RBC Transfusion Research Articles

Transfused Red Blood Cell Characteristics and Kidney Transplant Outcomes Among Patients Receiving Early Posttransplant Transfusion

Red blood cell transfusion (RBCT) is frequently required in the early post-kidney transplant period, but long-term outcomes associated with RBCT is controversial. Therefore, it may be relevant to investigate the association between RBCT characteristics and transplant outcomes. To study the association between RBC storage duration and transplant outcomes. This was a nationwide retrospective cohort study based on data linking between 2 prospective French nationwide registries. Clinical transplant parameters, outcomes, and RBCT characteristics were extracted from the CRISTAL registry of the Agence de la Biomédecine and the national database of the Etablissement Français du Sang. All 12 559 patients having received a first kidney transplant in France between January 1, 2002, and December 31, 2008, were included. Patients were followed up from transplant to graft loss, death with a functional graft, or data retrieval in June 2016. Data were analyzed from April 2019 to June 2022. Clinical outcomes of transplant recipients who underwent early RBCT were analyzed considering transfusion characteristics. Cox proportional hazards regression models were fitted to evaluate transplant failure defined as graft loss or death with a functional graft. Among 12 559 patients who underwent kidney transplant, 3483 received an RBCT during the first 14 days posttransplant. The median (IQR) age of patients was 53.0 (41.5-61.2) years, and 1929 patients (55.4%) were male. Median (IQR) follow-up was 7.8 (7.6-8.0) years. In multivariable analysis, longer (vs shorter) storage duration of transfused RBC was associated with a decrease in risk of transplant failure (hazard ratio, 0.99; 95% CI, 0.98-1.00 for each additional storage day; P = .06). Patients transfused with at least 1 RBC unit stored for more than 20 days had a 5% absolute decrease in transplant failure at 3 years and 7% at 5 years compared with those who received RBC stored for less than 20 days. In this study, longer RBC storage duration was associated with a decreased risk of transplant failure among patients who received kidney transplants and RBC transfusions. Preferential use of RBC with longer storage duration might improve kidney graft survival following transplant and transfusion.

Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019.

Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. Single-center, retrospective study, 2010-2019. Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. None. Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.

Uterus-preserving surgical management of placenta accreta spectrum disorder: a large retrospective study

BackgroundThe two-child policy implemented in China resulted in a surge of high-risk pregnancies among advanced maternal aged women and presented a window of opportunity to identify a large number of placenta accreta spectrum (PAS) cases, which often invoke severe blood loss and hysterectomy. We thus had an opportunity to evaluate the surgical outcomes of a unique conservative PAS management strategy for uterus preservation, and the impacts of magnetic resonance imaging (MRI) in PAS surgical planning.MethodsCross-sectional study, comparing the outcomes of a new uterine artery ligation combined with clover suturing technique (UAL + CST) with the existing conservative surgical approaches in a maternal public hospital with an annual birth of more than 20,000 neonates among all placenta previa cases suspecting of PAS between January 1, 2015 and December 31, 2018.ResultsFrom a total of 89,397 live births, we identified 210 PAS cases from 400 singleton pregnancies with placenta previa. Aside from 2 self-requested natural births (low-lying placenta), all PAS cases had safe cesarean deliveries without any total hysterectomy. Compared with the existing approaches, the evaluated UAL + CST had a significant reduction in intraoperative blood loss (β=-312 ml, P < .001), RBC transfusion (β=-1.08 unit, P = .001), but required more surgery time (β = 16.43 min, P = .01). MRI-measured placenta thickness, when above 50 mm, can increase blood loss (β = 315 ml, P = .01), RBC transfusion (β = 1.28 unit, P = .01), surgery time (β = 48.84 min, P < .001) and hospital stay (β = 2.58 day, P < .001). A majority of percreta patients resumed normal menstrual cycle within 12 months with normal menstrual fluid volume, without abnormal urination or defecation.ConclusionsA conservative surgical management approach of UAL + CST for PAS is safe and effective with a low complication rate. MRI might be useful for planning PAS surgery.Clinical trial registration number: ChiCTR2000035202.

Hematologic Malignancy: Who Cares in the End? A Retrospective Cohort Study of Markers of Quality End-of-Life Care.

Early palliative care is increasingly used in solid organ malignancy but is less established in patients with hematologic malignancy. Disease-related factors increase the demand for hospitalization, treatment, and supportive care in patients with hematologic malignancy. The terminal phase of illness in patients with hematologic malignancy can be difficult to predict, resulting in complexities in establishing a standard for quality end-of-life care. This is a retrospective single-center cohort study of adult patients with hematologic malignancy who died between October 2019 and July 2022. Patients were identified, and disease characteristics, therapy, and outcomes were extracted from medical records. Descriptive statistics are reported and univariate analyses were performed across a range of factors to assess for associations. A total of 229 patients were identified, with a median age of 77 years and 35% female. In the final 30 days of life, 65% presented to the emergency department, 22% had an ICU admission, 22% had an invasive procedure, 48% received cytotoxic therapy, 61% received a RBC transfusion, and 46% received a platelet transfusion. Use of intensive chemotherapy was particularly associated with hospitalization and ICU admission. A total of 74% referred to palliative care, with a median time from referral to death of 13 days. Of these patients, one-third were referred within the last 5 days of life. In terms of place of death, 54% died in the acute hospital setting and 30% in hospice, with a median hospice length of stay of 4 days. These findings highlight the need for further research into quality indicators for end of life in hematologic malignancy and earlier integration of specialist supportive and palliative care in both inpatient and outpatient settings.

