Need For RBC Transfusion Research Articles

Factors associated with acute kidney injury after on-pump coronary artery bypass grafting

BackgroundAcute kidney injury (AKI) frequently occurs as a complication of cardiac surgery and cardiopulmonary bypass (CPB). Its prevalence and severity are determined by various preoperative and intraoperative factors. The aim of this study was to examine the risk factors for AKI following on-pump coronary artery bypass grafting (CABG).MethodsA retrospective analysis of clinical records from a single medical center was performed. The primary determinant for AKI analysis was the creatinine-level changes within the first 48 h after surgery. Records of 120 patients from a prospective cohort study were examined.ResultsAn AKI incidence of 26% occurred in the study cohort. The univariate analysis revealed that patients who developed AKI had notably higher EuroSCORE II values (2.00 ± 0.98 vs. 1.49 ± 0.74, p = 0.006) and higher initial levels of urea (7.62 ± 2.94 vs. 6.12 ± 1.71, p = 0.002) and creatinine (0.108 ± 0.039 vs. 0.091 ± 0.016, p = 0.003). Additionally, they exhibited a more frequent occurrence of initial albumin levels below 40 g/l (9 (34.6%) vs. 11 (14.9%) cases, p = 0.030) and a lower initial hemoglobin level (137.8 ± 13.2 g/l vs. 146.6 ± 13.6 g/l, p = 0.005) in comparison to patients without this complication. Moreover, those with AKI had a significantly longer hospital stay duration (14.3 ± 5.45 days vs. 12.6 ± 3.05 days, p = 0.048). Logistic regression indicated one risk factor, oxygen delivery during CPB, that correlated with the onset of AKI in the early postoperative period.ConclusionThe prevalence of AKI was higher among patients with a higher EuroSCORE II, lower preoperative hemoglobin, increased preoperative levels of creatinine and urea, infrequent albumin levels below 40 g/L, diminished oxygen delivery during CPB, and greater need for RBC transfusion and furosemide, but it did not correlate with the duration of CPB.

The Relationship Between Transfusion in Cardiac Surgery Patients and Adverse Outcomes

ObjectivesTo understand if RBC transfusions are independently associated with a risk of mortality, prolonged intubation, or infectious, cardiac, or renal morbid outcomes. DesignRetrospective review. SettingSingle-institution, university hospital. Participants2458 Patients undergoing CABG and/or valvular surgery from July 2014 through January 2018. InterventionsNo interventions were done. Measurements and Main ResultsOur primary outcome was the occurrence of the adverse event, prolonged intubation. Infectious, cardiac, and renal composite outcomes were also defined. These composites, along with mortality, were individually analyzed and then combined to form the “any adverse events” composite. Preoperative demographic and intraoperative parameters were analyzed as univariate risk factors for adverse outcomes. Logistic regression was used to screen variables with a p-value criterion of p < 0.05 for entry into the model selection procedure. Backward selection algorithm was used with variable entry and retention criteria of p < 0.05 to select the final multivariable model. Multivariable logistic regression models were used to determine whether there was an association between volume of RBC transfusion and the defined adverse event after adjusting for covariates. A p-value<0.01 was considered statistically significant in the final model of each aim to adjust for multiple comparison. The final logistic models for each of the following outcomes indicates increased risk of that outcome per each additional unit of RBC transfused. For prolonged intubation the OR=1.493, p<0.0001, for the infectious composite outcome, the OR= 1.358, p<0.0001, for adverse renal outcomes, the OR=1.247, p<0.0001, and for any adverse event, the OR=1.467, p<0.0001. ConclusionsWe demonstrate a strong independent association between RBC transfusion volume and adverse outcomes after cardiac surgery. Efforts should be undertaken such as preoperative anemia management and control of coagulopathy in order to minimize the need for RBC transfusion.

Intraoperative tranexamic acid administration in cranial meningioma surgery: a meta-analysis of prospective randomized, double-blinded, and placebo-controlled trials.

Cranial meningioma surgeries often involve significant blood loss and transfusions. Tranexamic acid (TXA) has been used to reduce blood loss in various surgeries. This meta-analysis of randomized placebo-controlled trials (RCTs) evaluates the impact of TXA in cranial meningioma surgery. Pubmed, Web of Science, and Cochrane Library were searched for RCTs. Studies were compared for: Blood loss, operative time, hospital stay, reoperation rates, allogeneic and autologous transfusion, and incidence of complications. Seven RCTs with 490 patients receiving TXA and 491 receiving placebos were included. TXA significantly shortened operative time (Mean Difference (MD): -20.95; 95%CI: -39.94 to -1.95; p=0.03). Blood loss was lower with TXA (MD: -262.7 ml; 95%CI: -397.6 to -127.8; p=0.0001). Odds of reoperation were not significantly different (OR: 0.44; 95%CI: 0.13-1.45; p=0.18). TXA significantly reduced the need for RBC transfusions (OR: 0.47; 95%CI: 0.22-0.99; p<0.05). No significant differences were observed regarding postoperative seizures (OR: 1.06; 95%CI: 0.56-2.03; p=0.85), hydrocephalus (OR: 0.25; 95%CI: 0.03-2.29; p=0.22), or hematoma (OR: 0.52; 95%CI: 0.22-1.28; p=0.16). Hospital stay was shortened in the TXA group (MD: -1.23; 95%CI: -2.41 to -0.05; p=0.04). This meta-analysis suggests that a single intraoperative dose of TXA reduces blood loss, allogeneic blood transfusions and shortens surgery time.

