Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis
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Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis. / Gagelmann, Nico; Hobbs, Gabriela S; Campodonico, Edoardo; Helbig, Grzegorz; Novak, Polona; Schroeder, Thomas; Schneider, Artur; Rautenberg, Christina; Reinhardt, Hans Christian; Bosques, Linette; Heuser, Michael; Panagiota, Victoria; Thol, Felicitas; Gurnari, Carmelo; Maciejewski, Jaroslaw P; Ciceri, Fabio; Rathje, Kristin; Robin, Marie; Pagliuca, Simona; Rubio, Marie-Thérèse; Rocha, Vanderson; Funke, Vaneuza; Hamerschlak, Nelson; Salit, Rachel; Scott, Bart L; Duarte, Fernando; Mitrus, Iwona; Czerw, Tomasz; Greco, Raffaella; Kröger, Nicolaus.
In: AM J HEMATOL, Vol. 99, No. 5, 05.2024, p. 844-853.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Splenic irradiation for myelofibrosis prior to hematopoietic cell transplantation: A global collaborative analysis
AU - Gagelmann, Nico
AU - Hobbs, Gabriela S
AU - Campodonico, Edoardo
AU - Helbig, Grzegorz
AU - Novak, Polona
AU - Schroeder, Thomas
AU - Schneider, Artur
AU - Rautenberg, Christina
AU - Reinhardt, Hans Christian
AU - Bosques, Linette
AU - Heuser, Michael
AU - Panagiota, Victoria
AU - Thol, Felicitas
AU - Gurnari, Carmelo
AU - Maciejewski, Jaroslaw P
AU - Ciceri, Fabio
AU - Rathje, Kristin
AU - Robin, Marie
AU - Pagliuca, Simona
AU - Rubio, Marie-Thérèse
AU - Rocha, Vanderson
AU - Funke, Vaneuza
AU - Hamerschlak, Nelson
AU - Salit, Rachel
AU - Scott, Bart L
AU - Duarte, Fernando
AU - Mitrus, Iwona
AU - Czerw, Tomasz
AU - Greco, Raffaella
AU - Kröger, Nicolaus
N1 - © 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.
PY - 2024/5
Y1 - 2024/5
N2 - Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse.
AB - Splenomegaly is the clinical hallmark of myelofibrosis. Splenomegaly at the time of allogeneic hematopoietic cell transplantation (HCT) is associated with graft failure and poor graft function. Strategies to reduce spleen size before HCT especially after failure to Janus kinase (JAK) inhibition represent unmet clinical needs in the field. Here, we leveraged a global collaboration to investigate the safety and efficacy of splenic irradiation as part of the HCT platform for patients with myelofibrosis. We included 59 patients, receiving irradiation within a median of 2 weeks (range, 0.9-12 weeks) before HCT. Overall, the median spleen size prior to irradiation was 23 cm (range, 14-35). Splenic irradiation resulted in a significant and rapid spleen size reduction in 97% of patients (57/59), with a median decrease of 5.0 cm (95% confidence interval, 4.1-6.3 cm). The most frequent adverse event was thrombocytopenia, with no correlation between irradiation dose and hematological toxicities. The 3-year overall survival was 62% (95% CI, 48%-76%) and 1-year non-relapse mortality was 26% (95% CI, 14%-38%). Independent predictors for survival were severe thrombocytopenia and anemia before irradiation, transplant-specific risk score, higher-intensity conditioning, and present portal vein thrombosis. When using a propensity score matching adjusted for common confounders, splenic irradiation was associated with significantly reduced relapse (p = .01), showing a 3-year incidence of 12% for splenic irradiation versus 29% for patients with immediate HCT and 38% for patients receiving splenectomy. In conclusion, splenic irradiation immediately before HCT is a reasonable approach in patients experiencing JAK inhibition failure and is associated with a low incidence of relapse.
KW - Humans
KW - Spleen
KW - Splenomegaly/etiology
KW - Primary Myelofibrosis/radiotherapy
KW - Hematopoietic Stem Cell Transplantation/methods
KW - Thrombocytopenia/complications
KW - Recurrence
KW - Transplantation Conditioning/methods
KW - Graft vs Host Disease/etiology
U2 - 10.1002/ajh.27252
DO - 10.1002/ajh.27252
M3 - SCORING: Journal article
C2 - 38357714
VL - 99
SP - 844
EP - 853
JO - AM J HEMATOL
JF - AM J HEMATOL
SN - 0361-8609
IS - 5
ER -
