Risk of interpersonal violence during and after pregnancy among people with schizophrenia: a population-based cohort study.

BACKGROUND: Schizophrenia is associated with increased risk of experiencing interpersonal violence. Little is known about risk specifically around the time of pregnancy. METHODS: This population-based cohort study included all individuals (aged 15-49 yr) listed as female on their health cards who had a singleton birth in Ontario, Canada, between 2004 and 2018. We compared those with and without schizophrenia on their risk of an emergency department (ED) visit for interpersonal violence in pregnancy or within 1 year postpartum. We adjusted relative risks (RRs) for demographics, prepregnancy history of substance use disorder and history of interpersonal violence. In a subcohort analysis, we used linked clinical registry data to evaluate interpersonal violence screening and self-reported interpersonal violence during pregnancy. RESULTS: We included 1 802 645 pregnant people, 4470 of whom had a diagnosis of schizophrenia. Overall, 137 (3.1%) of those with schizophrenia had a perinatal ED visit for interpersonal violence, compared with 7598 (0.4%) of those without schizophrenia, for an RR of 6.88 (95% confidence interval [CI] 5.66-8.37) and an adjusted RR of 3.44 (95% CI 2.86-4.15). Results were similar when calculated separately for the pregnancy (adjusted RR 3.47, 95% CI 2.68-4.51) period and the first year postpartum (adjusted RR 3.45, 95% CI 2.75-4.33). Pregnant people with schizophrenia were equally likely to be screened for interpersonal violence (74.3% v. 73.8%; adjusted RR 0.99, 95% CI 0.95-1.04), but more likely to self-report it (10.2% v. 2.4%; adjusted RR 3.38, 95% CI 2.61-4.38), compared with those without schizophrenia. Among patients who did not self-report interpersonal violence, schizophrenia was associated with an increased risk for a perinatal ED visit for interpersonal violence (4.0% v. 0.4%; adjusted RR 6.28, 95% CI 3.94-10.00). INTERPRETATION: Pregnancy and postpartum are periods of higher risk for interpersonal violence among people with schizophrenia compared with those without schizophrenia. Pregnancy is a key period for implementing violence prevention strategies in this population.

The association between social class and the impact of treatment for mental health problems: a systematic review and narrative synthesis.

PURPOSE: This systematic review aimed to synthesise all quantitative literature on the association between social class and the effectiveness of interventions for mental health disorders. METHODS: Systematic literature searches (inception-March 2021) were conducted across 7 databases, and all quantitative studies meeting inclusion criteria, examining the impact of social class on access to treatment, or intervention effectiveness, or the impact of treatment on social mobility, were synthesised narratively. RESULTS: Evidence suggests that lower social class may be associated with reduced access to primary and secondary mental health care and increased likelihood of access via crisis services, and patients of lower social class may not benefit from all mental health interventions, with reduced effectiveness. While limited, there was some indication that psychosocial interventions could encourage increased employment rates. CONCLUSION: Social class is associated with the effectiveness of psychological interventions, and should be considered when designing new interventions to prevent barriers to access and improve effectiveness.

Feasibility of the cardiac output response to stress test in suspected heart failure patients.

BACKGROUND: Diagnostic tools available to support general practitioners diagnose heart failure (HF) are limited. OBJECTIVES: (i) Determine the feasibility of the novel cardiac output response to stress (CORS) test in suspected HF patients, and (ii) Identify differences in the CORS results between (a) confirmed HF patients from non-HF patients, and (b) HF reduced (HFrEF) vs HF preserved (HFpEF) ejection fraction. METHODS: Single centre, prospective, observational, feasibility study. Consecutive patients with suspected HF (N = 105; mean age: 72 ± 10 years) were recruited from specialized HF diagnostic clinics in secondary care. The consultant cardiologist confirmed or refuted a HF diagnosis. The patient completed the CORS but the researcher administering the test was blinded from the diagnosis. The CORS assessed cardiac function (stroke volume index, SVI) noninvasively using the bioreactance technology at rest-supine, challenge-standing, and stress-step exercise phases. RESULTS: A total of 38 patients were newly diagnosed with HF (HFrEF, n = 21) with 79% being able to complete all phases of the CORS (91% of non-HF patients). A 17% lower SVI was found in HF compared with non-HF patients at rest-supine (43 ± 15 vs 51 ± 16 mL/beat/m2, P = 0.02) and stress-step exercise phase (49 ± 16 vs 58 ± 17 mL/beat/m2, P = 0.02). HFrEF patients demonstrated a lower SVI at rest (39 ± 15 vs 48 ± 13 mL/beat/m2, P = 0.02) and challenge-standing phase (34 ± 9 vs 42 ± 12 mL/beat/m2, P = 0.03) than HFpEF patients. CONCLUSION: The CORS is feasible and patients with HF responded differently to non-HF, and HFrEF from HFpEF. These findings provide further evidence for the potential use of the CORS to improve HF diagnostic and referral accuracy in primary care.

