Pre-transplant Serum Ferritin Research Articles

Development of a nomogram to predict the risk of secondary failure of platelet recovery in patients with β-thalassemia major after hematopoietic stem cell transplantation: a retrospective study.

Secondary failure of platelet recovery (SFPR) is a common complication that influences survival and quality of life of patients with β-thalassemia major (β-TM) after hematopoietic stem cell transplantation (HSCT). A model to predict the risk of SFPR in β-TM patients after HSCT was developed. A retrospective study was used to develop the prediction model. The clinical data for 218 β-TM patients who received HSCT comprised the training set, and those for another 89 patients represented the validation set. The least absolute shrinkage and selection operator regression algorithm was used to identify the critical clinical factors with nonzero coefficients for constructing the nomogram. Calibration curve, C-index, and receiver operating characteristic curve assessments and decision curve analysis (DCA) were used to evaluate the calibration, discrimination, accuracy, and clinical usefulness of the nomogram. Internal and external validation were used to test and verify the predictive model. The nomogram based on pretransplant serum ferritin, hepatomegaly, mycophenolate mofetil use, and posttransplant serum albumin could be conveniently used to predict the SFPR risk of thalassemia patients after HSCT. The calibration curve of the nomogram revealed good concordance between the training and validation sets. The nomogram showed good discrimination with a C-index of 0.780 (95% CI: 70.3-85.7) and 0.868 (95% CI: 78.5-95.1) and AUCs of 0.780 and 0.868 in the training and validation sets, respectively. A high C-index value of 0.766 was reached in the interval validation assessment. DCA confirmed that the nomogram was clinically useful when intervention was decided at the possibility threshold ranging from 3% to 83%. We constructed a nomogram model to predict the risk of SFPR in patients with β-TM after HSCT. The nomogram has a good predictive ability and may be used by clinicians to identify SFPR patients early and recommend effective preventive measures.

Impact of Iron Overload and Iron Chelation with Deferasirox on Outcomes of Patients with Severe Aplastic Anemia after Allogeneic Hematopoietic Stem Cell Transplantation

Patients suffering from severe aplastic anemia (SAA) need frequent blood transfusions during allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, these transfusions can result in an excess of iron in the body tissues, which can negatively impact the success of transplantation. This study aimed to examine the impact of pretransplantation iron overload (IO) on the outcomes of allo-HSCT in patients with SAA. It also investigated whether iron chelation (IC) therapy is necessary to enhance transplantation outcomes in SAA patients by providing guidelines for determining when excess iron should be chelated. The study consisted of 2 parts. In cohort 1, which was retrospective and conducted from April 2012 to December 2018, SAA patients receiving their first allo-HSCT were divided into 2 groups based on their pretransplantation serum ferritin (SF) level: the IO group (SF >1000 ng/mL; n=17) and the non-IO group (SF ≤1000 ng/mL; n=48). Cohort 2, a prospective clinical trial conducted from January 2019 to July 2020, included SAA patients diagnosed with IO who were treated with IC therapy using deferasirox at a dose of 10 to 30 mg/kg. Patients were separated into 2 groups based on their pretransplantation SF level: the IC success (ICsuccess) group (SF ≤1000 ng/mL; n=18) and the IC failure (ICfailure) group (SF >1000 ng/mL; n=28). All participants were evaluated for the correlation between pretransplantation SF level and transplantation outcomes. A P value <.05 was considered statistically significant. There was no significant difference in the speed of engraftment among the 3 cell lineages or in the incidence of 100-day grade II-IV acute graft-versus-host disease (aGVHD), grade III-IV aGVHD, or 3-year chronic GVHD between the 2 groups in both cohorts. Of note, however, in cohort 1, both 1-year overall survival (OS) (41.2% versus 83.3%; P < .001) and 3-year OS (35.3% versus 83.3%; P < .001) were significantly worse in the IO group. Furthermore, 180-day transplantation related mortality (TRM) (47.1% versus 14.6%; P=.005) and 1-year TRM (52.9% versus 16.7%; P=.002) were significantly higher in the IO group. The IO group was significantly associated with inferior 3-year OS in both univariate and multivariate analyses. In cohort 2, 1-year OS (88.9% versus 42.9%; P=.003) and 3-year OS (83.3% versus 42.9%; P=.007) were significantly better in the ICsuccess group, whereas 180-day TRM (11.1% versus 39.3%; P=.040) and 1-year TRM (11.1% versus 57.1%; P=.003) were significantly lower in the ICsuccess group. These differences were confirmed in both univariate and multivariate analyses. This study involving 2 cohorts shows that pre-HSCT IO has a negative impact on transplantation outcomes in SAA patients. Chelating excess iron with an SF level <1000 ng/mL was found to be necessary and could potentially improve the outcomes.

The impact of pretransplant serum ferritin on haploidentical hematopoietic stem cell transplant for acquired severe aplastic anemia in children and adolescents.

