Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

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Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. / Mollgard, Lars; Saft, Leonie; Treppendahl, Marianne Bach; Dybedal, Ingunn; Norgaard, Jan Maxwell; Astermark, Jan; Ejerblad, Elisabeth; Garelius, Hege; Dufva, Inge Hogh; Jansson, Monika; Jadersten, Martin; Kjeldsen, Lars; Linder, Olle; Nilsson, Lars; Vestergaard, Hanne; Porwit, Anna; Gronbaek, Kirsten; Lindberg, Eva Hellstrom.

In: Haematologica, Vol. 96, No. 7, 2011, p. 963-971.

Research output: Contribution to journalArticle

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Mollgard, L, Saft, L, Treppendahl, MB, Dybedal, I, Norgaard, JM, Astermark, J, Ejerblad, E, Garelius, H, Dufva, IH, Jansson, M, Jadersten, M, Kjeldsen, L, Linder, O, Nilsson, L, Vestergaard, H, Porwit, A, Gronbaek, K & Lindberg, EH 2011, 'Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities', Haematologica, vol. 96, no. 7, pp. 963-971. https://doi.org/10.3324/haematol.2010.039669

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Mollgard L, Saft L, Treppendahl MB, Dybedal I, Norgaard JM, Astermark J, Ejerblad E, Garelius H, Dufva IH, Jansson M, Jadersten M, Kjeldsen L, Linder O, Nilsson L, Vestergaard H, Porwit A, Gronbaek K, Lindberg EH. 2011. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. Haematologica. 96(7):963-971. https://doi.org/10.3324/haematol.2010.039669

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Mollgard, Lars ; Saft, Leonie ; Treppendahl, Marianne Bach ; Dybedal, Ingunn ; Norgaard, Jan Maxwell ; Astermark, Jan ; Ejerblad, Elisabeth ; Garelius, Hege ; Dufva, Inge Hogh ; Jansson, Monika ; Jadersten, Martin ; Kjeldsen, Lars ; Linder, Olle ; Nilsson, Lars ; Vestergaard, Hanne ; Porwit, Anna ; Gronbaek, Kirsten ; Lindberg, Eva Hellstrom. / Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. In: Haematologica. 2011 ; Vol. 96, No. 7. pp. 963-971.

RIS

TY - JOUR

T1 - Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

AU - Mollgard, Lars

AU - Saft, Leonie

AU - Treppendahl, Marianne Bach

AU - Dybedal, Ingunn

AU - Norgaard, Jan Maxwell

AU - Astermark, Jan

AU - Ejerblad, Elisabeth

AU - Garelius, Hege

AU - Dufva, Inge Hogh

AU - Jansson, Monika

AU - Jadersten, Martin

AU - Kjeldsen, Lars

AU - Linder, Olle

AU - Nilsson, Lars

AU - Vestergaard, Hanne

AU - Porwit, Anna

AU - Gronbaek, Kirsten

AU - Lindberg, Eva Hellstrom

PY - 2011

Y1 - 2011

N2 - Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization for del(5q31). Design and Methods Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial and treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q) and a complex karyotype, four had monosomy 5, and one had del(5q) identified by fluorescence in situ hybridization only. Results Major and minor cytogenetic responses, assessed by fluorescence in situ hybridization, were achieved in 5/26 (19%) and 2/26 (8%) patients, respectively, who received one or more dose of lenalidomide, while two patients achieved only a bone marrow response. Nine of all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped therapy due to progressive disease and nine because of complications, most of which were disease-related. Response rates were similar in patients with isolated del(5q) and in those with additional aberrations. Interestingly, patients with TP53 mutations responded less well than those without mutations (2/13 versus 5/9, respectively; P = 0.047). No responses were observed among 11 cases with deleterious TP53 mutations. Conclusions Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449).

AB - Background Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization for del(5q31). Design and Methods Twenty-eight patients at diagnosis or with relapsed disease and not eligible for standard therapy (16 with acute myeloid leukemia, 12 with intermediate-risk 2 or high-risk myelodysplastic syndrome) were enrolled in this prospective phase II multicenter trial and treated with lenalidomide up to 30 mg daily for 16 weeks. Three patients had isolated del(5q), six had del(5q) plus one additional aberration, 14 had del(5q) and a complex karyotype, four had monosomy 5, and one had del(5q) identified by fluorescence in situ hybridization only. Results Major and minor cytogenetic responses, assessed by fluorescence in situ hybridization, were achieved in 5/26 (19%) and 2/26 (8%) patients, respectively, who received one or more dose of lenalidomide, while two patients achieved only a bone marrow response. Nine of all 26 patients (35%) and nine of the ten who completed the 16 weeks of trial responded to treatment. Using the International Working Group criteria for acute myeloid leukemia and myelodysplastic syndrome the overall response rate in treated patients with acute myeloid leukemia was 20% (3/15), while that for patients with myelodysplastic syndrome was 36% (4/11). Seven patients stopped therapy due to progressive disease and nine because of complications, most of which were disease-related. Response rates were similar in patients with isolated del(5q) and in those with additional aberrations. Interestingly, patients with TP53 mutations responded less well than those without mutations (2/13 versus 5/9, respectively; P = 0.047). No responses were observed among 11 cases with deleterious TP53 mutations. Conclusions Our data support a role for higher doses of lenalidomide in poor prognosis patients with myelodysplastic syndrome and acute myeloid leukemia with deletion 5q. (Clinicaltrials.gov identifier NCT00761449).

KW - lenalidomide

KW - myelodysplastic syndrome

KW - acute myeloid leukemia

KW - P53

KW - mutation

U2 - 10.3324/haematol.2010.039669

DO - 10.3324/haematol.2010.039669

M3 - Article

VL - 96

SP - 963

EP - 971

JO - Haematologica-The Hematology Journal

T2 - Haematologica-The Hematology Journal

JF - Haematologica-The Hematology Journal

SN - 1592-8721

IS - 7

ER -