Improvements in Health-Related Quality of Life after Exagamglogene Autotemcel in Patients with Transfusion-Dependent Beta-Thalassemia

Background: Transfusion-dependent β-thalassemia (TDT), an inherited hematological disorder which requires life-long, chronic red blood cell transfusion (RBC) and regular iron chelation therapy, has a substantial negative impact on health-related qualify of life (HRQoL). Exagamglogene autotemcel (exa-cel) is a one-time, non-viral, ex vivo CRISPR-Cas9 gene-edited cell therapy in phase 3 clinical trials that has been shown to eliminate the need for RBC transfusions and achieve transfusion independence. Here, we report HRQoL data from a pre-specified interim analysis of the exa-cel CLIMB TDT-111 study. Methods: CLIMB TDT-111 is an ongoing, 24-mo, phase 3 trial of a single dose of exa-cel in patients aged 12-35 years with TDT and a history of ≥100 mL/kg/year or ≥10 U/year of packed RBC transfusions for 2 years prior to screening. Changes in patient-reported outcome (PRO) measures including EuroQol Quality of Life Scale 5 dimensions 5 levels of severity (EQ-5D-5L, including descriptive system and visual analog scale [VAS]) and Functional Assessment of Cancer Therapy Bone Marrow Transplant (FACT-BMT, including FACT-General [FACT-G] and bone marrow transplant subscale [BMTS]) for adults and the EuroQol Quality of Life Scale 5 dimensions youth (EQ-5D-Y) and Pediatric Quality of Life Inventory (PedsQL) for adolescents were assessed through month 24 as a secondary endpoint in the trial. Data are presented as of 16 January 2023 for the 24 adults (aged ≥18-35 years) and 11 adolescents (aged ≥12 to &amp;lt; 18 years) who had been followed for ≥16 months after exa-cel infusion. Results: Clinically meaningful improvements, exceeding the minimal clinically important difference (MCID) thresholds, were observed in all PRO measures in adults. Baseline mean EQ-5D-5L health utility US index score (n=24, mean [SD]: 0.85 [0.18]) was near the general population norm and in line with baseline scores previously reported for adult patients with TDT. By month 24, both EQ-5D-5L health utility US index scores and EQ VAS scores showed substantial improvement (mean [SD] changes at month 24 [n=15]: 0.12 [0.26] and 10.2 [20.9] points; MCIDs 0.078 and 7 to 10, respectively). FACT-G Total Score improved from baseline by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 10.3 [17.0] points; MCID 3 to 7), with improvements observed in all 4 subscales (physical, social/family, emotional, and functional well-being). BMTS score improved by month 12 and was sustained through month 24 (mean [SD] change at month 24 [n=15] 6.8 [4.7] points; MCID 2 to 3). For adolescents, EQ VAS scores improved through month 18 (mean [SD] change from baseline 4.8 [6.1] points). Total PedsQL score improved by month 6 and was sustained through month 18 (mean [SD] change from baseline [n=7] 14.1 [9.2] points; MCID 4.36). Physical functioning and psychosocial health scores, sub-components of PedsQL, both showed sustained improvement through month 18 (mean [SD] change [n=7] 19.2 [9.1] and 11.4 [10.9] points; MCID of 6.66 and 5.30 points, respectively). Improvement in psychosocial score was observed in all 3 subscales (social, emotional, and school functioning). Conclusion: Adults and adolescents infused with exa-cel reported sustained and clinically meaningful improvements in their HRQoL, with improvements observed across different instruments and domains, including physical, emotional, social/family and functional well-being and overall health status. These results demonstrate the broad clinical benefits of exa-cel in patients with TDT.

Premature infants receiving delayed cord clamping with and without cord milking: a randomized control trial

BackgroundPreterm infants often have long hospital stays and frequent blood tests; they often develop anemia requiring multiple blood transfusions. Placental transfusion via delayed cord clamping (DCC) or umbilical cord milking (UCM) helps increase blood volume. We hypothesized umbilical cord milking (UCM), together with DCC, would be superior in reducing blood transfusions.ObjectivesTo compare the effects of DCC and DCC combined with UCM on hematologic outcomes among preterm infants.MethodsOne hundred twenty singleton preterm infants born at 280/7- 336/7 weeks of gestation at Thammasat University Hospital were enrolled in an open-label, randomized, controlled trial. They were placed into three groups (1:1:1) by a block-of-three randomization: DCC for 45 s, DCC with UCM performed before clamping (DCM-B), and DCC with UCM performed after clamping (DCM-A). The primary outcomes were hematocrit levels and number of infants receiving blood transfusions during the first 28 days of life. Intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC) were secondary outcomes. Analyses were performed with an intent-to-treat approach.ResultsOne hundred twenty preterm infants were randomized. There was no statistically significant difference in neonatal outcomes; hematocrit on admission 54.0 ± 5.5, 53.3 ± 6.0, and 54.3 ± 5.8 (p = 0.88), receiving blood transfusions 25%, 20%, and 12.5% (p = 0.24), incidence of NEC 7.5, 0 and 10% (p = 0.78) in the DCC, DCM-B and DCM-A groups, respectively. There were no preterm infants with severe IVH, polycythemia, maternal or neonatal death.ConclusionThe placental transfusion techniques utilized, DCC and DCC combined with UCM, provided the same benefits for preterm infants born at GA 28 and 33 weeks in terms of reducing the need for RBC transfusions, severities of IVH and incidence of NEC without increasing comorbidity.Trial registrationTCTR20190131002. Registered 31 January 2019—Retrospectively registered.

