Transfusion Burden Research Articles

Transfusion burden and willingness to pay for temporary alleviation of anemia status in transfusion-dependent beta-thalassemia patients in China

BackgroundTransfusion-dependent β-thalassemia (TDT) is one of the global public health concerns highlighted by the World Health Organization. Patients with TDT require regular blood transfusion to survive. However, the availability of blood resources is extremely limited. The purpose of this study was to investigate transfusion burden and willingness to pay (WTP) for temporary remission of anemia status among patients with TDT and to explore the associated factors.MethodsAdult patients with TDT were recruited through cluster sampling across several high-incidence provinces in China. Consenting patients completed online questionnaires on demographic information, transfusion burden and WTP with real-time WeChat communication assistance from researchers. The guiding techniques of double-bounded dichotomous choices and open-ended questions in the contingent valuation method (CVM) were used to obtain participants’ WTP for 1 unit of leukocyte-depleted red blood cells. WTP calculations were performed using maximum likelihood estimation, with further insights gained through subgroup analysis based on gender, family monthly income level and convenience of blood transfusion.ResultsThe analysis included 149 TDT patients from five high-incidence provinces, with an average monthly income of $198.5. Patients received an average of 3.7 units per transfusion, 15.4 times annually, with an average WTP of $70.4 per unit (95% CI [62.0, 78.9]). Estimated WTP for temporary anemia alleviation per transfusion totaled $260.6, exceeding monthly income by 1.32 times. Higher WTP was observed among males, higher-income households, and those with at least junior education. Lower WTP was noted among patients with lower transfusion volumes and those needing to travel for transfusion or during hospitalization for blood transfusion.ConclusionHigh WTP indicated a strong desire for temporary anemia relief. Most TDT patients faced significant economic and transfusion burden. The evident gap in meeting clinical needed underscores the urgent demand for innovative treatments to reduce transfusion dependency, potentially transforming TDT care and improving socioeconomic well-being and clinical outcomes. These findings supported evidence-based decision-making for TDT pharmacoeconomics and efficient healthcare resource allocation in China.

Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa.

Luspatercept, an inhibitor of the transforming growth factor beta (TGF-β) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic. By January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55-95) were treated with luspatercept ± ESA at two Charles University hematology centers in Prague and Hradec Králové. According to the WHO 2016 classification, the cohort included 32 MDS-RS-MLD, seven MDS-MLD, two patients with 5q- + ring sideroblasts (RS), 12 RARS-T, and 1 patient with CMML-0 + RS. SF3B1 mutation data were available for 45 patients. All patients were in the IPSS-R and IPSS-M lower-risk groups (except four IPSS-M high). The median follow-up was 17 months (range, 1-54). All patients were transfusion-dependent. Thirty-five (64.8%) patients had a high transfusion burden (HTB) with ≥ 4 transfusion units (TU)/8 weeks, and 19 (35.2%) had a low transfusion burden (LTB) (< 4 TU/8 weeks). The median time between diagnosis and initiation of luspatercept was 27 months (range, 4-156). ESA were used prior to luspatercept in 45 patients, and luspatercept was used as first-line treatment in nine patients. Thirty-one (61%) patients were treated simultaneously with ESA. Only patients who received luspatercept for ≥ 8 weeks (51 patients) were assessed. We evaluated the achievement of transfusion independence (TI) lasting 8, 12, 16, and 24 weeks. Thirty-two (62.7%) patients achieved TI for ≥ 8 weeks, 31 (60.7%) for ≥ 12 weeks, 29 (56.8%) for ≥ 16 weeks, and 25 (49%) for ≥ 24 weeks. Hematologic improvement (HI) without TI was achieved in six patients (11.7%). Overall, HI + TI was achieved in 38 patients (74.5%). Epoetin alfa was used simultaneously in 31 patients (60.7%). In 21 (55.2%) of all responding patients, concomitant therapy with epoetin alfa led to an improved response, with 16 reaching TI. Thirteen (25.5%) patients were nonresponders. Eight (21%) patients experienced therapy failure and became transfusion-dependent again. Optimal response required a gradual increase in the luspatercept dose to 1.75 mg/kg in up to 35 patients, with 23 responders (TI + HI). Response rates varied by transfusion burden: 79% in LTB and 50% in HTB reached TI. Of RS+ patients, 70% reached TI, while only one out of five RS- patients achieved TI. Among 39 SF3B1-positive patients, 61.6% achieved TI. In the low and very low IPSS-M groups, 86% of patients responded (TI + HI), compared to 62% in the moderate-low group. Luspatercept was well-tolerated, with no adverse events higher than grade II toxicity. We have demonstrated in real-world clinical practice that luspatercept is a very effective agent, even in an unselected, pretreated, significantly TD MDS population. The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.

Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor–Naive or –Experienced Myelofibrosis Treated With Momelotinib

PurposeAnemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor–naive and –experienced patients. MethodsAll RBC units transfused were collected during the baseline and 24-week treatment periods, initially in a single-arm phase 2 study as proof-of-concept analysis, and then versus comparators (ruxolitinib, best available therapy [BAT], and danazol) in the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM studies, respectively. ResultsIn the phase 2 study, mean transfusion requirement changed by −1.5 units/28 days, with 85% of patients (35/41) achieving numeric transfusion reduction. Across SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM, mean transfusion requirements decreased with momelotinib (−0.1, −0.36, and −0.86 units/28 days), while mean requirements with ruxolitinib, BAT, and danazol changed by +0.39, 0, and ‒0.28 units/28 days, respectively. Overall, 87% (185/213), 77% (79/103), and 85% (110/130) of patients had improved or stable transfusion intensities with momelotinib versus 54% (117/216), 62% (32/52), and 63% (41/65) with ruxolitinib, BAT, and danazol. ConclusionThese novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators. Trial registrationClinicalTrials.gov identifiers: NCT02515630, NCT01969838, NCT02101268, NCT04173494.

Assessment of transfusion-induced iron overload with T2*MRI in survivors of childhood acute lymphoblastic leukemia: A case control study

IntroductionChildhood acute lymphoblastic leukemia survivors receiving multiple packed red blood transfusions may be at risk of vital organ iron deposition causing long-term complications. This study was undertaken to assess the prevalence and severity of iron overload in the liver and heart by magnetic resonance imaging. MethodsA case-control study was conducted on 60 acute lymphoblastic leukemia survivors aged from 6 to 18 years and 60 healthy, age- and sex-matched children as a control group. The hematological profile, and serum ferritin was assessed and the iron content of the liver and heart was measured by T2* magnetic resonance imaging. ResultsTwenty-six (43.3 %) and two (3.3 %) patients had elevated liver and myocardial iron concentrations, respectively. The statistics show a significantly positive correlation between liver T2* magnetic resonance and serum ferritin. The total volume of blood transfused and duration of follow up were associated with elevated liver iron concentrations (p-values = 0.036 and 0.028 respectively). Myocardial T2* magnetic resonance lacked correlation with serum ferritin and transfusion therapy ConclusionLiver iron overload was detected in children and adolescents after acute lymphoblastic leukemia therapy. The risk of iron overload was related mainly to the transfusion burden during therapy. These patients need monitoring after therapy to assess their need for future chelation therapy.

