How I treat anemia in older adults.

ABSTRACT: With the global growing older adult population, clinicians face the common, yet complex challenge of how to evaluate and manage anemia in this population. Older age predisposes to common causes of anemia such as nutritional deficiencies, inflammatory disorders, chronic kidney disease, and hematologic malignancies. Failure to diagnose and appropriately manage anemia may result in decreased quality of life, impaired cognition, impaired mobility, and increased mortality. Anemia diagnosis in older adults presents a diagnostic conundrum because anemia may have a single cause, may be multifactorial, or may have no apparent cause even after an extensive evaluation. We believe a systematic approach to diagnosis ensures appropriate testing and avoids the pitfall of undertreatment and overtreatment. In this article we present our recommended approach through common scenarios for the management of anemia in the older adult.

Effect of Low-Dose Aspirin Versus Placebo on Incidence of Anemia in the Elderly : A Secondary Analysis of the Aspirin in Reducing Events in the Elderly Trial.

BACKGROUND: Daily low-dose aspirin increases major bleeding; however, few studies have investigated its effect on iron deficiency and anemia. OBJECTIVE: To investigate the effect of low-dose aspirin on incident anemia, hemoglobin, and serum ferritin concentrations. DESIGN: Post hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial. (ClinicalTrials.gov: NCT01038583). SETTING: Primary/community care in Australia and the United States. PARTICIPANTS: Community-dwelling persons aged 70 years or older (≥65 years for Black persons and Hispanic persons). INTERVENTION: 100 mg of aspirin daily or placebo. MEASUREMENTS: Hemoglobin concentration was measured annually in all participants. Ferritin was measured at baseline and 3 years after random assignment in a large subset. RESULTS: 19 114 persons were randomly assigned. Anemia incidence in the aspirin and placebo groups was 51.2 events and 42.9 events per 1000 person-years, respectively (hazard ratio, 1.20 [95% CI, 1.12 to 1.29]). Hemoglobin concentrations declined by 3.6 g/L per 5 years in the placebo group and the aspirin group experienced a steeper decline by 0.6 g/L per 5 years (CI, 0.3 to 1.0 g/L). In 7139 participants with ferritin measures at baseline and year 3, the aspirin group had greater prevalence than placebo of ferritin levels less than 45 µg/L at year 3 (465 [13%] vs. 350 [9.8%]) and greater overall decline in ferritin by 11.5% (CI, 9.3% to 13.7%) compared with placebo. A sensitivity analysis quantifying the effect of aspirin in the absence of major bleeding produced similar results. LIMITATIONS: Hemoglobin was measured annually. No data were available on causes of anemia. CONCLUSION: Low-dose aspirin increased incident anemia and decline in ferritin in otherwise healthy older adults, independent of major bleeding. Periodic monitoring of hemoglobin should be considered in older persons on aspirin. PRIMARY FUNDING SOURCE: National Institutes of Health and Australian National Health and Medical Research Council.

Association Between Pretreatment Skeletal Muscle and Outcomes After CAR T-Cell Therapy.

BACKGROUND: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell-associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. PATIENTS AND METHODS: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. RESULTS: The median age of the cohort was 63.1 years (range, 18.5-82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05-2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; P<.05) compared with those with normal muscle mass. Abnormal skeletal muscle was independently associated with risk of disease progression (HR, 1.70; 95% CI, 1.11-2.57) and worse survival (HR, 2.44; 95% CI, 1.49-4.00) at 1 year compared with normal skeletal muscle. Individuals who had abnormal skeletal muscle and high lactate dehydrogenase (LDH) levels at baseline had poor 1-year PFS (17%) and OS (12%) compared with those with normal skeletal muscle and LDH levels (72% and 82%, respectively; P<.001). Patients who had abnormal skeletal muscle and LDH levels had a 5-fold risk (HR, 5.34; 95% CI, 2.97-9.62) of disease progression and a 10-fold risk (HR, 9.73; 95% CI, 4.81-19.70) of death (reference: normal skeletal muscle, normal LDH), independent of prior lines of therapy, extent of residual disease at time of CAR T-cell therapy, functional status, or product. CONCLUSIONS: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.

Effect of Aging and Predonation Comorbidities on the Related Peripheral Blood Stem Cell Donor Experience: Report from the Related Donor Safety Study.