Haploidentical hematopoietic stem cell transplant (haplo-HSCT) provides an important alternative for children and adolescents with acquired severe aplastic anemia (SAA) lacking matched donors. To test whether pretransplant serum ferritin (SF) represents a candidate predictor for survival and a potential biomarker for graft-versus-host disease (GvHD) in pediatric haplo-HSCT, we retrospectively evaluated 147 eligible patients with SAA who underwent haplo-HSCT. The patients were divided into the low-SF group(<1000 ng/mL) and the high-SF group (≥ 1000 ng/mL). We found that SF ≥1000 ng/mL independently increased the risk of grade II-IV aGvHD (HR=2.596; 95% CI, 1.304-5.167, P=0.007) and grade III-IV aGvHD (HR=3.350; 95% CI, 1.162-9.658, P=0.025). Similar probabilities of transplant-related mortality at 100 days were observed in the two groups (6.19 ± 2.45%vs 8.00 ± 3.84%, P=0.168). The two-year overall survival (85.29 ± 3.89%vs 92.00% ± 3.84%, P=0.746) and failure-free survival (83.23% ± 4.08%vs 83.37% ± 6.27%, P=0.915) were comparable. GvHD-/failure-free survival were 60.06 ± 5.10% and 75.56 ± 6.87%, respectively (P=0.056). In conclusion, elevated pretransplant SF level is associated with higher incidences of grade II-IV aGvHD and grade III-IV aGvHD. However, it is not associated with worse survival after haplo-HSCT for children and adolescent patients with SAA.

Further Prognostic Factors for Stratification of Patients in the High-Risk HCT-CI Group Undergoing Allogeneic HCT

IntroductionThe Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI), which is based on the function of main organs, is a useful tool for pre-transplant risk assessments. The HCT-CI has been widely applied for determining treatment strategies for patients with hematological diseases. Due to high non-relapse mortality (NRM), patients categorized in the high-risk HCT-CI group require careful consideration regarding allogeneic HCT. As the c-estimate of the HCT-CI is approximately 0.65, further stratification methods are needed when deciding on allogeneic HCT for patients in the high-risk HCT-CI group.Some biomarkers, such as serum albumin (Alb), C-reactive protein (CRP) and pre-transplant serum ferritin (SF), were independently reported to be useful prognostic indicators for allogeneic HCT. Moreover, the Glasgow prognostic score (GPS), which assesses the combined CRP and Alb, was reported to predict the survival of patients with solid organ malignancies independently of chemo/radiotherapy or stages of cancer. It may also be a useful tool for prediction of prognosis with allogeneic HCT.AimsTo identify further prognostic factors for stratification of patients in the high-risk HCT-CI group undergoing allogeneic HCT.Patients and methodsWe analyzed 189 patients with hematological disease who underwent allogeneic HCT between 2006 and 2016 at our facility. We evaluated prognostic factors for NRM as follows: the HCT-CI (high-risk), the GPS (score 2), SF (>1000 ng/dl), age (>40), sex (female to male), conditioning regimens (myeloablative) and donor sources (cord blood or others, matched related or not). The GPS was constructed as previously described. Briefly, patients with both an elevated CRP (>1 mg/dl) and hypoalbuminemia (<3.5 g/dl) were allocated a score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a score of 1. Patients in whom neither of these abnormalities was present were allocated a score of 0. The score of the HCT-CI and values of CRP, Alb and SF were collected within 28 days before allogeneic HCT.ResultsSeventy-two patients were categorized in low-, 44 patients were categorized in intermediate- and 54 patients were categorized in high-risk HCT-CI groups in our study. The patients in the high-risk HCT-CI group had a poor prognosis on univariate analysis. The one-year NRM of patients in the low/intermediate- and high-risk HCT-CI groups were 13.3% and 23.5%, respectively (p=0.027). We evaluated further prognostic factors for patients in the high-risk HCT-CI group. In the univariate analysis, cord blood and GPS score of 2 were extracted as poor prognostic factors. The one-year NRM of patients with non-cord blood or cord blood grafts were 15.6% and 42.1%, respectively (p<0.002). The one-year NRM of patients with a GPS score of 0-1 or 2 were 16.7% vs NA, respectively (p<0.001). In the multivalent analysis, cord blood, GPS score of 2 and >40 years of age were found to be independent poor prognostic factors for NRM (cord blood: hazard ratio 7.47, p=0.009, GPS score of 2: hazard ratio 4.76, p=0.012, >40 years of age: hazard ratio 3.47, p=0.015). Even in the high-risk HCT-CI group, patients with a GPS score of 0-1 or with grafts other than cord blood exhibited a similar NRM in low/intermediate-risk HCT-CI group. Moreover, these were not poor prognostic factors for patients in the low/intermediate-risk HCT-CI group.ConclusionCord blood, the GPS (score 2) and age (>40) were extracted as poor prognostic factors for patients in the high-risk HCT-CI group. For adaptation of allogeneic HCT for patients in the high-risk HCT-CI group with one or more of these factors, NRM should be carefully monitored. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Validation of Pre-Transplant Biomarker Measurement and Risk Score for Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplant (HCT)

Validation of Pre-Transplant Biomarker Measurement and Risk Score for Non-Relapse Mortality after Allogeneic Hematopoietic Cell Transplant (HCT)

Pre-Transplant Transferrin Saturation Levels As a Predictive Marker for Invasive Fungal Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

