Circulating N‐cadherin levels are a negative prognostic indicator in patients with multiple myeloma

N‐cadherin (cadherin 2, type 1, N‐cadherin (neuronal); CDN2) is a homotypic adhesion molecule that is upregulated in breast, prostate and bladder cancer. Here we investigated the prognostic significance of upregulated N‐cadherin expression in multiple myeloma (MM). Our results indicate that N‐cadherin protein and gene expression is abnormally increased in trephine biopsies and CD38⁺⁺/CD138⁺ plasma cells from MM patients, when compared with those of normal donors. In addition, levels of circulating N‐cadherin were elevated in a subset of patients with MM (n = 81; mean: 14·50 ng/ml, range: 0–146·78 ng/ml), relative to age‐matched controls (n = 27; mean: 2·66 ng/ml, range: 0–5·96 ng/ml), although this did not reach statistical significance. Notably, patients with abnormally high levels of N‐cadherin (>6 ng/ml) had decreased progression‐free survival (P = 0·036; hazard ratio: 1·94) and overall survival (P = 0·002; hazard ratio: 3·15), when compared with patients with normal N‐cadherin levels (≤6 ng/ml). Furthermore, multivariate analyses revealed that the combination of N‐cadherin levels and International Staging System (ISS) was a more powerful prognostic indicator than using ISS alone. Collectively, our studies demonstrate that circulating N‐cadherin levels are a viable prognostic marker for high‐risk MM patients.     

Clinical and laboratory characteristics of children with venous thromboembolism and protein C‐deficiency: an observational Israeli‐German cohort study

Venous thromboembolism [TE] is a multifactorial disease and protein C deficiency [PCD] constitutes a major risk factor. In the present study the prevalence of PCD and the clinical presentation at TE onset, including neonatal purpura fulminans, in a cohort of children are reported. In 367 unselected children (0·1–19 years) recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. Twenty‐five of 338 children (7·4%) had PCD. Mean age at first TE onset was 10 years (range 0·1–18). Leading thromboembolic manifestations were neonatal purpura fulminans (n = 5), TE of cerebral veins (n = 3), stroke (n = 2) deep veinthrombosis (DVT) of the leg (n = 10), DVT & pulmonary embolism (n = 2) and DVT & pelvic veins (n = 3). Concomitant risk factors for TE were identified in 12 patients, whereas 13 children spontaneously developed TE. A positive family history of DVT was found in 10 children. In this unselected cohort of paediatric patients with symptomatic TE the overall prevalence of PCD was 7·4%; 1·5% presented with neonatal purpura fulminans. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high‐risk population.     

Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard‐risk acute lymphoblastic leukaemia in first complete remission

We retrospectively investigated outcomes of haploidentical donor (HID) transplant for adults with standard‐risk acute lymphoblastic leukaemia (ALL) in first complete remission (CR1) compared with human leucocyte antigen (HLA)‐matched sibling donor (MSD) and HLA‐matched unrelated donor (MUD) transplants. A total of 348 adult patients were enrolled, including 127 HID, 144 MSD and 77 MUD recipients. The cumulative incidence of grade II–IV acute graft‐versus‐host disease (aGVHD) was 39·5%, 24·0% and 40·3% for HID, MSD and MUD, respectively (P = 0·020). However, there was no difference in grade III–IV aGVHD (11·4%, 7·7%, 13·5%, respectively, P = 0·468). The 5‐year cumulative transplant‐related mortality was 16·4%, 11·6% and 19·6% (P = 0·162), the 5‐year relapse rate post‐transplantation was 14·8%, 21·1% and 16·7% (P = 0·231), the 5‐year overall survival was 70·1%, 73·7% and 69·8% (P = 0·525), and the 5‐year disease‐free survival was 68·7%, 67·3% and 63·7%, respectively (P = 0·606). Furthermore, the 3‐year GVHD‐free, relapse‐free survival was not different (50·8%, 54·9% and 52·2%, respectively, P = 0·847). Our results indicate that the outcomes of HID transplants are equivalent to those of MSD and MUD, and that HID transplantation is a valid alternative for standard‐risk adults with ALL in CR1 who lack matched donors.     