Heart failure (HF) is a global pandemic affecting 26 million people worldwide with an estimated 1 million people in the United Kingdom. Accurate early diagnosis of HF and the initiation of evidence-based treatment is essential to reduce morbidity and mortality and the associated burden on healthcare. As there are no state-of-the-art approaches, early diagnosis is challenging and often inaccurate, as initial signs and symptoms are nonspecific. We have developed an innovative test, named CORS (cardiac output response to stress test), to help general practitioners identify HF, which uses a method similar to an electrocardiogram and measures heart function at rest and during short step exercise. We recruited suspected HF patients from specialist HF diagnostic clinics in secondary care to complete the CORS test. We successfully demonstrated that 79% of patients with newly diagnosed HF (n = 38) and 91% of non-HF patients (n = 67) were able to complete all phases of the CORS test. Our findings demonstrate that newly diagnosed HF patients are able to complete this test, which provides further evidence for the potential use of the CORS test to improve HF diagnostic and referral accuracy in primary care.

Long term trends in natriuretic peptide testing for heart failure in UK primary care: a cohort study.

AIMS: Heart failure (HF) is a malignant condition with poor outcomes and is often diagnosed on emergency hospital admission. Natriuretic peptide (NP) testing in primary care is recommended in international guidelines to facilitate timely diagnosis. We aimed to report contemporary trends in NP testing and subsequent HF diagnosis rates over time. METHODS AND RESULTS: Cohort study using linked primary and secondary care data of adult (≥45 years) patients in England 2004-18 (n = 7 212 013, 48% male) to report trends in NP testing (over time, by age, sex, ethnicity, and socioeconomic status) and HF diagnosis rates. NP test rates increased from 0.25 per 1000 person-years [95% confidence interval (CI) 0.23-0.26] in 2004 to 16.88 per 1000 person-years (95% CI 16.73-17.03) in 2018, with a significant upward trend in 2010 following publication of national HF guidance. Women and different ethnic groups had similar test rates, and there was more NP testing in older and more socially deprived groups as expected. The HF detection rate was constant over the study period (around 10%) and the proportion of patients without NP testing prior to diagnosis remained high [99.6% (n = 13 484) in 2004 vs. 76.7% (n = 12 978) in 2017]. CONCLUSION: NP testing in primary care has increased over time, with no evidence of significant inequalities, but most patients with HF still do not have an NP test recorded prior to diagnosis. More NP testing in primary care may be needed to prevent hospitalization and facilitate HF diagnosis at an earlier, more treatable stage.

Accidental injury, self-injury, and assault among children of women with schizophrenia: a population-based cohort study.

OBJECTIVE: We aimed to compare the risk for injury overall and by intent (accidental injury, self-injury, and assault) among children born to women with versus without schizophrenia. METHODS: Using health administrative data from Ontario, Canada, children born from 2003 to 2017 to mothers with (n = 3769) and without (n = 1,830,054) schizophrenia diagnosed prior to their birth were compared on their risk for child injury, captured via emergency department, hospitalization, and vital statistics databases up to age 15 years. Cox proportional hazard models generated hazard ratios for time to first injury event (overall and by intent), adjusted for potential confounders (aHR). We stratified by child sex and age at follow-up: 0-1 (infancy), 2-5 (pre-school), 6-9 (primary school), and 10-15 (early adolescence) planning to collapse age categories as needed to obtain stable and reportable estimates. RESULTS: Maternal schizophrenia was associated with elevated risk for child injury overall (105.4 vs. 89.4/1000 person-years (py), aHR 1.08, 95% CI 1.03-1.14), accidental injury (104.7 vs. 88.1/1000py, 1.08, 1.03-1.14), for self-injury (0.4 vs. 0.2/1000py, 2.14 1.18-3.85), and assault (1.0 vs. 0.3/1000py, 2.29, 1.45-3.62). By child sex, point estimates were of similar magnitude and direction, though not all remained statistically significant. For accidental injury and self-injury, the risk associated with maternal schizophrenia was most elevated in 10-15-year-olds. For assault, the risk associated with maternal schizophrenia was most elevated among children in the 0-1 and 2-5-year-old age groups. CONCLUSION: The elevated risk of child injury associated with maternal schizophrenia, especially for self-injury and assault, suggests that targeted monitoring and preventive interventions are warranted.