Single-Unit Transfusion Policy in Autologous Hematopoietic Stem Cell Transplantation: Less is Not Worse

Single-unit red blood cell (1-RBC) transfusion policy has shown to effectively reduce transfusion burden while maintaining comparable clinical outcomes in hematological patients compared to the classical double-unit policy. However, its effects specifically after autologous stem cell transplantation (ASCT) have not been previously studied. We aimed to evaluate the impact of the 1-RBC policy on transfusion burden in a homogeneous cohort of patients undergoing ASCT. We retrospectively compared the transfusion requirements and the clinical outcomes of 187 patients transplanted from May 2019 to December 2022 under a 1-RBC policy, with a historical cohort of 153 patients transplanted from January 2016 to April 2019 under a double-unit policy. The 1-RBC policy was associated with a 32% reduction in RBC utilization and lower number of RBC transfusions at day 30 after transplantation (median 2 versus 3 units; P < .0001), with an odds ratio of 0.49 in multivariate analysis (P = .03). However, the number of transfusion episodes remained similar (median of 2 in both arms; P = .34). No significant differences in length of stay, hemoglobin levels at discharge or 30‐day mortality were observed. In conclusion, transitioning to the 1-RBC represents a straightforward action in current practice that significantly reduces blood transfusions in patients undergoing ASCT, without negatively impacting clinical outcomes.

Outpatient ATG-free hematopoietic transplantation for aplastic anemia in limited-resource environments offers excellent results: Data from a single LATAM center

ObjectiveTo document the results of outpatient hematopoietic stem cell transplantation (HSCT) from the peripheral blood (PB) of sibling donors without anti-thymocyte globulin (ATG) in the conditioning regimen. Material and methodsPatients from a low-income population with severe AA who received a PB, unmanipulated sibling HLA-identical HSCT between 2000 and 2020 at a single institution were studied. Survival was the primary outcome. ResultsForty-one transplants were performed. Time between diagnosis and transplant was five months (1–104). Median age was 37 (range, 4–61) years; 25 (61 %) recipients were males and 32 (78 %) had treatment failure, 9 (22 %) have not received treatment. ATG was administered in 5 (12.2 %) cases; the graft source was PB in 38 (92.7 %) transplants. Twenty-six (63.4 %) transplants were carried out in the outpatient setting. Infections developed in 14 (34.1 %) patients. Primary graft failure (GF) occurred in 3 (7.3 %) patients. The 15-year OS was 81 %, EFS was 77.4 %. Patients with high pre-HSCT transfusion burden had lower OS (p = 0.035) and EFS (p = 0.026). Previous treatment failure and age were not associated with lower OS (p = 0.115, p = 0.069) or EFS (p = 0.088, p = 0.5, respectively). ConclusionsHLA-identical T-cell replete outpatient HSCT from the PB of sibling donors for AA patients using ATG-free conditioning offers excellent long-term survival.

Transfusion independence after lenalidomide discontinuation in patients with del(5q) myelodysplastic neoplasm: a HARMONY Alliance study.

Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.

Care Patterns and Barriers to Outpatient Care for Adults With AML Following Intensive Chemotherapy at NCCN Member Institutions.

Prolonged hospitalization following intensive (re)induction chemotherapy for acute myeloid leukemia (AML), while standard, is costly and resource intense, limits inpatient bed capacity, and negatively impacts quality of life. Early hospital discharge (EHD) following completion of chemotherapy has proven safe as an alternative at select institutions, but is not widely implemented. From February 2023 through May 2023, the NCCN Best Practices Committee conducted a survey evaluating AML hospitalization patterns, care models, and barriers to EHD at its 33 member institutions. A total of 30 (91%) institutions completed the survey; two-thirds treat >100 patients with AML annually and 45% treat more than half of these with intensive chemotherapy. In the (re)induction setting, 80% of institutions keep patients hospitalized until blood count recovery, whereas 20% aim to discharge patients after completion of chemotherapy if medically stable and logistically feasible. The predominant reasons for the perceived need for ongoing hospitalization were high risk of infection, treatment toxicities, and lack of nearby/accessible housing. There was no significant association between ability to practice EHD and annual AML volume or treatment intensity patterns (P=.60 and P=.11, respectively). In contrast, in the postremission setting, 87% of centers support patients following chemotherapy in the outpatient setting unless toxicities arise requiring readmission. Survey responses showed that 80% of centers were interested in exploring EHD after (re)induction but noted significant barriers, including accessible housing (71%), transportation (50%), high toxicity/infection rate (50%), high transfusion burden (50%), and limited bed availability for rehospitalization (50%). Hospitalization and care patterns following intensive AML therapy vary widely across major US cancer institutions. Although only 20% of surveyed centers practice EHD following intensive (re)induction chemotherapy, 87% do so following postremission therapy. Given the interest in exploring the EHD approach given potential advantages of EHD for both patients and health care systems, strategies to address identified medical and logistical barriers should be explored.