The effects of two fixation methods on blood loss in patients with trochanteric fracture: dynamic hip screw vs. proximal femoral nail anti-rotation.

Aim The two most commonly used implants for treatment of trochanteric fractures are the dynamic hip screw (DHS) and proximal femoral nail antirotation (PFNA). The aim of this study was to evaluate blood loss in patients with trochanteric fracture treated with DHS or PFNA. Methods This retrospective comparative study included 61 patients with trochanteric fracture, who were divided according to a surgical method into DHS and PFNA groups. In the PFNA group, a short third generation gamma-nail was used for osteosynthesis (Supernail GT, Lima Corporate, Italy), and in the DHS group a dynamic hip screw was used (Synthes, Oberdorf, Switzerland). Complete blood count with haemoglobin and haematocrit values was taken preoperatively and on the first day postoperatively and a number of red blood cell transfusions (RBC) were evaluated. Electronic medical records from 2022 were used to collect patient data. Results There were no significant differences in terms of gender and age between the groups (p=0.510 and p=0.087, respectively), as well as in the fracture type distribution (p=0.886). The duration of postoperative hospitalisation was similar between the groups (p=0.643). There was no statistically significant association between the number of RBC transfusions and fixation method (p=0.091), as well as in postoperative haemoglobin and haematocrit levels between the groups (p=0.180 and p=0.225, respectively). Conclusion Both DHS and PFNA implants are safe surgical techniques for the treatment of trochanteric fractures, with similar blood loss, number of blood transfusions and hospital stay.

Impact of Delayed Cord Clamping on Red Blood Cell Transfusion and Related Outcomes in Very Low Birth Weight Infants.

Delayed cord clamping (DCC) for 30 to 60 seconds after birth facilitates placental transfusion, increases blood volume, and decreases red blood cell (RBC) transfusion in preterm infants. Study objective was to determine (1) RBC transfusion burden over a 5-year period, (2) impact of DCC practice on RBC transfusions, and (3) association of RBC transfusion on outcomes in very low birthweight (VLBW) preterm infants. A retrospective medical chart review was performed in 787 VLBW infants between 2016 and 2020. Demographic factors, DCC status, number of RBC transfusions, and neonatal outcomes were determined in eligible infants. Adjusted association between DCC, RBC transfusion, and outcomes were determined using logistic and linear regression methods. Of the 538 eligible VLBW infants, 62% (N = 332) received RBC transfusions. Proportion receiving RBC transfusion were significantly higher for infants <1,000 g (N = 217, 65.4%) and gestational age (GA) <29 weeks (N = 256, 77.1%) than larger (1,001-1,250 g, N = 77, 23.2% and 1,251-1,500 g, N = 38, 11.4%) and older GA ≥ 29 weeks' infants (N = 76, 22.9%, p < 0.05). Of the 81/538 (15.1%) who received DCC, 48 (59.2%) received no RBC transfusion (p < 0.001). In multivariable logistic regression analysis, preterm infants with DCC were 55% less likely to receive RBC transfusions as compared with infants with no DCC. At any given GA, the number of RBC transfusions in preterm infants with DCC was 25% lower as compared with infants without DCC (p < 0.05). Transfusion was associated with 8-fold increased odds for bronchopulmonary dysplasia and 4-fold increased odds for medical and surgically treated patent ductus arteriosus compared with no transfusion. There was no significant association of transfusion with neonatal sepsis, laser treated retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. DCC was significantly associated with reduced RBC transfusion, but fewer preterm infants received DCC. Further research is needed to explore the feasibility of providing neonatal resuscitation during DCC in preterm infants. · Delayed cord clamping significantly reduced the need for RBC transfusions.. · Fewer very preterm infants received DCC.. · Future research is needed to explore feasibility of neonatal resuscitation during DCC..

Evaluation of the Potential for Improvement of Clinical Outcomes in Trauma Patients with Massive Hemorrhage by Maintaining a High Plasma-to-Red Blood Cell Ratio during the First Hour of Hospitalization.

Several reports indicate that early plasma transfusion may promote survival and reduce the incidence of traumatic coagulopathy in situations of massive bleeding. Consequently, it is recommended to maintain a plasma and RBC transfusion ratio between 1 : 1 and 1 : 2 at the start of admission. This retrospective study examined the effect of an early high plasma : RBC ratio on mortality rates by adopting a massive transfusion protocol (MTP) that forced an early and rapid issue of plasma products. Patients who received massive transfusions at a single trauma center between January 2014 and May 2020 were included in the study. A new protocol was established in January 2020, wherein a fixed amount of plasma was issued following MTP activation. Patients who underwent massive transfusions before and after the adoption of the new protocol were compared. In total, 1059 patients met the inclusion criteria. Fifty-one patients who underwent MTP were propensity score-matched with the patients who received a nonprotocolized massive transfusion. The MTP group had a higher plasma : RBC ratio at 1 h (0.8 vs. 0.2) and 4 h of hospitalization (1.1 vs. 0.6), with no significant between-group difference in the plasma : RBC ratio at 24 h of hospitalization. The MTP group had a lower 24 h mortality rate than the control group. There was no significant difference in the 30-day mortality. Using MTP to achieve a high plasma : RBC ratio in the early period of hospitalization appeared to affect 24-hour mortality; however, 30-day mortality did not change.