A Case of PNH with Abdominal Pain, AKI and Hemolytic Anemia

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder affecting 1 to 10 people per million. With an associated 10-year mortality, PNH is a life-threatening disorder where the complement system of the body's innate immune system prematurely lyses red blood cells. It can be characterized by a number of clinical features, the most common being hemolytic anemia, pancytopenia, and thrombosis. 45 year old African American male presented with a chief complaint of shortness of breath x 2-3 days. Reports associated dry, nonproductive cough, congestion, myalgias onset one week prior. He was taking two tablets of Advil daily since symptom onset. He has a past medical history of right sided BKA after motor vehicle accident and currently uses a prosthetic leg. No other significant past medical history noted. On ED admission, the patient was febrile to 103.2F, tachycardic to 110 beats per minute, tachypneic to 26 breaths per minute, and normotensive to 128/64. On physical exam, there was conjunctival pallor, no scleral icterus, and right BKA. The remainder of the physical exam was unremarkable. Labs on admission were notable for anemia (Hgb 3.9, baseline of 9.2, 2 years prior), AKI (Cr 7.3, baseline of 0.9), elevated LDH 2336, and low Haptoglobin <10. Platelet count WNL throughout admission however there was a drop from 242 to 180 between Day 1 and 2 of admission. Peripheral smear did not show schistocytes however ADAMTS13 sent per heme/onc consult. Anemia improved to Hgb 7.6 on Day 3 of admission status post 4 units packed red blood cell transfusion. Workup for hemolytic anemia with AKI was pursued: Direct Coombs test negative, PNH screen sent. SPEP and UPEP unremarkable. On Day 6 of admission, flow cytometry showed evidence of PNH clone upon analysis of RBCs, granulocytes, and monocytes. AKI was attributed to ATN s/t heme-pigment deposition vs NSAID use and Cr trended down to 2.9 prior to discharge. On day 7 of admission, patient developed severe abdominal pain, not associated with fevers, chills, nausea, vomiting, or diarrhea. Pain moderately improved with Norco, ultrasound imaging was negative, and unable to CTA given renal function. Pt was started empirically on therapeutic anticoagulation with Lovenox, as the literature reports a high incidence of venous and/or arterial thrombosis in PNH w/granulocyte count >50% (89.8% in this patient). Patient was discharged the next day with close outpatient hematology follow-up with plan to start eculizumab. Given patient's presentation of fever, symptomatic anemia, and AKI the differential diagnosis included: hemoglobinopathies, red cell membrane disorders, PNH, DIC, TTP, HUS, AIHA, and infections such as malaria or HIV. It was difficult to identify PNH as the cause in this patient on ED presentation as there was no reported urine discoloration. Though classified as an acquired disorder through mutation of a gene on the X chromosome, it occurs in equal distribution among men and women. PNH specifically occurs through the mutation of a gene involved in the synthesis of glycosylphosphatidylinositol (GPI), an anchor protein for complement regulatory proteins that prevent complement-induced hemolysis of red blood cells. The resulting GPI deficiency leads to the unregulated formation of complement attack complexes that damage the cell membrane causing them to lyse. This intravascular hemolysis is seen as decreased levels of Hgb and hemoglobinuria that leads to elevated levels of LDH as seen with this patient. The degree of hemolysis and PNH clone size can increase risk of thrombosis, the leading cause of death in patients with PNH. Strong indicators for the start of PNH therapy are severe anemia, thrombosis, renal dysfunction, and dyspnea. The typical management of PNH in patients with thrombosis is shown in this case as the patient is put on therapeutic anticoagulation and plans for eculizumab, a monoclonal antibody that is a complement inhibitor used to prevent hemolysis. This PNH therapy will likely be administered lifelong and decrease the need for RBC transfusions as well as decrease thromboembolic rate. If the patient is unresponsive to eculizumab they become a strong candidate for allogeneic stem transplantation. This patient meets the popular standard for starting primary prophylaxis for management of thrombosis with a PNH clone size >50%.

S901 Rural versus Urban Differences in Inflammatory Bowel Disease (IBD) Hospitalizations: An Analysis of the National Inpatient Sample (NIS)

Introduction: Inflammatory bowel disease (IBD) is a significant cause of adult hospitalizations in the United States. There are fundamental differences in demographic distribution, socioeconomic status, access to care, and healthcare infrastructure between rural and urban areas in the US. However, very limited data evaluating these differences is available. The study aims to compare outcomes of IBD patients in these two different settings and explore the causes for any observed differences. Methods: Data obtained from the national inpatient sample (NIS) 2016–2019 database was evaluated for IBD admissions in rural and urban hospitals of the US. The primary outcome assessed was inpatient mortality, while secondary outcomes included odds of developing bowel perforation, septic shock, perianal disease, need for RBC transfusion, total hospital charges (THC), and length of stay (LOS). Results: A total of 348,469 adult IBD hospitalizations occurred during the study period. Out of this number, 24,044 patients were managed in rural settings, while 324,425 patients were managed in urban settings. The mean age of rural IBD patients was 48 years old while it was 44 years old in urban areas. Rural IBD patients had shorter inpatient LOS (3.94 days vs 5.03 days, p< 0.001) and THC ($24,515 vs $48,754, p< 0.001) than urban IBD patients. There was no difference between patient groups regarding inpatient mortality, developing septic shock, bowel perforation, need for RBC transfusion, and odds of developing perianal disease. Conclusion: The current study indicates most IBD care variables assessed between rural/urban settings were not different. However, differences were observed in LOS and THC between rural and urban IBD patients. The high cost of health care in urban settings most likely contributed to observed differences in the THC due to advanced treatments not being readily available in the rural environment. Increased access to subspecialist practices more comforTable with IBD patient care in urban areas also may contribute to a prolonged LOS as they likely deal with more medically complex patients who require advanced diagnostic testing not available at rural institutions. Improved understanding of rural/urban IBD patient severity variations and care access/availability are needed to accurately ascertain the reason behind these differences.

MDS-502 Supportive Care in Low-Risk Myelodysplastic Syndromes: Role of Erythropoiesis Stimulating Agents (ESAs)

Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients, and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS. An analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non transfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed. 183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum erythropoietin (EPO) concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118). ORR was 83.6% (153/183); no difference among WHO and IPSS subgroups was found. 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group, 83.2% exhibited again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group, 89.8% exhibited again normocytosis, while 10.2% become macrocytic. In these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibited again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibited again macrocytosis, while 24% become normocytic. These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly due to stimulating erythroid production in MDS clones; in the minority of patients probably it happens due to recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses.