Disease burden, management strategies, and unmet needs in α-thalassemia due to hemoglobin H disease.

Alpha-thalassemia is an inherited blood disorder caused by impaired α-globin chain production, leading to anemia and other complications. Hemoglobin H (HbH) disease is caused by a combination of mutations generally affecting the expression of three of four α-globin alleles; disease severity is highly heterogeneous, largely driven by genotype. Notably, non-deletional mutations cause a greater degree of ineffective erythropoiesis and hemolysis, higher transfusion burden, and increased complication risks versus deletional mutations. There are limited treatment options for HbH disease, and effective therapies are needed. This review discusses the pathophysiology of HbH disease, current management strategies, unmet needs, and emerging treatment options.

Luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): primary analysis of a phase 3, open-label, randomised, controlled trial

The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial. COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting). Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis. Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups. Celgene and Acceleron Pharma.

Roxadustat versus placebo for patients with lower-risk myelodysplastic syndrome: MATTERHORN phase 3, double-blind, randomized controlled trial.

In patients with lower-risk myelodysplastic syndromes/neoplasms (MDS), response to first-line therapy is limited and transient. The MATTERHORN randomized, double-blind, phase 3 trial evaluated roxadustat versus placebo for patients with transfusion-dependent, lower-risk MDS. Eligible patients had very low-, low-, or intermediate-risk MDS with or without prior erythropoiesis-stimulating agent treatment, and a transfusion burden of 1-4 packed red blood cell (pRBC) units every 8 weeks (Q8W). Patients were randomized (3:2) to oral roxadustat (2.5 mg/kg) or placebo, both three times weekly, with best supportive care. Primary efficacy endpoint was transfusion independence (TI) for ≥56 days within 28 weeks (TI responders). MATTERHORN was terminated due to interim analysis outcomes not meeting statistical significance. In total, 272 patients were screened, and 140 patients were enrolled (82, roxadustat, and 58, placebo). At final analysis, 38/80 (47.5%) patients and 19/57 (33.3%) in the roxadustat and placebo arms, respectively, were TI responders (p = .217). A greater percentage of patients in the roxadustat arm with a transfusion burden of ≥2 pRBC units Q4W were TI responders (36.1%; 13/36) compared with the placebo arm (11.5%; 3/26; p-nominal = .047). The seven on-study deaths (4, roxadustat, and 3, placebo) were considered unrelated to treatment. Three roxadustat patients progressed to acute myeloid leukemia. Despite MATTERHORN not meeting its primary endpoint, a numerically higher TI rate was achieved with roxadustat treatment compared with placebo. Further analyses are needed to confirm the MDS patient subgroups deriving clinical benefit from this novel treatment.

EE310 The Burden of Blood Transfusions Associated With Lower-Risk Myelodysplastic Syndromes (LR-MDS): Findings From a Survey of Health Care Professionals (HCPs) in Brazil, Germany, and Japan

EE310 The Burden of Blood Transfusions Associated With Lower-Risk Myelodysplastic Syndromes (LR-MDS): Findings From a Survey of Health Care Professionals (HCPs) in Brazil, Germany, and Japan

Safety and efficacy of luspatercept for the treatment of anemia in patients with myelofibrosis

AbstractThe ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non–transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542.

Clinical benefit of luspatercept treatment (tx) in transfusion-dependent (TD), erythropoiesis-stimulating agent (ESA)–naive patients (pts) with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) in the COMMANDS trial.