A transfusion risk stratification score to facilitate quality management in cardiopulmonary bypass.

Our previous showed that a blood management program in the cardiopulmonary bypass (CPB) department, reduced red blood cell (RBC) transfusion and complications, but assessing transfusion practice solely based on transfusion rates was insufficient. This study aimed to design a risk stratification score to predict perioperative RBC transfusion to guide targeted measures for on-pump cardiac surgery patients. We analyzed data from 42,435 adult cardiac patients. Eight predictors were entered into the final model including age, sex, anemia, New York Heart Association classification, body surface area, cardiac surgery history, emergency surgery, and surgery type. We then simplified the score to an integer-based system. The area under the receiver operating characteristic curve (AUC), Hosmer-Lemeshow goodness-of-fit test, and a calibration curve were used for its performance test. The score was compared to existing scores. The final score included eight predictors. The AUC for the model was 0.77 (95% CI, 0.76-0.77) and 0.77 (95% CI, 0.76-0.78) in the training and test set, respectively. The calibration curves showed a good fit. The risk score was finally grouped into low-risk (score of 0-13 points), medium-risk (14-19 points), and high-risk (more than 19 points). The score had better predictive power compared to the other two existing risk scores. We developed an effective risk stratification score with eight variables to predict perioperative RBC transfusion for on-pump cardiac surgery. It assists perfusionists in proactively preparing blood conservation measures for high-risk patients before surgery.

Acute Chest Syndrome in Sickle Cell Disease.

Acute chest syndrome (ACS) is the leading cause of mortality among individuals with sickle cell disease (SCD) accounting for 25% of all deaths. The etiologies and clinical manifestations of ACS are variable among children and adults, with a lack of clear risk stratification guidelines for the practicing clinician. In addition, the management of ACS is based on limited evidence and is currently guided primarily by expert opinion. This manuscript reviews the pathophysiology, risk factors, and current management strategies for ACS through a review of published data on this subject between 1988 and 2022. Blood transfusion is often used as a therapeutic intervention for ACS to increase blood's oxygen-carrying capacity and reduce complications by reducing hemoglobin S (HbS) percentage, based on the very low quality of the evidence about its efficacy. The benefit of RBC transfusion for ACS has been described in case series and observational studies, but randomized studies comparing simple transfusion vs. exchange transfusions for ACS are lacking. In this review, we conclude that the development of clinical and laboratory risk stratification is necessary to further study an optimal management strategy for individuals with ACS to avoid transfusion-related complications while minimizing mortality.

Identification of novel mutations in patients with Diamond-Blackfan anemia and literature review of RPS10 and RPS26 mutations.

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow failure syndrome characterized by erythroid aplasia, physical malformation, and cancer predisposition. Twenty ribosomal protein genes and three non-ribosomal protein genes have been identified associated with DBA. To investigate the presence of novel mutations and gain a deeper understanding of the molecular mechanisms of disease, targeted next-generation sequencing was performed in 12 patients with clinically suspected DBA. Literatures were retrieved with complete clinical information published in English by November 2022. The clinical features, treatment, and RPS10/RPS26 mutations were analyzed. Among the 12 patients, 11 mutations were identified and 5 of them were novel (RPS19, p.W52S; RPS10, p.P106Qfs*11; RPS26, p.R28*; RPL5, p.R35*; RPL11, p.T44Lfs*40). Including 2 patients in this study, 13 patients with RPS10 mutations and 38 patients with RPS26 mutations were reported from 4 and 6 countries, respectively. The incidences of physical malformation in patients with RPS10 and RPS26 mutations (22% and 36%, respectively) were lower than the overall incidence in DBA patients (~50%). Patients with RPS26 mutations had a worse response rate of steroid therapy than RPS10 (47% vs. 87.5%), but preferred RBC transfusions (67% vs. 44%, p = 0.0253). Our findings add to the DBA pathogenic variant database and demonstrate the clinical presentations of the DBA patients with RPS10/RPS26 mutations. It shows that next-generation sequencing is a powerful tool for the diagnosis of genetic diseases such as DBA.