Phase 2 study of tabalumab,a human anti‐B‐cell activating factor antibody,with bortezomib and dexamethasone in patients with previously treated multiple myeloma

In this double‐blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N  = 72), tabalumab 100 mg (N  = 74), or tabalumab 300 mg (N  = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m² on a 21‐day cycle. No significant intergroup differences were observed among primary (median progression‐free survival [mPFS ]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR ) [95% confidence interval (CI )] = 1·13 [0·80–1·59], P  =  0·480; tabalumab 300 mg vs. placebo HR [95% CI ] = 1·03 [0·72–1·45], P  =  0·884). The most commonly‐reported treatment‐emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF 13B) expression (n  = 162) had significantly longer mPFS than those with high BAFF expression (n  = 55), using the 75th percentile cut‐off point (mPFS [95% CI ] = 8·3 [7·0–9·3] months vs. 5·8 [3·7–6·6] months; HR [95% CI ] = 1·59 [1·11–2·29], P  =  0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma.     

Favourable outcomes of poor prognosis diffuse large B‐cell lymphoma patients treated with dose‐dense Rituximab,high‐dose Methotrexate and six cycles of CHOP‐14 compared to first‐line autologous transplantation

The optimal therapeutic approach for young diffuse large B‐cell lymphoma (DLBCL) patients with high‐intermediate and high‐risk age‐adjusted international prognostic index (aaIPI) remains unknown. Hereby we report a 10‐year single‐centre study of 63 consecutively treated patients. To optimize outcome, two approaches were carried out: Cohort 1 patients received four cycles R‐CHOP‐21 (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone over 21 days) followed by first‐line high‐dose chemotherapy with autologous stem‐cell support (HDCT‐ASCT), resulting in 2‐year progression‐free (PFS) and overall survival (OS) of 60·6% and 67·9%. 39·4% of those patients were not transplanted upfront, mainly due to early progressive disease (24·2%). Cohort 2 patients received an early intensified protocol of six cycles of CHOP‐14 (cyclophosphamide, daunorubicin, vincristine, prednisolone over 14 days) with dose‐dense rituximab and high‐dose methotrexate resulting in promising overall response‐ (93·3%) and complete remission (90%) rates and sustained survival (2‐year PFS and OS: 93·3%). In an intention‐to‐treat analysis, 2‐year PFS (60·6% vs. 93·3%, hazard ratio [HR] 7·2, P = 0·009) and OS (69·7% vs. 93·3%, HR 4·95, P = 0·038) differed significantly, in favour of the early intensified protocol (Cohort 2). In a multivariate Cox‐regression model, PFS (HR 8·12, 95% confidence interval [CI] 1·83–35·9, P = 0·006) and OS (HR 5·86, 95% CI 1·28–26·8, P = 0·02) remained superior for Cohort 2 when adjusted for aaIPI3 as the most important prognostic factor. Survival of young poor‐prognosis DLBCL patients appears superior after early therapy intensification.     

Clinical utility of next‐generation sequencing‐based minimal residual disease in paediatric B‐cell acute lymphoblastic leukaemia

We assessed the clinical utility of next‐generation sequencing (NGS)‐based monitoring of minimal residual disease (MRD) in a uniformly treated cohort of 79 patients with paediatric B‐cell acute lymphoblastic leukaemia. Bone marrow samples were collected at the time of diagnosis, days 33 and 80, pre‐ (4–5 months) and post‐ (24 months) maintenance therapy time points, and at relapse. We identified leukaemia‐specific CDR3 sequences in 72 of 79 patients (91%) and detected MRD in 59 of 232 samples. Although MRD was detected in 28 of 55 samples (51%) on day 33, the frequencies of MRD detection decreased to 25% (16/65) at day 80, 19% (11/58) at 4–5 months and 7·4% (4/54) at 24 months. In a univariate analysis, positive MRD results on day 80 [relative risk (RR) 95% confidence interval (CI) = 7·438 (2·561–21·6), P < 0·001], at 4–5 months [RR (95% CI) = 10·24 (3·374–31·06), P < 0·001], and at 24 months [RR (95% CI) = 19·26 (4·974–74·59), P < 0·001] exhibited statistically significant associations with inferior leukaemia‐free survival; this was confirmed using a Cox proportional hazard model. Our study suggests the promising potential of NGS‐MRD for patients with B‐cell ALL.     