Recommendations for occupational therapy interventions for adults with ADHD: a consensus statement from the UK adult ADHD network.

BACKGROUND: ADHD is neurodevelopmental disorder which persists into adulthood. Presently, therapeutic approaches are mainly pharmacological and psychological whilst the role, scope and approaches of occupational therapists have not been adequately described. RESULTS: In this consensus statement we propose that by assessing specific aspects of a person's occupation, occupational therapists can deploy their unique skills in providing specialist interventions for adults with ADHD. We also propose a framework with areas where occupational therapists can focus their assessments and give practice examples of specific interventions. CONCLUSIONS: Occupational therapists have much to offer in providing interventions for adults with ADHD. A unified and flexible approach when working with adults with ADHD is most appropriate and further research on occupational therapy interventions is needed.

Screening for atrial fibrillation: a call for evidence.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and prevalence is predicted to double over the next 30 years due to changing demographics and the rise in prevalence of risk factors such as hypertension and diabetes. Atrial fibrillation is associated with a five-fold increased stroke risk, but anticoagulation in eligible patients can reduce this risk by around 65%. Many people with AF currently go undetected and therefore untreated, either because they are asymptomatic or because they have paroxysmal AF. Screening has been suggested as one approach to increase AF detection rates and reduce the incidence of ischaemic stroke by earlier initiation of anticoagulation therapy. However, international taskforces currently recommend against screening, citing the cost implications and uncertainty over the benefits of a systematic screening programme compared to usual care. A number of large randomized controlled trials have commenced to determine the cost-effectiveness and clinical benefit of screening using a range of devices and across different populations. The recent AppleWatch study demonstrates how advances in technology are providing the public with self-screening devices that are increasingly affordable and accessible. Health care professionals should be aware of the implications of these emerging data for diagnostic pathways and treatment. This review provides an overview of the gaps in the current evidence and a summary of the arguments for and against screening.

Obesity, self-reported symptom severity, and quality of life in people with atrial fibrillation: A community-based cross-sectional survey.

BACKGROUND AND AIMS: Intentional weight loss may reduce symptom severity of atrial fibrillation (AF) in relatively young AF patients with overweight. We examined whether symptom severity and quality of life (QoL) are associated with weight status in the general population with AF. METHODS AND RESULTS: Patients with electrocardiogram-confirmed AF completed validated questionnaires: the EuroQol 5 Dimensions QoL questionnaire and the Toronto Atrial Fibrillation Severity Scale (AFSS). The AFSS assessed the AF burden scoring on AF-related symptoms and the total AF burden measured as a combination of duration, frequency, and severity of an irregular heartbeat. Generalized liner models examined the association of body mass index (BMI) with AF severity and QoL adjusting for confounders. Between 2018 and 2019, 882 of 1901 (46%) mailed questionnaires were returned completed. Participants had a mean (SD) age of 74 (10) years old and a BMI of 27.4 (5.6) kg/m2. Sixteen percent reported having never experienced an irregular heartbeat. A 5 kg/m2 higher BMI was associated with a 0.65 (95%CI: 0.25 to 1.06) higher symptom score, where 3 points represent a clinically relevant change in state. A 5 kg/m2 higher BMI was associated with a -1.61 (95%CI: -2.72 to -0.50) lower QoL score. The coefficient of the total AF burden for a 5 kg/m2 higher BMI was 0.17 (95% CI: -0.01 to 0.68). CONCLUSION: BMI was positively associated with symptoms and negatively associated with one of the two measures of QoL, but not with the total AF burden. However, the strength of association was small and not clinically meaningful.