6565 Background: There is an unmet need for effective tx that provides durable benefit for pts with anemia due to lower-risk MDS (LR-MDS). Here we report clinically meaningful responses to luspatercept tx in TD, ESA-naive pts with LR-MDS in the COMMANDS trial. Methods: Eligible pts were ≥ 18 years of age, had LR-MDS with or without ring sideroblasts and &lt; 5% bone marrow blasts, endogenous serum erythropoietin &lt; 500 U/L, required red blood cell (RBC) transfusions (defined as 2−6 RBC units/8 weeks [wk] for ≥ 8 wk prior to randomization), and were ESA-naive. Pts were randomized 1:1 to subcutaneous administration of luspatercept (1.0–1.75 mg/kg) once every 3 wk or epoetin alfa (EA; 450–1050 IU/kg) once weekly for ≥ 24 wk. New assessments of clinical benefit reported here include achievement and duration of ≥ 50% reduction in RBC units transfused over ≥ 12 wk (wk 1–end of tx [EOT]), transfusion burden (TB) on tx (wk 1–24), time to first transfusion, achievement and cumulative duration of all separate RBC transfusion independence (RBC-TI) ≥ 12 wk response episodes, and mean hemoglobin (Hb) increase ≥ 1.5 g/dL over wk 1–24. Results: As of March 31, 2023, 151/182 (83.0%) luspatercept- and 121/181 (66.9%) EA-treated pts achieved ≥ 50% reduction in RBC units transfused over ≥ 12 wk (wk 1–EOT; P= 0.0002), with median (95% confidence interval [CI]) durations of 130.0 (120.6–not evaluable [NE]) and 77.0 (54.9–123.1) wk, respectively ( P = 0.0004). A greater proportion of luspatercept vs EA pts achieved ≥ 50% reduction in RBC units transfused over ≥ 12 wk (wk 1–EOT), regardless of baseline (BL) TB: 105/118 (89.0%) luspatercept vs 82/111 (73.9%) EA pts with BL TB &lt; 4 RBC units/8 wk and 46/64 (71.9%) luspatercept vs 39/70 (55.7%) EA pts with TB ≥ 4 RBC units/8 wk. The median (interquartile range) number of RBC units transfused during wk 1–24 of tx was 1.0 (0–5.0) in the luspatercept arm and 3.0 (0–8.0) in the EA arm. The median (95% CI) time to first transfusion was 155.0 (80.0–266.0) days for luspatercept vs 42.0 (23.0–55.0) days for EA pts ( P &lt; 0.0001). Among pts who achieved RBC-TI ≥ 12 wk (wk 1–24), 22/124 (17.7%) luspatercept pts vs 12/88 (13.6%) EA pts achieved ≥ 2 separate RBC-TI ≥ 12 wk response episodes and cumulative median (95% CI) duration of all response episodes was 147.9 (122.0–NE) wk in the luspatercept arm and 95.1 (73.1–NE) wk in the EA arm ( P = 0.0067). Mean Hb increase ≥ 1.5 g/dL over wk 1–24 was achieved by 135/182 (74.2%) luspatercept pts and 95/181 (52.5%) EA pts ( P &lt; 0.0001). Conclusions: Significantly greater proportions of luspatercept vs EA pts achieved improvements in Hb levels, reduction in TB and RBC units transfused, and had durable RBC-TI responses. Luspatercept provided clinically meaningful outcomes, supporting its use as the preferred tx for ESA-naive pts with LR-MDS-associated anemia. Clinical trial information: NCT03682536 .

