The effect of prior exposure to imatinib on transplant-related mortality

Michael Deininger, Michael Schleuning, Hilde Greinix, Herbert Gottfried Sayer, Thomas Fischer, Jesus Martinez, Richard Maziarz, Eduardo Olavarria, Leo Verdonck, Kerstin Schaefer, Conxa Boqué, Edgar Faber, Arnon Nagler, Enrico Pogliani, Nigel Russell, Liisa Volin, Urs Schanz, Gottfried Doelken, Michael Kiehl, Axel FauserBrian Druker, Anna Sureda, Simona Iacobelli, Ronald Brand, Rainer Krahl, Thoralf Lange, Andreas Hochhaus, Alois Gratwohl, Hans Kolb, Dietger Niederwieser

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Abstract

Background and Objectives. Imatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, relapse is common in patients with advanced or high risk disease. Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT. Design and Methods. We retrospectively analyzed 70 patients with CML and 21 with Ph+ ALL who had received imatinib prior to SCT. Data were retrieved by directly contacting centers. Multivariate analysis was used to define factors associated with major outcomes (engraftment, graft-versus-host disease, relapse, non-relapse mortality) in addition to descriptive statistics. For the CML patients major outcomes were compared with those of historical controls drawn from the EBMT registry. Results. At SCT, 44% of CML patients were in accelerated phase or blast crisis and 40% of ALL patients had active disease compared to 84% and 95% prior to imatinib. At 24 months, estimated transplant-related mortality was 44% and estimated relapse mortality 24%. Factors associated with shorter overall and progression-free survival were advanced disease at SCT and a female donor/male recipient pairing. No unusual organ toxicities were observed. Compared to historical controls, prior imatinib treatment did not influence overall survival, progression-free survival or non-relapse mortality, while there was a trend towards higher relapse mortality and significantly less chronic graft-versus-host disease. Interpretations and Conclusions. Within the limits of a heterogeneous and relatively small cohort of patients, we found no evidence that imatinib negatively affects major outcomes after SCT, suggesting that imatinib prior to SCT is safe.

Original languageEnglish (US)
Pages (from-to)452-459
Number of pages8
JournalHaematologica
Volume91
Issue number4
StatePublished - Apr 2006

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Stem Cell Transplantation
Transplants
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Recurrence
Graft vs Host Disease
Disease-Free Survival
Blast Crisis
Philadelphia Chromosome
Imatinib Mesylate
Registries
Therapeutics
Multivariate Analysis
Tissue Donors
Survival

Keywords

  • B-cell chronic lymphoproliferative disorders
  • Biclonality
  • FISH
  • Immunophenotype
  • Intraclonal evolution

ASJC Scopus subject areas

  • Hematology

Cite this

Deininger, M., Schleuning, M., Greinix, H., Sayer, H. G., Fischer, T., Martinez, J., ... Niederwieser, D. (2006). The effect of prior exposure to imatinib on transplant-related mortality. Haematologica, 91(4), 452-459.

The effect of prior exposure to imatinib on transplant-related mortality. / Deininger, Michael; Schleuning, Michael; Greinix, Hilde; Sayer, Herbert Gottfried; Fischer, Thomas; Martinez, Jesus; Maziarz, Richard; Olavarria, Eduardo; Verdonck, Leo; Schaefer, Kerstin; Boqué, Conxa; Faber, Edgar; Nagler, Arnon; Pogliani, Enrico; Russell, Nigel; Volin, Liisa; Schanz, Urs; Doelken, Gottfried; Kiehl, Michael; Fauser, Axel; Druker, Brian; Sureda, Anna; Iacobelli, Simona; Brand, Ronald; Krahl, Rainer; Lange, Thoralf; Hochhaus, Andreas; Gratwohl, Alois; Kolb, Hans; Niederwieser, Dietger.

In: Haematologica, Vol. 91, No. 4, 04.2006, p. 452-459.

Research output: Contribution to journalArticle

Deininger, M, Schleuning, M, Greinix, H, Sayer, HG, Fischer, T, Martinez, J, Maziarz, R, Olavarria, E, Verdonck, L, Schaefer, K, Boqué, C, Faber, E, Nagler, A, Pogliani, E, Russell, N, Volin, L, Schanz, U, Doelken, G, Kiehl, M, Fauser, A, Druker, B, Sureda, A, Iacobelli, S, Brand, R, Krahl, R, Lange, T, Hochhaus, A, Gratwohl, A, Kolb, H & Niederwieser, D 2006, 'The effect of prior exposure to imatinib on transplant-related mortality', Haematologica, vol. 91, no. 4, pp. 452-459.
Deininger M, Schleuning M, Greinix H, Sayer HG, Fischer T, Martinez J et al. The effect of prior exposure to imatinib on transplant-related mortality. Haematologica. 2006 Apr;91(4):452-459.
Deininger, Michael ; Schleuning, Michael ; Greinix, Hilde ; Sayer, Herbert Gottfried ; Fischer, Thomas ; Martinez, Jesus ; Maziarz, Richard ; Olavarria, Eduardo ; Verdonck, Leo ; Schaefer, Kerstin ; Boqué, Conxa ; Faber, Edgar ; Nagler, Arnon ; Pogliani, Enrico ; Russell, Nigel ; Volin, Liisa ; Schanz, Urs ; Doelken, Gottfried ; Kiehl, Michael ; Fauser, Axel ; Druker, Brian ; Sureda, Anna ; Iacobelli, Simona ; Brand, Ronald ; Krahl, Rainer ; Lange, Thoralf ; Hochhaus, Andreas ; Gratwohl, Alois ; Kolb, Hans ; Niederwieser, Dietger. / The effect of prior exposure to imatinib on transplant-related mortality. In: Haematologica. 2006 ; Vol. 91, No. 4. pp. 452-459.
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AU - Fischer, Thomas

AU - Martinez, Jesus

AU - Maziarz, Richard

AU - Olavarria, Eduardo

AU - Verdonck, Leo

AU - Schaefer, Kerstin

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AU - Iacobelli, Simona

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N2 - Background and Objectives. Imatinib is an effective treatment for chronic myeloid leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, relapse is common in patients with advanced or high risk disease. Such patients may be eligible for allogeneic stem cell transplantation (SCT), raising the question whether imatinib therapy may compromise the outcome of subsequent SCT. Design and Methods. We retrospectively analyzed 70 patients with CML and 21 with Ph+ ALL who had received imatinib prior to SCT. Data were retrieved by directly contacting centers. Multivariate analysis was used to define factors associated with major outcomes (engraftment, graft-versus-host disease, relapse, non-relapse mortality) in addition to descriptive statistics. For the CML patients major outcomes were compared with those of historical controls drawn from the EBMT registry. Results. At SCT, 44% of CML patients were in accelerated phase or blast crisis and 40% of ALL patients had active disease compared to 84% and 95% prior to imatinib. At 24 months, estimated transplant-related mortality was 44% and estimated relapse mortality 24%. Factors associated with shorter overall and progression-free survival were advanced disease at SCT and a female donor/male recipient pairing. No unusual organ toxicities were observed. Compared to historical controls, prior imatinib treatment did not influence overall survival, progression-free survival or non-relapse mortality, while there was a trend towards higher relapse mortality and significantly less chronic graft-versus-host disease. Interpretations and Conclusions. Within the limits of a heterogeneous and relatively small cohort of patients, we found no evidence that imatinib negatively affects major outcomes after SCT, suggesting that imatinib prior to SCT is safe.

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