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Safety and efficacy of G-CSF after allogeneic hematopoietic cell transplantation using post-transplant cyclophosphamide: clinical and in vitro examination of endothelial activation

Bone Marrow Transplantation volume 59, pages 1466–1476 (2024)Cite this article

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Abstract

Since 2021 the use of G-CSF was implemented in allo-HCT with PTCY-based prophylaxis with the aim of shortening the aplastic phase and reducing infectious complications. This study investigates the effectiveness of this change in protocol performed at our institution. One-hundred forty-six adults undergoing allo-HCT with PTCY-based prophylaxis were included, and among them, 58 (40%) received G-CSF. The median of days to neutrophil engraftment was shorter in the G-CSF group (15 vs. 20 days, p < 0.001). Patients receiving G-CSF had a lower incidence of day +30 bacterial bloodstream infections (BSI) than the rest (20.7% vs. 47.7%, p < 0.001). GVHD, SOS, and TA-TMA incidences were comparable between groups, and using G-CSF did not impact on survival. Endothelial activation was investigated using EASIX and by the measurement of soluble biomarkers in cryopreserved plasma samples obtained on days 0, +7, +14 and +21 of 39 consecutive patients (10 received G-CSF) included in the study. EASIX, VWF:Ag, sVCAM-1, sTNFRI, ST2, REG3α, TM and NETs medians values were comparable in patients receiving G-CSF and those who did not. Compared with allo-HCT performed without G-CSF, the addition of G-CSF to PTCY-based allo-HCT accelerated neutrophil engraftment contributing on decreasing BSI incidence, and without inducing additional endothelial activation.

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Fig. 1: Engraftment information and main early transplant complications.
Fig. 2: Main post-transplant outcomes.
Fig. 3: EASIX and soluble biomarkers dynamics.
Fig. 4: Bacterial bloodstream infection cumulative incidence according to donor type.

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Acknowledgements

We thank our patients and the nursing and support staff in the Hematopoietic Cell Transplant Program and Laboratory of Hemostasis at Hospital Clinic de Barcelona.

Funding

This study was supported by Instituto de Salud Carlos III (projects: PI19/00888 and FIS PI22/00367; co-funded by the Euopean Union), Agencia de Gestión de Ayudas Universitarias y de Investigación (AGAUR 2021-SGR-01118), Deutsche José Carreras Leukämie-Stiftung (23 R/2021), and Fundació Marató de TV3 (202026-10).

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Author notes

  1. These authors contributed equally: María Queralt Salas, Maribel Díaz-Ricart.

Authors and Affiliations

  1. Hemostasis and Erythropathology Laboratory, Hematopathology, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Barcelona, Spain

    Silvia Escribano-Serrat, Blanca De Moner, Julia Martinez-Sanchez, Alex Ramos, Pilar Gómez, Estefanía García, Lidia Martín & Maribel Díaz-Ricart

  2. Research Biomedical Institute August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Silvia Escribano-Serrat, María Suárez-Lledó, Joan Cid, Miquel Lozano, Francesc Fernández-Avilés, Carmen Martínez, Montserrat Rovira, María Queralt Salas & Maribel Díaz-Ricart

  3. Blood Bank Department, Biomedical Diagnostic Center, Banc de Sang i Teixits, Hospital Clínic de Barcelona, Barcelona, Spain

    Alexandra Pedraza

  4. Hematopoietic Transplantation Unit, Hematology Department, (ICAMS), Hospital Clínic de Barcelona, Barcelona, Spain

    María Suárez-Lledó, Cristina Moreno, Laia Guardia, Francesc Fernández-Avilés, Carmen Martínez, Montserrat Rovira & María Queralt Salas

  5. Apheresis and Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, (ICAMS), Hospital Clínic Barcelona, Barcelona, Spain

    Paola Charry, Joan Cid & Miquel Lozano

  6. Fundacio i Institut de Recerca Josep Carreras Contra la Leucemia (Campus Clínic), Barcelona, Spain

    Blanca De Moner & Enric Carreras

  7. Medical Intensive Care Unit, Hospital Clínic de Barcelona, Barcelona, Spain

    Helena Ventosa-Capell

  8. Pharmacy Clinic Department, Hospital Clínic de Barcelona, Barcelona, Spain

    Inés Monge-Escartín, Gisela Riu & Esther Carcelero

Authors
  1. Silvia Escribano-Serrat
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Contributions

MQS, MDR and SES designed the study, analyzed, interpreted the results and wrote the paper. SES updated the data base. BDM, JMS, AR, HVC, PG, EG and LM conducted the experimental analysis. AP, MSL, PC, BDM, JMS, AR, HVC, CM, LG, IM, GR, EC, JC, ML, EC, FFA, CM, and MR provided valuable input into the study, interpretation of the results, and statement of the conclusions. All authors reviewed and approved the manuscript.

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Correspondence to María Queralt Salas.

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Escribano-Serrat, S., Pedraza, A., Suárez-Lledó, M. et al. Safety and efficacy of G-CSF after allogeneic hematopoietic cell transplantation using post-transplant cyclophosphamide: clinical and in vitro examination of endothelial activation. Bone Marrow Transplant 59, 1466–1476 (2024). https://doi.org/10.1038/s41409-024-02388-y

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