Hodgkin lymphoma: a negative interim‐PET cannot circumvent the need for end‐of‐treatment‐PET evaluation

We examined the outcome of a cohort of patients with Hodgkin lymphoma (HL) in order to assess if fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) at the end of treatment (end‐PET) can be omitted when the interim PET (int‐PET) is negative. Seventy‐six ABVD(adriamycin, bleomycin, vinblastine, dacarbazine)‐treated patients were retrospectively included. No change in treatment was made on the basis of int‐PET results. Suspicious foci on end‐PET received biopsy confirmation whenever possible. Median follow‐up was 58·9 months. Uptake on int‐PET higher than liver (scores 4–5) was rated positive according to the Lugano classification, while a positive end‐PET corresponded to scores 3, 4 and 5. Fifteen patients had treatment failure. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy of int‐PET were 46·7%, 85·2%, 43·8%, 86·7% and 77·6%, respectively. For end‐PET the figures were: 80%, 93·4%, 75%, 95% and 90·8%. Eight patients with negative int‐PET had treatment failure; six of them were identified as non‐responders with end‐PET. The 5‐year progression‐free survival (PFS) was 87% for patients with negative int‐PET versus 56% with positive int‐PET. The 5‐year PFS was 96% with negative end‐PET versus 23% with positive end‐PET. The prognostic information from int‐PET as regards PFS (log‐rank test P = 0·0048) was lower than that provided by end‐PET (P < 0·0001). Int‐PET predicted only half of the failures. When used in clinical routine, a negative int‐PET study cannot obviate the need for end‐PET examination.     

Prognostic value of complete remission status at end‐of‐treatment FDG‐PET in R‐CHOP‐treated diffuse large B‐cell lymphoma: systematic review and meta‐analysis

This study systematically reviewed and meta‐analysed the prognostic value of complete remission status at end‐of‐treatment ¹⁸F‐fluoro‐2‐deoxy‐d ‐glucose positron emission tomography (FDG‐PET) in diffuse large B‐cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R‐CHOP). The systematic PubMed/MEDLINE search yielded seven suitable studies comprising a total of 737 R‐CHOP‐treated DLBCL patients who were in complete remission at end‐of‐treatment FDG‐PET. Overall, the methodological quality of included studies was reasonable. The disease relapse rate among all patients with complete remission status according to end‐of‐treatment FDG‐PET ranged from 7·0% to 20·0%, with a weighted summary proportion of 13·7%. Five of seven studies reported progression‐free survival (PFS) of these patients at various specific time points, i.e., 2‐year PFS (n = 1), estimated 3‐year PFS (n = 3) and 5‐year PFS (n = 1), which was 83%, 85–86·4% and 75%, respectively. Three of seven studies reported overall survival (OS) of these patients at various specific time points, i.e., estimated 3‐year OS (n = 2) and estimated 5‐year OS (n = 1), which were 90%, 93·6% and 83%, respectively. In conclusion, a non‐negligible proportion of R‐CHOP‐treated DLBCL patients who achieve complete remission according to end‐of‐treatment FDG‐PET experiences disease relapse during follow‐up.     

Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma: post‐hoc analyses from a phase III trial

This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B‐cell non‐Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28‐d cycles of 85 mg/m² pixantrone dimaleate (equivalent to 50 mg/m² in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line. Median number of cycles was 4 (range, 2–6) with pixantrone and 3 (2–6) with comparator. In 3rd or 4th line, pixantrone was associated with higher complete response (CR) (23·1% vs. 5·1% comparator, P = 0·047) and overall response rate (ORR, 43·6% vs. 12·8%, P = 0·005). In 3rd or 4th line with previous rituximab (20 pixantrone, 18 comparator), pixantrone produced better ORR (45·0% vs. 11·1%, P = 0·033), CR (30·0% vs. 5·6%, P = 0·093) and progression‐free survival (median 5·4 vs. 2·8 months, hazard ratio 0·52, 95% confidence interval 0·26–1·04) than the comparator. Similar results were found in patients without previous rituximab. There were no unexpected safety issues. Pixantrone monotherapy is more effective than comparator in relapsed or refractory aggressive B‐cell NHL in the 3rd or 4th line setting, independently of previous rituximab.     

