The transplant iron score as a predictor of stem cell transplant survival

Abstract

Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semiquantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (≥ 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections.

The Impact of Iron Overload on Transplant-Related Complications and Prognosis of Acute Leukemias.

“…10 Iron overload prior to transplant has been suggested to predispose to a higher rate of lethal infections. 19,23 International Journal of Hematology and Oncology A higher threshold of pre-transplant serum ferritin levels may predict HSCT outcomes. 27 Pretransplantation serum ferritin may have significant prognostic value in patients with MDS undergoing myeloablative allogeneic HSCT, inducing a significant increase of non-relapse mortality.…”

“…[15][16][17][18] Iron overload may predispose to a higher rate of infections associated with transplantation. [19][20][21][22][23] Stem cell sources, distinct diseases and different protocols may also affect the impact of iron overload on the process of transplantation. [24][25][26][27][28] Unfortunately, some of the studies evaluating iron overload in transplant setting did not precisely show the patients with iron overload, mainly due to ignoring consideration of transferrin saturation along with hyperferritinemia for elimination of non-iron overload etiologies of hyperferritinemia (Table 1).…”

Znaczenie terapii chelatującej u pacjentów z przeładowaniem żelaza w wyniku częstych transfuzji krwi

“…Za wysoki "wskaźnik żelazowy" uznano jego wartość powyżej 2. Wskaźnik ten jest predyktorem przeżycia chorych po allo-HSCT -im jest wyż-szy, tym większe jest ryzyko zgonu [13]. Według Lim i wsp.…”

Diagnosis and Management of Aplastic Anemia

“…Nonetheless, the majority of aplastic patients in these studies tended to have high ferritin levels or high aggregate "iron scores" at a level the reports associated with increased 100-day mortality, acute GVHD occurrence, bacteremia/infection, and decreased overall survival. 47,48 However, the associations between iron overload and adverse outcomes observed may be skewed by the prevailing myelodysplasia diagnosis in the study cohorts, and this and other confounding factors may contribute to these observed outcomes. There is as yet no data in aplastic anemia that directly address the value of chelation-related decreases in iron compared with the natural presentation to HSCT with less iron-loaded status.…”