Long-Term Immune Reconstitution in ADA-Deficient Patients Treated With Elapegademase: A Real-World Experience.

BACKGROUND: ADAGEN, a bovine-based enzyme replacement therapy (ERT), has been used to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2018, ADAGEN was replaced by REVCOVI (elapegademase), a modified bovine recombinant protein. OBJECTIVE: To determine the real-life long-term benefits of REVCOVI in ADA-SCID. METHODS: Data on ERT, infectious and noninfectious complications, and metabolic and immune evaluations were collected from 17 patients with ADA-SCID treated for 6 months or more with REVCOVI. RESULTS: Eleven patients had previously received ADAGEN for 16 to 324 months, whereas 6 patients were ERT-naive. REVCOVI was administered twice weekly at 0.4 mg/kg/wk in ERT-naive patients, whereas patients transitioning to REVCOVI from ADAGEN typically continued at the same frequency and equivalent dosing as ADAGEN, resulting in a significantly lower (P = .007) total REVCOVI dose in the transitioning group. REVCOVI treatment in the ERT-naive group led to the resolution of many clinical and laboratory complications of ADA deficiency, whereas there were no new adverse effects among the transitioning patients. REVCOVI treatment increased plasma ADA activity and decreased dAXP (which included deoxyadenosine mono-, di-, and tri phosphate) among most patients, effects that persisted throughout the 7- to 37-month treatment periods, except in 2 patients with incomplete adherence. Among some patients, after 0.5 to 6 months, injection frequency was reduced to once a week, while maintaining adequate metabolic profiles. All ERT-naive infants treated with REVCOVI demonstrated an increase in the number of CD4+ T and CD19+ B cells, although these counts remained stable but lower than normal in most transitioning patients. CONCLUSIONS: REVCOVI is effective for the management of ADA-SCID.

Granulocyte Colony-Stimulating Factor Is Safe and Well Tolerated following Allogeneic Transplantation in Patients with Sickle Cell Disease.

Granulocyte colony-stimulating factor (G-CSF) used after hematopoietic stem cell transplantation (HSCT) can enhance neutrophil recovery in patients rendered neutropenic by the preparative regimen. G-CSF is contraindicated in patients with sickle cell disease (SCD), because life-threatening complications can ensue in the presence of sickle vasculopathy. The safety profile of G-CSF after HSCT for SCD has not been described, however. We report clinical outcomes in the first 100 days post-HSCT in 62 patients supported with G-CSF until neutrophil recovery on a clinical trial of reduced- intensity conditioning HSCT for SCD. The patients received G-CSF for a median of 9 days (range, 5 to 33 days) post-transplantation from the best available stem cell source. Preparation for transplantation included a target hemoglobin S level of ≤45%. Neutrophil engraftment (absolute neutrophil count >0.5 × 103/mL) was achieved at a median of 13 days (range, 10 to 34 days), and platelet engraftment (>50 × 103/mL) was achieved at a median of 19 days (range, 12 to 71 days). The median duration of inpatient hospitalization following stem cell infusion (day 0) was 21.5 days (range, 11 to 33 days). No patient developed SCD-related complications following G-CSF use. The most common organ toxicities encountered between G-CSF initiation (on day +7) and day +100 were anorexia (n = 14), hypertension (n = 11), and electrolyte imbalance requiring correction (n = 9). Central nervous system-related events were noted in 5 patients, all of whom had preexisting cerebral vasculopathy/moyamoya disease, attributed to reversible posterior leukoencephalopathy syndrome in the presence of calcineurin inhibitor therapy and hypertension. We conclude that G-CSF does not adversely impact SCD HSCT recipients and can be safely used post-transplantation to enhance neutrophil recovery.

Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases.

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.

Worldwide Network for Blood and Marrow Transplantation (WBMT) recommendations for establishing a hematopoietic cell transplantation program (Part I): Minimum requirements and beyond.

Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize its safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Yet, structured recommendations are not commonly available. Here, the Transplant Center and Recipient Issues Standing Committee for the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements to establish a transplant program. First, we solicited components from committee members and grouped them in domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services and quality). Subsequently, reviewers scored all elements on a 7-point scale, from an absolute requirement (score of 1) to not required (score of 7). An independent group of five experienced transplant physicians reviewed the rankings. Minimum requirements to establish any HCT program were identified among elements with mean score of ≤2.0, and specific elements for allogeneic and autologous HCT were identified. Mean scores >2.0-4.0 were classified as preferred recommendation, and mean scores of >4.0 to ≤7.0 were considered ideal recommendations for advanced and complex types of transplantation. This structured set of recommendations guides the prioritization of minimum requirements to establish a transplant program and to set the path for expansion and further development.

Worldwide Network for Blood and Marrow Transplantation Recommendations for Establishing a Hematopoietic Cell Transplantation Program, Part I: Minimum Requirements and Beyond.

Hematopoietic cell transplantation (HCT) is a highly complex procedure that requires a dedicated multidisciplinary team to optimize safety. In addition, institutions may have different needs regarding indications based on regional disease prevalence or may have an interest in developing specialized services. Structured recommendations are not commonly available, however. The Transplant Center and Recipient Issues Standing Committee of the Worldwide Network for Blood and Marrow Transplantation (WBMT) organized a structured review of all pertinent elements for establishing a transplantation program. First, we solicited components from committee members and grouped them into domains (infrastructure, staff, cell processing laboratory, blood banking, laboratory, radiology, pharmacy, HLA testing, ancillary services, and quality). Subsequently, reviewers scored each element on a 7-point scale, ranging from an absolute requirement (score of 1) to not required (score of 7). An independent group of 5 experienced transplantation physicians reviewed the rankings. The minimum requirements for establishing any HCT program were identified among elements with mean score of ≤2.0, and specific elements for allogeneic and autologous HCT were identified. Mean scores of >2.0 to 4.0 were classified as preferred recommendation, and mean scores of >4.0 to ≤ 7.0 were considered ideal recommendations for advanced and complex types of transplantation. This structured set of recommendations guides the prioritization of minimum requirements to establish a transplantation program and set the stage for expansion and further development.

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study.

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m2 ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers. Seventeen patients received marrow from an HLA-identical sibling donor and five patients received marrow from an 8/8 HLA-allele matched unrelated donor. Before BMT, patients had stroke, acute chest syndrome, recurrent pain events, were receiving regular red blood cell transfusions, or had an elevated tricuspid regurgitant jet (TRJ) velocity, which fulfilled eligibility criteria. Four patients developed grades II-III acute GVHD (18%) and six developed chronic GVHD (27%) that was moderate in two and severe in one patient. One patient died of intracranial hemorrhage and one of GVHD. Nineteen patients had stable donor chimerism, 1-year post-transplant. One patient who developed secondary graft failure survives disease-free after a second BMT. The one-year overall survival and event-free survival (EFS) are 91% (95% CI 68%-98%) and 86% (95% CI, 63%-95%), respectively, and 3-year EFS is 82%. Statistically significant improvements in the pain interference and physical function domains of health-related quality of life were observed. The study satisfied the primary endpoint of 1-year EFS ≥70%. This regimen is being studied in a prospective clinical trial comparing HLA-matched donor BMT with standard of care in adults with severe SCD (NCT02766465).

Functional and Radiologic Assessment of the Brain after Reduced-Intensity Unrelated Donor Transplantation for Severe Sickle Cell Disease: Blood and Marrow Transplant Clinical Trials Network Study 0601.