The development of reduced-intensity approaches for allogeneic hematopoietic cell transplantation has resulted in growing numbers of older related donors (RDs) of peripheral blood stem cells (PBSCs). The effects of age on donation efficacy, toxicity, and long-term recovery in RDs are poorly understood. To address this we analyzed hematologic variables, pain, donation-related symptoms, and recovery in 1211 PBSC RDs aged 18 to 79 enrolled in the Related Donor Safety Study. RDs aged > 60 had a lower median CD34+ level before apheresis compared with younger RDs (age > 60, 59 × 106/L; age 41 to 60, 81 × 106/L; age 18 to 40, 121 × 106/L; P < .001). This resulted in older donors undergoing more apheresis procedures (49% versus 30% ≥ 2 collections, P < .001) and higher collection volumes (52% versus 32% > 24 L, P < .001), leading to high percentages of donors aged > 60 with postcollection thrombocytopenia <50 × 109/L (26% and 57% after 2 and 3days of collection, respectively). RDs aged 18 to 40 had a higher risk of grades 2 to 4 pain and symptoms pericollection, but donors over age 40 had more persistent pain at 1, 6, and 12 months (odds ratio [OR], 1.7; P = 0.02) and a higher rate of nonrecovery to predonation levels (OR, 1.7; P = .01). Donors reporting comorbidities increased significantly with age, and those with comorbidities that would have led to deferral by National Marrow Donor Program unrelated donor standards had an increased risk for persistent grades 2 to 4 pain (OR, 2.41; P < .001) and failure to recover to predonation baseline for other symptoms (OR, 2.34; P = .004). This information should be used in counseling RDs regarding risk and can assist in developing practice approaches aimed at improving the RD experience for high-risk individuals.

Related peripheral blood stem cell donors experience more severe symptoms and less complete recovery at one year compared to unrelated donors.

Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation-related toxicities, we conducted a prospective observational trial of 11,942 related and unrelated donors aged 18-60 years. Bone marrow (BM) was collected at 37 transplant and 78 National Marrow Donor Program centers, and peripheral blood stem cells (PBSC) were collected at 42 transplant and 87 unrelated donor centers in North America. Possible presence of medical comorbidities was verified prior to donation, and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following. Multivariate analyses showed similar experiences for BM collection in related and unrelated donors; however, related stem cell donors had increased risk of moderate [odds ratios (ORs) 1.42; P<0.001] and severe (OR 8.91; P<0.001) pain and toxicities (OR 1.84; P<0.001) with collection. Related stem cell donors were at increased risk of persistent toxicities (OR 1.56; P=0.021) and non-recovery from pain (OR 1.42; P=0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors with more significant comorbidities were at especially high risk for grade 2-4 pain (OR 3.43; P<0.001) and non-recovery from toxicities (OR 3.71; P<0.001) at one year. Related donors reporting grade ≥2 pain had significant decreases in Health-Related Quality of Life (HR-QoL) scores at one month and one year post donation (P=0.004). In conclusion, related PBSC donors with comorbidities are at increased risk for pain, toxicity, and non-recovery at one year after donation. Risk profiles described in this study should be used for donor education, planning studies to improve the related donor experience, and decisions regarding donor deferral. Registered at clinicaltrials.gov identifier:00948636.

Reduced-Intensity Allogeneic Transplant for Acute Myeloid Leukemia and Myelodysplastic Syndrome Using Combined CD34-Selected Haploidentical Graft and a Single Umbilical Cord Unit Compared with Matched Unrelated Donor Stem Cells in Older Adults.

Haplo/cord transplantation combines an umbilical cord blood (UCB) graft with CD34-selected haploidentical cells and results in rapid hematopoietic recovery followed by durable UCB engraftment. We compared outcomes of transplants in older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) who received either HLA-matched unrelated donor (MUD) cells or haplo/cord grafts. Between 2007 and 2013, 109 adults ages 50 and older underwent similar reduced-intensity conditioning with fludarabine and melphalan and antibody-mediated T cell depletion for AML (n = 83) or high-risk MDS (n = 26) followed by either a MUD (n = 68) or haplo/cord (n = 41) graft. Patient characteristics were similar for each graft source except for more minority patients receiving a haplo/cord transplant (P = .01). One half of the AML patients were not in remission. Two-year progression-free survival (PFS), overall survival (OS), and graft-versus-host disease-free relapse-free survival were 38%, 48%, and 32.1% for MUD and 33%, 48%, and 33.8% for haplo/cord transplants (P = .62 for PFS; P = .97 for OS; P= .84), respectively. Acute grades II to IV and chronic graft-versus-host-disease rates did not differ at 19.5% and 4.9% in haplo/cord compared with 25% and 7.4% after MUD (P = .53 and P = .62, respectively). Multivariate analysis confirmed no significant differences in transplant outcomes by donor type. Haplo/cord reduced-intensity transplantation achieves similar outcomes relative to MUD in older AML and MDS patients, making this a promising option for those without matched donors.