Multiple infusions of mesenchymal stromal cells induce sustained remission in children with steroid‐refractory,grade III–IV acute graft‐versus‐host disease

Mesenchymal stromal cell (MSC) infusions have been reported to be effective in patients with steroid‐refractory, acute graft‐versus‐host disease (aGvHD) but comprehensive data on paediatric patients are limited. We retrospectively analysed a cohort of 37 children (aged 3 months‐17 years) treated with MSCs for steroid‐refractory grade III–IV aGvHD. All patients but three received multiple MSC infusions. Complete response (CR) was observed in 24 children (65%), while 13 children had either partial (n = 8) or no response (n = 5). Cumulative incidence of transplantation‐related mortality (TRM) in patients who did or did not achieve CR was 17% and 69%, respectively (P = 0·001). After a median follow‐up of 2·9 years, overall survival (OS) was 37%; it was 65% vs. 0% in patients who did or did not achieve CR, respectively (P = 0·001). The median time from starting steroids for GvHD treatment to first MSC infusion was 13 d (range 5–85). Children treated between 5 and 12 d after steroid initiation showed a trend for better OS (56%) and lower TRM (17%) as compared with patients receiving MSCs 13–85 d after steroids (25% and 53%, respectively; P = 0·22 and 0·06, respectively). Multiple MSC infusions are safe and effective for children with steroid‐refractory aGvHD, especially when employed early in the disease course.     

Autologous stem cell transplantation outcomes in elderly patients with B cell Non‐Hodgkin Lymphoma

The precise role of autologous haematopoietic stem cell transplantation (ASCT) remains unclear in patients over 60 years of age. There is potential for increased procedural morbidity and mortality, and differences in disease biology that could impact outcomes. We performed a retrospective single‐centre review of 81 elderly B‐cell Non‐Hodgkin Lymphoma patients undergoing ASCT. Five‐year overall survival (OS) and progression‐free survival (PFS) was 54·7% and 49·1% respectively. Non‐relapse mortality (NRM) at 100 days and 1 year was 1·3% and 2·5%, suggesting no major excess compared to younger cohorts. OS and PFS were significantly worse in those over 65 years compared to those aged 60–64 (47·6% vs. 57·7%, P = 0·0437, and 27·6% vs. 57·7%, P = 0·0052 at 5 years). This resulted largely from an increased relapse risk (RR) (53·8% vs. 30·1%, P = 0·0511) rather than excess NRM, and age remained independently significant for PFS on multivariate analyses [Hazard ratio 2·56 (1·35–4·84, P = 0·0052) for PFS and 1·89 (0·99–3·61, P = 0·054) for OS]. Our data adds to the growing body of evidence demonstrating that ASCT can be an effective treatment strategy with an acceptable safety profile in selected elderly patients. Further evaluation of its overall benefit is warranted, however, in those over 65 years of age, as RR appears to be considerably higher.     

Validation and reliability of a disease‐specific quality of life measure (the TranQol) in adults and children with thalassaemia major

This study aimed to demonstrate the validity, reliability and responsiveness of a new disease‐specific quality of life (QoL) questionnaire for children and adults with thalassaemia major, the Transfusion‐dependent QoL questionnaire (TranQol). 106 participants (51 adults and 55 children) were recruited from six North American thalassaemia treatment centres with a mean age of 20·7 years (standard deviation [SD] 9, range 7–51 years). The mean total TranQol score was 71 (SD 17, 32–97) on a scale of 0–100. Patients with co‐morbidities had significantly lower scores (63 vs. 75, P = 0·001). TranQol scores showed substantial agreement (P < 0·001) with the Health Utilities Index Mark 3 (all patients, r = 0·65), the Pediatric QoL (children, r = 0·77) and the Short Form (36) physical (adults, r = 0·69) and mental summary scores (r = 0·76). In the subgroup who rated their QoL as better, there was a 4·0 point (SD 9·0) improvement in TranQol scores, from baseline of 67·1–71·1 one week later (P = 0·008). Test–retest reliability was excellent (intra‐class correlation coefficient, 0·93). The TranQol was valid, with acceptable correlation for all administered measures and was reliable and responsive to change. The TranQol can be incorporated into future studies of thalassaemia major.     

