An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease.

ABSTRACT: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108.

Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial.

We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.

Transcranial doppler velocity in iron-deficient Nigerian children with sickle cell anemia.

Oral iron supplementation in iron deficient children with sickle cell anemia and normal transcranial Doppler ultrasound (TCD) velocities does not reduce arterial flow in the middle cerebral artery.

Relapsed or refractory large B-cell lymphoma after chimeric antigen receptor T-cell therapy: Current challenges and therapeutic options.

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR-T therapy have poor outcomes. Multiple mechanisms of CAR-T therapy failure have been proposed but management of these patients remains a challenge. As CAR-T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR-T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody-drug conjugates and next-generation CAR-T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR-T therapy and provide a framework for the ideal sequencing of these novel agents.

NCCN Guidelines® Insights: Hematopoietic Cell Transplantation, Version 3.2022.

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease-a major complication of allogeneic HCT-to enable the patient and clinician to assess management options in the context of an individual patient's condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.

Reduction in seroprevalence of viral transfusion-transmitted infections in southwest Nigeria in children with sickle cell disease using an enhanced screening strategy.

Blood transfusion is an integral component in the management of children and adults with sickle cell disease (SCD). Concerns about blood safety due to the high risk of bloodborne infections in sub-Saharan Africa limits the application of this cost-effective strategy in the management of individuals with SCD. In a single-centre, retrospective, longitudinal study in southwest Nigeria, we hypothesised that the use of stringent blood donor selection, along with very sensitive enzyme-linked immunosorbent assay (ELISA) screening methods would reduce transfusion-transmitted infections (TTIs). Among 45 002 eligible blood donors at the Lagos University Teaching Hospital in Nigeria, over a 5-year review period (2015-2019), the seroprevalence rate of viral TTIs was 9.83%. The seroprevalence rates for human immunodeficiency, hepatitis B, and hepatitis C viruses were 1.37%, 6.2%, and 2.25% respectively. Among 172 children with SCD, 71% (122/172) on regular blood transfusion and 29% (50/172) who had never been transfused or had less than two transfusions per lifetime, none acquired any TTIs using our enhanced screening approach during the study period. Thus, safe blood transfusion practices can be provided for children with SCD in sub-Saharan Africa with the use of stringent donor selection protocols and fourth-generation ELISA kits for TTI screening.

Cerebral Hemodynamics and Executive Function in Sickle Cell Anemia.

BACKGROUND AND PURPOSE: Individuals with sickle cell anemia experience cognitive deficits, even in the absence of cerebral infarcts or strokes. This study tested the hypothesis that elevated cerebral blood flow and oxygen extraction fraction are associated with lower executive function in individuals with sickle cell anemia. METHODS: Three-Tesla brain magnetic resonance imaging was performed, including anatomic, gray matter cerebral blood flow, and global oxygen extraction fraction imaging. Executive function was measured using the working memory index from an age-appropriate Wechsler battery and tasks from the National Institutes of Health Toolbox Cognition Battery. Bivariate and multivariate models were examined (significance: P<0.05). RESULTS: Fifty-four participants (age range=6-31 years) with sickle cell anemia were enrolled. Hematocrit was positively related to fluid cognition, cerebral blood flow was inversely related to working memory and inhibitory control, and oxygen extraction fraction was inversely related to processing speed. Associations remained significant in multivariate analyses controlling for age, income, and infarcts. CONCLUSIONS: Elevated cerebral blood flow and oxygen extraction fraction, markers of hemodynamic impairment, are associated with deficits in executive function in individuals with sickle cell anemia.

Low rates of anti-recipient isohemagglutinins in ABO incompatible hematopoietic stem cell transplants.

