Outcomes after chimeric antigen receptor T-cell therapy across large B-cell lymphoma subtypes.

Not available.

A national service for delivering CD19 CAR-Tin large B-cell lymphoma - The UK real-world experience.

CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR-T in the UK. Consecutive patients with r/r LBCL approved for CAR-T by the National CAR-T Clinical Panel between December 2018 and November 2020 across all UK CAR-T centres were included. 404/432 patients were approved [292 axicabtagene ciloleucel (axi-cel), 112 tisagenlecleucel (tisa-cel)], 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi-cel, 57% (44% CR) for tisa-cel. The 12-month progression-free survival was 41.8% (axi-cel) and 27.4% (tisa-cel). Median overall survival for the intention-to-treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi-cel and 7.9%/3.9% for tisa-cel. This prospective RW population of CAR-T eligible patients offers important insights into the clinical benefit of CD19 CAR-T in LBCL in daily practice. Our results confirm long-term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR-T failure.

Antiepileptic drugs for seizure control in people with neurocysticercosis.

BACKGROUND: Neurocysticercosis is the most common parasitic infection of the brain. Epilepsy is the most common clinical presentation, though it may also present with headache, symptoms of raised intracranial pressure, hydrocephalus and ocular symptoms depending upon the localisation of the parasitic cysts. Anthelmintic drugs, anti-oedema drugs, such as steroids, and antiepileptic drugs (AEDs) form the mainstay of treatment.This is an updated version of the original Cochrane Review published in 2015, Issue 10. OBJECTIVES: To assess the effects (benefits and harms) of AEDs for the primary and secondary prevention of seizures in people with neurocysticercosis.For the question of primary prevention, we examined whether AEDs reduce the likelihood of seizures in patients who have neurocysticercosis but have not had a seizure.For the question of secondary prevention, we examined whether AEDs reduce the likelihood of further seizures in patients who have had at least one seizure due to neurocysticercosis.As part of primary prevention studies, we also aimed to examine which AED has been found to be beneficial in people with neurocysticercosis in terms of duration, dose and side-effect profile. SEARCH METHODS: For the latest update of this review, we searched the following databases on 8 July 2019: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to July 05, 2019) and LILACS (1982- ). CRS Web includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised or quasi-randomised, controlled trials from Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP). We also checked the references lists of identified studies, and contacted experts in the field and colleagues to search for additional studies and for information about ongoing studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials.Single-blind, double-blind or unblinded studies were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors screened all citations for eligibility (MS screened the initially identified 180 citations, MF and BDM screened the 48 citations identified for the purpose of this update).Two review authors independently extracted data and evaluated each study for risk of bias. MAIN RESULTS: We did not find any trials that investigated the role of AEDs in preventing seizures among people with neurocysticercosis, presenting with symptoms other than seizures.We did not find any trials that evaluated evaluating individual AEDs in people with neurocysticercosis.We found one trial, comparing two AEDs in people with solitary neurocysticercosis with seizures. However, we excluded this study from the review as it was of poor quality.We found four trials that compared the efficacy of short term versus longer term AED treatment for people with solitary neurocysticercosis (identified on computed tomography (CT) scan) presenting with seizures. In total, 466 people were enrolled. These studies compared various AED treatment durations, six, 12 and 24 months. The risk of seizure recurrence with six months treatment compared with 12 to 24 months treatment was not statistically significant (odds ratio (OR) 1.34 (95% confidence interval (CI) 0.73 to 2.47; three studies, 360 participants; low-certainty evidence)). The risk of seizure recurrence with six to 12 months compared with 24 months treatment was not statistically significant (OR 1.36 (95% CI 0.72 to 2.57; three studies, 385 participants; low-certainty evidence)).Two studies co-related seizure recurrence with CT findings and suggested that persistent and calcified lesions had a higher recurrence risk and suggest longer duration of treatment with AEDs. One study reported no side effects, while the rest did not comment on side effects of drugs. None of the studies addressed the quality of life of the participants.These studies had certain methodological deficiencies such as a small sample size and a possibility of bias due to lack of blinding, which affect the results of this review. AUTHORS' CONCLUSIONS: Despite neurocysticercosis being the most common cause of epilepsy worldwide, there is currently no evidence available regarding the use of AEDs as seizure prophylaxis among people presenting with symptoms other than seizures. For those presenting with seizures, there is no reliable evidence regarding the duration of treatment required. There is therefore a need for large scale randomised controlled trials to address these questions.

Unrelated and related donor transplantation for beta-thalassemia major: A single-center experience from India.