▪IntroductionInvasive fungal disease (IFD) following allogeneic hematopoietic stem cell transplantation (allo-HCT) is a well-known, potentially fatal complication. Previous multicenter, prospective observational studies (Girmenia et al., 2014; Sun et al., 2015) have showed that the incidence of IFD after allo-HCT was approximately 9.0%, and risk factors were disease status, development of IFD prior to allo-HCT, alternative donor source (cord blood donor and unrelated donor), diabetes mellitus, prophylaxis of IFD, and acute or chronic graft-versus-host disease (GVHD).Iron has a pivotal role in various types of fungal growth and iron overload impairs the host immune system, leading to IFD. Moreover, some retrospective studies have reported that elevated pre-transplant serum ferritin levels, as a marker of iron overload, might be associated with the development of IFD (Dadwal et al., 2015). Although use of ferritin and transferrin saturation (TSAT) to assess iron status is extremely common, whether pre-transplant TSAT levels might be related to the development of IFD after allo-HCT has not been fully examined.We therefore investigated risk factors of IFD, including iron overload markers such as ferritin and TSAT.Patients and MethodsWe retrospectively analyzed data from consecutive patients undergoing allo-HCT between 1 April 2007 and 31 December 2014. We excluded three patients with active IFD at initiation of the conditioning regimen and two patients undergoing double-cord blood transplantation. Proven or probable IFD cases were defined as IFD. According to our institution guidelines, we administered IFD prophylaxis in all patients. We used Cox proportional hazards models with time-dependent covariates to investigate risk factors for IFD.ResultsA total of 285 patients were eligible. Twenty-one patients developed IFD within 1 year after allo-HCT. Median time to onset was 77 days (range, 8-363 days). Pathogens included Aspergillus (n=12), Candida (n=2), and others (n=7).Notably, none of our participants from HLA-matched or one-antigen mismatched sibling donors developed IFD. The significant univariate risk factors were as follows: disease status (malignancies in complete remission, non-malignancies, and chronic myelogenous leukemia in chronic phase vs. others), donor type (cord blood vs. haploidentical peripheral blood with post-transplant cyclophosphamide (PT-CY) vs. others), GVHD prophylaxis (calcineurin inhibitor (CNI) plus methotrexate (MTX) vs. CNI plus mycophenolate mofetil (MMF) vs. PT-CY vs. others), use of antithymocyte globulin (ATG), TSAT, and hematologic relapse after transplant or refractory at transplant. However, development of IFD prior to allo-HCT, diabetes mellitus, and acute or chronic GVHD were not related to the development of IFD.In the multivariate model considering pre-transplant factors, although use of ATG (hazard ratio (HR) 2.68, 95% confidence interval (CI): 1.07-6.02, P=0.04) was significant, disease status (HR 2.04, 95% CI: 0.78-5.32, P=0.15) and TSAT (HR 1.02, 95% CI: 1.00-1.03, P=0.07) were marginally but significantly associated with development of IFD. Regarding post-transplant factors, in model 2, hematologic relapse after transplant or refractory at transplant (HR 9.63, 95% CI: 3.86-24.02, P<0.01), TSAT (HR 1.02, 95% CI: 1.00-1.04, P=0.03), CNI plus MMF (vs. CNI plus MTX) among GVHD prophylaxis (HR 3.48, 95% CI: 1.07-11.30, P=0.04) were significant. In model 3, hematologic relapse after transplant or refractory at transplant (HR 10.42, 95% CI: 4.21-25.79, P<0.01), TSAT (HR 1.02, 95% CI: 1.00-1.03, P=0.05), and use of ATG (HR 2.72, 95% CI: 1.08-6.82, P=0.03) were significant. Remarkably, 33 of 55 patients who underwent ATG received PT-CY (n=55) to prevent GVHD.ConclusionOur results suggest that pre-transplant TSAT value might be useful for predicting development of IFD. Further investigation might be warranted to validate the generalizability of this marker. DisclosuresHino:Novartis: Research Funding.

Clinical Significance of Pretransplant Serum Ferritin Level in Patients with Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation

To investigate the correlation between pretransplant serum ferritin (SF) level and prolonged or prolonged isolated thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical data of 35 patients with PT after allo-HSCT were retrospectively analyzed, and 35 patients were matched according to age and sex as a controls from 424 allo-HSCT patients with normal platelet count. The serum ferritin level before the transplantation was analyzed. The potential risk factors were analyzed by chi-square test and Fisher's exact test as well as univariate and multivariate logistic regression. The survival curve was estimated by the Kaplan-Meier model to explore its clinical significance. In addition, ROC curve was used to verify the predictive power of SF. Compared with control group, the SF level in the PT group before transplantation significantly increased (P=0.001). Multivariate analysis results showed that SF level before transplantation was a risk factor for prolonged thrombocytopenia after HSCT, and patients with SF≥1000 ng / ml showed a higher risk of death (P=0.014). ROC curve showed that SF level could be used as a predictor of prolonged thrombocytopenia after allo-HSCT. The SF level before allo-HSCT relates with occurrence and prognosis of PT in patients after allo-HSCT. Detection of SF level can provide guidance for the intervention of prolonged thrombocytopenia after HSCT.