Stroke and cognitive decline are hallmarks of sickle cell disease (SCD). The natural history of SCD predicts progressive loss of 1 IQ point per year attributable to disease-related pathology. Hematopoietic cell transplantation (HCT) is curative by reverting to donor-derived erythropoiesis, but evidence that HCT can positively influence disease-induced cognitive decline is lacking. The Sickle Cell Unrelated Transplant Trial prospectively evaluated cognition and brain magnetic resonance imaging (MRI) findings at 2 years after reduced-intensity conditioning followed by unrelated donor HCT. Thirteen study participants completed pre-HCT and post-HCT assessments of intelligence. The mean age of participants was 12.5 ± 3.3 years (range, 6.7 to 17.4 years). Eleven of the 13 recipients completed imaging studies at baseline and post-HCT. Seven had overt stroke pre-HCT, and 1 had an elevated transcranial Doppler velocity with abnormal MRI. The mean Full-Scale IQ was stable: 90.9 ± 13 at baseline and 91.2 ± 13 post-HCT. The mean Performance IQ was 89.9 ± 13 at baseline versus 90.9 ± 13 post-HCT, and mean Verbal IQ was 93.4 ± 13 at baseline versus 93.2 ± 13 post-HCT, respectively. Six recipients had stable MRI; 2 showed resolution of all areas of infarction. Three had additional infarcts post-HCT noted at the 2-year time point. This is the first report describing stabilization of IQ and central nervous system outcomes after unrelated donor HCT despite previous central nervous system morbidity and post-HCT posterior reversible encephalopathy syndrome. These preliminary results post-HCT suggest that HCT may stabilize the cognitive decline of SCD and should continue to be followed over the long term.

Tailoring a Survivorship Care Plan: Patient and Provider Preferences for Recipients of Hematopoietic Cell Transplantation.

This study aimed to develop a survivorship care plan (SCP) that can be individualized to facilitate long-term follow-up care of hematopoietic cell transplantation (HCT) survivors. A sample SCP was developed that included 2 documents: a treatment summary and preventive care recommendations that combined data on treatment exposures routinely submitted by HCT centers to the Center for International Blood and Marrow Transplant Research (CIBMTR) with long-term follow-up guidelines. Focus groups were conducted by phone to characterize the critical patient-centered elements of the SCP. Focus group eligibility criteria included (1) adult patients >1 year post-HCT and their caregivers (3 groups; n = 22), (2) HCT physicians and advanced practice providers (APPs) (2 groups; n = 14), (3) HCT nurses and social workers (4 groups; n = 17), and (4) community health care professionals (3 groups; n = 24). Transcripts were analyzed for saturation of key themes using NVivo 10 software. Patients and caregivers suggested combining the treatment summary and care guidelines into a single document. They also requested sections on sexual and emotional health and the immune system. Providers wanted the treatment summary to focus only on what they absolutely must know. Themes were similar across healthcare professionals, although screening for psychosocial issues was emphasized more by the nurses and social workers. All preferred to receive the SCP electronically; however, hardcopy was considered necessary for some patients. All felt that the SCP would facilitate appropriate post-HCT care. This study highlights the need for an SCP instrument to facilitate HCT survivorship care. Furthermore, it demonstrates the feasibility and value of engaging HCT recipients, caregivers, and providers in developing an SCP. Their feedback was incorporated into a final SCP that was subsequently tested in a randomized trial.

Immune Reconstitution and Infection Patterns after Early Alemtuzumab and Reduced Intensity Transplantation for Nonmalignant Disorders in Pediatric Patients.

Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for many nonmalignant disorders (NMD) and is curative or prevents disease progression. Reduced-intensity conditioning (RIC) in HSCT for NMD may reduce regimen-related acute toxicities and late complications. Myeloablation is often replaced by immune suppression in RIC regimens to support donor engraftment. The pace of immune reconstitution after immune suppression by RIC regimens is influenced by agents used, donor source, and graft-versus-host disease prophylaxis/treatment. In a multicenter trial (NCT 00920972) of HSCT for NMD, a RIC regimen consisting of alemtuzumab, fludarabine, and melphalan was substituted for myeloablation. Alemtuzumab was administered early (days -21 to -19) to mitigate major lymphodepletion of the incoming graft and the risk of graft rejection. Immune reconstitution and infectious complications were prospectively monitored for 1-year post-HSCT. Seventy-one patients met inclusion criteria for this report and received marrow or peripheral blood stem cell transplants. Immune reconstitution and infections are reported for related donor (RD) and unrelated donor (URD) transplants at 3 time-points (100days, 6 months, and 1 year post-HSCT). Natural killer cell recovery was rapid, and numbers normalized in both cohorts by day +100. Mean CD3, CD4, and CD8 T-lymphocyte numbers normalized by 6 months after RD HSCT and by 1 year in the URD group. CD4 and CD8 T-lymphocyte counts were significantly higher in patients who received RD HSCT at 6 months and at 1 year, respectively, post-HSCT compared with patients who received URD HSCT. The pace of CD19 B-cell recovery was markedly different between RD and URD cohorts. Mean B-cell numbers were normal by day 100 after RD HSCT but took 1 year post-HSCT to normalize in the URD cohort. Despite these differences in immune reconstitution, the timing and nature of infections did not differ between the groups, presumably because of comparable T-lymphocyte recovery. Immune reconstitution occurred at a faster pace than in prior reports using RIC with T-cell depletion. The incidence of infections was similar for both cohorts and occurred most frequently in the first 100days post-HSCT. Viral and fungal infections occurred at a lower incidence in this cohort, with "early" alemtuzumab compared with regimens administering serotherapy in the peritransplantation period. Patients were susceptible to bacterial infections primarily in the first 100days irrespective of donor source and had no increase in mortality from the same. The overall mortality rate from infections was 1.4% at 1 year. Close monitoring and prophylaxis against bacterial infections in the first 100days post-HSCT is necessary but is followed by robust immune reconstitution, especially in the T-cell compartment.