INTRODUCTION: Isohemagglutinins occur naturally and form in an 'opposite' (antigen-negative) pattern to a patient's ABO blood type. Patients undergoing minor and bidirectional ABO incompatible hematopoietic stem cell transplantation (HSCT) may demonstrate detectable antibodies against their native blood type. In this study, we sought to characterize the rates of such antibody formation and evaluate the clinical significance of our findings. MATERIALS AND METHODS: An internal database of HSCT patients at an academic medical center was queried for ABO incompatible transplant patients from 2009-2019. Serum typing results, clinical histories, and laboratory data were compiled and reviewed. RESULTS: A total of 182 minor and bidirectional ABO incompatible HSCT patients were identified. Anti-recipient isohemagglutinins were found in 9% (16/182) of the HSCT patients. The rate was higher in patients with minor incompatibility (12%: 15/127) versus bidirectional ABO incompatibility (2%: 1/55) (p = 0.04). No anti-recipient isohemagglutinins were identified in umbilical cord HSCT patients (0%: 0/7). Serologic agglutination reactions of recipient isohemagglutinins were overall mostly weak (13/16 weak + to 1+). There was a trend towards a higher rate of acute graft-versus-host-disease in patients with anti-recipient isohemagglutinins compared to those without (75% vs. 53%; p = 0.12), though not statistically significant. Rates of alloimmunization to minor red cell antigens were similar between the two groups. Few patients showed laboratory evidence of hemolysis at 12 months follow up. DISCUSSION AND CONCLUSIONS: Anti-recipient isohemagglutinins occur at low rates in ABO incompatible HSCT and are significantly more common in minor ABO incompatible transplant compared to bidirectional transplants. Larger cohort studies are needed to better understand the relationship between anti-recipient isohemagglutinins and HSCT outcomes.

Primary prevention of stroke in children with sickle cell anemia in sub-Saharan Africa: rationale and design of phase III randomized clinical trial.

Strokes in children with sickle cell anemia (SCA) are associated with significant morbidity and premature death. Primary stroke prevention in children with SCA involves screening for abnormal transcranial Doppler (TCD) velocity coupled with regular blood transfusion therapy for children with abnormal velocities, for at least one year. However, in Africa, where the majority of children with SCA live, regular blood transfusions are not feasible due to inadequate supply of safe blood, cost, and the reluctance of caregivers to accept transfusion therapy for their children. We describe the Primary Prevention of Stroke in Children with Sickle Cell Disease in Nigeria Trial [StrokePreventioninNigeria (SPRING) trial, NCT02560935], a three-center double-blinded randomized controlled Phase III clinical trial to 1) determine the efficacy of moderate fixed-dose (20 mg/kg/day) versus low fixed-dose (10 mg/kg/day) hydroxyurea therapy for primary stroke prevention; 2) determine the efficacy of moderate fixed-dose hydroxyurea for decreasing the incidence of all cause-hospitalization (pain, acute chest syndrome, infection, other) compared to low fixed-dose hydroxyurea. We will test the primary hypothesis that there will be a 66% relative risk reduction of strokes in children with SCA and abnormal TCD measurements, randomly allocated, for a minimum of three years to receive moderate fixed-dose versus low fixed-dose hydroxyurea (total n = 220). The results of this trial will advance the care of children with SCA in sub-Saharan Africa, while improving research capacity for future studies to prevent strokes in children with SCA.

Low educational level of head of household, as a proxy for poverty, is associated with severe anaemia among children with sickle cell disease living in a low-resource setting: evidence from the SPRING trial.

Severe anaemia, defined as haemoglobin level < 6·0 g/dl, is an independent risk factor for death in individuals with sickle cell disease living in resource-limited settings. We conducted a cross-sectional study of 941 children with sickle cell anaemia, who had been defined as phenotype HbSS or HbSß0 thalassaemia, aged five to 12 years, and were screened for enrollment into a large primary stroke prevention trial in Nigeria (SPRING; NCT02560935). The main aim of the study was to determine the prevalence and risk factors for severe anaemia. We found severe anaemia to be present in 3·9% (37 of 941) of the SPRING study participants. Severe anaemia was significantly associated with the lower educational level of the head of the household (P = 0·003), as a proxy for poverty, and a greater number of children per room in the household (P = 0·004). Body mass index was not associated with severe anaemia. The etiology of severe anaemia in children living with sickle cell anaemia in Nigeria is likely to be multifactorial with an interplay between an individual's disease severity and other socio-economic factors related to poverty.

The use of venetoclax-based salvage therapy for post-hematopoietic cell transplantation relapse of acute myeloid leukemia.

For patients with high risk myeloid disease, allogeneic hematopoietic cell transplantation (HCT) is the only potentially curative therapy. Unfortunately, many of these patients relapse after HCT and have a limited survival. The recent approval of venetoclax, an orally bioavailable BCL-2 inhibitor, resulted in significant responses in treatment naïve acute myeloid leukemia (AML), and off-label use in the relapsed/refractory setting is increasing. We report the outcomes of 21 patients who underwent allogeneic HCT for myeloid disease, relapsed with AML, and were treated with venetoclax. Several patients had poor risk features including antecedent hematologic malignancy (6/21), complex karyotype (6/21), and TP53 mutations (5/21). The median age was 64.5 years and time from HCT to relapse was 5.7 months (range: 0.9 to 44.9 months). Of the 19 patients who were assessed for response, there were meaningful treatment responses seen in eight patients: five CR, three CRi, zero PR, for an ORR of 42.1%. Treatment effect was seen in six additional patients, including four in the morphologic leukemia-free state. Nine patients maintained their response for ≥3 months and eight were receiving therapy at data cut. Post-HCT AML relapse has an exceedingly poor outcome, and venetoclax-based therapy is a potent therapy option that should be studied prospectively in this setting.