The role of informal carers in the diagnostic process of heart failure: a secondary qualitative analysis.

BACKGROUND: Heart failure (HF) is a common clinical syndrome, particularly in older people, and symptoms can develop gradually. The aim of this study was to explore the role of informal carers in the HF diagnostic process. METHODS: Secondary analysis of qualitative interviews with 16 participants with a new diagnosis of HF. Original interviews were conducted in the participant's home, with carers present in some cases. Interview transcripts were re-analysed using the Framework Method for themes pertaining to informal carers and how they were involved in the diagnostic process. RESULTS: Informal carers often noticed symptoms, such as breathlessness, before participants. In some cases, carers colluded with participants in normalising symptoms but over time, when symptoms failed to resolve or got worse, they encouraged participants to seek medical help. Adult children of participants commonly initiated help-seeking behaviour. During the diagnostic process, carers coordinated participants' healthcare through advocacy and organisation. Carers were keen to be informed about the diagnosis, but both participants and carers struggled to understand some aspects of the term 'heart failure'. CONCLUSIONS: Carers play a crucial role in HF diagnosis, particularly in initiating contact with healthcare services, and should be empowered to encourage people with HF symptoms to seek medical help. Improving public awareness of HF could mean informal carers are more likely to notice symptoms. The important role of carers in supporting the patient's route to diagnosis should be incorporated into future care pathways and explored in further research.

Prospective associations between recalled parental bonding and perinatal depression: a cohort study in urban and rural Turkey.

PURPOSE: Recalled experiences of parental bonding may be important in the aetiology of perinatal depression. We hypothesized that lower recalled parental bonding would be associated with perinatal depression. METHOD: In a cohort study of perinatal depression in Turkey, 677 women were recruited in their third trimester. Parental Bonding Inventory (PBI) scores at baseline were investigated as predictors of depression on the Edinburgh Postnatal Depression Scale (EPDS) at 4, 14 and 21 months after childbirth in mothers without depression at baseline. RESULTS: Poor parental bonding scores, apart from paternal control and overprotection, were independently associated with antenatal depression. Incident postnatal depression at 4 months was predicted by parental overprotection, at 14 months by parental care and overprotection, and at 21 months by paternal control and overprotection. CONCLUSIONS: Less satisfactory parenting recalled in the antenatal period was an independent predictor of postnatal depression; however, the different bonding subscales varied as predictors according to the timing of the depression assessment after childbirth.

Correction to: Prospective associations between recalled parental bonding and perinatal depression: a cohort study in urban and rural Turkey.

The article 'Prospective associations between recalled parental bonding and perinatal depression: a cohort study in urban and rural Turkey, written by Berker Duman, Vesile Senturk Cankorur, Clare Taylor and Robert Stewart was originally published electronically on the publisher's internet portal (currently SpringerLink) on January 10, 2018 without open access.

Survival following a diagnosis of heart failure in primary care.

Background: Heart failure is a common long term condition affecting around 900 000 people in the UK and patients commonly present to primary care. The prognosis of patients with a code of heart failure in their primary care record is unknown. Objective: The study sought to determine the overall survival rates for patients with heart failure in a primary care population from the time of diagnosis. Methods: Survival analysis was carried out using UK primary care records from The Health Improvement Network (THIN) between 1 January 1998 and 31 December 2012. Patients age 45 or over with a first diagnostic label of heart failure were matched by age, sex and practice to people without heart failure. Outcome was death in the heart failure and no heart failure cohorts. Kaplan-Meier curves were used to compare survival. Age-specific survival rates at 1, 5 and 10 years were determined for men and women with heart failure. Survival rates by year of diagnosis and case definition were also calculated. Results: During the study period, 54313 patients had a first diagnostic code of heart failure. Overall survival rates for the heart failure group were 81.3% (95%CI 80.9-81.6), 51.5% (95%CI 51.0-52.0) and 29.5% (95%CI 28.9-30.2) at 1, 5 and 10 years respectively and did not change over time. Conclusions: In a primary care population, the survival of patients diagnosed with heart failure did not improved over time. Further research is needed to explain these trends and to find strategies to improve outlook.