Randomized controlled trial of individualized treatment summary and survivorship care plans for hematopoietic cell transplantation survivors.

Survivorship Care Plans (SCPs) may facilitate long-term care for cancer survivors, but their effectiveness has not been established in hematopoietic cell transplantation recipients. We evaluated the impact of individualized SCPs on patient-reported outcomes among transplant survivors. Adult (≥18 years at transplant) survivors who were 1-5 years post transplantation, proficient in English, and without relapse or secondary cancers were eligible for this multicenter randomized trial. SCPs were developed based on risk-factors and treatment exposures using patient data routinely submitted by transplant centers to the Center for International Blood and Marrow Transplant Research and published guidelines for long-term follow up of transplant survivors. Phone surveys assessing patient-reported outcomes were conducted at baseline and at 6 months. The primary end point was confidence in survivorship information, and secondary end points included cancer and treatment distress, knowledge of transplant exposures, health care utilization, and health-related quality of life. Of 495 patients enrolled, 458 completed a baseline survey and were randomized (care plan=231, standard care=227); 200 (87%) and 199 (88%) completed the 6-month assessments, respectively. Patients' characteristics were similar in the two arms. Participants on the care plan arm reported significantly lower distress scores at 6 months and an increase in the Mental Component Summary quality of life score assessed by the Short Form 12 (SF-12) instrument. No effect was observed on the end point of confidence in survivorship information or other secondary outcomes. Provision of individualized SCPs generated using registry data was associated with reduced distress and improved mental domain of quality of life among 1-5 year hematopoietic cell transplantation survivors. Trial registered at clinicaltrials.gov 02200133.

Access to hematopoietic stem cell transplant for patients with sickle cell anemia.

Hematopoietic stem cell transplantation (HSCT) is a curative therapy for patients with phenotypically severe sickle cell anemia, and survival rates following matched-sibling HSCT are very high. However, despite cure rates much higher than HSCT for malignant diseases, the field has been slow to adopt this treatment modality for sickle cell anemia. This article explores some of the social forces that may contribute to this dichotomy.

Easy-to-Read Informed Consent Form for Hematopoietic Cell Transplantation Clinical Trials: Results from the Blood and Marrow Transplant Clinical Trials Network 1205 Study.