Patient (pt) experience with and perceptions of transfusion-dependent (TD) and transfusion-independent (TI) myelofibrosis (MF): A qualitative interview study.

e23110 Background: MF is a rare myeloproliferative neoplasm for which Janus kinase inhibitors are the standard of care. Some Janus kinase inhibitors can exacerbate anemia, a hallmark feature of MF that increases in severity with disease progression. Red blood cell transfusions are an important component of anemia management, but transfusion dependence is an independent predictor of poor survival outcomes and is inversely correlated with quality of life (QOL). The current study aimed to elicit the perceived direct and indirect burden of transfusion dependence and its impact on pts with MF. Methods: Concept elicitation interviews were conducted remotely with Janus kinase inhibitor–experienced and symptomatic (MF Symptom Assessment Form v4.0 Total Symptom Score [TSS] ≥10) pts with MF across the US, UK, Germany, Italy, Spain, and Poland (N = 20). Five TD pts (≥2 blood transfusions in any 1 mo over the last 3 mo) and 15 TI pts (≤1 blood transfusion in any 1 mo over the last 3 mo) participated in 60-minute interviews, which followed a semistructured guide including open-ended questions and completion of ranking exercises and sociodemographic and clinical forms. Results: Of 20 pts, mean age was 59 years, 50% were male, and85% received a diagnosis of anemia after their MF diagnosis. Pts with anemia experienced a range of related symptoms, including fatigue (94%), weakness (53%), and night sweats (29%). These symptoms impacted several QOL domains, including emotional (88%) and physical (71%) health and social life (71%). Most pts (18 of 20) had received a transfusion in the past, of whom 5 were TD. In addition to higher transfusion burden, TD pts had higher symptom burden than TI pts (mean TSS, 30.8 vs 27.9).TD pts endorsed challenges with frequent transfusions relating to clinical concerns/safety (100%), convenience (100%), and travel (80%), all of which remained concerns when thinking about being TD in the future (40% each). These challenges resulted in emotional (80%) and physical (60%) impacts and impacts to activities of daily living (60%). Four of 5 (80%) reported that going ≥12 weeks without a transfusion would be helpful and positively impact their QOL. Similarly, TI pts felt it was important to remain TI, with 73% expressing concerns about becoming TD in the future. Regarding the most important MF treatment outcomes, MF symptom reduction and overall survival were the most common (40% each) among TD pts, and reduction/avoidance of transfusion was the most common (40%) among TI pts. Conclusions: These interviews characterize the substantial negative experiences with and perceptions of anemia and transfusions in pts with MF who are TD and those who are TI but concerned about becoming TD in the future. These findings highlight the value of treatment options that reduce/eliminate transfusion burden and prevent future transfusions in improving the experiences of pts with MF.

Preliminary safety and efficacy of oral azacitidine (Oral-AZA) in patients (pts) with low-/Intermediate (Int)-risk myelodysplastic syndromes (MDS): Phase 2 results from the ASTREON trial.