Evaluating a nurse scholarship programme: realising potential.

Evaluation is an integral component of any nurse education programme and ideally requires a multi-method approach. This article describes both the formative and summative evaluation of the St Mark's Burdett nurse scholarship from the perspective of the health professionals involved. During the nursing scholar's specialty placements, their achievements were recorded alongside a more detailed insight into their ongoing development during weekly supervision sessions. The summative evaluation comprised recording their attendance at taught study days, progress in academic modules and one-to-one interviews. A survey was also conducted to gather feedback about the scholarship. The evaluation indicated that this programme helped the nursing scholars gain exposure to a broad range of gastrointestinal nursing clinical environments, provided them with the resources needed to continue to develop academically and professionally, and helped them to achieve career progression in specialist nursing.

Pathogenic copy number variants and SCN1A mutations in patients with intellectual disability and childhood-onset epilepsy.

BACKGROUND: Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy. METHODS: We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation. RESULTS: 8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort. CONCLUSIONS: We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults.

Safe mobilization of CD34+ cells in adults with ß-thalassemia and validation of effective globin gene transfer for clinical investigation.

We conducted a pilot trial to investigate the safety and effectiveness of mobilizing CD34(+) hematopoietic progenitor cells (HPCs) in adults with ß-thalassemia major. We further assessed whether thalassemia patient CD34(+) HPCs could be transduced with a globin lentiviral vector under clinical conditions at levels sufficient for therapeutic implementation. All patients tolerated granulocyte colony-stimulating factor well with minimal side effects. All cell collections exceeded 8 × 10(6) CD34(+) cells/kg. Using clinical grade TNS9.3.55 vector, we demonstrated globin gene transfer averaging 0.53 in 3 validation runs performed under current good manufacturing practice conditions. Normalized to vector copy, the vector-encoded ß-chain was expressed at a level approximating normal hemizygous protein output. Importantly, stable vector copy number (0.2-0.6) and undiminished vector expression were obtained in NSG mice 6 months posttransplant. Thus, we validated a safe and effective procedure for ß-globin gene transfer in thalassemia patient CD34(+) HPCs, which we will implement in the first US trial in patients with severe inherited globin disorders. This trial is registered at www.clinicaltrials.gov as #NCT01639690.

The prevalence and correlates of self-harm in pregnant women with psychotic disorder and bipolar disorder.

Women with severe mental illness are at increased risk of suicide in the perinatal period, and these suicides are often preceded by self-harm, but little is known about self-harm and its correlates in this population. This study aimed to investigate the prevalence of suicidal ideation and self-harm, and its correlates, in women with psychotic disorders and bipolar disorder during pregnancy. Historical cohort study using de-identified secondary mental healthcare records linked with national maternity data. Women pregnant from 2007 to 2011, with ICD-10 diagnoses of schizophrenia and related disorders, bipolar disorder or other affective psychoses were identified. Data were extracted from structured fields, natural language processing applications and free text. Logistic regression was used to examine the correlates of self-harm in pregnancy. Of 420 women, 103 (24.5 %) had a record of suicidal ideation during the first index pregnancy, with self-harm recorded in 33 (7.9 %). Self-harm was independently associated with younger age (adjusted odds ratio (aOR) 0.91, 95 % CI 0.85-0.98), self-harm in the previous 2 years (aOR 2.55; 1.05-6.50) and smoking (aOR 3.64; 1.30-10.19). A higher prevalence of self-harm was observed in women with non-affective psychosis, those who discontinued or switched medication and in women on no medication at the start of pregnancy, but these findings were not statistically significant in multivariable analyses. Suicidal thoughts and self-harm occur in a significant proportion of pregnant women with severe mental illness, particularly younger women and those with a history of self-harm; these women need particularly close monitoring for suicidality.

The characteristics and health needs of pregnant women with schizophrenia compared with bipolar disorder and affective psychoses.