PO-701-01 NINE MONTH READMISSION RATES AND CLINICAL OUTCOMES OF ANTICOAGULATION VERSUS WATCHMAN DEVICE IN OCTOGENARIANS

Atrial Fibrillation (AF), the most common arrhythmia in older adults, is fraught with an increased risk of stroke. Studies which have demonstrated non-inferiority of Left atrial appendage occlusion (LAAO) with a watchman device compared to oral anticoagulation for stroke risk reduction in AF did not include patients greater than 80 years of age, making it difficult to generalize these results to this population. This study compared nine month clinical outcomes in patients aged 80 and above who had LAAO with a watchman device to those who were only on oral anticoagulation for AF. This was a retrospective cohort study using samples from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project NRD. We included patients aged 80 and above admitted between January 2016 and December 2018 with a primary diagnosis of AF or atrial flutter who had undergone LAAO with a watchman device or were only on oral anticoagulation. Clinical outcomes were assessed at 9 months after index admission. Primary outcomes were all-cause readmissions, readmissions due to intracranial hemorrhage (ICH), stroke or TIA. Secondary outcomes were readmissions due to gastrointestinal (GI) bleeding, hematuria and need for RBC transfusions, colonoscopy or upper endoscopy. Analysis was done with STATA 17 (Stata Statistical Software: Release 17. College Station, TX: StataCorp LLC). Owing to differences in baseline characteristics, an adjusted analysis for the baseline characteristics was included. Our study consisted of a total of 491,329 patients in the anticoagulation group and 2030 patients in the watchman group. Baseline characteristics are depicted in table 1. At 9 month follow up, patients in the watchman group had a significantly higher frequency of all-cause readmissions compared to the anticoagulation group (8% vs 6%, P value 0.02, adjusted Odds Ratio 1.3, 95% CI 1.02 - 1.6). There were no significant differences in secondary outcomes between both groups as depicted in table 2. All-cause readmissions were significantly increased in the watchman group at 9 month follow-up despite no significant differences found in ICH, stroke and GI bleeding related readmissions between both groups. More studies are needed to support these findings.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Erythropoiesis Stimulating Agents (ESAS) in Supportive Care of Low-Risk Myelodysplastic Syndromes: Recamds Registry FINAL Results

Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs.Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion-dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed.183 patients, treated with standard-dose ESAs, have been retrospectively analyzed. Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1-118).ORR was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease(non-responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic-responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic-responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion-dependence, regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic.These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis.It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses. [Display omitted] DisclosuresMartinelli: Roche: Consultancy; Stemline Therapeutics: Consultancy; Abbvie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celgene /BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Incyte: Consultancy; Daichii Sankyo: Consultancy; Astellas: Consultancy, Speakers Bureau.

MDS-391: Role of Erythropoiesis-Stimulating Agents (ESAs) in Supportive Care of Low-Risk Myelodysplastic Syndromes

Context: Erythropoiesis-stimulating agents (ESAs) are the frontline treatment in low-risk anemic MDS patients, and employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It is a matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs. Objective: Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS. An analysis of the erythropoietic response to ESA therapy in a cohort of anemic, non-transfusion-dependent MDS patient, enrolled in a retrospective registry, RECAMDS, a subgroup of Italian register, was performed. Design: Real-world analysis. Setting: Low-risk MDS. Patients: One hundred eighty-three patients treated with standard-dose ESAs have been retrospectively analyzed. Data analysis was performed according to IWG 2006 criteria at baseline and after 3 and 6 months of continuous treatment, with a sub-analysis of the patients according to WHO and R-IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl and mean serum EPO concentration of 51 mU/L after a mean time from diagnosis of 6 months (r.1–118). Interventions: ESAs to manage low-risk MDS. Main outcome measures: Results were evaluated according to IMWG 2006 criteria. Results: ORR was 83.6% (153/183); no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while the other 21/183 (11.2%) achieved response after 6 months. Nineteen patients with stable disease (non-responders, according to IWG criteria), in whom treatment was continued, achieved response after 9 months. In the macrocytic-responders group, 83.2% exhibited repeat macrocytosis after 3 months, while 16.8% became normocytic. In the normocytic-responders group, 89.8% exhibited repeat normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia with transfusion-dependence, which was regarded as first signs of progression of disease. Non-responders were 30/183 (16.3%): in the macrocytic non-responders group, 89% exhibit macrocytosis again after 3 months, while 11% became normocytic; in the normocytic group, 76% exhibited macrocytosis again, while 24% became normocytic. Conclusions: These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs, mainly stimulation of erythroid production in MDS clones. In the minority of patients, it likely happens due to recruiting residual polyclonal erythropoiesis. It is interesting to note that stimulating effects of ESAs last, even when the expression of dysplasia progresses.

Assessment By MRI T2*of Iron Accumulation and Removal in Transfusion Dependent MDS Patients