Red Blood Cell Conservation and Use in the Cardiovascular Operating Rooms at Ben Taub General Hospital

A conservative hemoglobin transfusion threshold is noninferior to a liberal threshold in cardiac surgery. However, red blood cell (RBC) transfusion remains common during cardiac surgery. The authors' single-center, retrospective study aimed to decrease RBC transfusions for hemoglobin >7.5 g/dL in nonemergent cardiovascular surgeries utilizing cardiopulmonary bypass (CPB), by educating the anesthesiology and surgical staff on the benefits of a conservative threshold for transfusions, and incorporating the discussion and routine use of blood conservation methods for all nonemergent cardiac surgeries. This was a single-center, retrospective study that included all nonemergent coronary artery bypass grafting and single-valve cases utilizing CPB from January 2018 to December 2021 before and after the intervention in July 2019. The data involved a single community hospital. A total of 417 patients were included in the study. The authors adopted a conservative threshold for blood transfusion and implemented a collaborative multidisciplinary approach to blood conservation. Baseline patient characteristics were summarized, and the incidence of RBC transfusion before and after the intervention on July 26, 2019, were compared by Wilcoxon rank sum and chi-square tests. Multivariate logistic regression was used. The intervention was significantly associated with reduced RBC transfusion rate after adjusting for confounding variables (p < 0.05). The odds of receiving an RBC transfusion among patients after the intervention was 0.615 times the odds among patients before intervention (95% CI: 0.3913-0.9663). The authors' goal was to improve patient outcomes and the quality of perioperative care during cardiac surgery. By implementing a protocol and educating anesthesiologists, surgeons, and perfusionists, they successfully decreased the incidence of RBC transfusion above a hemoglobin of 7.5 g/dL.

#4927 DARBEPOETIN ALFA ONCE IN 4 WEEKS CORRECTS ANEMIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE NOT ON DIALYSIS

Abstract Background and Aims In anemia management in patients with CKD not on dialysis (CKD ND), darbepoetin alfa (DA), which has shorter half-life but lower cost than continuous erythropoietin receptor activator (C.E.R.A.), is preferred in actual clinical practice in Korea. The current study evaluated the efficacy and safety of DA every 4 weeks (Q4W) compared to C.E.R.A. Q4W administration for in erythropoiesis-stimulating agent (ESA)-naïve patients with CKD ND. Method In this randomized, prospective, noninferiority study, 40 ESA-naïve patients with CKD ND were randomized 1:1 to receive either DA or C.E.R.A. Q4W during a 12-week correction period and 24-week efficacy evaluation period (EEP). Two primary efficacy end points were analysed: 1) the mean difference in the changes in haemoglobin (Hb) levels between baseline and EEP and 2) the Hb response rates defined as the proportion of patients who reached the target Hb level range (10-11 g/dL) during correction period. The non-inferiority margin is pre-defined as: 1) The lower limit of the 95% confidence interval (CI) is &amp;gt;-0.75 g/dL for the mean difference in the changes in Hb levels and 2) &amp;gt;60% for Hb response rates. Safety profiles including changes in blood pressure (BP), laboratory safety parameters, and frequency of all adverse events (AEs) were monitored and analysed during study period. Results The mean difference in the changes in Hb levels between the two groups was [0.375 g/dL; 95% confidence interval (CI), -0.446 to 1.196)] and [-0.070 g/dL; 95% CI, -0.730 to -0.590] in the intent-to-treat (ITT) and per-protocol (PP) population, respectively (Fig. 1). The Hb response rates in correction period were comparable between DA and C.E.R.A. group; [100%; 95% CI, 81.4 to 100] versus [94.1%; 95% CI, 71.3 to 99.8)] and [100%; 95% CI, 79.4 to 100] versus [100%; 95% CI: 88.2 to 100)] in ITT and PP population, respectively (Fig. 2). The mean estimated glomerular filtration rate, systolic and diastolic BP, sodium, and potassium level over time were not different during total study period between two groups (P = 0.264, 0.999, 0.823, 0.941, and 0.978). All of the AEs in each group were reported to be mild to moderate in intensity. Peripheral edema, neck pain, herpes zoster, and dyspnea occurred in DA group (20%) and urinary tract infection, dyspnea, and femur neck fracture occurred in C.E.R.A. group (15%). There were no serious AEs which led to discontinuation of the treatment. All AEs were mild to moderate in severity, and they are probably not associated with the study drugs and were successfully cured. The reasons for discontinuation of the drugs were starting HD or follow-up loss, but not due to the administered study drugs. No subjects received RBC transfusion or iron replacement therapy in both groups. There was no death during the study period. Conclusion These study results suggest that DA Q4W has non-inferiority in anemia correction efficacy and similar safety profiles compared to C.E.R.A. Q4W in ESA-naïve patients with CKD ND.

Efficacy and safety results from the COMMANDS trial: A phase 3 study evaluating luspatercept vs epoetin alfa in erythropoiesis-stimulating agent (ESA)-naive transfusion-dependent (TD) patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS).