Frequency and Risk Factors Associated with Cord Graft Failure after Transplant with Single-Unit Umbilical Cord Cells Supplemented by Haploidentical Cells with Reduced-Intensity Conditioning.

Delayed engraftment and cord graft failure (CGF) are serious complications after unrelated cord blood (UCB) hematopoietic stem cell transplantation (HSCT), particularly when using low-cell-dose UCB units. The haplo-cord HSCT approach allows the use of a lower dose single UCB unit by co-infusion of a CD34(+) selected haploidentical graft, which provides early transient engraftment while awaiting durable UCB engraftment. We describe the frequency, complications, and risk factors of CGF after reduced-intensity conditioning haplo-cord HSCT. Among 107 patients who underwent haplo-cord HSCT, 94 were assessable for CGF, defined as <5% cord blood chimerism at day 60 in the myeloid and CD3 compartments, irrespective of neutrophil and platelet counts. CGF occurred in 14 of 94 assessable patients (15%). Median survival after CGF was 12.7 months with haploidentical or mixed haploidentical-autologous hematopoiesis persisting in the 7 surviving. Median progression-free survival after CGF was 7.7 months and was not statistically different from those without CGF (10.47 months; P = .18). In univariate analyses, no UCB factors were associated with CGF, including cell dose, cell viability, recipient major ABO mismatch against the UCB unit, or degree of HLA match. We also found no association of CGF with recipient cytomegalovirus serostatus, haploidentical donor age, or day 30 haploidentical chimerism. However, higher haploidentical total nucleated and CD34(+) cell doses and day 30 UCB chimerism < 5% in either the myeloid or CD3 compartments were associated with greater risk of CGF. We conclude that assessing chimerism at day 30 may foretell impending CGF, and avoidance of high haploidentical cell doses may reduce risk of CGF after haplo-cord HSCT. However, long-term survival is possible after CGF because of predominant haploidentical or mixed chimerism and hematopoietic function.

The prognostic value of serum C-reactive protein, ferritin, and albumin prior to allogeneic transplantation for acute myeloid leukemia and myelodysplastic syndromes.

We sought to confirm the prognostic importance of simple clinically available biomarkers of C-reactive protein, serum albumin, and ferritin prior to allogeneic hematopoietic cell transplantation. The study population consisted of 784 adults with acute myeloid leukemia in remission or myelodysplastic syndromes undergoing unrelated donor transplant reported to the Center for International Blood and Marrow Transplant Research. C-reactive protein and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas each center provided pre-transplant albumin. In multivariate analysis, transplant-related mortality was associated with the pre-specified thresholds of C-reactive protein more than 10 mg/L (P=0.008) and albumin less than 3.5 g/dL (P=0.01) but not ferritin more than 2500 ng/mL. Only low albumin independently influenced overall mortality. Optimal thresholds affecting transplant-related mortality were defined as: C-reactive protein more than 3.67 mg/L, log(ferritin), and albumin less than 3.4 g/dL. A 3-level biomarker risk group based on these values separated risks of transplant-related mortality: low risk (reference), intermediate (HR=1.66, P=0.015), and high risk (HR=2.7, P<0.001). One-year survival was 74%, 67% and 56% for low-, intermediate- and high-risk groups. Routinely available pre-transplant biomarkers independently risk-stratify for transplant-related mortality and survival.

Race and ethnicity influences collection of granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells from unrelated donors, a Center for International Blood and Marrow Transplant Research analysis.

Little information exists on the effect of race and ethnicity on collection of peripheral blood stem cells (PBSC) for allogeneic transplantation. We studied 10,776 donors from the National Marrow Donor Program who underwent PBSC collection from 2006 to 2012. Self-reported donor race/ethnic information included Caucasian, Hispanic, Black/African American (AA), Asian/Pacific Islander (API), and Native American (NA). All donors were mobilized with subcutaneous filgrastim at an approximate dose of 10 µg/kg/day for 5 days. Overall, AA donors had the highest median yields of mononuclear cells per liter and CD34(+) cells per liter of blood processed (3.1 × 10(9) and 44 × 10(6), respectively), whereas Caucasians had the lowest median yields at 2.8 × 10(9) and 33.7 × 10(6), respectively. Multivariate analysis of CD34(+) per liter mobilization yields using Caucasians as the comparator and controlling for age, gender, body mass index, and year of apheresis revealed increased yields in overweight and obese AA and API donors. In Hispanic donors, only male obese donors had higher CD34(+) per liter mobilization yields compared with Caucasian donors. No differences in CD34(+) per liter yields were seen between Caucasian and NA donors. Characterization of these differences may allow optimization of mobilization regimens to allow enhancement of mobilization yields without compromising donor safety.