Introduction: Transfusion dependency in Myelodysplastic syndrome (MDS) patients is associated with shortened over-all survival and leukemia-free survival; however, it is not clear whether this detrimental effect is mediated by transfusional iron overload itself or whether the need for RBC transfusion is a surrogate marker of disease severity. Additionally, despite the negative effects of anemia and transfusion dependence on disease outcomes and patient quality of life, the clinical impact of iron overload in MDS remains controversial. Overall, the most common non-leukemic cause of death in MDS is heart failure. Recent T2* cardiac MRI (CMR) studies have shown that cardiac iron accumulation in MDS patients is variable and infrequent. T2* CMR is noninvasive, robust and the best available modality for assessing iron organ quantification. The current study assessed iron overload in transfusion dependent MDS patients using ferritin levels combined with myocardial and liver iron quantification using T2* CMR. The study monitored iron accumulation dynamics while on iron chelation therapy. Methods: We collected retrospectively clinical data in 18 RBC transfusion dependent MDS patients that had a CMR in our institution; some of the patients have serial scans. All scans were obtained using a 1.5 T scanner (Signa HDx ver 15 GE). Scans interpretation was performed using a dedicated workstation (Medis Medical imaging version 7.6, the Netherlands) for left ventricular ejection fraction measurement and T2* investigation as previously described. T2* values were recorded in milliseconds and converted to mg/gr dry tissue of myocardial liver and pancreatic tissue. Results: Ten of 18 patients were chelated. During the study period 4 patients have died from pneumonia, brain tumor, complications of Allo BMT and transformation to AML. Demographic data and prognostic score of MDS are shown in table 1. Before the first CMR, patients were treated with median of 48 PC (14-145) with median ferritin levels 1691.3ng/ml (269.4-3730ng/ml). In Table 2 we show iron accumulation in the first CMR. Iron accumulation in the heart was seen in 2 patients. The results are shown as severity of accumulation and not absolute numbers, as normal and abnormal range is different in the different organs. Seven patients had yearly serial CMR done, 6 of them were treated with iron chelation. We found iron accumulation in the heart in 4 of them. In table 3 we show example of a patient that was treated with chelation. Another patient, that had decrease ejection fraction with only moderate accumulation in the heart in CMR, improved her heart function with chelation. During the study period all patients continue to be transfusion dependent except 1 patient that became transfusion independent. She was transfused with 182 PC with maximal ferritin of 6926ng/ml. She was chelated with deferiprone and then with desferal. She is now transfusion independent for a year. Conclusion: Blood transfusion dependency in MDS patients, leads to high ferritin levels and evidences in CMR of iron accumulation in parenchymal orangs including the heart. During the study 4 patients had evidence of iron accumulation in the heart with 2 of them with severe accumulation that improved with iron chelation. Liver and pancreas accumulation was seen in 12 and 8 patients accordingly. Prospective studies documenting the correlation between chelation therapy and improvement in organ damage and survival are needed. Disclosures No relevant conflicts of interest to declare.

PB2258 ERYTHROPOIESIS STIMULATING AGENTS (ESAS) IN MANAGEMENT OF MYELODYSPLASTIC SYNDROMES: RECAMDS TRIAL

Background:Erythropoiesis stimulating agents (ESAs) are the frontline treatment in low‐risk anemic MDS patients and an employment of this therapy in the earlier stage of the disease can delay the need for RBC transfusion, hypothetically by slowing the disease course. It's matter of debate whether the clinical response is a result of proliferation and maturation of the dysplastic clone or stimulation of residual normal erythropoiesis by ESAs.Aims:Macrocytosis is one of the cytological hallmarks of dyserithropoiesis in MDS: an analysis of the erythropoietic response to ESAs therapy in a cohort of anemic non trasfusion‐dependent MDS patients, enrolled in a retrospective register, RECAMDS, subgroup of Italian register, was performed.Methods:183 patients, treated with standard‐dose ESAs, have been retrospectively analyzed (Table 1). Data analysis was performed, according to IWG 2006 criteria, at the baseline, after 3 and 6 months of continuous treatment, with a subanalysis of the patients according to WHO and R‐IPSS risk stratification. ESAs were started at mean Hb concentration of 9.31 g/dl, mean serum EPO concentration: 51 mU/L, after a mean time from diagnosis of 6 months (r.1‐118).Results:Overall response rate (ORR) was 83.6% (153/183), no difference among WHO and IPSS subgroups was found: 132/183 (72.1%) achieved response after 3 months of treatment, while other 21/183 (11.2%) after 6 months. 19 patients with stable disease (non‐responders, according to IWG criteria), in which treatment was continued, achieved response after 9 months. In the macrocytic‐responders group 83.2% exhibits again macrocytosis after 3 months, while 16.8% become normocytic. In the normocytic‐responders group 89.8% exhibits again normocytosis, while 10.2% become macrocytic: in these patients, after 3 months, there was a contemporary worsening in neutropenia and thrombocytopenia, with transfusion‐dependence, regarded as first signs of progression of disease. Non‐responders were 30/183 (16.3%): in the macrocytic non‐responders group 89% exhibit again macrocytosis after 3 months, while 11% become normocytic; in the normocytic group 76% exhibits again macrocytosis, while 24% become normocytic.Summary/Conclusion:These preliminary data can suggest that, in the majority of MDS patients responsive to ESAs, the increase of Hb concentration occurs mainly stimulating erythroid production in MDS clones; in the minority of patients probably it happens recruiting residual polyclonal erythropoiesis.It is interesting to note that stimulating effects of ESAs last even when the expression of dysplasia progresses.

SF3B1 Mutation Is an Independent Predictor of Parenchymal Iron Overload in Myelodysplastic Syndromes