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with ß-thalassemia major. A matched sibling or a related donor is usually found in only 25%-30% of the patients. There are limited data on matched unrelated donor (MUD) transplants from India. We reviewed HSCT outcome in 56 children with TM who underwent 57 transplants at our center. Related donor (RD) (n=43) and MUD (n=14) transplants were performed with TreoFluT-based conditioning regimen in majority (95%) of patients. Peripheral blood stem cells (PBSC) were the preferred (85%) source of stem cells. The overall survival (OS) at 1 year in RD and MUD groups was 87.6±5.2% and 85.7±9.4% at a median follow-up of 25 (1-92) months and 22.5 (1-50) months, respectively (P=.757). The thalassemia-free survival (TFS) at 1 year was 87.6±5.2% and 77.1±11.7% with a median follow-up of 24 (1-92) and 16.5 (1-50) months, respectively (P=.487). Although acute (14% vs 64%) and chronic graft-versus-host disease (GVHD) (13.9% vs 42.9%), infectious (39.5% vs 71.4%), and non-infectious (37.2% vs 78.5%) complications are higher in MUD transplant group, the present data show a comparable OS and TFS among RD and MUD group with treosulfan-based regimen using PBSC grafts.

Cost Effectiveness of Hematopoietic Stem Cell Transplantation Compared with Transfusion Chelation for Treatment of Thalassemia Major.

Hematopoietic stem cell transplantation (HSCT) is the only cure for thalassemia major (TM), which inflicts a significant 1-time cost. Hence, it is important to explore the cost effectiveness of HSCT versus lifelong regular transfusion-chelation (TC) therapy. This study was undertaken to estimate incremental cost per quality-adjusted life-year (QALY) gained with the intervention group HSCT, and the comparator group TC, in TM patients. A combination of decision tree and Markov model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. Results are presented using societal perspective. Incremental cost per QALY gained with use of HSCT as compared with TC was 64,096 (US$986) in case of matched related donor (MRD) and 1,67,657 (US$2579) in case of a matched unrelated donor transplantation. The probability of MRD transplant to be cost effective at the willingness to pay threshold of Indian per capita gross domestic product is 94%. HSCT is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of TC.

Post stem cell transplantation revaccination: A survey of the current practices in India.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) recipients are more susceptible to infections from vaccine preventable diseases (VPDs) than the general population. Indian stem cell transplant registry (ISCTR) post-BMT vaccination guidelines were formulated in 2015. The objective of the survey was to assess the compliance to these guidelines among transplant physicians in India. MATERIALS AND METHODS: This is a cross-sectional survey executed as the quantitative research strategy to explore the various aspects of vaccination practices among transplant physicians in India. The 'data collection tool' included 36 predetermined questions related to vaccination of the patients and their close contacts. Theoretical construct of the questionnaire was face-validated and questionnaire survey forms were emailed individually as attachments or by google forms. This study is being reported based on the checklist for reporting results of internet e-surveys statement guidelines. RESULTS: Survey forms were sent to 105 transplant physicians in India, 62% of whom responded representing 78.8% of transplant centers in India. More than 90% of allogeneic transplant physicians and 64% of autologous transplant physicians offered vaccination. Over two third of the physicians responded that they would discontinue vaccination at the onset of cGVHD. Fewer than one third physicians offered vaccination against Hepatitis A, Typhoid or Meningococcal infections. Forty two percent of respondents were unaware of the ISCTR post-BMT vaccination protocol. Only 47% of respondents reported complete adherence to any of the protocols they were following. Immune reconstitution to guide vaccination was available only to 13.3 percent of respondents. CONCLUSION: There is a need to improve the implementation strategies of vaccination in HSCT recipients to increase the adherence and continuation of it even in the presence of GVHD. There is also a need to extend the vaccination among VPDs especially prevalent in India.

Un-manipulated Haploidentical Transplant in Wiskott-Aldrich Syndrome.

BACKGROUND: Allogeneic stem cell transplant is the only curative treatment for Wiskott-Aldrich syndrome. CASE CHARACTERISTICS: 18-months-old boy with no sibling, cord blood or matched unrelated donor transplant options. OUTCOME: Doing well 7 years after haplo-identical stem cell transplantation using unmanipulated bone marrow as the stem cell source. MESSAGE: Father as a haplo-identical donor is a feasible option.

Antiepileptic drugs for seizure control in people with neurocysticercosis.