Pre-Conditioning Serum Uric Acid as a Risk Factor for Sinusoidal Obstruction Syndrome of the Liver in Children Undergoing Hematopoietic Stem Cell Transplantation

Objective:Uric acid (UA), a known danger signal released from injured cells, is a valuable sign of inflammation. We aimed to evaluate the association of serum UA levels before the start of conditioning regimens with the risk of hepatic sinusoidal obstruction syndrome (SOS) development after hematopoietic stem cell transplantation (HSCT).Materials and Methods:Two hundred and twenty-two children who underwent allogeneic HSCT at the Pediatric BMT Unit of Hacettepe University between 2000 and 2014 were included in this retrospective study. Serum UA levels were measured before conditioning as an indicator of the pre-transplant inflammatory status of the patients. Patients with and without a diagnosis of SOS were compared regarding primary diagnosis, previously described risk factors for SOS, and pre-conditioning serum UA.Results:SOS was diagnosed in 42 patients who had higher pre-conditioning serum UA levels compared to those who did not. Pre-transplant serum creatinine, gamma-glutamyl transferase, bilirubin, ferritin, and C-reactive protein levels did not differ significantly among patients with and without SOS; however, serum albumin was lower in the patients who developed SOS. Receiver operating characteristic analysis revealed that a pre-conditioning UA level higher than 3.32 mg/dL was predictive of SOS. When applied to a multivariate model, only pre-conditioning UA and albumin levels remained significant risk factors for SOS (UA: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.26-5.12, p=0.009; albumin: OR, 0.45, 95% CI, 0.22-0.95, p=0.037).Conclusion:Our results suggest that pre-conditioning serum UA is an independent risk factor for SOS, and it might be used as an early predictor of hepatic SOS together with previously described clinical and laboratory parameters.

Pre- Transplant Ferritin Predicts Overall Survival and Non-Relapse Mortality in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation for Myelofibrosis

Background: Elevated serum ferritin (SF) is common in patients with myelofibrosis (MF) given the frequent red-cell transfusion requirements and impaired iron metabolism. The dysregulation of iron metabolism is associated with increased hepcidin levels which predict for inferior survival in patients with MF (Pardanani et al AJH 2013). High pre-transplant SF negatively impacts overall survival and non-relapse mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for hematological malignancies (Chee et al BMT 2017 &amp; Yan et al 2018). However, the impact of elevated pre-transplant SF specifically on post-alloHCT outcomes has not been described in MF. Methods: We conducted a retrospective study of patients with MF undergoing allo-HCT at Mayo clinic Rochester, Arizona, and Florida from January 1st 2012 - December 31st 2019. We abstracted demographic and outcome variables to evaluate the impact of pre-transplant ferritin levels on post-transplant outcomes. We used a Receiver Operand Characteristic Curve to identify a pre-transplant serum ferritin (SF) of ≥ 1,123 ng/mL as the cutoff which best correlated with poor survival. Results: We identified 67 patients with MF who underwent allo-HCT during the study period with readily available data. Patients with a pre-transplant ferritin ≥ 1,123 ng/mL (n=18) had a median age of 59.4 years and were predominantly male (n=9, 50%) with primary myelofibrosis (n=12, 67%), had a DIPSS-plus int-2 (n=10, 56%) and high (n=6, 33%) risk categories and received a reduced-intensity conditioning (n=14, 78%) from a matched-unrelated donor (n=7, 50%) Table1. Patients with SF ≥ 1,123 ng/mL had a worse overall survival (OS) (median OS= 12.64 months [95%CI=6.08-19.20 months] vs. not-reached (NR) p=0.001). Patients with elevated SF had an increased non-relapse mortality (NRM) rate at 6 months (16.7%, [95%CI=0.4-37.2%]) vs 8.2%,[95%CI= 2.6-18.1%] p=0.021) and 12 months (33.3% [95%CI=13.0-55.4%] vs 10.4% [95%CI=3.8-21.0%] p=0.021) Patients with ≥ 1,123 ng/mL SF had a non-statistically significant higher rate of acute graft-vs-host disease grades 3-4 (28% vs 12.2% p=0.13) but similar rates of moderate to severe chronic graft-vs-host disease (31% vs 28% p=0.78). In the univariate analysis, SF ≥1,123 ng/mL and a Hematopoietic stem cell transplant comorbidity index (HCT-CI) ≥3 were associated with an increased risk of mortality (Hazard ratio [HR]=4.18 [95%CI=1.64-10.62] p=0.003] and HR=4.42 [95%CI=1.70-11.46] p=0.003, respectively). Both retained significance in multivariate analysis SF ≥1,123 ng/mL (HR= 2.80 [95%CI= 1.0-7.6], p=0.04)] and HCT-CI score ≥ 3 (HR 3.10 [95%CI= 1.12-8.62, p=0.03]) after adjusting for age, DIPSS-plus score, conditioning regimen intensity, donor type, CMV risk, prior use of ruxolitinib, and ABO mismatch. We grouped the patients into low, intermediate and high risk categories using SF level and HCT-CI scores as detailed in Figure 1. The risk category based on SF and HCT-CI was statistically significant in impacting OS and NRM in this cohort. The 12 month OS rate was lower in the high risk category (44.4% [95%CI= 13.6%-71.9%]) when compared to the intermediate (64.6%, [95%CI=39.7%-81.3%]) and low risk (91.9%, [95%CI= 76.9%-97.3%], p=0.0002) categories. Similarly, the 12 month NRM rate was higher in the high risk category (44.4%, [95%CI=11.0%-74.2%]) when compared to the intermediate (25%, [95%CI=8.7%-45.5%]) and low risk (5.3% [95%CI=0.9%-15.9%], p=0.0046) categories. Conclusion: In patients undergoing allogeneic SCT for myelofibrosis, serum ferritin ≥ 1,123 ng/mL is a predictor of high NRM and inferior OS. Combining ferritin serum levels with HCT-CI may help in better patient selection for allo-HCT in MF population. Larger patient cohort is warranted to confirm our findings. Disclosures Kharfan-Dabaja: Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Shah:Dren Bio: Consultancy.

