Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis
Abstract Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, splenomegaly, constitutional symptoms and cytopenia with a proinflammatory and profibrotic cytokine phenotype involving the JAK-STAT pathway. Ruxolitinib is a JAK 1/2 inhibitor with proven efficacy on sple...
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| Language: | English |
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Springer
2025-04-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04046-8 |
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| author | Sara Villar Emmanuel Curis Marie-Hélène Schlageter Nelly Bosselut Amandine Charbonnier Marie-Thérèse Rubio Pascal Turlure Hélène Labussière Jacques-Olivier Bay Jérome Cornillon Laure Vincent Corentin Orvain Jean-Jacques Kiladjian David Michonneau Gérard Socié Marie Robin |
| author_facet | Sara Villar Emmanuel Curis Marie-Hélène Schlageter Nelly Bosselut Amandine Charbonnier Marie-Thérèse Rubio Pascal Turlure Hélène Labussière Jacques-Olivier Bay Jérome Cornillon Laure Vincent Corentin Orvain Jean-Jacques Kiladjian David Michonneau Gérard Socié Marie Robin |
| author_sort | Sara Villar |
| collection | DOAJ |
| description | Abstract Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, splenomegaly, constitutional symptoms and cytopenia with a proinflammatory and profibrotic cytokine phenotype involving the JAK-STAT pathway. Ruxolitinib is a JAK 1/2 inhibitor with proven efficacy on splenomegaly and constitutional symptoms, but it does not reverse fibrosis or the risk of leukemic transformation. While hematopoietic stem cell transplantation remains the only curative approach, it is still associated with a relatively high non-relapse mortality (NRM) rate, partly due to GVHD. The potential role of ruxolitinib or its withdrawal on NRM remains to be elucidated, and inflammatory cytokines might be implicated. In this report, we compared cytokine profiles in patients with myelofibrosis not treated with ruxolitinib (n = 18) or who received ruxolitinib and stopped it at conditioning regimen initiation (n = 53), at three different time points. At baseline, MF patients without ruxolitinib had increased inflammatory cytokine levels (CD25, REG3A, IL18 and ST2) as compared to MF patients on ruxolitinib. On day 0 and week 1 post-transplantation, levels of these cytokines were similar with and without ruxolitinib. On the other hand, cytokine levels at baseline did not predict grades 2–4 acute GVHD or hyperacute GVHD. These findings suggest that baseline cytokine profile in MF patients does not impact the risk of GVHD. Stopping ruxolitinib just before conditioning regimen may not influence GVHD risk more than in MF patients who have not received ruxolitinib. The potential benefit of a later ruxolitinib discontinuation on D0 or after transplantation ruxolitinib requires further investigation. |
| format | Article |
| id | doaj-art-b66489976e6248bab4e66b12ee229f1b |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-b66489976e6248bab4e66b12ee229f1b2025-08-20T03:08:25ZengSpringerCancer Immunology, Immunotherapy1432-08512025-04-0174611110.1007/s00262-025-04046-8Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosisSara Villar0Emmanuel Curis1Marie-Hélène Schlageter2Nelly Bosselut3Amandine Charbonnier4Marie-Thérèse Rubio5Pascal Turlure6Hélène Labussière7Jacques-Olivier Bay8Jérome Cornillon9Laure Vincent10Corentin Orvain11Jean-Jacques Kiladjian12David Michonneau13Gérard Socié14Marie Robin15Clínica Universidad de NavarraUR 7537 BioSTM (Biostatistics), Faculté de Pharmacie de Paris, Université Paris CitéBiologie Cellulaire, Hôpital Saint-Louis, U1131 INSERM, IRS, Université de Paris-CitéBiologie Cellulaire, Hôpital Saint-Louis, U1131 INSERM, IRS, Université de Paris-CitéService d’Hématologie, CHU AmiensService d’Hématologie, CHRU BraboisService d’Hématologie, CHU Dupuytren LimogesHôpital Lyon Sud, Hospices Civils de LyonService de Thérapie Cellulaire et d’hématologie Clinique Adulte, CHU de Clermont-Ferrand, Site EstaingCHU Saint EtienneService d’Hématologie Clinique, CHU MontpellierService d’Hématologie, Hôpital d’Angers, INSERM, CRCINA, Université d’AngersAP-HP, Hôpital Saint-Louis, Centre d’Investigations Cliniques, INSERM, CIC1427, Université Paris CitéService d’Hématologie-Greffe, Hôpital Saint-Louis, APHP, Université de Paris-CitéService d’Hématologie-Greffe, Hôpital Saint-Louis, APHP, Université de Paris-CitéService d’Hématologie-Greffe, Hôpital Saint-Louis, APHP, Université de Paris-CitéAbstract Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by marrow fibrosis, splenomegaly, constitutional symptoms and cytopenia with a proinflammatory and profibrotic cytokine phenotype involving the JAK-STAT pathway. Ruxolitinib is a JAK 1/2 inhibitor with proven efficacy on splenomegaly and constitutional symptoms, but it does not reverse fibrosis or the risk of leukemic transformation. While hematopoietic stem cell transplantation remains the only curative approach, it is still associated with a relatively high non-relapse mortality (NRM) rate, partly due to GVHD. The potential role of ruxolitinib or its withdrawal on NRM remains to be elucidated, and inflammatory cytokines might be implicated. In this report, we compared cytokine profiles in patients with myelofibrosis not treated with ruxolitinib (n = 18) or who received ruxolitinib and stopped it at conditioning regimen initiation (n = 53), at three different time points. At baseline, MF patients without ruxolitinib had increased inflammatory cytokine levels (CD25, REG3A, IL18 and ST2) as compared to MF patients on ruxolitinib. On day 0 and week 1 post-transplantation, levels of these cytokines were similar with and without ruxolitinib. On the other hand, cytokine levels at baseline did not predict grades 2–4 acute GVHD or hyperacute GVHD. These findings suggest that baseline cytokine profile in MF patients does not impact the risk of GVHD. Stopping ruxolitinib just before conditioning regimen may not influence GVHD risk more than in MF patients who have not received ruxolitinib. The potential benefit of a later ruxolitinib discontinuation on D0 or after transplantation ruxolitinib requires further investigation.https://doi.org/10.1007/s00262-025-04046-8MyelofibrosisCytokinesRuxolitinibGraft-versus-host disease |
| spellingShingle | Sara Villar Emmanuel Curis Marie-Hélène Schlageter Nelly Bosselut Amandine Charbonnier Marie-Thérèse Rubio Pascal Turlure Hélène Labussière Jacques-Olivier Bay Jérome Cornillon Laure Vincent Corentin Orvain Jean-Jacques Kiladjian David Michonneau Gérard Socié Marie Robin Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis Cancer Immunology, Immunotherapy Myelofibrosis Cytokines Ruxolitinib Graft-versus-host disease |
| title | Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis |
| title_full | Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis |
| title_fullStr | Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis |
| title_full_unstemmed | Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis |
| title_short | Ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis |
| title_sort | ruxolitinib stopped before transplantation does not induce cytokine release in myelofibrosis |
| topic | Myelofibrosis Cytokines Ruxolitinib Graft-versus-host disease |
| url | https://doi.org/10.1007/s00262-025-04046-8 |
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