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Effect of prophylactic or pre-emptive use of tyrosine kinase inhibitors post-Allo SCT in bcr-abl positive acute lymphoblastic leukemia: a subanalysis of GITMO ph-positive ALL study

Bone Marrow Transplantation volume 57, pages 834–836 (2022)Cite this article

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To the Editor,

We read the interesting study of the EBMT reporting the experience with tyrosine kinase inhibitors TKIs in Philadelphia-positive adult acute lymphoblastic leukemia (Ph-pos ALL) relapsing post allogeneic stem cell transplantation (post-Allo-SCT) [1]. In this study the majority of patients (111/140) received second and third generation TKIs for a hematologic relapse, with a five-year progression free survival of 23% [1]. Unfortunately, despite an EBMT position paper, published in 2016, the strategy of use of TKI post-Allo-SCT is still heterogeneous and their preventive effect, when employed before the occurrence of cytologic relapse, is not yet established [2,3,4,5,6,7]. Recently, in this context, we performed a sub-analysis of our previously published GITMO study (ClinicalTrials.gov NCT03821727) which included 441 adult patients with Ph-pos ALL, all treated in the induction phase with TKIs ± chemotherapy and undergoing Allo-SCT in Italy from 2005 to 2017 [8]. The aim of this sub-analysis was to evaluate the strategy of use of TKIs post-Allo-SCT (prophylactic or pre-emptive) in patients transplanted in the first cytologic complete remission (cCR) and to analyze the effect on disease free survival (DFS) post-Allo-SCT, according to TKIs preventive strategy adopted and to the Minimal Residual Disease (MRD) status pre-Allo-SCT. We included in this analysis only the Ph-pos ALL cases of the GITMO study in first cCR before Allo-SCT and receiving a TKI post-Allo-SCT, regardless of the pre-Allo-SCT MRD status (either positive or negative) [8]. Patients who started TKIs post-Allo-SCT to treat cytological relapse were excluded. TKIs were administered after Allo-SCT either prophylactically (starting with negative MRD post-Allo-SCT) or pre-emptively (starting at the first post-SCT MRD positivity). The decision on the TKI strategy after Allo-SCT was made according to the policy of each transplant center. The MRD (BCR-ABL), defined according to ELN criteria, was monitored monthly for the first 6-8 months post-Allo-SCT and then every 2 months thereafter.

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Fig. 1: Disease Free Survival in patients treated with post Allo-SCT TKIs.

References

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Acknowledgements

This analysis has been presented, as oral session at the European Hematology Association Congress 2021 (EHA 2021).

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Authors and Affiliations

  1. Hematology and SCT Unit, Università di Udine, Azienda Sanitaria-Universitaria Friuli Centrale, Udine, Italy

    Anna Candoni, Davide Lazzarotto, Maria Vittoria Dubbini & Renato Fanin

  2. Department of Oncology-Hematology, Universita’ degli Studi di Milano e Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy

    Alessandro Rambaldi

  3. Section of Hematology, University of Modena and Reggio Emilia, Modena, Italy

    Paola Bresciani

  4. Dipartimento di Oncologia, Presidio Molinette-AOU Città della Salute e della Scienza, Trapianto Allogenico di Cellule Staminali, Torino, Italy

    Alessandro Busca

  5. Rome Transplant Network, Università Tor Vergata, Roma, Italy

    William Arcese

  6. Hematology, Department of Translational and Precision Medicine, Sapienza University, Policlinico Umberto I, Roma, Italy

    Anna Paola Iori

  7. SC Ematologia, Azienda Ospedaliera S Croce e Carle, Cuneo, Italy

    Roberto Sorasio

  8. Centro Unico Regionale Trapianto Cellule Staminali e Terapie Cellulari A. Neri, Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy

    Giuseppe Irrera

  9. Hematology and BMT Unit, San Raffaele Scientific Institute, University Vita-Salute San Raffaele, Milano, Italy

    Fabio Ciceri

  10. Institute of Hematology L. and A. Seragnoli, University Hospital S. Orsola-Malpighi, Bologna, Italy

    Francesca Bonifazi

Authors
  1. Anna Candoni
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  2. Davide Lazzarotto
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  8. Anna Paola Iori
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  11. Renato Fanin
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  12. Fabio Ciceri
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on behalf of GITMO

Contributions

AC conceptualized the analysis and wrote the letter; AC and DL performed the analysis. FB and RF contributed to the revision of the letter. All authors collected the data and contributed to the final approval of the manuscript.

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Correspondence to Anna Candoni.

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Candoni, A., Lazzarotto, D., Rambaldi, A. et al. Effect of prophylactic or pre-emptive use of tyrosine kinase inhibitors post-Allo SCT in bcr-abl positive acute lymphoblastic leukemia: a subanalysis of GITMO ph-positive ALL study. Bone Marrow Transplant 57, 834–836 (2022). https://doi.org/10.1038/s41409-022-01618-5

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