Retrospective Evaluation of Relationship Between Iron Overload and Transplantation Complications in Pediatric Patient Who Underwent Allogeneic Stem Cell Transplantation Due to Acute Leukemia and Myelodysplastic Syndrome.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. Retrospective observational cohort study. To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load. Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43±9.42 and 118.56±10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P<0.011 for both). Ferritin level was not associated with rates of engraftment syndrome, veno-occlusive disease, early/late infection, relapse, or overall and disease-free survival. In our study, significant result especially in terms of acute liver GVHD, was important to emphasize the need to be more careful in terms of acute liver GVHD risk in early liver pathologies in patients with high levels of ferritin after transplantation. In future large studies may be helpful to explain the relationship between acute liver GVHD and high ferritin levels.

Predicting the Outcome in Egyptian Patients with Severe Aplastic Anemia Following Allogeneic Hematopoietic Stem Cell Transplantation Using Matched Sibling Donors

Patients presented with pancytopenia in the presence of bone marrow (BM) hypoplasia, aplastic anemia (AA), may get cured by specific medical care, if patients are under 40 years, mainly in the form of allogeneic hematopoietic stem cell transplantation (allo-HSCT) which is the treatment of choice for severe AA (SAA) in young age. In Egypt, SAA may get allo-HSCT only with availability of matched sibling (MSD). Success rate of allo HSCT-MSD is still suboptimal although it is a life challenging and expensive procedure with an outcome difficult to predict. Reports suggest that measurement of serum ferritin may help in predicting favorable MSD-alloHSCT outcome. Evidences showed that total infused CD34 cells and/ or measurements of hematogones (HGs) levels at the time of engraftment by flow cytometry may better predict the outcome of MSD-alloHSCT. HGs, normal B lymphocyte precursors, levels may be affected by the status of BM and humoral immunity. Elevated HGs have been noticed in healthy children, called reactive HGs. Regenerative HGs exist in non-malignant disorders such as autoimmune diseases, congenital cytopenia, acquired immunodeficiency and neoplastic disorders such as lymphoma. In addition they have been found in response to regeneration of humoral immunity post chemotherapy and post allo-HSCT. We aimed to examine predictive value of HGs in comparison to pre-transplant ferritin and/ or infused CD34⁺ counts for a favorable outcome of SAA patients treated with allo-HSCT from MSD. This is a prospective cross-sectional study, following institutional approval. In total 21 patients with SAA were consented and enrolled. All patients were treated with MSD allo-HSCT, between December 2013 and January 2016. Patients &gt; 40years age, clinically unfit, with abnormal cytogenetic, diagnosed with inherited BM failure or paroxysmal nocturnal hemoglobinuria (PNH) were excluded. HGs were measured in BM samples at engraftment using flow cytometry where cells were stained with an anti-CD34, anti-CD38, anti- CD10, anti-CD19, and lineage (Lin) mixture (anti-CD3, -CD4, -CD8 -CD20, -CD14, and -CD56). Early HGs referred to both CD38ˉCD10⁺ CD19ˉCD34⁺ and CD38-CD10⁺CD19ˉCD34ˉ. Late HGs referred to CD38⁺CD10⁺CD19⁺CD34ˉ, and CD38⁺CD10ˉCD19⁺CD34ˉ cellss. The mean ± SD of early HG was 0.8 ± 1.6 and median with range was 0.05 (0-7.8) while mean ± SD of late HG was 0.6 ± 0.5 (p=0.4) and median with range 0.4 (0-1.4). Total HG mean ± SD was 0.7±1.2 and median with range 0.2 (0 - 7.8).Interestingly the mean ± SD of HG levels were higher in survivors vs non-survivors (2.3 ± 3.4 vs. 0.2 ± 0.2; P=0.01). Infused CD34 count (10^6) were in survivors vs non-survivors (6.7 ± 3 vs 7.8 ± 4) while pre-transplant serum ferritin levels (pm/mL) were in survivors vs non-survivors (1493 ± 1025 vs 1213 ± 371) without showing significant differences. Using ROC curve analysis, it showed the following for engraftment HGs%, best cut-off value was 0.37%, with AUC of 0.88, likelihood ratio (LR) of 3.85, it was the most sensitive 76.9% (95% CI; 35.4-84.8) and specific 80% (95% CI; 28.4 - 99.5) predicting favorable MSD-alloHSCT outcome. Infused CD34⁺ count showed best cut-off level of 6.8 x 10⁶ cells/kg, 0.63 for AUC, 3.13 for LR; 62% sensitivity (95% CI; 46.2-95) and 80% specificity (95% CI; 28.4-99.5). Pre-transplant serum ferritin showed best cut-off level of 1337, 0.59 for AUC; 1.6 LR; 64% for sensitivity (95%CI; 35.14 - 87.24) and only 60% specific (95% CI, 14.66 - 94.73). Moreover, patients with high HG (&gt;0.37%; 57% vs. &lt;0.37%;43%) had significantly high white cell count (WBCs); (median; 5 x 10⁹ /L, range; 2-9 vs 3.5,1.3-5; 95% CI; -3.5 to -0.1; p=0.03), absolute neutrophil count (ANC); (0.7 ± 0.4 vs 2 ± 0.8; p=0.0004), platelet; (26 ± vs 89 ± 46; p=0.001), at engraftment time in addition to superior OS (P=0.005). There was no difference in incidence of acute and chronic GVHD, infections or transfusion frequency rate among survivors with HGs below or above 0.37%. Noticeably donor age of transplanted patients with high HGs tended to be younger. Neither pre-transplant ferritin level nor infused CD 34⁺ count showed any impact on the OS (P=0.9 and 0.1 respectively). In sum HGs% FCM assay may be a highly sensitive and specific biomarker predicting HSCT outcome in SAA patients.. Estimating HGs% at engraftment time seem to be a promising predictor for the outcome of MSD-alloHSCT in SAA patients. SAA patients with HGs 0.37% or higher had better OS. Disclosures No relevant conflicts of interest to declare.