6509 Background: There is an unmet need for new treatment (tx) options in lower-risk MDS (LR-MDS) to address cytopenias and prevent progression to higher-risk MDS and acute myeloid leukemia. Here, we report safety and preliminary efficacy data from phase 2 of the ASTREON study, which evaluated 14-day Oral-AZA regimens in pts with Low-/Int-risk MDS. Methods: ASTREON is a phase 2/3, multicenter study evaluating safety and efficacy of Oral-AZA plus best supportive care (BSC) in pts with Low-/Int-risk MDS (NCT05469737). Phase 2 is an open-label, dose optimization study to determine the recommended phase 3 Oral-AZA dose. Eligible pts (≥ 18 years of age with Revised International Prognostic Scoring System [IPSS-R] Low-/Int-risk MDS and ≥ 1 cytopenia) were randomized 1:1 to receive Oral-AZA 200 mg or 300 mg QD for 14 d per 28-d cycle plus BSC. Primary endpoints are rates of adverse events (AEs) and complete remission (CR) within 6 cycles per International Working Group (IWG) 2006 criteria. Secondary endpoints include achievement of overall response (OR) (including CR, partial remission, marrow CR, hematologic improvement-erythroid response [HI-E], HI-platelet response, and HI-neutrophil response per IWG 2006 criteria); best OR; and OR duration. HI rates within 6 cycles were calculated by investigator assessment per IWG 2006 criteria for pts who received ≥ 75% of the cycle 1 dose and had ≥ 1 post-baseline (BL) efficacy assessment (modified intent-to-treat [mITT] population). Results: As of December 4, 2023, 47 pts were randomized and received ≥ 1 Oral-AZA dose (200 mg, n = 24; 300 mg, n = 23); 6 and 5 pts discontinued tx in the 200 mg and 300 mg arms. The median (range) tx durations were 24.1 (12.1–34.1) and 24.7 (7.7–39.1) wk for the 200 mg and 300 mg arms, respectively. IPSS-R scores and RBC transfusion burden at BL were balanced between tx arms. Most pts (42/47 [89.4%]) had prior MDS tx, including but not limited to erythropoiesis-stimulating agents, lenalidomide, luspatercept, and imetelstat. AE rates were similar between arms: 11/24 (45.8%) vs 12/23 (52.2%) pts in the 200 mg vs 300 mg arms reported ≥ 1 tx-related grade 3 or 4 tx-emergent AE. The most common tx-related AEs in both arms were hematologic and gastrointestinal. Tx-related serious AEs occurred in 1/24 and 3/23 pts in the 200 mg and 300 mg arms, respectively. One death occurred in the 300 mg arm and was considered tx-related. In the mITT population, 8/22 and 7/21 pts achieved any HI in the 200 mg and 300 mg arms, respectively. Six pts in each dose group achieved HI-E. Among mITT pts with anemia at BL, 6/19 (31.6%) pts in the 200 mg and 5/18 (27.8%) pts in the 300 mg arm achieved HI-E. Updated results will be presented. Conclusions: The safety of Oral-AZA 200 mg and 300 mg was consistent with the known Oral-AZA safety profile. Preliminary efficacy data support continued evaluation of Oral-AZA in LR-MDS. Clinical trial information: NCT05469737 .

A call for improved anemia treatments in myelofibrosis: A single-center retrospective study.

e18531 Background: Anemia in myelofibrosis (MF) is associated with poor prognosis and decreased quality of life. Effective treatments are limited, posing a significant challenge in clinical management. This study aims to provide insights into the treatment of anemia in MF patients from an underserved urban tertiary care center. Methods: We retrospectively reviewed 88 MF patients referred to our center in the Bronx, NY between 2000 and 2023. Demographic data, presence of anemia (hemoglobin ≦10 g/dl) at time of diagnosis or referral (TODR), transfusion dependence ( ≥ 2 units on ≥2 occasions within 8 weeks), anemia treatments, disease modifying treatment, and anemia response to treatments (as defined by the IWG-MRT and ELN consensus report) were assessed via non-parametric tests and univariate cox regression. Events were defined as death from any cause or development of anemia. Patients with missing data were excluded. Results: Among 88 patients analyzed, 77 (87.5%) experienced anemia during the study period. Overall survival (OS) for anemic patients was 7.7 years with 31 deaths, versus only 1 death in the non-anemic group. 51 (60%) of patients were anemic at TODR. For patients not anemic at TODR, median time to anemia (TTA) was 31 months. Patients with HMR (n=24) had faster median TTA than those without (22 vs. 49 months, p = 0.1). All triple-negative (TN) patients (n=8) were anemic at TODR and had statistically lower initial hemoglobin compared to patients with driver mutations (7.4 g/dl vs. 9.9 g/dl, p = 0.0023). Among anemic patients (n=77), age &gt; 65 was associated with poorer OS (HR 2.293, CI 1.076 - 4.887, p=.0315), while transfusion dependency (HR 2.093, CI 0.4777 - 0.9422, p=0.0697) and Ruxolitinib use (HR 2.843, CI 0.9912 - 8.155, HR 0.052) approached significance. Secondary anemia treatments did not impact OS (HR 0.9346, CI 0.4537 - 1.925, p=.854) and are summarized in the table. Most patients received Ruxolitinib (68.8%) and hydroxyurea (35.06%), while fewer received Momelotinib (N = 4), Pacritinib (N = 6), or Fedratinib (N = 4). Conclusions: Our findings highlight the limited effectiveness of current treatments in reducing transfusion burden and anemia in MF, and that patients of higher genetic risk may be more susceptible to developing anemia. Transfusion dependency and treatment non-response are marginally associated with poorer outcomes, emphasizing the need for newer therapies. [Table: see text]