Because of the complexity of hematopoietic cell transplant trial treatments, informed consent forms are often long and difficult to read. We evaluated a 2-column easy-to-read informed consent (ETRIC) form that incorporates elements of health literacy and readability in participants and centers participating in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) clinical trials. In a randomized study 198 adult patients from 25 centers potentially eligible to participate in 4 BMT CTN interventional trials were randomized to the ETRIC form or a standard consent form for that trial. Both forms were written at no more than an eighth-grade reading level. The primary endpoint was objective comprehension score on the Quality of Informed Consent, part A (QuIC-A) instrument. In a parallel evaluation study, 2 moderators conducted semistructured interviews of 49 investigators, research staff, and institutional review board (IRB) members at 9 BMT CTN trial sites. The mean QuIC-A scores were comparable in 152 patients (77%) assessable for the primary endpoint (ETRIC form, 80.5; standard form, 81.8; P = .37). In regression analysis there was no significant association between the consent type and QuIC-A score. In the evaluation study dominant themes identified on qualitative analyses included general comfort and willingness to use the ETRIC template and that its formatting and layout enhancements would offer additional value to research participants, investigators, and IRBs. IRB language preferences and requirements, length, and prior experience with alternative consent formats were perceived as barriers. Among patients considering participation in BMT CTN clinical trials, the formatting enhancements of the ETRIC form did not alter comprehension of the trial. Despite local challenges to implementation, trial sites generally viewed the ETRIC form favorably and expressed willingness to use it over standard consent form.

Ethical Challenges in Hematopoietic Cell Transplantation for Sickle Cell Disease.

Hematopoietic cell transplantation (HCT) using an HLA-identical sibling donor offers a very high likelihood of cure with good outcomes for patients with sickle cell disease (SCD), and alternative donor HCT for SCD is an area of active clinical research. Thus, HCT is a potential option for a growing number of patients with SCD. This expanded use of HCT has raised several ethical questions. Who is eligible for HCT, in terms of both disease severity and psychosocial factors? Should affected children with matched sibling donors undergo HCT only when they have declared themselves as having significant symptomatology? Regarding donors, special ethical challenges include the use of preimplantation genetic diagnosis to conceive an HLA-identical sibling. In this review, we critically analyze various ethical challenges related to HCT for SCD, and offer recommendations to guide clinical care.

Relationship between Mixed Donor-Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease.

Mixed donor chimerism after hematopoietic cell transplantation for sickle cell disease (SCD) can result in resolution of disease symptoms, but symptoms recur when donor chimerism is critically low. The relationship between chimerism, hemoglobin S (HbS) level, and symptomatic disease was correlated retrospectively in 95 patients who had chimerism reports available at day 100 and at 1 and 2 years after transplantation. Recurrent disease was defined as recurrence of vaso-occlusive crises, acute chest syndrome, stroke, and/or HbS levels > 50%. Thirty-five patients maintained full donor chimerism (myeloid or whole blood) through 2 years. Donor chimerism was less than 10% (defined as graft failure) in 13 patients during this period. Mixed chimerism was reported in the remaining 47 patients (range, 10% to 94%). The lowest documented donor chimerism without symptomatic disease was 26%. Of 12 surviving patients with recurrent disease, 2 had recurrence of symptoms before documented graft failure (donor chimerism of 11% and 17%, respectively). Three patients underwent second transplantation for graft failure. None received donor leukocyte infusion to maintain mixed chimerism or prevent graft failure. We conclude stable donor chimerism greater than 25% is associated with resolution of SCD-related symptoms, and HbS levels in transplant recipients should be interpreted in context of the sickle trait status of the donors.

Obstetric hemorrhage and safe blood for transfusion in Ethiopia: the challenges of bridging the gap.

BACKGROUND: Obstetric hemorrhage is a leading cause of maternal death in sub-Saharan Africa, and the shortage of blood for transfusion is a contributory factor. In Ethiopia, the National Blood Bank Service continues to be confronted with challenges in its efforts to ensure the availability of blood for health care facilities. This paper reviews the available data on the contribution of obstetric hemorrhage to maternal mortality and examines the current status of the blood supply in Ethiopia. STUDY DESIGN AND METHODS: We reviewed the published literature and data from the Ethiopian Federal Ministry of Health. To assess the status of the current blood supply, we applied the five cornerstones of a safe and effective blood donor service advocated by the World Health Organization. RESULTS: Our review indicates that there are insufficient national data on the prevalence of obstetric hemorrhage and the contribution of blood supply shortage to maternal death. Also, transfusion safety may be compromised by inadequate testing of donated blood and ineffective hospital transfusion policies. CONCLUSION: To overcome the shortage of blood to treat obstetric hemorrhage, the first step is to evaluate the demand and supply gap by acquiring comprehensive data on the current status of the blood supply and the prevalence of obstetric hemorrhage in Ethiopia. Subsequent steps would include the implementation of transfusion policies, the optimization of whole blood collection, ensuring quality-assured testing of donated blood, and the implementation of transfusion guidelines for the appropriate use of blood products. Strategies for long-term, viable solutions to maintain an adequate blood supply should be simultaneously developed.