Effect of pre-transplantation serum ferritin on outcomes in patients undergoing allogeneic hematopoietic stem cell transplantation: A meta-analysis.

Background:Pre-transplantation serum ferritin (SF) has been considered to be a potential prognostic biomarker in patients undergoing allogeneic hematopoietic stem cell transplantation (allogeneic HSCT), but this conclusion remains controversial. Thus, we performed a meta-analysis to investigate the prognostic significance of pre-transplantation SF in patients undergoing allogeneic HSCT.Methods:We systematically searched PubMed, Embase, and Web of Science up to September 2017, and finally identified a total of 25 eligible studies with 4545 patients.Results:The pooled results of our meta-analysis showed that high pre-transplantation SF was markedly related to worse overall survival (OS) [hazard ratio (HR) = 1.82; 95% confidence interval (95% CI): 1.47–2.26; P < .001], nonrelapse mortality (NRM) (HR = 2.28; 95% CI: 1.79–2.89; P < .001), and progression-free survival (PFS) (HR = 1.72; 95% CI: 1.27–2.33; P < .001). In addition, high pre-transplantation SF was closely associated with a lower incidence of chronic graft versus host disease (cGVHD) (OR = 0.74, 95% CI: 0.58–0.96; P < .05), and a higher incidence of blood stream infections (BSIs) (OR = 1.67, 95% CI: 0.93–3.01; P = .09). However, no significance relationship was found between elevated pre-transplantation SF and acute graft versus host disease (aGVHD) (OR = 1.08, 95% CI:.72–1.62; P = .70).Conclusion:In patients undergoing allogeneic HSCT for hematological malignancies, elevated pre-transplantation SF was significantly associated with worse OS and PFS, higher incidence of NRM and BSI, and lower incidence of cGVHD, but it had no effect on aGVHD. Considering the limitations in our meta-analysis, more prospective and homogeneous clinical studies are needed to further confirm our findings.

Refinement of the Glasgow Prognostic Score as a pre-transplant risk assessment for allogeneic hematopoietic cell transplantation.

The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) is a widely used tool for pre-transplant risk assessment. Allogeneic hematopoietic cell transplantation (HCT) is performed on patients with diverse backgrounds, highlighting the need for other predictors to complement the HCT-CI and support bedside decision-making. There is a strong body of evidence supporting the use of pre-transplant serum ferritin (SF) in risk assessments of allogeneic HCT. We additionally found that the Glasgow Prognostic Score (GPS), which assesses inflammatory biomarkers and predicts survival of patients with solid organ malignancies, is a useful predictive marker for overall survival (OS) and non-relapse mortality (NRM) in allogeneic HCT, independent of HCT-CI and SF. In this study, we refined the GPS by adding pre-transplant SF to improve its prognostic ability and enable better stratification; we call this revised index the HCT-specific revised Glasgow Prognostic Score (HCT-GPS). We observed that the HCT-GPS more accurately predicted NRM and early-term OS than the GPS. Moreover, the HCT-GPS provides an independent prognostic factor adjusted for the HCT-CI and disease status, and stratifies patients into four risk groups by OS and NRM. Thus, the HCT-GPS is a useful index for predicting early-term complications after allogeneic HCT in patients with hematopoietic diseases.

Pretransplant C-reactive protein, ferritin, albumin, and platelet count as prognostic biomarkers of hematopoietic stem cell transplantation outcome in hematological malignancies

Aim To study the prediction of prognosis after hematopoietic stem cell transplantation (HSCT) by clinically available biomarkers prior to transplantation (CRP, Ferritin, albumin and platelet count). Background Previous studies have shown that a number of objective laboratory “biomarkers” are of interest in pre-HSCT risk-assessment: Serum albumin inversely correlates with age, smoking, obesity and hypertension, and predicts cardiovascular mortality. Serum ferritin is an acute phase reactant, and elevated levels suggest iron overload, which has been linked to post-HSCT infections. Finally low platelet count, could indicate poor marrow function related to persistent malignancy or effects of prior treatment. Methods The study included patients admitted at the Bone marrow transplantation Units in Egypt (Ain Shams University Hospitals and Maadi Armed Forces Medical Compound and Sheikh Zayed Specialized Hospital) between August 2015 and December 2016. The study population consisted of 30 adults aged from 18 to 60 years; 26 patients were subjected to autologous-HSCT to treat high-risk or relapsing NHL, MM, relapsing HL, and 4 patients subjected to allogeneic-HSCT to treat 1st complete remissiom (CR) AML, 2nd CR AML. The biomarkers included pre-transplant serum albumin, platelet count, C-reactive protein (CRP) and serum ferritin were centrally quantified by (ELISA) technique. All patients were followed up till day +90 post transplant. Results Shock developed post-transplant in patients with CRP ˃10 mg/L (P=0.026) while non-relapse mortality was associated with the pre-specified thresholds of platelet count Conclusion We conclude that elevated level of pre-transplant CRP, s.ferritin associated with high NRM without statistically significant difference while NRM was higher in patients with normal s.albumin pre-transplant without statistically significant difference, low platelet count

