Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation

Hernández‐Boluda, Juan Carlos; Pereira, Arturo; Kröger, Nicolaus; Beelen, Dietrich; Robin, Marie; Bornhäuser, Martin; Angelucci, Emanuele; Vı́tek, Antonı́n; Blau, Igor Wolfgang; Niittyvuopio, Riitta; Finke, Jürgen; Cornelissen, Jan J.; Passweg, Jakob; Dreger, Peter; Petersen, Eefke; Kanz, Lothar; Sanz, Jaime; Zuckerman, Tsila; Zinger, Nienke; Iacobelli, Simona; Hayden, Patrick; Czerw, Tomasz; McLornan, Donal; Yakoub‐Agha, Ibrahim

doi:10.1038/s41375-020-0815-z

Cited by 38 publications

(35 citation statements)

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“…Overall, 40% were alive at 5 years after transplantation, a lower figure than the 50% to 65% long-term survival reported in recent series of allo-HCT in all-age MF patients. 10,14,[21][22][23][24] Increased NRM (37% at 5 years), mostly attributed to GVHD, was the main cause of worse survival, as the relapse rate F I G U R E 3 Excess mortality associated with transplant as compared to conventional drug treatment in myelofibrosis patients aged 65 or older. Ratios higher than one imply greater mortality in the transplant group F I G U R E 4 Estimated survival according to sex in myelofibrosis patients aged 65 years or older managed with conventional drug treatment A, or allo-HCT B [Color figure can be viewed at wileyonlinelibrary.com] (25% at 5 years) was comparable to that reported in younger MF patients.…”

Section: Discussionmentioning

confidence: 99%

“…Ratios higher than one imply greater mortality in the transplant group F I G U R E 4 Estimated survival according to sex in myelofibrosis patients aged 65 years or older managed with conventional drug treatment A, or allo-HCT B [Color figure can be viewed at wileyonlinelibrary.com] (25% at 5 years) was comparable to that reported in younger MF patients. 10,14,[22][23][24][25][26] Busulfan-based conditioning was associated with lower NRM and improved survival, whereas harboring the JAK2 mutation and the CMV-negative donor to CMV-positive recipient combination implied higher NRM and shorter overall survival. None of these factors had any influence on relapse risk.…”

Section: Discussionmentioning

confidence: 99%

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Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry

et al. 2021

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“…Response to MF‐directed treatment was assessed by the local center; patients were defined as having progressive disease if they demonstrated increasing splenomegaly, worsening of constitutional symptoms or new onset cytopenias. Myeloablative conditioning was defined as busulfan dose >8 mg/kg, or melphalan >140 mg/m 2 ; 22 the definitions of engraftment, aGVHD and cGHVD were as previously reported 23 . No universal definition on relapse after transplant is still available for MF, all the patients recorded as relapsed in the Registry were taken into account for CIR analysis, as previously published 24 .…”

Section: Methodsmentioning

confidence: 99%

Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT)

Polverelli

Mauff²,

Kröger

et al. 2020

American J Hematol

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The role of spleen size and splenectomy for the prediction of post‐allogeneic hematopoietic stem cell transplant (allo‐HCT) outcome in myelofibrosis remains under debate. In EBMT registry, we identified a cohort of 1195 myelofibrosis patients transplanted between 2000‐2017 after either fludarabine‐busulfan or fludarabine‐melphalan regimens. Overall, splenectomy was performed in 202 (16.9%) patients and its use decreased over time (28.3% in 2000‐2009 vs 14.1% in 2010‐2017 period). By multivariate analysis, splenectomy was associated with less NRM (HR 0.64, 95% CI 0.44‐0.93, P = .018) but increased risk of relapse (HR 1.43, 95% CI 1.01‐2.02, P = .042), with no significant impact on OS (HR 0.86, 95% CI 0.67‐1.12, P = .274). However, in subset analysis comparing the impact of splenectomy vs specific spleen sizes, for patients with progressive disease, an improved survival was seen in splenectomised subjects compared to those patients with a palpable spleen length ≥ 15 cm (HR 0.44, 95% CI 0.28‐0.69, P < .001), caused by a significant reduction in NRM (HR 0.26, 95% CI 0.14‐0.49, P < .001), without significantly increased relapse risk (HR 1.47, 95% CI 0.87‐2.49, P = .147). Overall, despite the possible biases typical of retrospective cohorts, this study highlights the potential detrimental effect of massive splenomegaly in transplant outcome and supports the role of splenectomy for myelofibrosis patients with progressive disease and large splenomegaly.