7003 Background: Most pts with LR-MDS have limited responses to ESAs, thus there is an unmet need to treat anemia and reduce TD. Here we report interim results from the open-label, randomized phase 3 COMMANDS trial (NCT03682536) comparing the efficacy and safety of luspatercept vs epoetin alfa in ESA-naive pts with LR-MDS. Methods: Eligible pts were ≥ 18 years old with IPSS-R-defined LR-MDS with or without RS, &lt; 5% bone marrow blasts, sEPO levels &lt; 500 U/L, required RBC transfusions (defined as 2–6 RBC units/8 weeks [wk] for ≥ 8 wk immediately prior to randomization), and were ESA naive. Pts were randomized 1:1 to receive subcutaneous luspatercept (starting dose 1.0 mg/kg, titration up to 1.75 mg/kg) once every 3 wk or epoetin alfa (starting dose 450 IU/kg, titration up to 1050 IU/kg) weekly for ≥ 24 wk. Primary endpoint was achievement of RBC transfusion independence (TI) ≥ 12 wk within the first 24 wk, with a mean hemoglobin increase ≥ 1.5 g/dL. Secondary endpoints included achievement of hematologic improvement-erythroid (HI-E) response ≥ 8 wk per IWG 2006 criteria, RBC-TI 24 wk and ≥ 12 wk, and safety. Results: As of Aug 31, 2022, 178 pts received luspatercept and 176 epoetin alfa, with median treatment durations of 41.6 and 27.0 wk, respectively. Baseline pt characteristics were balanced across treatment arms. Of 301 pts included in the efficacy analysis, 86 (58.5%) pts receiving luspatercept vs 48 (31.2%) epoetin alfa achieved the primary endpoint of RBC-TI ≥ 12 wk with concurrent mean Hb increase ≥ 1.5 g/dL within the first 24 wk ( P &lt; 0.0001). HI-E ≥ 8 wk was achieved by 109 (74.1%) luspatercept and 79 (51.3%) epoetin alfa pts ( P &lt; 0.0001 ). Within the first 24 wk of treatment, RBC-TI 24 wk and ≥ 12 wk was achieved by 70 (47.6%) and 98 (66.7%) luspatercept pts, respectively, vs 45 (29.2%) and 71 (46.1%) epoetin alfa pts ( P = 0.0006 and 0.0002). Treatment-emergent adverse events (TEAEs; any grade) were reported by 164 (92.1%) luspatercept and 150 (85.2%) epoetin alfa pts; 8 (4.5%) and 4 (2.3%) pts discontinued due to TEAEs. Treatment-related AEs were reported by 54 (30.3%) luspatercept and 31 (17.6%) epoetin alfa pts. AML progression was reported in 4 (2.2%) luspatercept and 5 (2.8%) epoetin alfa pts. Overall rates of death were comparable between arms during treatment and post-treatment (32 [18.0%] luspatercept, 32 [18.2%] epoetin alfa pts). Conclusions: Compared with epoetin alfa, luspatercept led to clinically meaningful and statistically significant improvements in RBC-TI and erythroid response, as well as duration of response. Luspatercept safety results were consistent with previous findings. These data show, for the first time, superiority of an innovative therapy over ESAs in ESA-naive pts with TD LR-MDS. Luspatercept could represent a new standard of care for pts with TD LR-MDS. Clinical trial information: NCT03682536 .

A randomized, double-blind, phase 3 study of jaktinib versus hydroxyurea (HU) in patients (pts) with intermediate-2 or high-risk myelofibrosis (MF).

7015 Background: Ruxolitinib and HU are recommended by Chinese MF guideline for splenomegaly. There is an unmet need for new treatments. Jaktinib, a novel JAK and AVCR1 inhibitor, showed promising activity on splenomegaly, anemia, and MF symptoms in a phase 2 study (NCT03886415). Here we present the interim results of a phase 3 study, which assessed the efficacy and safety of jaktinib compared to HU. Methods: Pts aged ≥ 18 with primary or post-ET/PV MF, DIPSS Int-2 or high risk, and no prior or ≤10 days’ treatment with a JAK inhibitor were enrolled and randomly assigned (2:1) to receive jaktinib 100 mg bid plus HU placebo or HU 0.5g bid plus jaktinib placebo, stratified by DIPSS risk status (Int-2 or high risk). One interim analysis was pre-specified to be conducted when 70 pts completed the week (wk) 24 visit or met the criteria for treatment termination before wk 24. The primary endpoint was the proportion of pts with a spleen volume reduction of ≥ 35% from baseline (SVR35) at wk 24, measured by MRI/CT images and assessed centrally. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with a ≥ 50% reduction in Total Symptom Score (TSS50), improvement of anemia, safety, etc. Results: This interim analysis (cut-off: April 8, 2022) included 47 pts receiving jaktinib and 23 receiving HU. 66.0% (jaktinib) and 69.6% (HU) had a baseline hemoglobin (Hb) &lt; 100 g/L. 59.6% (jaktinib) and 69.6% (HU) were JAK2V617F positive. The SVR35 rates at wk 24 were 72.3% for jaktinib vs. 17.4% for HU ( p≤0.0001). The best spleen response rates were 80.9% of jaktinib-treat pts vs. 26.1% of HU-treated pts ( p≤0.0001). The median maximum percentage change from baseline in spleen volume were -46.59% vs. -18.50%. The TSS50 rates at wk 24 were 63.8% for jaktinib vs. 43.5% for HU ( p = 0.1163). 5 of 7 jaktinib-treated and two of 5 HU-treated pts who required RBC transfusion at baseline achieved a ≥50% decrease in RBC transfusion by wk 24. In transfusion-independent pts with baseline Hb ≤100 g/L, 39.3% for jaktinib and 15.4% for HU had a ≥20 g/L Hb increase. The most common grade ≥3 hematological treatment emergent adverse events (TEAEs) (jaktinib vs. HU) were anemia (25.5% vs. 43.5%), thrombocytopenia (17.0% vs. 39.1%), leukopenia (2.1% vs. 21.7%), neutropenia (2.1% vs. 21.7%) and decreased lymphocyte count (2.1% vs. 13.0%). Most common non-hematological TEAEs were upper respiratory tract infection (21.3% vs. 21.7%), elevated bilirubin (12.8% vs. 26.1%), fever (12.8% vs. 21.7%) and diarrhea (10.6% vs. 21.7%), predominantly of grade 1 or 2. TEAEs leading to treatment discontinuation occurred in 8.5% of jaktinib and 17.4% of HU. Conclusions: Jaktinib demonstrated significant clinical benefits over HU in MF pts for spleen response with improved symptom response and less cytopenias. Jaktinib may be a new treatment option for MF pts, especially for those with anemia. Clinical trial information: NCT04617028 .

