cell transplantation (allo-HSCT). Blood (ASH Annual Meeting Abstracts) 118: abstract 1957 Detrait MY, Chevallier P, Sobh M, Guillaume T, Thomas X, Morissetet S et al (2011) Outcome of high-risk and refractory AML/MDS patients receiving a FLAMSA sequential chemotherapy regimen followed by reduced-intensity conditioning (RIC) and allogeneic hematopoeitic stem cell transplantation (allo-HSCT). Blood (ASH Annual Meeting Abstracts) 118: abstract 1957
5.
Zurück zum Zitat Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474PubMedCrossRef Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474PubMedCrossRef
6.
Zurück zum Zitat Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18:295–304PubMedCrossRef Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA et al (1974) Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 18:295–304PubMedCrossRef
7.
Zurück zum Zitat Lee SJ, Vogelsang G, Flowers ME (2003) Chronic graft-versus-host disease. Biol Blood Marrow Transplant 9:215–233PubMedCrossRef Lee SJ, Vogelsang G, Flowers ME (2003) Chronic graft-versus-host disease. Biol Blood Marrow Transplant 9:215–233PubMedCrossRef
8.
Zurück zum Zitat Bader P, Beck J, Frey A, Schlegel PG, Hebarth H, Handgretinger R et al (1998) Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. Bone Marrow Transplant 21:487–495PubMedCrossRef Bader P, Beck J, Frey A, Schlegel PG, Hebarth H, Handgretinger R et al (1998) Serial and quantitative analysis of mixed hematopoietic chimerism by PCR in patients with acute leukemias allows the prediction of relapse after allogeneic BMT. Bone Marrow Transplant 21:487–495PubMedCrossRef
9.
Zurück zum Zitat Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ (2005) Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23:5675–5687PubMedCrossRef Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ (2005) Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23:5675–5687PubMedCrossRef
10.
Zurück zum Zitat Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant 40:381–387PubMedCrossRef Scrucca L, Santucci A, Aversa F (2007) Competing risk analysis using R: an easy guide for clinicians. Bone Marrow Transplant 40:381–387PubMedCrossRef
11.
Zurück zum Zitat Rowe JM, Li X, Cassileth PA, Appelbaum FR, Schiffer CA, Wiernik PH et al (2005) Very poor survival of patients with AML who relapse after achieving a first complete remission: The Eastern Cooperative Oncology Group experience. Blood (ASH Annual Meeting Abstracts) 106: abstract 546 Rowe JM, Li X, Cassileth PA, Appelbaum FR, Schiffer CA, Wiernik PH et al (2005) Very poor survival of patients with AML who relapse after achieving a first complete remission: The Eastern Cooperative Oncology Group experience. Blood (ASH Annual Meeting Abstracts) 106: abstract 546
12.
Zurück zum Zitat Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM et al (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28:3730–3738PubMedCrossRef Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM et al (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28:3730–3738PubMedCrossRef
13.
Zurück zum Zitat Estey EH (2012) Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 87:89–99PubMedCrossRef Estey EH (2012) Acute myeloid leukemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 87:89–99PubMedCrossRef
14.
Zurück zum Zitat Schoch C, Kern W, Schnittger S, Buchner T, Hiddemann W, Haferlach T (2004) The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica 89:1082–1090PubMed Schoch C, Kern W, Schnittger S, Buchner T, Hiddemann W, Haferlach T (2004) The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica 89:1082–1090PubMed
15.
Zurück zum Zitat Federmann B, Faul C, Vogel W, Kanz L, Bethge WA (2010) Outcome of patients aged ≥60 after allogeneic hematopoietec cell transplantation: age has no impact on survival. Blood (ASH Annual Meeting Abstracts) 116: abstract 3540 Federmann B, Faul C, Vogel W, Kanz L, Bethge WA (2010) Outcome of patients aged ≥60 after allogeneic hematopoietec cell transplantation: age has no impact on survival. Blood (ASH Annual Meeting Abstracts) 116: abstract 3540
16.
Zurück zum Zitat Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland MC, Heinecke A et al (2005) Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood 106:3314–3321PubMedCrossRef Stelljes M, Bornhauser M, Kroger M, Beyer J, Sauerland MC, Heinecke A et al (2005) Conditioning with 8-Gy total body irradiation and fludarabine for allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia. Blood 106:3314–3321PubMedCrossRef
17.
Zurück zum Zitat Buchholz S, Dammann E, Stadler M, Krauter J, Beutel G, Trummer A et al (2012) Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome. Eur J Haematol 88:52–60PubMedCrossRef Buchholz S, Dammann E, Stadler M, Krauter J, Beutel G, Trummer A et al (2012) Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity conditioning and allogeneic stem cell transplantation in patients with high-risk, relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic syndrome. Eur J Haematol 88:52–60PubMedCrossRef
18.