Early viral reactivation despite excellent immune reconstitution following haploidentical Bone marrow transplant with post-transplant cytoxan for sickle cell disease.

BACKGROUND: Haploidentical bone marrow transplant (haplo-BMT) offers near universal donor availability as a curative modality for individuals with severe sickle cell disease (SCD). However, the required intense immunodepletion is associated with increased infectious complications. A paucity of data exists on immune reconstitution following haplo-BMT for SCD. METHODS: A multi-institution learning collaborative was developed in the context of a phase II clinical trial of a non-myeloablative, related haplo-BMT with post-transplant cyclophosphamide for SCD. We report results from a cohort of 23 patients for whom immune reconstitution data up to one year were available. RESULTS: Median age was 14.8 years. Out of 23, 18 participants received pre-conditioning with azathioprine, hydroxyurea, and hypertransfusions. 70% (16/23) of participants had multiple indications for haplo-BMT. We observed excellent immune reconstitution of CD4, CD8, CD19, and CD56 cellular subsets by 6 months post transplant. Engraftment rate and event-free survival in this cohort were 100% and 96%, respectively. 70% (16/23) of patients had at least one viral reactivation or infection, including CMV 35% (8/23), HHV-6 22% (5/23), and polyoma virus 17% (4/23), with no cases of post-transplant lymphoproliferative disease. CONCLUSION: Further prospective studies are needed to better characterize immune reconstitution and the immunologic basis for increased viral reactivation following haplo-BMT with post-transplant cyclophosphamide for SCD.

Haploidentical Bone Marrow Transplantation with Post-Transplantation Cyclophosphamide Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Learning Collaborative.

Curative therapy for individuals with severe sickle cell disease (SCD) who lack an HLA-identical sibling donor has been frustratingly elusive. In with the goal of improving engraftment while minimizing transplantation-related morbidity, a multi-institutional learning collaborative was developed in the context of a Phase II clinical trial of nonmyeloablative, related HLA-haploidentical (haplo) bone marrow transplantation (BMT) with post-transplantation cyclophosphamide. All eligible participants had hemoglobin SS, and 89% (16 of 18) had an identifiable donor. The median patient age was 20.9 years (IQR, 12.1 to 26.0 years), and the most common indication for transplantation was overt stroke (in 69%; 11 of 16). In the first 3 patients, the conditioning regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and low-dose total body irradiation. Graft-versus-host disease (GVHD) prophylaxis included post-transplantation cyclophosphamide, mycophenolate mofetil, and sirolimus. Primary graft rejection occurred in 2 of the 3 patients (67%), which triggered the study-stopping rule. To reduce graft rejection risk, thiotepa was added to the conditioning regimen, and then 15 patients (including 2 with previous graft rejection) underwent haplo-BMT with this thiotepa-augmented conditioning regimen. At a median follow-up of 13.3 months (interquartile range [IQR], 3.8 to 23.1 months), 93% (14 of 15) had >95% stable donor engraftment at 6 months, with 100% overall survival. The median time to neutrophil engraftment (>500) was 22 days (IQR, 19 to 27 days), and that for platelet engraftment (>50 x 109/L) was 28 days (IQR, 27 days to not reached). Two patients had grade III-IV acute GVHD, 1 patient had mild chronic GVHD, and 86% of patients (6 of 7) were off immunosuppression therapy by 1-year post-transplantation. Our data suggest that haplo-BMT with post-transplantation cyclophosphamide and thiotepa improves donor engraftment without significantly increasing morbidity or mortality and could dramatically expand curative options for individuals with SCD.

Differential cerebral hemometabolic responses to blood transfusions in adults and children with sickle cell anemia.

BACKGROUND: Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized. PURPOSE: To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA. STUDY TYPE: Prospective, longitudinal study. SUBJECTS: Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days. FIELD STRENGTH/SEQUENCE: 3.0T T1 -weighted, T2 -weighted, and T2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography. ASSESSMENT: Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume. STATISTICAL TESTS: Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing. RESULTS: In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004). DATA CONCLUSION: Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;49:466-477.

Multidisciplinary care results in similar maternal and perinatal mortality rates for women with and without SCD in a low-resource setting.

