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Response to: Correspondence on "G-CSF as a suitable alternative to GM-CSF to boost dinutuximab-mediated neutrophil cytotoxicity in neuroblastoma treatment" by Mora et al
  1. Paula Martinez Sanz1,
  2. Dieke J van Rees1,
  3. Hanke L Matlung1,
  4. Godelieve A M Tytgat2 and
  5. Katka Franke1
  1. 1Department of Blood Cell Research, Sanquin Research, Amsterdam, The Netherlands
  2. 2Department of Pediatric Oncology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
  1. Correspondence to Paula Martinez Sanz; p.martinezsanz{at}

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Dear Editor,

We appreciate the interest of Dr Mora and Dr Chantada1 in our recently published work proposing granulocyte colony-stimulating factor (G-CSF) as a suitable alternative to improve antibody treatment of patients with high-risk neuroblastoma.2 The authors strongly advocate finding ways to increase accessibility of granulocyte-monocyte colony-stimulating factor (GM-CSF, sargramostim), used in combination with dinutuximab in North America, also in countries where this treatment is currently not available. We fully agree that all relevant stakeholders should participate in finding a permanent solution to prevent potentially suboptimal treatment of patients with high-risk neuroblastoma in the absence of sargramostim. Part of this solution might be identification of another suitable cytokine with potential to increase neutrophil-mediated killing of neuroblastoma cells as the inaccessibility of sargramostim may remain a problem in the future.

As neutrophils have been shown to be the main effector cells in the destruction of dinutuximab-opsonized GD2+ cells,3 the choice for a cytokine that increases production, release, and activation state of these immune cells is a highly reasonable one. Dr Mora and Dr Chantada urge for caution in using G-CSF as an alternative as this cytokine is not interchangeable with GM-CSF and may pose safety risks as previously suggested.4–6 We agree that G-CSF cannot fully recapitulate the biological properties of GM-CSF, but it is in our opinion the next closest alternative and deserves proper evaluation in follow-up clinical studies. Two of the studies reporting detrimental effects of G-CSF in patients with neuroblastoma were published by the same group5 6 and suggest caution in administering G-CSF during chemotherapy cycles. These findings triggered opposed responses in the clinical field.7 The main argument was that concentrations of G-CSF used in preclinical studies were much higher than equivalent dosages used in patients. Also, use of G-CSF to support intensive induction chemotherapy regimens had been shown to be safe and not affecting overall tumor response to therapy.7 We have shown in our study that long-term in vitro exposure to G-CSF in high concentrations does not alter the phenotype of neuroblastoma cell lines and primary cells, nor their sensitivity to dinutuximab-mediated killing, further suggesting safety of such a treatment for patients with neuroblastoma.

As proposed in our study, a thorough clinical evaluation of safety, clinical efficacy and effect on overall survival of G-CSF in combination with dinutuximab in patients with high-risk neuroblastoma should be performed, ideally in a randomized and multicenter clinical trial.


Paula Martinez Sanz, MSc

Dieke van Rees, MSc

Hanke L. Matlung, PhD

Godelieve A M. Tytgat, PhD

Katka Franke, PhD

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  • Contributors All authors reviewed, revised, and approved this response letter.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; internally peer reviewed.

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