Clinical outcomes by SF3B1 mutation status in patients (pts) with lower-risk myelodysplastic syndrome (LR-MDS) retreated with erythropoiesis-stimulating agents (ESAs).

7071 Background: Pts with SF3B1-mutated LR-MDS often have a more favorable prognosis versus those with SF3B1 wildtype. A sizeable number of pts with LR-MDS undergo ESA treatment even after experiencing ESA failure in first line. This study evaluated the outcomes of pts with LR-MDS retreated with ESAs in routine clinical practice, stratified by SF3B1 status. Methods: This retrospective cohort study included pts with LR-MDS in the US community setting who initiated ESAs as first-line therapy between January 1, 2016 and June 30, 2019, and were followed through June 30, 2021. Eligible pts discontinued ESAs (treatment gap ≥ 3 wk for epoetin alfa or ≥ 6 wk for darbepoetin alfa) and subsequently reinitiated ESA therapy at least once during follow-up. Ring sideroblasts (RS) ≥ 15% served as a surrogate for pts with unknown SF3B1 mutation status. Outcomes included ESA switches, dose reductions and escalations, ESA failure, and overall survival (OS). Primary ESA failure was defined as no rise in hemoglobin (Hb) ≥ 1.5 g/dL or no decrease in RBC transfusion requirement by 8 wk of treatment. Transfusion-dependent (TD) status was evaluated for pts who were transfusion independent (TI) at baseline. Results: A total of 82 pts with LR-MDS and repeat ESA treatment were included. Median age at start of ESA treatment was 79 y (interquartile range [IQR], 72–85). Diagnosis of MDS-RS, MDS with isolated del(5q), MDS with multilineage dysplasia, and MDS with single lineage dysplasia was reported in 30 (36%), 7 (9%), 9 (11%), and 9 (11%) pts, respectively; 27 (33%) had unknown classification. Median follow-up was 26 mo (IQR, 13–38) with 65% failing ESA therapy by 8 wk. Table shows pts’ SF3B1 mutation status, median OS, pts who had an ESA switch, dose reduction or escalation, experienced ESA failure, and pts who were TI at baseline and became TD during follow-up. Results were similar when RS was not used as a surrogate, and when analyses were limited to pts who were treated with ESAs only throughout follow-up. Conclusions: In this study of pts with LR-MDS retreated with ESAs, primary ESA failure was high with nearly half of TI pts becoming TD during follow-up. OS was poor regardless of SF3B1 status – 2–4 times lower than the remaining life expectancy for a 79-y-old (108 mo for men; 125 mo for women). Although treatment options were limited during the study period, the high primary failure rate suggests that pts with LR-MDS may benefit from alternatives to ESAs. [Table: see text]

A phase 2 randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): ELEVATE-TNBC.

TPS1130 Background: Improving outcomes in patients (pts) with TNBC remains a high unmet need. Immune checkpoint inhibitors (ICIs) + chemotherapy (chemo) is approved for newly diagnosed pts with PD-L1+ tumors. Further, single-agent sacituzumab govitecan (SG), a Trop-2–directed antibody-drug conjugate, is approved for pts with mTNBC who received ≥2 prior systemic therapies (≥1 for metastatic disease). However, more options are needed for pts with PD-L1–negative mTNBC and for those with disease progression on chemo ± ICI. Magrolimab is a monoclonal antibody that blocks CD47, a “don’t eat me” signal often overexpressed on TNBC cells. Magrolimab blockade of CD47 induces macrophage-mediated phagocytosis of tumor cells and has shown preclinical activity and promising clinical efficacy in hematologic malignancies. Certain chemos, including taxanes, enhance prophagocytic signals on tumor cells, which may lead to synergistic antitumor activity with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab + nab-paclitaxel/paclitaxel or + SG in mTNBC. Methods: This open-label study has 2 cohorts (C) with safety run-in and phase (ph) 2 portions. Eligible pts are ≥18 y with measurable disease per RECIST 1.1. C1 pts have PD-L1–negative untreated mTNBC. C2 pts have mTNBC and received 1 prior line of therapy in the advanced setting, a taxane in the neoadjuvant/adjuvant or metastatic setting, and, if PD-L1+, an ICI. Exclusion criteria include active central nervous system disease, RBC transfusion dependence, and prior treatment with CD47/SIRPα-targeting agents. C1 assesses nab-paclitaxel/paclitaxel + magrolimab (safety run-in) or ± magrolimab (ph 2; randomized 1:1). C2 assesses magrolimab + SG (safety run-in and ph 2). In C1 safety run-in, magrolimab is given intravenously (IV) as a 1-mg/kg priming dose on day (D) 1 of cycle 1 to mitigate on-target anemia, followed by 30 mg/kg (cycle 1: D8, 15, 22; cycle 2: D1, 8, 15, 22; cycle 3+: D1, 15) (28-d cycles). In C2 safety run-in, pts receive a 1-mg/kg priming dose on D1, followed by 30 mg/kg (cycle 1: D8, 15; cycle 2: D1, 8, 15) and 60 mg/kg (cycle 3+: D1) (21-d cycles). The recommended ph 2 dose (RP2D) is determined in the safety run-in, with de-escalation if prespecified dose-limiting toxicity (DLT) criteria are met. Once RP2D is determined, the ph 2 cohorts will follow their respective dose schedules. Nab-paclitaxel/paclitaxel and SG are given IV per standard of care. The primary endpoints are incidence of DLTs, adverse events, and abnormal lab results by CTCAE v5.0 (safety run-in); progression-free survival by RECIST 1.1 (ph 2 C1); and confirmed objective response rate by RECIST 1.1 (C2; pooled safety run-in and ph 2). Planned enrollment is ≈144 pts. Clinical trial information: NCT04958785 .