In Africa, the maternal mortality rate in sickle cell disease (SCD) is ~10%. Our team previously demonstrated an 89% decrease in mortality rate in a before-and-after feasibility study among women with SCD living in low-resource setting in Ghana. In the same cohort including additional participants with and without SCD, we used a prospective cohort design to test the hypothesis that implementing a multidisciplinary care team for pregnant women with SCD in low-resource setting will result in similar maternal and perinatal mortality rates compared to women without SCD. We prospectively enrolled pregnant women with and without SCD or trait and followed them up for 6-week postpartum. We tested the newborns of mothers with SCD for SCD. We recruited age and parity matched pregnant women without SCD or trait as the comparison group. Maternal and perinatal mortality rates were the primary outcomes. A total of 149 pregnant women with SCD (HbSS, 54; HbSC, 95) and 117 pregnant women without SCD or trait were included in the analysis. Post-intervention, maternal mortality rates were 1.3% and 0.9% in women with and without SCD, respectively (P = 1.00); the perinatal mortality rates were 7.4% and 3.4% for women with and without SCD, respectively (P = 0.164). Among the mothers with SCD, ~15% of newborns had SCD. Multidisciplinary care of pregnant women with SCD may reduce maternal and perinatal mortality rates to similar levels in pregnant women without SCD in low-resource settings. Newborns of mothers with SCD have a high rate of SCD.

Increased Patient Activation Is Associated with Fewer Emergency Room Visits and Hospitalizations for Pain in Adults with Sickle Cell Disease.

OBJECTIVE: Recurrent vaso-occlusive pain episodes, the most common complication of sickle cell disease (SCD), cause frequent health care utilization. Studies exploring associations between patient activation and acute health care utilization for pain are lacking. We tested the hypothesis that increased activation and self-efficacy are associated with decreased health care utilization for pain in SCD. METHODS: In this cross-sectional study of adults with SCD at a tertiary medical center, we collected demographics, SCD phenotype, Patient Activation Measure levels, and self-efficacy scores using structured questionnaires. We reviewed charts to obtain disease-modifying therapy and acute health care utilization, defined as emergency room visits and hospitalizations, for vaso-occlusive pain episodes. Negative binomial regression analyses were used to test the hypothesis. RESULTS: We surveyed 67 adults with SCD. The median age was 27.0 years, 53.7% were female, and 95.5% were African American. Median health care utilization for pain over one year (range) was 2.0 (0-24). Only one-third of participants (38.8%) were at the highest activation level (median [range] = 3 [1-4]). Two-thirds (65.7%) of participants had high self-efficacy (median [range] = 32.0 [13-45]). Regressions showed significant association between health care utilization and activation (incidence rate ratio [IRR] = 0.663, P = 0.045), self-efficacy (IRR = 0.947, P = 0.038), and male sex (IRR = 0.390, P = 0.003). Two outliers with high activation, self-efficacy, and health care utilization also had addictive behavior. CONCLUSIONS: Many individuals with SCD have suboptimal activation and reduced self-efficacy. Higher activation and self-efficacy were associated with lower health care utilization for pain. Additional studies are needed to evaluate interventions to improve activation and self-efficacy and reduce acute health care utilization for pain.

Contraceptive Methods and the Impact of Menstruation on Daily Functioning in Women with Sickle Cell Disease.

OBJECTIVES: Women with sickle cell disease (SCD) are living longer as a result of advances in the care of their underlying disease. With the population growing of women living with SCD, reproductive health issues in this population have become an emphasized area of medical care. We sought to describe current patterns of contraception use, menstruation, and quality-of-life (QOL) measures in women with SCD. METHODS: Using a cross-sectional study design, we administered paper surveys at two academic medical centers to women aged 10 to 55 years with SCD to capture current contraceptive use, characteristics of menstrual cycles, and QOL metrics. RESULTS: Of the 103 women who participated, 12.7% (13/102) experienced a duration of menses >7 days (defined here as prolonged menstrual bleeding). Approximately half of women (51.5%, 53/103) used some form of contraception, with depot medroxyprogesterone acetate injections and condoms being the most common. During their last menstrual periods, women with both dysmenorrhea and prolonged menstrual bleeding (6.9%, 7/102) were more likely to experience more days of poor QOL, with more nights with sleep disturbance (P = 0.001) and more days with trouble taking care of themselves (P = 0.003), as well as being unable to do things they previously enjoyed (P = 0.001), compared with those with neither phenomenon (28.2%, 29/103). CONCLUSIONS: Dysmenorrhea and prolonged menstrual bleeding negatively affect the QOL of women with SCD. Menstrual histories and preventive measures for menstruation-related morbidity should be incorporated into routine evaluations of women with SCD.