BACKGROUND: Most women with psychotic disorders and bipolar disorders have children but their pregnancies are at risk of adverse psychiatric and fetal outcome. The extent of modifiable risk factors - both clinical and socio-demographic - is unclear as most studies have used administrative data or recruited from specialist tertiary referral clinics. We therefore aimed to investigate the socio-demographic and clinical characteristics of an epidemiologically representative cohort of pregnant women with affective and non-affective severe mental illness. METHODS: Women with severe mental illness were identified from a large electronic mental health case register in south London, and a data linkage with national maternity Hospital Episode Statistics identified pregnancies in 2007-2011. Data were extracted using structured fields, text searching and natural language processing applications. RESULTS: Of 456 pregnant women identified, 236 (51.7%) had schizophrenia and related disorders, 220 (48.3%) had affective psychosis or bipolar disorder. Women with schizophrenia and related disorders were younger, less likely to have a partner in pregnancy, more likely to be black, to smoke or misuse substances and had significantly more time in the two years before pregnancy in acute care (inpatient or intensive home treatment) compared with women with affective disorders. Both groups had high levels of domestic abuse in pregnancy (recorded in 18.9%), were from relatively deprived backgrounds and had impaired functioning measured by the Health of the Nation Outcome Scale. Women in the affective group were more likely to stop medication in the first trimester (39% versus 25%) whereas women with non-affective psychoses were more likely to switch medication. CONCLUSIONS: A significant proportion of women, particularly those with non-affective psychoses, have modifiable risk factors requiring tailored care to optimize pregnancy outcomes. Mental health professionals need to be mindful of the possibility of pregnancy in women of childbearing age and prescribe and address modifiable risk factors accordingly.

Multiprofessional heart failure self-development framework.

OBJECTIVE: Heart failure remains a key public health priority across the globe. The median age of people with heart failure admitted to hospital in the UK is 81 years old. Many such patients transcend the standard interventions that are well characterised and evidenced in guidelines, into holistic aspects surrounding frailty, rehabilitation and social care. Previous published competency frameworks in heart failure have focused on the value of doctors, nurses and pharmacists. We aimed to provide an expert consensus on the minimum heart failure-specific competencies necessary for multiple different healthcare professionals, including physiotherapists, occupational therapists, dietitians and cardiac physiologists. METHODS: The document has been developed focussing on four main parts, (1) establishing a project working group of expert professionals, (2) a literature review of previously existing published curricula and competency frameworks, (3) consensus building, which included developing a structure to the framework with ongoing review of the contents to adapt and be inclusive for each specialty and (4) write up and dissemination to widen the impact of the project. RESULTS: The final competency framework displays competencies across seven sections; knowledge (including subheadings on heart failure syndrome, diagnosis and clinical management); general skills; heart failure-specific skills; clinical autonomy; multidisciplinary team working; teaching and education; and research and development. CONCLUSION: People with heart failure can be complex and have needs that require input from a broad range of specialties. This publication focuses on the vital impact of wider multidisciplinary groups and should help define the generic core heart failure-specific competencies needed to support future pipelines of professionals, who regularly interact with and deliver care for patients with heart failure.

Safety and persistence of adoptively transferred autologous CD19-targeted T cells in patients with relapsed or chemotherapy refractory B-cell leukemias.

We report the findings from the first 10 patients with chemotherapy-refractory chronic lymphocytic leukemia (CLL) or relapsed B-cell acute lymphoblastic leukemia (ALL) we have enrolled for treatment with autologous T cells modified to express 19-28z, a second-generation chimeric antigen (Ag) receptor specific to the B-cell lineage Ag CD19. Eight of the 9 treated patients tolerated 19-28z(+) T-cell infusions well. Three of 4 evaluable patients with bulky CLL who received prior conditioning with cyclophosphamide exhibited either a significant reduction or a mixed response in lymphadenopathy without concomitant development of B-cell aplasia. In contrast, one patient with relapsed ALL who was treated in remission with a similar T-cell dose developed a predicted B-cell aplasia. The short-term persistence of infused T cells was enhanced by prior cyclophosphamide administration and inversely proportional to the peripheral blood tumor burden. Further analyses showed rapid trafficking of modified T cells to tumor and retained ex vivo cytotoxic potential of CD19-targeted T cells retrieved 8 days after infusion. We conclude that this adoptive T-cell approach is promising and more likely to show clinical benefit in the setting of prior conditioning chemotherapy and low tumor burden or minimal residual disease. These studies are registered at www.clinicaltrials.org as #NCT00466531 (CLL protocol) and #NCT01044069 (B-ALL protocol).