Serum ferritin is a different predictor from transfusion history for allogeneic transplantation outcome in patients with severe aplastic anemia

ABSTRACTObjectives: Severe aplastic anemia (SAA) patients receive more red blood cell (RBC) transfusions as supportive management. We aim to clarify the associations between transfusion history or pre-transplantation serum ferritin (SF) and the overall survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) among SAA patients.Material and methods: We retrospectively investigated 96 SAA patients undergoing allo-HSCT, and grouped them according to pre-transplantation duration. Pre-transplantation SF, transfused units and other iron-related parameters were collected. Comparisons in transplantation outcomes and complications were made in groups with different SF levels and different transfusion histories.Results: Among the 96 SAA patients, 45 patients received transplantation within 2 months after diagnosis (short-term pre-transplantation period), and the rest of the patients had long-term pre-transplantation treatment. Among the patients with short-term pre-transplantation treatment, a higher risk of death was seen in the high-ferritin group (p < 0.05). Elevated SF also predicted a trend in incidence of higher bloodstream infection (p = 0.108). Significant correlations were observed between pre-transplantation SF and infection incidence, as well as transfusion history. However, for patients with longer pre-transplantation duration, transfusion history was associated with worse outcome (p = 0.026), in terms of higher incidence of acute graft versus host disease (p = 0.048). High SF was only significantly associated with prolonged RBC transfusion dependence post-transplantation (p = 0.044).Discussion and conclusions: Transfusion history was a stronger predictor of outcome than SF in patients undergoing transplantation more than 2 months after diagnosis.

Excellent Outcomes of Combined Haploidentical and Cord-Blood (Haplo-Cord) Transplantation and HLA-Matched Sibling (Matched-Sib) Donor Transplantation for High-Risk Patients with Severe Aplastic Anemia (SAA) Refractory to Immunosuppressive Therapy

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for SAA unresponsive to immunosuppressive therapy (IST). For SAA patients (pts) with a HLA-identical sibling donor, the use of peripheral-blood (PB) grafts have been reported to have increased risk of graft-versus-host disease (GVHD) compared with using the bone marrow (BM) as the stem cell source. For pts lacking an HLA-identical donor, transplantation using unrelated cord blood (UCB) or haplo-identical donors has historically been associated with high graft failure rates and poor survival. Here we report and compare the clinical outcomes for two novel transplantation strategies under investigation at our center aimed at improving engraftment and survival and reducing GVHD in high-risk SAA pts refractory to IST: combined haploidentical and cord-blood (haplo-cord) transplants vs. HLA-matched sibling (matched-sib) donor PB HSCT with partial T-cell depletion.Methods: Forty-seven pts with SAA or SAA evolved to MDS that was unresponsive to IST underwent HSCT at a single center between 2008 and 2016, and received either a haplo-cord transplant (n= 28; pt eligibility included lack a HLA-matched donor but availability of a haploidentical relative, a ≥4/6 HLA matched UCB unit and severe neutropenia with an ANC<500 cells/µL) or an HLA matched-sib transplant (n=19). Both cohorts were treated with cyclophosphamide, ATG, and fludarabine, with the haplo-cord cohort also receiving 200 cGy of total body irradiation. For the haplo-cord cohort, pts received a CD34-selected G-CSF mobilized haplo-donor allograft combined with a ≥ 4/6 HLA-matched UCB unit (minimum TNC dose ≥1.5x107 cells/kg). For the matched-sib cohort, pts received G-CSF-mobilized PBSC-allograft containing high numbers of CD34+ selected cells combined with BM transplant equivalent-dose of non-mobilized CD3+T-cells/kg from a ≥9/10 HLA-matched sibling donor. GVHD prophylaxis included tacrolimus and MMF (haplo-cord) or CSA and MTX (matched-sib). Results: The median age at transplant was 20 years (range 5-49) in haplo-cord and 22 years (6-67) in matched-sib. Pts were heavily transfused and allo-immunized: pre-transplant serum ferritin was markedly elevated at a median 3368 µg/l (range 980-21465) and 1978 µg/l (161-13928) for haplo-cord and matched-sib cohorts, respectively. For the haplo-cord cohort, 18 pts received a 4/6 and 10 pts received a ≥5/6 HLA-matched UCB unit; UCB units contained a median of 3.6x107 TNCs/kg and 1.5x105 CD34+ cells/kg; haplo-grafts contained a median of 3.2x106 CD34+ cells/kg and 1.0x103 CD3+ T-cells/kg. For the matched-sib cohort, PBSC allografts from 10/10 (n=18) or 9/10 (n=1) HLA-matched donors contained a median of 8x106CD34+ cells/kg and 2x107 non-mobilized CD3 T-cells/kg. At a median follow-up of 40 months in haplo-cord and 32 months in matched-sib, most post-transplant clinical outcomes were comparable between two cohorts. In both cohorts, all pts (100%) had donor engraftment with neutrophil recovery occurring at a median of 10 days (range 6-28) in haplo-cord and 14 days (10-23) in matched-sib (Figure); median times to platelet recovery were 28 and 18 days. No patients in the matched-sib and only one pt (4%) in haplo-cord group developed late graft failure. The 200-day survival were 100% and 95%, and overall survival at 5 years were 91% and 87% in haplo-cord and matched-sib cohorts, respectively (Figure, P=0.7). The cumulative incidences of grade II-IV and III-IV acute GVHD were 37% and 4% in haplo-cord, compared to 21% and 11% in matched-sib. The cumulative incidence of chronic GVHD was higher in haplo-cord than matched-sib (45% vs.12%), however, only 8% and 0% extensive chronic GVHD occurred in two cohorts, respectively. Conclusion: Both transplant regimens being studied our center for SAA pts with high-risk ATG-refractory disease resulted in rapid neutrophil recovery, durable donor engraftment and excellent long-term survival. Despite pts being heavily transfused, iron overloaded and HLA allo-immunized, adverse outcomes of graft failure, severe acute grade III-IV GVHD and extensive chronic GVHD rarely occurred with either transplant approach. Remarkably, most transplant outcomes including survival were similar between haplo-cord and matched-sib cohorts, establishing haplo-cord transplantation to be a viable and promising transplant strategy for SAA pts who lack an HLA identical sibling. [Display omitted] DisclosuresYoung:GSK/Novartis: Research Funding.