Somatic mutations of RNA splicing machinery were identified in myelodysplastic syndromes (MDS), and a strong association was found between SF3B1 mutation and disease phenotype with ring sideroblasts. Recent studies showed that this mutation identifies a distinct group of MDS with ring sideroblasts, characterized by isolated erythroid dysplasia with a high degree of expanded but ineffective erythropoiesis, resulting in inappropriately low hepcidin levels. In this work we analyzed the relationship between SF3B1 mutation, body iron status, hepcidin level and liver and cardiac iron overload detected with MRI T2* in patients with MDS.We studied 34 patients with MDS diagnosed according to WHO criteria 2008 at the Department of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy and at Ospedale Galliera, Genova, Italy (8 patients with RA or RCMD, 20 with RARS or RCMD-RS, 6 with RAEB-1 or -2). Serum hepcidin-25 measurements were performed by a validated Mass Spectrometry based method (SELDI-TOF MS). SF3B1 mutations were analyzed on DNA from circulating granulocytes on an Illumina HiSeq. Magnetic Resonance Imaging (MRI) examinations were performed with a validated scanner using a gradient echo T2* technique.Somatic mutations of SF3B1 were detected in 19 of 34 patients, with a median variant allele frequency of 0.40 (range 0.12-0.54). Ten of 19 SF3B1-mutated and 10 of 15 SF3B1 wild-type patients (67%) were RBC transfusion-dependent (median number of RBC transfusions 32, range 7-490).Variable hepcidin levels were found in the patients studied (median value 13.24 nM, range 3.25-75.56, versus 29.19 nM, range 3.26-66.15, in SF3B1-mutated and SF3B1 wild-type patients, respectively). We calculated the hepcidin to ferritin ratio, as a measure of adequacy of hepcidin levels relative to body iron stores, which was inversely related to the SF3B1 mutation (median value 0.015 nmol/mcg, range 0.004-0.035, versus 0.035, range 0.002-0.17, in SF3B1-mutated and SF3B1 wild-type patients, respectively, P=.04). In a multivariable regression model adjusted for RBC transfusion requirement, the hepcidin to ferritin ratio was independently associated with SF3B1 mutation (P=.042), indicating a blunted hepcidin response to iron overload in SF3B1-mutated patients.We then investigated the relationship between SF3B1 mutation status and parenchymal iron overload estimated by liver and cardiac MRI. Median hepatic T2* in the study population was 7 ms, ranging from 1.49 to 30.08. Focusing the analysis on patients with RBC transfusion-dependency, a higher prevalence of hepatic iron overload (defined as MRI T2* values less than 6.3 ms) was observed in SF3B1-mutated compared with SF3B1 wild-type patients (9/10 versus 5/10 respectively). In a multivariable regression analysis adjusted for RBC transfusion history, SF3B1 mutation was an independent predictor of hepatic T2* value (P=.038). When the analysis was limited to patients without RBC transfusion need, two SF3B1-mutated patients showed a liver iron overload, associated with mild increased in AST and ALT values. Cardiac iron overload defined as MRI T2* values less than 10 ms was detected in two out of 10 patients receiving more than 50 RBC units, both of them carrying SF3B1 mutation.In conclusion, our study shows that MDS patients carrying a somatic mutation of SF3B1 have inappropriately low hepcidin levels, resulting in parenchymal iron loading due to excessive iron absorption and reticuloendothelial release. These results suggest that SF3B1 mutation may be associated with liver iron overload even in untransfused patients, as observed in congenital iron loading anemias. These results may be relevant for decision-making concerning treatment of transfusion iron overload in MDS patients. DisclosuresNo relevant conflicts of interest to declare.

Clinical outcome of early relaparotomy after elective open repair of abdominal aortic aneurysms.

PurposeThe aim of this study was to retrospectively evaluate the association of need for early relaparotomy with clinical outcomes after elective open repair of abdominal aortic aneurysms (AAAs).MethodsA total of 292 consecutive patients who underwent elective open AAA repair at Asan Medical Center from January 2001 to December 2010 were included in this study, and we compared the demographics, clinical characteristics, related risk factors, and clinical outcomes of early relaparotomy versus nonrelaparotomy patients.ResultsThe incidence of early relaparotomy during a single hospital stay was 4.1% (n = 12), and the most common causes were bowel ischemia (n = 5, 41.7%) and postoperative bleeding (n = 3, 25.0%). Among the demographics and clinical characteristics significantly associated with relaparotomy were: age (P = 0.025), chronic obstructive pulmonary disease (COPD) (P = 0.010), number of RBC units transfused during the AAA repair (P = 0.022) and in the following week (P = 0.005), and length of intensive care (P < 0.001) and overall hospital stay (P < 0.001). On multivariate analysis, presence of COPD (P = 0.009) and number of RBC units transfused during the AAA repair (P = 0.006) were statistically significantly associated with relaparotomy. Furthermore, early relaparotomy was associated with perioperative (within 30 days) (P = 0.048) and overall in-hospital mortality (P = 0.001).ConclusionEarly relaparotomy has an adverse effect on clinical outcomes: increased mortality and hospital length of stay. Presence of COPD and need for RBC transfusion are associated with early relaparotomy.