Zurück zum Zitat Kayser S, Dohner K, Krauter J, Kohne CH, Horst HA, Held G et al (2011) The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2,853 adult patients with newly diagnosed AML. Blood 117:2137–2145PubMedCrossRef Kayser S, Dohner K, Krauter J, Kohne CH, Horst HA, Held G et al (2011) The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2,853 adult patients with newly diagnosed AML. Blood 117:2137–2145PubMedCrossRef
19.
Zurück zum Zitat Klepin HD, Balducci L (2009) Acute myelogenous leukemia in older adults. Oncologist 14:222–232PubMedCrossRef Klepin HD, Balducci L (2009) Acute myelogenous leukemia in older adults. Oncologist 14:222–232PubMedCrossRef
20.
Zurück zum Zitat de Witte T, Oosterveld M, Span B, Muus P, Schattenberg A (2002) Stem cell transplantation for leukemias following myelodysplastic syndromes or secondary to cytotoxic therapy. Rev Clin Exp Hematol 6:72–85PubMedCrossRef de Witte T, Oosterveld M, Span B, Muus P, Schattenberg A (2002) Stem cell transplantation for leukemias following myelodysplastic syndromes or secondary to cytotoxic therapy. Rev Clin Exp Hematol 6:72–85PubMedCrossRef
21.
Zurück zum Zitat Cannas G, Huynh A, Morisset S, Sobh M, Raus N, Garban F et al (2009) Safety and efficacy of FLAMSA regimen followed by allogeneic hematopoietic stem cell transplantation from related and unrelated donors in high risk acute leukemia and MDS patients: a study from the Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC) Registry. Blood (ASH Annual Meeting Abstracts) 114: abstract 4335 Cannas G, Huynh A, Morisset S, Sobh M, Raus N, Garban F et al (2009) Safety and efficacy of FLAMSA regimen followed by allogeneic hematopoietic stem cell transplantation from related and unrelated donors in high risk acute leukemia and MDS patients: a study from the Societe Française De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC) Registry. Blood (ASH Annual Meeting Abstracts) 114: abstract 4335
22.
Zurück zum Zitat Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED (1981) Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 304:1529–1533PubMedCrossRef Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED (1981) Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. N Engl J Med 304:1529–1533PubMedCrossRef
23.
Zurück zum Zitat Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L et al (1989) Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 73:1720–1728PubMed Sullivan KM, Weiden PL, Storb R, Witherspoon RP, Fefer A, Fisher L et al (1989) Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 73:1720–1728PubMed
24.
Zurück zum Zitat Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–562PubMed Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ et al (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–562PubMed
25.
Zurück zum Zitat Ringden O, Hermans J, Labopin M, Apperley J, Gorin NC, Gratwohl A (1996) The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Leuk Lymphoma 24:71–79PubMedCrossRef Ringden O, Hermans J, Labopin M, Apperley J, Gorin NC, Gratwohl A (1996) The highest leukaemia-free survival after allogeneic bone marrow transplantation is seen in patients with grade I acute graft-versus-host disease. Acute and Chronic Leukaemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Leuk Lymphoma 24:71–79PubMedCrossRef
26.
Zurück zum Zitat Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R et al (2012) Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood 119:1599–1606PubMedCrossRef Schmid C, Labopin M, Nagler A, Niederwieser D, Castagna L, Tabrizi R et al (2012) Treatment, risk factors, and outcome of adults with relapsed AML after reduced intensity conditioning for allogeneic stem cell transplantation. Blood 119:1599–1606PubMedCrossRef
27.
Zurück zum Zitat Craddock CF (2008) Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML. Bone Marrow Transplant 41:415–442PubMedCrossRef Craddock CF (2008) Full-intensity and reduced-intensity allogeneic stem cell transplantation in AML. Bone Marrow Transplant 41:415–442PubMedCrossRef
28.
Zurück zum Zitat Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F et al (2007) Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia. Blood 109:5063–5064PubMedCrossRef Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F et al (2007) Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia. Blood 109:5063–5064PubMedCrossRef
Metadaten
Titel
Allogeneic hematopoietic cell transplantation with reduced-intensity conditioning following FLAMSA for primary refractory or relapsed acute myeloid leukemia
verfasst von
Dominik Schneidawind
Birgit Federmann
Christoph Faul
Wichard Vogel
Lothar Kanz
Wolfgang Andreas Bethge
Publikationsdatum
01.10.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Annals of Hematology / Ausgabe 10/2013
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-013-1774-5

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