Increased Bone Marrow Iron Scores Are Strongly Correlated With Elevated Serum Ferritin Levels and Poorer Survival in Patients With Iron Overload That Underwent Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience.

Iron overload is one of the most significant problems as a leading cause of death in patients with leukemia and those who underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). In the current study, we retrospectively evaluated the bone marrow iron scores (BMIS) in patients who underwent alloHSCT (n= 125). The first available bone marrow biopsy specimens prior to the alloHSCT procedure or date of hospitalization (control group) were assessed in a blinded fashion using a standardized scoring system. A total of 125patients were enrolled in the study. Seventy-six (60.8%) of the patients were male, and 49 (39.2%) were female. The median level of pre-transplant serum ferritin was 1023.00 ng/mL (range, 393.80-1627.50 ng/mL). The majority of the patients were diagnosed with acute leukemia (83; 66.4%) and lymphomas (20; 16.0%). The median time for neutrophil engraftment was 14.00 days (range, 13.00-16.00 days) and 11.00 days (range, 10.00-14.00 days) for platelet engraftment. The peri-transplant mortality was similar to international mortality rates (3; 2.4%). The overall survival and disease-free survival were strongly correlated with the degree of BMIS, and both were significantly poorer in patients with high bone marrow iron content (P< .001 and P= .012, respectively). The validation of BMIS for risk stratification in patients who undergo alloHSCT may predict posttransplant outcomes.

A Meta-Analysis for Effects of Elevated Pre-Transplantation Serum Ferritin on the Outcomes in Patients Undergoing Hematopoietic Stem Cell Transplantation

ABSTRACTThe level of pre-transplantation serum ferritin (SF) is one of the factors related to outcome for patients undergoing allogeneic hematopoietic stem cell transplantation. We searched PubMed and Cochrane Library databases from 2000 to 2014. The primary efficacy outcome was overall survival rate and non-relapse mortality. Twenty clinical trials were selected from 189 studies identified. The combined hazard ratio indicated a significantly lower overall survival rate and a higher non-relapse mortality rate in patients with elevated SF before transplantation. This indicates that elevated pre-transplantation SF affects outcome in patients undergoing allogeneic hematopoietic stem cell transplantation.

Evaluation of a pre-transplant serum biomarker score for allogeneic hematopoietic stem cell transplant (HCT) and association with clinical factors.

e18537Background: A recent national registry study in patients with AML and MDS found pre-transplant serum c-reactive protein (CRP), ferritin and albumin were associated with overall survival (OS) ...

Influence of Pretransplantation Serum Ferritin on Children Beta-Thalassemia Major Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Objectives: To evaluate the influence of pretransplantation serum ferritin on children β-thalassemia major (β-TM) undergoing allogeneic hematopoietic stem cell transplantation.Methods: A retrospective analysis of 266 HLA-matched children with β-TM from January 2009 and November 2014 was performed. Transplantation conditioning regimen of these children was the NF-08-TM protocol. Median follow-up time was 28 months (3~62months). We observed the relationship between pretransplantation serum ferritin level and transplantation complications which included infection, graft versus host disease(GVHD),veno-occlusive disease(VOD) and death.Results: Transplantation-related death occurred in 18 of 266 patients (6.8%). Five-year overall survival (OS) was found to be 92.8%. Among various complications, only infection was significantly associated with the high serum ferritin level (t=-2.673, P=0.008), especially serum ferritin above 3449.5μg/L(P=0.000). Meanwhile infection was the most common complication and severe infection would be main cause of deaths.Conclusions: NF-08-TM conditioning regimen was the optimization for HLA-matched β-TM patients. High pretransplantation serum ferritin level would bring high infection occurrence. DisclosuresNo relevant conflicts of interest to declare.