The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia.

Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome-positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk, .89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk, .93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk, .9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk, .96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning.

Analysis of the Effect of Race, Socioeconomic Status, and Center Size on Unrelated National Marrow Donor Program Donor Outcomes: Donor Toxicities Are More Common at Low-Volume Bone Marrow Collection Centers.

Previous studies have shown that risks of collection-related pain and symptoms are associated with sex, body mass index, and age in unrelated donors undergoing collection at National Marrow Donor Program centers. We hypothesized that other important factors (race, socioeconomic status [SES], and number of procedures at the collection center) might affect symptoms in donors. We assessed outcomes in 2726 bone marrow (BM) and 6768 peripheral blood stem cell (PBSC) donors collected between 2004 and 2009. Pain/symptoms are reported as maximum levels over mobilization and collection (PBSC) or within 2 days of collection (BM) and at 1 week after collection. For PBSC donors, race and center volumes were not associated with differences in pain/symptoms at any time. PBSC donors with high SES levels reported higher maximum symptom levels 1 week after donation (P = .017). For BM donors, black males reported significantly higher levels of pain (OR, 1.90; CI, 1.14 to 3.19; P = .015). No differences were noted by SES group. BM donors from low-volume centers reported more toxicity (OR, 2.09; CI, 1.26 to 3.46; P = .006). In conclusion, race and SES have a minimal effect on donation-associated symptoms. However, donors from centers performing ≤ 1 BM collection every 2 months have more symptoms after BM donation. Approaches should be developed by registries and low-volume centers to address this issue.

Allotransplantation for patients age ≥40 years with non-Hodgkin lymphoma: encouraging progression-free survival.

Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age ≥40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL. Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age ≥65; P = .0008). Fewer patients aged ≥65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age ≥65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age ≥65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age ≥55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.

A prospective randomized wait list control trial of intravenous iron sucrose in older adults with unexplained anemia and serum ferritin 20-200 ng/mL.

Anemia is common in older persons and is associated with substantial morbidity and mortality. One third of anemic older adults have unexplained anemia of the elderly (UAE). We carried out a randomized, wait list control trial in outpatients with UAE and serum ferritin levels between 20 and 200 ng/mL. Intravenous iron sucrose was given as a 200-mg weekly dose for 5 weeks either immediately after enrollment (immediate intervention group) or following a 12-week wait list period (wait list control group). The primary outcome measure was changed in 6-minute walk test (6MWT) distances from baseline to 12 weeks between the two groups. Hematologic, physical, cognitive, and quality of life parameters were also assessed. The study was terminated early after 19 subjects enrolled. The distance walked in the 6MWT increased a mean 8.05±55.48 m in the immediate intervention group and decreased a mean 11.45±49.46 m in the wait list control group (p=0.443). The hemoglobin increased a mean 0.39±0.46 g/dL in the immediate intervention group and declined a mean 0.39±0.85 g/dL in the wait list control group (p=0.026). Thus, a subgroup of adults with UAE may respond to intravenous iron. Enrollment of subjects into this type of study remains challenging.

Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients.

Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50-73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59-3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14-2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07-2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13-2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54-4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults.

Optimization of Older Adults by a Geriatric Assessment-Guided Multidisciplinary Clinic Prior to CAR T-Cell Therapy.