Thalidomide and Hydroxyurea in Transfusion-Dependent Thalassemia: Efficacy, Safety Profile and Impact on Quality of Life

Transfusion-dependent thalassemia (TDT) is a major public health concern in India, requiring regular transfusions for survival. There is also significant morbidity caused by iron overload and transfusion related infections. Novel therapies targeting fetal hemoglobin induction are the need of the hour in resource-poor institutions for patients where transplant is not feasible for various reasons. This single arm, non-randomised prospective trial evaluated the efficacy and safety of a combination of low dose thalidomide and hydroxyurea in TDT along with the impact on quality of life (QoL). It included 41 TDT patients, who failed a reasonable trial of hydroxyurea. Complete response (CR) was defined as transfusion independence and partial response (PR) denoted at least a 50% reduction in transfusion requirement. The rest were defined as non-responders (NR). The mean age of the cohort was 20.78 years (range 12–45 years). There were 13 males and 28 females. Nineteen (46.3%), 7 (17.1%), and 15 (36.6%) patients achieved CR, PR, and no response respectively. The overall response rate (CR + PR) was 63.4%. There was a significant increase in hemoglobin levels with decrement in transfusion burden and ferritin levels. There were no significant adverse reactions. No significant predictors of response were found including amongst genetic modifiers. It improved the health related QoL amongst responders. The combination of thalidomide and hydroxyurea appear safe and effective in the reduction in transfusion requirement of TDT patients. The judicious use of these drugs can improve the quality of life and pave the way for patients not eligible for a stem cell transplant.

Blood Transfusion Burden Of General Surgical Diseases At The Rivers State University Teaching Hospital, Port Harcourt, Nigeria

Blood Transfusion Burden Of General Surgical Diseases At The Rivers State University Teaching Hospital, Port Harcourt, Nigeria

Combination of a TGF-β ligand trap (RAP-GRL) and TMPRSS6-ASO is superior for correcting β-thalassemia.

A recently approved drug that induces erythroid cell maturation (luspatercept) has been shown to improve anemia and reduce the need for blood transfusion in non-transfusion-dependent as well as transfusion-dependent β-thalassemia (BT) patients. Although these results were predominantly positive, not all the patients showed the expected increase in hemoglobin (Hb) levels or transfusion burden reduction. Additional studies indicated that administration of luspatercept in transfusion-dependent BT was associated with increased erythropoietic markers, decreased hepcidin levels, and increased liver iron content. Altogether, these studies suggest that luspatercept may necessitate additional drugs for improved erythroid and iron management. As luspatercept does not appear to directly affect iron metabolism, we hypothesized that TMPRSS6-ASO could improve iron parameters and iron overload when co-administered with luspatercept. We used an agent analogous to murine luspatercept (RAP-GRL) and another novel therapeutic, IONIS TMPRSS6-LRx (TMPRSS6-ASO), a hepcidin inducer, to treat non-transfusion-dependent BT-intermedia mice. Our study shows that RAP-GRL alone improved red blood cell (RBC) production, with no or limited effect on splenomegaly and iron parameters. In contrast, TMPRSS6-ASO improved RBC measurements, ameliorated splenomegaly, and improved iron overload most effectively. Our results provide pre-clinical support for combining TMPRSS6-ASO and luspatercept in treating BT, as these drugs together show potential for simultaneously improving both erythroid and iron parameters in BT patients.