Optimizing Dose Titration Of Ruxolitinib: The COMFORT-I Experience

BackgroundThe Janus-kinase (JAK) pathway plays a critical role in normal hematopoiesis. In two phase 3 studies, the JAK1/JAK2 inhibitor ruxolitinib (RUX) demonstrated clinical benefit over placebo (COMFORT-I) or best available therapy (COMFORT-II) in patients with intermediate-2 or high-risk myelofibrosis (MF). Anemia and thrombocytopenia, the most common adverse events associated with RUX treatment, were dose-dependent and expected based on RUX's mechanism of action. These events were successfully managed and few RUX-treated patients discontinued for anemia or thrombocytopenia (<1% for each event). The ability to identify patients who would most likely benefit from a dose adjustment may contribute to improved patient management. Therefore, an analysis was conducted in patients who received RUX in COMFORT-I to identify patient characteristics that could help select patients who would potentially benefit from closer monitoring and dose titration in the early period after initiation of therapy. MethodsIn COMFORT-I, starting doses in the patients randomized to RUX were 15 mg twice daily (BID) for patients with baseline platelet counts of 100–200 ×109/L (n=55) and 20 mg BID for those with platelet counts >200 ×109/L (n=100). Dose reductions were required for protocol-defined decreases in platelet counts; there was no protocol-mandated dose change for anemia. The time course of dose adjustments and the most common titrated doses by starting dose were evaluated. Logistic regression analyses with baseline hemoglobin (Hgb) level, platelet count, IPSS risk category, sex, and MF type as model effects were conducted to determine predictors of: 1) titration to a RUX dose of ≤10 mg BID within 8 weeks of starting therapy (early dose titration event); or 2) development of grade ≥3 anemia or new need for RBC transfusions (≥2 units of packed RBCs) within 12 weeks of therapy initiation (anemia event). Only baseline platelet count and Hgb emerged as significant predictors (alpha=0.05). Receiver operating characteristics (ROC) analyses were also conducted for these two predictors to determine a clinically relevant cutoff of the underlying predictor variable with a positive predictive value (PPV), true positive rate (TPR), and false positive rate (FPR) obtained at all possible cutoffs and a general goal of obtaining a TPR ≥ 50%, an FPR ≤ 10%, and a high PPV. ResultsApproximately 70% of patients had a dose adjustment within the first 12 weeks of initiating RUX treatment. At week 24, 77% of patients with baseline platelet counts of 100–200 ×109/L and 39% of those with baseline platelet counts >200 ×109/L had titrated to a reduced RUX dose relative to their starting dose. With longer-term follow-up (median 149 weeks), the mean dose over time in patients who continued on study was ∼10 mg BID for patients starting at 15 mg BID and ∼15 mg BID for those starting at 20 mg BID (Figure). [Display omitted] ROC analyses identified that a baseline platelet count range of less than 150–175 x109/L may predict which patients would experience an early titration event, while a baseline Hgb level of less than 10 mg/dL may predict which patients would experience an anemia event (Table).Table:Predictive Characteristics of Cut-points for Platelet Count and HgbPlatelet Count/ Early Dose Titration EventHgb/Anemia EventCut-point (x109/L)TPRFPRPPVCut-point (g/dL)TPRFPRPPV12518.5%3.3%80.0%8.513.6%0%100%15043.1%5.6%84.8%9.022.7%3.1%83.3%17552.3%7.8%82.9%9.531.8%4.6%82.4%20060.0%16.7%72.2%10.045.5%10.8%74.1%22569.2%21.1%70.3%10.561.4%18.5%69.2% ConclusionsIn COMFORT-I, most patients experienced a RUX dose adjustment in the first 12 weeks of treatment and stable doses were achieved with long-term therapy. Dose titration allowed most patients to maintain adequate platelet counts. After starting therapy at 15 or 20 mg BID, the majority of patients titrated to RUX doses of 10 mg BID or higher, which have been previously been shown to produce meaningful spleen volume reductions and symptom improvements (Mesa et al. 8th Annual Hematologic Malignancies Conference. Abstract 305; Verstovsek et al. ASH 2012. Abstract 800; Talpaz et al. ASH 2012. Abstract 176). A baseline platelet count of less than 150 ×109/L and baseline Hgb level of less than 10 g/dL may be clinically useful cutoffs for predicting which patients may benefit from closer monitoring shortly after treatment initiation of RUX and appropriate dose adjustments as needed. Disclosures:Mesa:Lilly: Research Funding; Genentech: Research Funding; NS Pharma: Research Funding; Gilead: Research Funding; Incyte Corporation: Research Funding. Komrokji:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Sun:Incyte Corporation: Equity Ownership; Incyte Corporation: Employment. Sandor:Incyte Corporation: Equity Ownership; Incyte Corporation: Employment. Verstovsek:Incyte Corporation: Research Funding.

Serum Ferritin Level At Referral Provides Independent Prognostic Information For Overall Survival In Primary Myelofibrosis

BackgroundRecent studies have suggested that increased circulating free light chains, inflammatory cytokines, hepcidin, ferritin, and ASXL1 mutated status have independent prognostic value for survival in primary myelofibrosis (PMF). In the current retrospective study, we studied all the aforementioned variables in the context of DIPSS-plus to examine their relative prognostic contributions for overall and leukemia-free survival. MethodsThe diagnosis of PMF was according to WHO criteria. The study population included all consecutive referrals to the Mayo Clinic, Rochester, MN where complete information on clinical and laboratory parameters and bone marrow karyotype was available. Inclusion to the study required availability of a research blood sample collected at referral. Levels of circulating free light chains (FLC) (J Clin Oncol. 2012 Apr 1;30(10):1087), inflammatory cytokines (J Clin Oncol. 2011 Apr 1;29(10):1356), hepcidin and ferritin (Am J Hematol. 2013 Apr;88(4):312) were determined as previously described. Disease-relevant mutations (ASXL1, SRSF2, EZH2, IDH-1/2, SF3B1, JAK2V617F and MPLW515) were identified as previously described (Leukemia. 2013 Apr 26. doi: 10.1038/leu.2013.119). ResultsA total of 224 PMF patients were studied (66% male; median age 63 years, range 18-83 years). The DIPSS-plus distribution was: Low 23 (10%), Int-1 26 (12%), Int-2 98 (44%), and High 77 (34%). Clinical characteristics were: unfavorable karyotype 13%, hemoglobin <10 g/dL 58%, leukocyte count >25 x 109/L 13%, platelet count <100 x 109/L 20%, peripheral blasts ≥1% 62%, red blood cell transfusion-dependent 38%, and constitutional symptoms 36%. Mutation frequencies were: JAK2V617F 61% (n=220), MPLW515 6% (n=204), ASXL1 34% (n=154), SRSF2 16% (n=189), IDH-1/2 3% (n=209), EZH2 1.5% (n=134), SF3B1 5% (n=91) and SETBP1 4% (n=114). Distribution of circulating biomarkers was: FLC >receiver operating characteristic (ROC) cutoff of 3.78 mg/dL 37% (n=222), interleukin (IL)-2R and/or IL-8 >3 standard deviations above normal mean (SD) 75% (n=197), ferritin ≥1000 mcg/L 18% (n=146), ferritin ≥500 30% (n=146), and hepcidin >3SD 72% (n=203).Median follow up from the time of referral was 45 months (range 1-317 months); during this period, 139 deaths (62%) and 27 (12%) leukemic transformations have been documented.The median overall survival of the entire cohort was 61 months. The following variables had DIPSS-plus independent predictive value for inferior survival: ferritin ≥1000 mcg/L (HR 1.9), ASXL1 mutated status (HR 1.7) and FLC >ROC cutoff (HR 2.0) and IL-2R and/or IL-8 >3SD (HR 1.6) (all p<0.05). When the aforementioned variables were added to the multivariate model (sequentially or altogether), only serum ferritin >1000 mcg/L retained its significance for overall survival independent of DIPSS-plus (HR 2.1; p=0.03). The predictive significance for increased ferritin level was maintained in RBC transfusion-dependent (ferritin ≥1000 mcg/L; n=26/54; median survival 21 versus 59 months; p=0.03) and -independent (ferritin >500 mcg/L; n=5/92; median survival 20 versus 80 months; p=0.0002) patients.Multivariable analysis identified the following predictors for inferior leukemia-free survival: SRSF2 mutated status (HR 4.8), unfavorable karyotype (HR 4.0), and circulating blasts ≥1% (HR 3.0) (p<0.05). ConclusionsWhen considering composite risk-assessment in PMF where input variables were disease-relevant mutations and circulating biomarkers in addition to traditional clinical parameters, only increased serum ferritin levels at time-of-referral retained adverse predictive value for overall survival independent of DIPSS-plus. The prognostic value of serum ferritin was independent of anemia and RBC transfusion need. It appears to more fully capture the severity of the underlying erythropoietic defect in PMF by also likely reflecting (as an acute-phase reactant) the marrow-suppressive effect of disease-related inflammation. The shortened survival in patients with increased ferritin levels was unrelated to iron overload since none of the deaths, where information was available, were caused by cardiac siderosis. Serum ferritin levels were not associated with leukemic transformation risk. In the latter analysis, only SRSF2 mutations, unfavorable karyotype and presence of circulating blasts were independently associated with inferior leukemia-free survival. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Evaluation of Azacitidine in Transfusion-Dependent, Epo-Refractory Patients with Lower-Risk Myelodysplastic Syndrome,