BACKGROUND: Neurocysticercosis is the most common parasitic infection of the brain. Epilepsy is the commonest clinical presentation, though it may also present with headache, symptoms of raised intracranial tension, hydrocephalus and ocular symptoms depending upon the localisation of the parasitic cysts. Anthelmintic drugs, anti-oedema drugs, such as steroids and antiepileptic drugs (AEDs) form the mainstay of treatment. OBJECTIVES: To assess the effects (benefits and harms) of AEDs for the primary and secondary prevention of seizures in people with neurocysticercosis. SEARCH METHODS: We searched the Cochrane Epilepsy Group Specialized Register (5 May 2015), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library April 2015, Issue 4), MEDLINE (1946 to 5 May 2015), LILACS (Latin American and Caribbean Literature in Health Sciences, 5 May 2015), SCOPUS (1823 to 15 April 2014), ClinicalTrials.gov (7 May 2015), and the WHO International Clinical Trials Registry Platform ICTRP (7 May 2015). We also checked the references lists of identified studies, and contacted experts in the field and colleagues to search for additional studies and for information about ongoing studies. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials.The studies may be single blind, double blind or unblinded. DATA COLLECTION AND ANALYSIS: One review author screened all citations for eligibility.Two review authors independently extracted data and evaluated each study for risk of bias. MAIN RESULTS: We did not find any trials that investigated the role of AEDs in preventing seizures among people with neurocysticercosis, presenting with symptoms other than seizures.We did not find any trials that evaluated evaluating individual AEDs in people with neurocysticercosis.We found one trial, comparing two AEDs in people with solitary neurocysticercosis with seizures. However, we excluded this study from the review as it was of poor quality.We found four trials that compared the efficacy of short term versus longer term AED treatment for people with solitary neurocysticercosis (identified on CT scan) presenting with seizures. In total, 466 people were enrolled. These studies compared various AED treatment durations, six, 12 and 24 months. The risk of seizure recurrence with six months treatment compared with 12 to 24 months treatment was not statistically significant (odds ratio (OR) 1.34, 95% confidence interval (CI) 0.73 to 2.47) (three studies n = 360, P 0.35). The risk of seizure recurrence with six to 12 months compared with 24 months treatment was not statistically significant (OR 1.36, 95% CI 0.72 to 2.57) (three studies, n = 385, P 0.34).Two studies co-related seizure recurrence with CT findings and suggested that persistent and calcified lesions had a higher recurrence risk and suggest longer duration of treatment with AEDs. One study reported no side effects, while the rest did not comment on side effects of drugs. None of the studies addressed the quality of life of the participants.These studies had certain methodological deficiencies such as a small sample size and a possibility of bias due to lack of blinding, which affect the results of this review. AUTHORS' CONCLUSIONS: Despite neurocysticercosis being the most common cause of epilepsy worldwide, there is currently no evidence available regarding the use of AEDs as prophylaxis for preventing seizures among people presenting with symptoms other than seizures. For those presenting with seizures, there is no reliable evidence regarding the duration of treatment required. There is therefore a need for large scale randomised controlled trials to address these questions.

Macrothrombocytopenia in north India: role of automated platelet data in the detection of an under diagnosed entity.

Congenital macrothrombocytopenia is being increasingly recognised because of the increasing availability of automated platelet counts during routine complete blood count. If not recognised, these patients may be unnecessarily investigated or treated. The study was done to assess the occurrence of macrothrombocytopenia in the North Indian population and the role of automated platelet parameters in its detection. This prospective study was done on patients whose blood samples were sent for CBC to the hematology laboratory of a tertiary care hospital. Samples were run on Advia-120, a 5-part differential automated analyzer. Routine blood parameters including platelet count, mean platelet volume (MPV), platelet cytogram pattern and platelet flagging was studied along with peripheral blood smear examination. ANOVA was used to compare difference in mean MPV in patients with macrothrombocytopenia, and those with secondary thrombocytopenia and ITP. Seventy five (0.6 %) patients with CBC evaluation were detected to have macrothrombocytopenia, majority (96 %) of North Indian origin. The MPV (fl) in the 75 patients ranged from 10.9 to 23.3 (mean 15.1 ± 3.1 fl) with a dispersed cytogram pattern distinct from that seen in patients with normal platelet count, raised platelet count or low platelets due to secondary thrombocytopenia (MPV-10.9 ± 2.6) or ITP (10.8 ± 3.5). The difference in mean MPV in these patients was statistically significant (p < 0.00001). Macrothrombocytopenia is an under diagnosed condition and may be initially suspected on automated blood counts. Along with a blood smear examination, automated data (MPV and platelet cytogram pattern) aids the diagnosis and can avoid unnecessary investigations and interventions for these patients.

Spurious platelet count due to cryoglobulins in a patient with smoldering myeloma.

Use of automated hematology analyzers for routine blood count reporting has increased the reproducibility and accuracy of test results. However, at times, these instruments may generate spurious test results. Such results can result in inappropriate investigations or treatment decisions in patients. Spuriously normal or high platelet counts carry the risk of under diagnosis of the true thrombocytopenia with adverse clinical implications. We present a patient with smoldering myeloma with spurious platelet count due to cryoglobulins.