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“…Still, there was no difference in the cumulative incidence of neutrophil and platelet engraftment achieved at day + 30 between the two groups. This observation might be related to the MAC regimens and ATG because some studies reported that MAC regimens or receiving ATG along with a conditioning regimen were protective against graft failure [ 40 , 41 ]. Moreover, the addition of bone marrow stem cells and the relatively large number of transfused cells might also partially explain the high engraftment rate in this study.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic stem cell transplantation may overcome the adverse impact of myelofibrosis on the prognosis of myelodysplastic syndrome

Xuan

Zhang

et al. 2021

Exp Hematol Oncol

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Purpose Myelofibrosis (MF) may serve as a poor prognostic factor in myelodysplastic syndromes (MDS). This study explored the impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the outcome of MDS patients with MF. Patients and Methods Three hundred and sixteen MDS patients were enrolled in this retrospective study. Based on the degree of MF, we divided the patients into 2 groups: grade 0–1 (MF-0/1) and grade 2–3 (MF-2/3) groups. The clinical features, treatments, and prognosis in MDS patients with MF were analyzed. Results Forty-three (13.6%) patients were diagnosed as MF-2/3. Complex karyotypes were more common in the MF-2/3 compared to MF-0/1 groups (P = 0.002). The overall response rate (ORR) of cytoreduction was 49.0%, along with 53.3% in the MF-0/1 and 16.7% in MF-2/3 groups (P = 0.017). In total, 141 patients underwent allo-HSCT, including 121 in the MF-0/1 and 20 in MF-2/3 groups. The median time to neutrophil reconstruction was 12 (range: 7–34) and 14 (range: 10–45) days (P = 0.005), and platelet reconstruction was 14 (range: 8–68) and 18 (range: 8–65) days (P = 0.045) in the MF-0/1 and MF-2/3 groups, respectively. However, the cumulative incidence of neutrophil and platelet engraftment achieved at day + 30 was not different between the two groups (P = 0.107, P = 0.303, respectively). Non-relapse mortality, relapse, and acute and chronic graft-versus-host disease were similar between the two groups (all P > 0.05). Among patients with allo-HSCT, the 2-year overall survival (OS) was 68.5% (95% CI: 60.1–76.9%) and 68.4% (95% CI: 47.4–89.4%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.636). Among patients without allo-HSCT, the 2-year OS was 49.9% (95% CI: 40.7–59.1%) and 19.2% (95% CI: 0–39.6%) in the MF-0/1 and MF-2/3 groups, respectively, (P = 0.002). In multivariate cox analysis, complex karyotype was an unfavorable factor for relapse (HR, 4.16; P = 0.006), disease-free survival (DFS) (HR, 2.16; P = 0.020), and OS (HR, 2.47; P = 0.009) post-transplantation. Conclusion Patients with MF-2/3 have more complex karyotypes and lower ORR of cytoreduction in MDS. Among patients without allo-HSCT, patients with MF-2/3 have a worse prognosis than those with MF-0/1. However, the adverse impact of MF on prognosis may be overcome by allo-HSCT.

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Determinants of survival in myelofibrosis patients undergoing allogeneic hematopoietic cell transplantation

Cited by 38 publications

References 44 publications

Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry

Allogeneic hematopoietic cell transplantation in older myelofibrosis patients: A study of the chronic malignancies working party of EBMT and the Spanish Myelofibrosis Registry

Impact of spleen size and splenectomy on outcomes of allogeneic hematopoietic cell transplantation for myelofibrosis: A retrospective analysis by the chronic malignancies working party on behalf of European society for blood and marrow transplantation (EBMT)

Allogeneic stem cell transplantation may overcome the adverse impact of myelofibrosis on the prognosis of myelodysplastic syndrome

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