Abstract 3798 Introduction:Transfusion-dependency (TD) in patients with low- and int-1-risk MDS is associated with increased morbidity and mortality (Malcovati, JCO 2007). Around 30% of such patients respond to Epo +/− G-CSF with a median duration of two years (Jadersten, Blood 2005). Azacitidine (Aza) has been reported to induce transfusion-independence (TI) in patients with lower-risk MDS (Lyons, JCO 2009). However, this treatment has not been systematically evaluated in patients with a well-documented resistance to Epo +/− G-CSF, neither has the benefit of the combination of Aza and Epo been evaluated in a prospective study. Methods:This prospective open-label, non-randomized phase II study will include 30 consecutive patients with IPSS low- or int-1-risk MDS and a RBC transfusion need of ≥4 units q 4 weeks. Patients should be refractory to full-dose Epo + G-CSF for >8 weeks, or considered ineligible for such treatment according to a predictive model based on serum erythropoietin levels and transfusion need (Hellstrom-Lindberg, Br J Hem 2003). Included patients are treated with Aza 75 mg/m2/d for five days q 28 days for six cycles. Patients remaining TD after six cycles are treated with another three Aza cycles, with the addition of Erythropoietin â 60,000 units/week. Primary endpoint is number of patients achieving TI after six cycles and secondary endpoints are number of patients achieving TI after another three cycles of Aza+Epo, effect on bone marrow morphology, peripheral blood parameters, and safety profile. Results:Twenty-eight patients were enrolled from January 2010 until August 2011, another six were screen failures. See table 1 for patient characteristics. Seventeen patients were previously treated with and refractory to Epo (60,000 units/week) + G-CSF (300 μg/week), whereas remaining patients scored “low” in the predictive model and were thus considered refractory upfront. Median number of transfusion units needed was 7 (4–14) during the 8 weeks preceding inclusion. Fifteen patients are so far evaluable for treatment with Aza alone and 6 patients for Aza+Epo. TI was achieved in 2/15 patients (13%) after Aza alone. No additional responses were observed after the addition of EPO. Twenty-three serious adverse events were reported in 12 patients, with neutropenic fever (n=8), infections (n=4), and diarrhea (n=2) being most common. Three patients pre-terminated the study, two due to sustained neutropenia and one due to leukemic transformation. Nadir values after each cycle of Aza were seen at Week 3 for thrombocytes (147±34×109) and at Week 4 for neutrophils (1.4±0.9 x109), respectively, reflecting a cytotoxic effect on hematopoiesis.Table 1:Patient characteristicsMedian (range) Age69y(55–80)Gender (M/F)18/10Median duration of disease2yMedian (range) transfusion units needed q 8 weeks7 units(4–14)Median (range) S-erythropoietin443 u/L(25–2313)WHO classification, nRA1RARS2RCMD12RCUD2RCMD-RS5RAEB-I3MDS/MPD3IPSS, nLow5Intermediate 123WPSS, nLow3Intermediate14High11IPSS Cytogenetics, nFavorable19Intermediate9Adverse0 Discussion:Aza can induce TI in patients with TD lower-risk MDS, but response rate is lower in this group of documented EPO-G-CSF-refractory patients compared to previous reports of less well-controlled cohorts. Since toxicity is substantial, candidate patients for this treatment must be selected carefully. The combination of Aza and Epo remains to be further evaluated. Disclosures:Off Label Use: Azacitidine for lower-risk MDS. Hellström-Lindberg:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding.

Myelodysplastic Syndromes: Dissecting the Heterogeneity

Myelodysplastic Syndromes: Dissecting the Heterogeneity

Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in children with hereditary spherocytosis

The course of hereditary spherocytosis (HS) may be subject to hemolytic episodes, sometimes requiring blood transfusion. The aim of this study was to evaluate the efficacy of a short course of steroid therapy in elevating hemoglobin levels during hemolytic crisis. The files of all patients followed for HS from 1968 to 2009 at our hospital were reviewed. Outcome of hemolytic crises was compared between steroid-treated and untreated patients; patients given packed red blood cell transfusion(s) or erythropoietin treatment were excluded. A good outcome was defined as an increase of at least 20% in hemoglobin level from the nadir within 1 week. Of the 118 patients with HS who attended our hospital during the study period, 20 were treated with steroids and 9 received no treatment. Mean nadir hemoglobin level in both groups was 6.9 g/dl. The study group had a total of 50 steroid-treated hemolytic crises of which 37 (74%) responded favorably to treatment. Treatment failure was significantly associated with a low dose (<1 mg/kg/day) or short duration (<1 week) of treatment. The nine untreated patients had 16 hemolytic crises, of which 25% had a good outcome. Steroid therapy was significantly more effective than no therapy in increasing hemoglobin level (P = 0.015) in these hemolytic crises. Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in patients with moderate HS and eventually will result in a reduced need for RBC transfusion.