Post-transplant ferritin level predicts outcomes after allogeneic hematopoietic stem cell transplant, independent from pre-transplant ferritin level

Fingrut, Warren; Law, Arjun; Lam, Wilson; Michelis, Fotios V.; Viswabandya, Auro; Lipton, Jeffrey H.; Kumar, Rajat; Mattsson, Jonas; Kim, Dennis Dong Hwan

doi:10.1007/s00277-020-04363-1

Cited by 6 publications

(4 citation statements)

References 36 publications

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“…We also observed a strong surge of ferritin values culminating on day 42 in the control arm and day 28 in the EPO arm. This ferritin peak has been observed previously 61 , 62 and may be explained in part by inactive erythropoiesis resulting in decreased marrow demand for iron, Tsat elevation by non‐utilization of serum iron, and further iron deposition in tissues. However, the ferritin peak was delayed relative to engraftment.…”

Section: Discussionsupporting

confidence: 66%

Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant

et al. 2021

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Hematopoietic cell transplantation (HCT) brings important alterations in erythropoiesis and iron metabolism. Hepcidin, which regulates iron metabolism, increases in iron overload or inflammation and decreases with iron deficiency or activated erythropoiesis. Erythroferrone (ERFE) is the erythroid regulator of hepcidin. We investigated erythropoiesis and iron metabolism after allogeneic HCT in 70 patients randomized between erythropoietin (EPO) treatment or no EPO, by serially measuring hepcidin, ERFE, CRP (inflammation), soluble transferrin receptor (sTfR, erythropoiesis), serum iron and transferrin saturation (Tsat; iron for erythropoiesis) and ferritin (iron stores).We identified biological and clinical factors associated with serum hepcidin and ERFE levels. Serum ERFE correlated overall with sTfR and reticulocytes and inversely with hepcidin. Erythroferrone paralleled sTfR levels, dropping during conditioning and recovering with engraftment. Inversely, hepcidin peaked after conditioning and decreased during engraftment. Erythroferrone and hepcidin were not significantly different with or without EPO. Multivariate analyses showed that the major determinant of ERFE was erythropoiesis (sTfR, reticulocytes or serum Epo). Pretransplant hepcidin was associated with previous RBC transfusions and ferritin. After transplantation, the major determinants of hepcidin were iron status (ferritin at all time points and Tsat at day 56) and erythropoiesis (sTfR or reticulocytes or ERFE), while the impact of inflammation was less clear and clinical parameters had no detectable influence. Hepcidin remained significantly higher in patients with high compared to low pretransplant ferritin. After allogeneic HCT with or without EPO therapy, significant alterations of hepcidin occur between pretransplant and day 180, in correlation with iron status and inversely with erythroid ERFE. | INTRODUCTIONErythropoiesis and iron metabolism are closely related, as iron is critical for the production of red blood cells, and erythropoiesis is an essential actor in the regulation of hepcidin, the regulator of iron metabolism. 1 Hepcidin limits iron absorption by the gut and iron release by macrophages and hepatocytes through binding to and degradation of

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Section: Discussionsupporting

confidence: 66%

Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant

et al. 2021

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“…39 Of note, also posttransplant ferritin levels have emerged as predictors of decreased OS and increased NRM, independently of pre-HSCT values. 40,41 Our study also exhibits some limitations. First, the retrospective design does not allow to reach definite conclusions.…”

Section: Discussionmentioning

confidence: 84%

“… 39 Of note, also posttransplant ferritin levels have emerged as predictors of decreased OS and increased NRM, independently of pre-HSCT values. 40 , 41 …”

Section: Discussionmentioning

confidence: 99%

ABO Mismatch in Allogeneic Hematopoietic Stem Cell Transplant: Effect on Short- and Long-term Outcomes

Valentini

Metafuni

Gallo

et al. 2021

Transplantation Direct

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“…[24][25][26][27][28] The immunomodulatory effects of transfusions have often been cited as the underlying mechanism. 29,30 Several studies have correlated high pre-and post-HSCT ferritin levels with poorer long-term transplant outcomes, [31][32][33] which may in part explain the association between prolonged RBC transfusion dependence and the inferior non-relapse outcomes seen in our study. However, although transfused blood products could exert deleterious effects through mechanisms discussed above, it is more likely that higher transfusion requirements, rather than the direct cause of inferior long-term posttransplant outcomes, are the consequences of the preexisting conditions that can also cause these inferior outcomes.…”

Section: Discussionmentioning

confidence: 67%

Lack of RBC transfusion independence by Day 30 following allogeneic hematopoietic stem cell transplant strongly predicts inferior survival and high non‐relapse mortality in acute myeloid leukemia patients

Yuan,

Yang,

Nakamura

et al. 2024

Transfusion

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BackgroundStudies have suggested that acute myeloid leukemia (AML) patients with incomplete hematologic recovery undergoing allogeneic stem cell transplantation (allo‐HSCT) had inferior overall survival (OS).Study Design and MethodsThis single‐center, retrospective study of AML patients evaluated the relationship between red blood cell (RBC) and platelet (PLT) transfusion requirements during the first 30 days and long‐term outcomes after allo‐HSCT through multivariate analyses.ResultsA total of 692 AML patients received peripheral blood stem cells (89.2%), marrow (5.6%), or umbilical cord (5.2%) from matched related (37.4%), unrelated (49.1%), or haploidentical (8.2%) donors in 2011–2017. Transfusion requirements during the first 30 days for RBC (89.5% transfused, median 3, range 1–18 units) or PLT (98.2% transfused, median 6, range 1–144 units) were variable. By Day 30, 56.7% (95% confidence interval [CI]: 52.8–60.3%) and 86.1% (95% CI: 83.2–88.5%) had achieved RBC and PLT transfusion independence, respectively.Median follow‐up among survivors (n = 307) was 7.1 years (range: 2.7–11.8). Lack of RBC transfusion independence by Day 30 was strongly and independently associated with worse 5‐year OS (39.2% vs. 59.6%, adjusted hazard ratio [HR] 1.83, 95% CI: 1.49–2.25), leukemia‐free survival (35.8% vs. 55.5%, HR = 1.75, 95% CI: 1.43–2.14), and NRM (29.7% vs. 13.7%, HR = 2.05, 95% CI: 1.45–2.89) (p < .001). There was no difference in relapse rates among patients who achieved or did not achieve RBC (p = .34) or PLT (p = .64) transfusion independence.ConclusionProlonged RBC dependence predicted worse survival and NRM rates, but not increased relapse. Posttransplant surveillance of such patients should be adjusted with more attention to non‐relapse complications.

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Post-transplant ferritin level predicts outcomes after allogeneic hematopoietic stem cell transplant, independent from pre-transplant ferritin level

Cited by 6 publications

References 36 publications

Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant

Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant

ABO Mismatch in Allogeneic Hematopoietic Stem Cell Transplant: Effect on Short- and Long-term Outcomes

Lack of RBC transfusion independence by Day 30 following allogeneic hematopoietic stem cell transplant strongly predicts inferior survival and high non‐relapse mortality in acute myeloid leukemia patients

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