The optimal means of assessing candidacy of older (65 years) adults for CAR T-cell therapy (CAR-T) are unknown. We explored the role of a geriatric assessment (GA)-guided multidisciplinary clinic (GA-MDC) in selecting and optimizing older adults for CAR-T. From 12/2017 - 4/2022, 61 patients were evaluated in a GA-MDC (median age, 73 years; range, 58-83). Most common diagnoses were NHL (n=42) and multiple myeloma (n=14). A non-binding recommendation ('Proceed' or 'Decline') regarding suitability for CAR-T was provided on each patient based on GA results. Fifty-three patients ultimately received CAR-T (Proceed=47, Decline=6). Among patients who received BCMA-directed (n=11) and CD19-directed (n=42) CAR-T, median OS was 14.2 months and 16.6 months, respectively. GA uncovered high rates of geriatric impairment among patients proceeding to CAR-T, with fewer impairments in those recommended 'Proceed'. Patients recommended 'Proceed' had shorter median length of stay (17 vs 31 days; p=0.05), lower rates of ICU admission (6% vs 50%; p=0.01) and were less likely to require rehabilitation services after discharge (11% vs 67%; p=0.01) than those recommended 'Decline'. In patients receiving CD19- and BCMA-directed CAR-T, a 'Proceed' recommendation was associated with superior OS compared to 'Decline' (median 16.6 vs 11.4 months, p=0.02 and median 16.4 vs 4.2 months, p=0.03, respectively). When controlling for Karnofsky performance status, CRP and LDH at time of lymphodepletion, the GA-MDC treatment recommendation remained prognostic for OS (HR 3.26; p=0.04). Patients optimized via the GA-MDC without serious vulnerabilities achieved promising outcomes while patients with high vulnerability experienced high toxicity and poor outcomes following CAR-T.

Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients.

Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients.

Reduced-intensity conditioning with combined haploidentical and cord blood transplantation results in rapid engraftment, low GVHD, and durable remissions.

We conducted a 45 patient prospective study of reduced-intensity conditioning (RIC) and transplantation of unrelated umbilical cord blood (UCB) and CD34(+) stem cells from a haploidentical family member. Median age was 50 years; weight was 80 kg. Fifty-eight percent had active disease. Neutrophil engraftment occurred at 11 days (interquartile range [IQR], 9-15) and platelet engraftment at 19 days (IQR, 15-33). In the majority of patients, early haploidentical engraftment was replaced by durable engraftment of UCB by 100 days, with regular persistence of minor host and/or haplo-hematopoiesis. Percentage of haplochimerism at day 100 correlated with the haplo-CD34 dose (P = .003). Cumulative incidence of acute GVHD (aGVHD) was 25% and chronic GVHD (cGVHD) was 5%. Actuarial survival at 1 year was 55%, progression-free survival (PFS) was 42%, nonrelapse mortality (NRM) was 28%, and relapse was 30%. RIC and haplo-cord transplantation results in fast engraftment of neutrophils and platelets, low incidences of aGVHD and cGVHD, low frequency of delayed opportunistic infections, reduced transfusion requirements, shortened length of hospital stay, and promising long-term outcomes. UCB cell dose had no impact on time to hematopoietic recovery. Therefore, UCB selection can prioritize matching, and better matched donors can be identified rapidly for most patients. This study is registered at http://clinicaltrials.gov as NCI clinical trial no. NCT00943800.

Biomarkers of erythropoiesis response to intravenous iron in a crossover pilot study in unexplained anemia of the elderly.

Anemia is common in older adults, but often unexplained. Previously, we conducted a randomized, controlled trial of intravenous (IV) iron sucrose to study its impact on the 6-minute walk test and hemoglobin in older adults with unexplained anemia and ferritin levels of 20-200 ng/mL. In this report, we present for the first time the response of hemoglobin, as well as the dynamic response of biomarkers of erythropoiesis and iron indices, in a pooled analysis of the initially IV iron-treated group of 9 subjects and the subsequently IV iron treated 10 subjects from the delayed treatment group. We hypothesized that there would be a reproducible hemoglobin response from IV iron, and that iron indices and erythropoietic markers would reflect appropriate iron loading and reduced erythropoietic stress. To investigate the biochemical response of anemia to IV iron, we studied the dynamics of soluble transferrin receptor (STfR), hepcidin, erythropoietin (EPO), and iron indices over 12 weeks after treatment. In total, all 19 treated subjects were evaluable: 9 from initial treatment and 10 after cross-over. Hemoglobin rose from 11.0 to 11.7 g/dL, 12 weeks after initiating IV iron treatment of 1000 mg divided weekly over 5 weeks. We found early changes of iron loading after 1-2 IV iron dose: serum iron increased by 184 mcg/dL from a baseline of 66 mcg/dL, ferritin by 184 ng/mL from 68 ng/mL, and hepcidin by 7.49 ng/mL from 19.2 ng/mL, while STfR and serum EPO declined by 0.55 mg/L and 3.5 mU/mL from 19.2 ng/mL and 14 mU/mL, respectively. The erythroid response and evidence of enhanced iron trafficking are consistent with the hypothesis that IV iron overcomes iron deficient or iron-restricted erythropoiesis. These data provide new insight that iron-restricted erythropoiesis is a potential and targetable mechanism for patients diagnosed with unexplained anemia of the elderly and offers support for larger prospective trials of IV iron among anemic older adults of low to normal ferritin.