Jaktinib in patients (pts) with myelofibrosis (MF) who were intolerant to ruxolitinib (RUX): An open-label, single-arm phase 2b study.

7061 Background: As the first approved Janus kinase inhibitor (JAKi) for pts with symptomatic MF, RUX showed superiority in spleen volume reduction with increased anemia and thrombocytopenia. However, there are few treatment options after RUX intolerance. Jaktinib, an oral novel JAK and ACVR1 inhibitor showed promising efficacy in Jaki-naïve pts with intermediate or high risk MF with mild side effects. Here we present the results of MF pts who were intolerant to RUX and received jaktinib 100 mg bid from a phase 2b study. Methods: Pts who had primary or post-ET/PV MF and were previously treated with RUX for ≥28 days who either required RBC transfusions or required more frequent transfusions on RUX, or had grade 3/4 anemia, thrombocytopenia or hematoma when receiving RUX, and with palpable spleen ≥5 cm were included. The primary endpoint was the proportion of pts with spleen volume reduction of ≥ 35% from baseline (SVR35) at week (wk) 24, assessed centrally on the basis of MRI/CT images. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with ≥ 50% reduction in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), anemia response, safety, etc. Results: A total of 45 patients received jaktinib 100 mg bid. The full analysis set (FAS) for efficacy included 44 pts who had completed the 24-week treatments and evaluations or terminated prior to wk 24, and excluded one pt because of incorrect diagnosis of MF. The median baseline TSS was 9.5, hemoglobin (Hb) was 79.5 g/L, and platelets was 132.5×109/L. While on RUX, 21 pts (48%) required RBC transfusion and all pts experienced those grade 3 hematological toxicities. In FAS, the SVR35 rate at wk 24 was 43% (19/44). Over the study phase, the best spleen response rate was 55% (24/44). The median time to achieve the first SVR35 was 12 weeks. Response was maintained in 80% pts for at least 24 weeks and median duration was not reached. At wk 24, 62% of the evaluable pts achieved a ≥ 50% improvement in TSS from baseline. Of 31 pts with baseline Hb ≤ 100 g/L, 13 (42%) had a ≥20 g/L Hb increase. Of 19 pts who required RBC transfusion at baseline, 11 (58%) had a 50% decrease in RBC infusion frequency. Of 9 transfusion-dependent pts at baseline, one became transfusion-independent. In the safety set (n = 45), the median jaktinib exposure time was 280 days. The most common grade ≥3 TEAEs were anemia (31%), thrombocytopenia (22%), pneumonia (18%), neutropenia (16%) and leukopenia (16%). Treatment discontinuation due to TEAEs occurred in five pts (11%). A dose reduction or temporary interruption due to TEAEs were reported in 12 pts (27%). Conclusions: Jaktinib demonstrated promising activities in MF pts who was intolerant to RUX by substantially reducing spleen volume, ameliorating MF-related symptom burdens, and elevating Hb levels. Jaktinib could be a viable treatment for MF pts with anemia in this setting. Clinical trial information: NCT04217993 .

Jaktinib in patients (pts) with myelofibrosis (MF) who were refractory to or relapsed after ruxolitinib: A single-arm, open-label, multicenter, phase 2 study.