Optimizing Antithymocyte Globulin Dosing for Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Based on Recipient Absolute Lymphocyte Count.

Antithymocyte globulin (ATG) is used as prophylaxis against graft-versus-host disease (GVHD). Current dosing regimens for ATG are empiric and weight-based, and do not account for patient-specific factors. Furthermore, the target of ATG, recipient T cells post-cytotoxic chemotherapy, is not a function of recipient weight. We hypothesized the recipient peripheral blood absolute lymphocyte count (ALC) on the day of ATG administration would interact with the dose of ATG administered to predict transplantation outcomes. We retrospectively analyzed 135 patients who received ATG for GVHD prophylaxis for unrelated allogeneic hematopoietic cell transplantation at 3 different doses: 10 mg/kg, 7.5 mg/kg, and 5 mg/kg. There was no difference in 2-year overall survival (OS) among ATG dosing groups; however, deaths from infectious complications were significantly higher with higher doses of ATG (3.7% versus 19% versus 26.7%; P = .02). Severity of chronic GVHD was lower with higher doses of ATG (28% versus 24% versus 4%; P = .03). In multivariate analysis, the median peripheral blood ALC on day of ATG administration and the total amount of ATG interacted to predict OS (hazard ratio, .09; P = .03). For low recipient ALC (10th percentile, or .56 × 102/µL), a higher total ATG dose was associated with a greater risk of death, whereas for high recipient ALC (90th percentile, or 24.96 × 102/µL), a higher ATG dose was associated with a lower risk of death. Our findings suggest that the interaction between ATG and its target, the recipient lymphocyte, could represent a new paradigm for ATG dosing.

Defining Incidence and Risk Factors for Catheter-Associated Bloodstream Infections in an Outpatient Adult Hematopoietic Cell Transplantation Program.

Allogeneic hematopoietic cell transplantation (HCT) patients are at an increased risk of developing central line-associated bloodstream infections (CLABSIs) due to prolonged periods of myelosuppression, immunosuppression, and indwelling catheter days. CLABSIs are among the most serious complications in HCT recipients and can lead to prolonged hospitalizations, intensive care unit admissions, lengthy antimicrobial therapies, and increased mortality. There is a lack of data regarding the incidence and risk factors associated with the development of CLABSIs in the HCT population undergoing outpatient transplantation. This was a single-center, retrospective analysis of adult patients who underwent allogeneic HCT between July 2012 and July 2016 in an outpatient transplant unit at a tertiary academic medical center. The primary outcome was the cumulative incidence of CLABSIs from the date of central line placement through the first 100 days post-transplantation. Secondary outcomes included risk factors for CLABSI, number of hospitalizations due to CLABSI, mortality rate at 6 months post-transplantation, and the cumulative incidence, speciation, and presence of multidrug resistance in identified microorganisms. Three hundred fifty-nine patients underwent allogeneic HCT at Vanderbilt University Medical Center and 352 were included for analysis. The cumulative incidence of CLABSIs was 9%, with the majority occurring within the first 30 days post HCT (67%). The use of a matched unrelated donor (MUD) and/or haploidentical donor (odds ratio, 3.993; 95% confidence interval [CI], 1.329 to 12.001; P = .0136) and use of an ablative conditioning regimen (odds ratio, 2.394; 95% CI, 1.052 to 5.446; P = .0374) were independently associated with development of a CLABSI on multivariate analysis. The most common organism implicated in CLABSI was Staphylococcus epidermidis (34%). Patients who developed a CLABSI had an almost 5 times higher risk of mortality at 6 months post-transplantation compared with patients who did not develop a CLABSI (hazard ratio, 4.932; 95% CI, 2.463 to 9.878; P < .001). There is a low incidence of CLABSIs in patients undergoing HCT in the outpatient setting. Patients who underwent HCT using a MUD or haploidentical donor and received ablative conditioning were at higher risk for developing CLABSIs. Overall mortality at 6 months post-transplantation was higher in patients who developed a CLABSI. Additional prospective studies are needed to confirm these observations.

NCCN Guidelines Insights: Multiple Myeloma, Version 3.2018.

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, evaluation, treatment, including supportive-care, and follow-up for patients with myeloma. These NCCN Guidelines Insights highlight the important updates/changes specific to the myeloma therapy options in the 2018 version of the NCCN Guidelines.