A trial of unrelated donor marrow transplantation for children with severe sickle cell disease.

Children with sickle cell disease experience organ damage, impaired quality of life, and premature mortality. Allogeneic bone marrow transplant from an HLA-matched sibling can halt disease progression but is limited by donor availability. A Blood and Marrow Transplant Clinical Trials Network (BMT CTN) phase 2 trial conducted from 2008 to 2014 enrolled 30 children aged 4 to 19 years; 29 were eligible for evaluation. The primary objective was 1-year event-free survival (EFS) after HLA allele-matched (at HLA-A, -B, -C, and -DRB1 loci) unrelated donor transplant. The conditioning regimen included alemtuzumab, fludarabine, and melphalan. Graft-versus-host disease (GVHD) prophylaxis included calcineurin inhibitor, short-course methotrexate, and methylprednisolone. Transplant indications included stroke (n = 12), transcranial Doppler velocity >200 cm/s (n = 2), ≥3 vaso-occlusive pain crises per year (n = 12), or ≥2 acute chest syndrome episodes (n = 4) in the 2 years preceding enrollment. Median follow-up was 26 months (range, 12-62 months); graft rejection was 10%. The 1- and 2-year EFS rates were 76% and 69%, respectively. The corresponding rates for overall survival were 86% and 79%. The day 100 incidence rate of grade II-IV acute GVHD was 28%, and the 1-year incidence rate of chronic GVHD was 62%; 38% classified as extensive. There were 7 GVHD-related deaths. A 34% incidence of posterior reversible encephalopathy syndrome was noted in the first 6 months. Although the 1-year EFS met the prespecified target of ≥75%, this regimen cannot be considered sufficiently safe for widespread adoption without modifications to achieve more effective GVHD prophylaxis. The BMT CTN #0601 trial was registered at www.clinicaltrials.gov as #NCT00745420.

Trends in United States blood collection and transfusion: results from the 2013 AABB Blood Collection, Utilization, and Patient Blood Management Survey.

BACKGROUND: AABB surveyed AABB institutional members about their 2013 blood collection, transfusion, and patient blood management (PBM) programs. Results were compared with previous US national surveys. STUDY DESIGN AND METHODS: The 2013 AABB Blood Collection, Utilization, and Patient Blood Management Survey was distributed to AABB blood centers (79) and hospitals (1068). Statistical procedures were used to estimate blood collection and transfusion. RESULTS: Estimated whole blood (WB) and red blood cell (RBC) collections in 2013 totaled 13.6 million units, a 12.1% decrease from 15.5 million units in 2011 (p < 0.0001). Transfusions of WB and RBC units by AABB hospitals totaled 6.1 million units, 7.3% fewer compared to 2011 (p = 0.036). There was no change in overall platelet (PLT) distributions by blood collectors but WB-derived (WBD) PLT distributions increased significantly (27.1%, p < 0.0001). Transfusion of PLTs increased 15.4% totaling 1.3 million units (p = 0.0423), including increases in apheresis PLT (12.2%) and WBD PLT transfusions (30.7%). Distribution of plasma for transfusion declined 22.4% (p < 0.0001), while transfused plasma decreased only 9.9% (p = 0.036). Hospitals reduced outdated WB, RBC, and PLT components by 14.9% to 26.1% and wasted plasma components by 19.0%. PBM programs were reported by 37.8% of AABB hospitals. CONCLUSIONS: Compared to 2011, WB and RBC collections declined significantly in 2013 and disproportionately to the significant reductions in WB and RBC transfusions. Distributions of PLTs and plasma for transfusion declined in 2013, as did transfusions of plasma, while transfusion of PLTs increased significantly. Decreases in outdated and wasted components by hospitals suggest improvements in product and inventory management. Ongoing national surveys allow for trend analysis and are important for future planning.