7062 Background: Currently, ruxolitinib is the only marketed Janus kinase inhibitor (JAKi) for pts with MF in China, which demonstrated symptomatic and splenic benefit with increased cytopenias. However, at least 50% of pts develop resistance or intolerance to ruxolitinib in the long-term follow up, for whom life expectancy is largely reduced. There are few therapeutic options after ruxolitinib failure. Jaktinib, an oral novel JAK and AVCR1 inhibitor showed promising activity in Jaki-naïve pts with intermediate or high risk MF with mild side effects. Here we present the results of jaktinib in MF pts who were refractory or relapsed to prior ruxolitinib therapy. Methods: Pts who had primary or post-ET/PV MF and were previously treated with ruxolitinib for at least 3 months and with either inadequate efficacy response (defined as &lt; 10% spleen volume reduction [SVR] by MRI/CT or &lt; 30% decrease in spleen size by palpation from baseline) or spleen regrowth to &lt; 10% SVR or &lt; 30% decrease in spleen size from baseline following an initial response were recruited to receive jaktinib 100 mg twice daily. The primary endpoint was the proportion of pts with SVR ≥ 35% from baseline (SVR35) at week (wk) 24, measured by MRI/CT images and assessed by Independent Review Committee. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with ≥ 50% reduction in MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS), improvement of anemia and safety. Results: A total of 34 pts were enrolled. The median duration of previous ruxolitinib treatment was 18.6 months (range 3.4-70.1). The median baseline TSS was 19.5 (range 1-55), hemoglobin (Hb) was 101.5 g/L (range 61-149), and platelets was 159×109/L (range 66-951). 11 pts (32.4%) achieved SVR35 at wk 24. The best spleen response rate was 38.2% (13/34). The median time to achieve the first SVR35 was 8.1 weeks, and the median duration of response was not reached. At wk 24, 13 pts (46.4%) achieved a ≥ 50% improvement in TSS from baseline. Of 16 transfusion-independent pts with Hb ≤ 100 g/L at baseline, 8 (50.0%) had a ≥20 g/L Hb increase by wk 24. Of 6 pts who required RBC transfusion at baseline, 2 had a 50% decrease in RBC infusion by wk 24. The median jaktinib exposure time was 231 days (range 96-371). 23 pts (67.6%) had one or more grade ≥3 treatment emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were anemia (32.4%, n = 11), thrombocytopenia (32.4%, n = 11), leukocytosis (20.6%, n = 7) and leukopenia (11.8%, n = 4). Treatment discontinuation due to TEAEs occurred in 2 pts (5.9%). A dose reduction or temporary interruption due to TEAEs were reported in 9 pts (26.5%). Conclusions: MF pts who were refractory/relapsed to ruxolitinib attained substantial spleen response, and reduction in MF-related symptom burden with jaktinib, which could be a new option for MF pts who have failed ruxolitinib. Clinical trial information: NCT04851535 .

The effects of three different low-molecular-weight heparins on blood loss after intramedullary nailing of trochanteric fractures.

The purpose of this study was to compare the effects of reviparin, dalteparin and enoxaparin on intraoperative blood loss in patients with trochanteric fracture treated with intramedullary nailing. This retrospective multicenter study included 100 patients with trochanteric fracture who were divided into three groups according to the low-molecular-weight heparin administered. In all cases, a short third generation Gamma nail was used for osteosynthesis. Complete blood count and number of red blood cell transfusions (RBC) were evaluated. The mean value of postoperative haemoglobin level was lower in the enoxaparin group compared to the reviparin group, with significant difference (p = 0.001; 95% CI 4.1-18.87). Patients in the dalteparin group received more RBC transfusions compared to the reviparin and enoxaparin group (p = 0.048). The use of enoxaparin and dalteparin in hip fracture patients can result in lower postoperative haemoglobin levels and more RBC transfusions compared to reviparin.

Rural-urban differences in characteristics, postoperative outcomes, and costs for patients undergoing knee arthroplasty: a national retrospective propensity score matched cohort study.

The rural-urban disparities in postoperative complications and costs among patients undergoing knee arthroplasty (KA) have not been thoroughly explored. This study aimed to determine whether such differences exist in this patient population. The study was conducted using data from the national Hospital Quality Monitoring System of China. Hospitalized patients undergoing KA from 2013 to 2019 were enrolled. Patient and hospital characteristics were compared between rural and urban patients, and differences in postoperative complications, readmissions, and hospitalization costs were analyzed using propensity score matching. Of the 146,877 KA cases analyzed, 71.4% (104,920) were urban patients and 28.6% (41,957) were rural patients. Rural patients tended to be younger (64.4±7.7y vs. 68.0±8.0y; P<0.001) and had fewer comorbidities. In the matched cohort of 36,482 participants per group, rural patients were found to be more likely to experience deep vein thrombosis (OR: 1.31, 95% CI: 1.17-1.46; P<0.001) and require RBC transfusion (OR: 1.38, 95% CI: 1.31-1.46; P<0.001). However, they had a lower incidence of readmission within 30 days (OR: 0.65, 95% CI: 0.59-0.72; P<0.001) and readmission within 90 days (OR: 0.61, 95% CI: 0.57-0.66; P<0.001) than their urban counterparts. In addition, rural patients incurred lower hospitalization costs than urban patients (57,396.2 Chinese Yuan [CNY] vs. 60,844.3 CNY; P<0.001). Rural KA patients had different clinical characteristics compared with urban patients. While they had a higher likelihood of deep vein thrombosis and RBC transfusion following KA than urban patients, they had fewer readmissions and lower hospitalization costs. Targeted clinical management strategies are needed for rural patients.