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Haplo-identical allografting with post-transplant cyclophosphamide in high-risk patients

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Abstract

Haplo-identical transplants (Haplo-Tx) are an important alternative for patients with hematological malignancies who lack a HLA-identical donor. Seventy-one T-replete Haplo-Tx were performed in 70 high-risk patients at our center; 22/70 (31%) patients with refractory/relapsed leukemia received sequential salvage therapy (SeqTh) with high-dose chemotherapy followed by Haplo-Tx during the chemotherapy-induced neutropenia. Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (days + 3 and + 4) with tacrolimus and mycophenolic acid. After a median follow-up of 29.2 months, 3-year overall survival (OS) and event-free survival (EFS) were 43.8 and 40.2%, while 3-year cumulative incidences (CIs) of non-relapse mortality (NRM) and relapse (RI) were 27 and 33%. Day 100 and day 400 CI of grade III–IV acute and moderate-severe chronic GVHD were 11 and 15%. Three-year RI was significantly lower in patients in complete remission (CR) versus those not in CR at the time of transplant (21.5 vs. 48%, p = 0.009) and in patients who received PBSC as compared to BM (22 vs. 45%, p = 0.009). In patients treated with SeqTh, 3-year OS was 19%, while 3-year RI and NRM were 52 and 28% at a median follow-up of 50 months. Overall, Haplo-Tx was feasible in heavily pretreated high-risk patients without a suitable HLA-identical donor.

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Acknowledgments

This work was partly supported by Progetti di Ricerca Finalizzata 2008-2009, Fondi di Ricerca Locale, Università degli Studi di Torino, Torino, Italy; by Fondazione Neoplasie Sangue (FO.NE.SA) ONLUS, Torino, Italy; and by Fondazione Cariplo (Grant per la Ricerca Biomedica 2015/0603 to B.B.). The authors would like to thank Maria Josè Fornaro and Sara Manetta for excellent secretarial support.

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  1. Lucia Brunello and Roberto Passera contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, SSD Trapianto Allogenico, Presidio Molinette, AOU Città della Salute e della Scienza di Torino, Via Genova 3, 10126, Torino, Italy

    Lucia Brunello, Chiara Maria Dellacasa, Luisa Giaccone, Moreno Festuccia, Giuseppe Lia, Enrico Maffini, Sara Butera, Alessandro Busca & Benedetto Bruno

  2. Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy

    Lucia Brunello, Luisa Giaccone, Dario Ferrero, Moreno Festuccia, Giuseppe Lia, Elena Crisà, Enrico Maffini, Sara Butera & Benedetto Bruno

  3. Division of Nuclear Medicine, AOU Città della Salute e della Scienza di Torino, Torino, Italy

    Roberto Passera

  4. Department of Oncology, Division of Hematology, Presidio Molinette, AOU Città della Salute e della Scienza di Torino, Torino, Italy

    Ernesta Audisio, Stefano D’Ardia, Bernardino Allione & Semra Aydin

  5. Department of Oncology, Division of Hematology Univ., Presidio Molinette, AOU Città della Salute e della Scienza di Torino, Torino, Italy

    Dario Ferrero & Elena Crisà

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  3. Chiara Maria Dellacasa
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Contributions

B.B, A.B, and L.G designed the study. L.B., L.G., A.B., and B.B. wrote the report. L.G., A.B., and B.B. supervised the clinical conduction of the study and data analysis. B.B, A.B., C.D., and L.G. supervised data collection, analyzed data, and reviewed and assisted in writing the manuscript. A.B., B.B., C.D., S.A., B.A., L.G., and M.F. recruited the patients. R.P. did the statistical analysis.

Corresponding author

Correspondence to Benedetto Bruno.

Ethics declarations

The study was approved by the Center Ethical Committee and conducted according to the Declaration of Helsinki.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Brunello, L., Passera, R., Dellacasa, C.M. et al. Haplo-identical allografting with post-transplant cyclophosphamide in high-risk patients. Ann Hematol 97, 2205–2215 (2018). https://doi.org/10.1007/s00277-018-3433-3

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  • DOI: https://doi.org/10.1007/s00277-018-3433-3

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