Donor‐derived myelodysplastic syndrome and acute leukaemia after allogeneic haematopoietic stem cell transplantation: incidence,natural history and treatment response

Donor‐derived myelodysplastic syndrome/acute leukaemia (DD‐MDS/AL) is a rare life‐threatening complication of allogeneic haematopoietic stem cell (HSC) transplantation. However, it is unknown whether the risk differs by HSC source. Therefore, we evaluated the incidence of DD‐MDS/AL in 2390 engrafted patients. With a median follow‐up of 7·1 years (1–20·8), the incidence of DD‐MDS/AL was 0·53% (95% confidence interval (CI), 0·01–1·41%], 0·56% (95%CI, 0·01–1·36%) and 0·56% (95%CI, 0·01–1·10%) in recipients of bone marrow (n = 1117), peripheral blood (n = 489) and umbilical cord blood (UCB, n = 784), respectively. While follow‐up is shorter in recipients of UCB and peripheral blood, incidence of DD‐MDS/AL is, thus far, similar between HSC sources.     

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

The Haematopoietic Cell Transplantation‐Comorbidity Index (HCT‐CI) was designed as a predictor of non‐relapse mortality after HCT. Chronic graft‐versus‐host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT‐CI could predict development of chronic GVHD or post‐chronic GVHD mortality. We retrospectively analysed data from 2909 patients treated with allogeneic HCT for malignant and non‐malignant haematological conditions at four institutions. In Cox regression models adjusted for potential confounders, increasing HCT‐CI was not statistically significantly associated with the development of chronic GVHD [hazard ratio (HR) = 1·02, P = 0·34]. Yet, the index was associated with an increased risk of non‐relapse mortality (HR = 1·29, P < 0·0001) as well as overall mortality (HR = 1·25, P < 0·001) following the development of chronic GVHD. The association between HCT‐CI and post‐chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT‐CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.     

Salvage therapy using FLT3 inhibitors may improve long‐term outcome of relapsed or refractory AML in patients with FLT3‐ITD

To determine the long‐term efficacy of FLT3 inhibitors (FLT3i) in the salvage setting for relapsed and refractory (rel/ref) acute myeloid leukemia (AML) with FLT3 internal tandem duplication (AML FLT3‐ITD), we conducted a retrospective study of 120 patients with rel/ref AML FLT3‐ITD who received salvage therapy with either FLT3i‐containing regimen (FLT3i group, N = 45) or conventional cytotoxic regimen (conventional group, N = 75). The median overall survival (OS) after the first salvage in the FLT3i group was 6·9 vs. 4·6 months in the conventional group (P = 0·17). The OS was better in the FLT3i group among patients with initial complete remission (CR) duration ≤12 months or with primary refractory disease (6·9 vs. 3·7 months; P < 0·01). The OS was better when FLT3i was combined with cytotoxic agents versus monotherapy (17 vs. 4·8 months; P = 0·017). Multivariate analysis revealed that the use of FLT3i was an independent predictor of OS (hazard ratio 0·58; 95% confidence interval, 0·38–0·88). Incorporating FLT3i into salvage strategies may improve long‐term outcome of patients with AML FLT3‐ITD. Prospective studies to validate this conclusion are warranted.     

Fertility and sexual function in long‐term survivors of haematological malignancy: using patient‐reported outcome measures to assess a neglected area of need in the late effects clinic

Problems of sexual function and fertility in long‐term survivors (≥5 years) of haematological malignancy are often neglected in clinic. Our centre carried out a questionnaire study in this population addressing patient‐perceived fertility and sexual function. 718 patients responded (56% of those invited; 39% Hodgkin, 45% non‐Hodgkin lymphoma, 16% acute leukaemia). Respondent women were more likely to remain childless than a normal control population. Self‐reported infertility was more likely in men than women [odds ratio (OR) 1·77, P = 0·001]. Myeloablative therapy increased the likelihood of childlessness (OR 2·48, P = 0·004). Few attended fertility support services (12%). 24% of men banked sperm and 29% of these used the sample, of which 46% resulted in successful pregnancy. Fertility clinic attendance and sperm storage was more likely post‐1990 (OR 4·05, P < 0·001; OR 5·05, P < 0·001 respectively). Reporting a negative impact of cancer on sexual function was more common in women than men (OR 2·20, P < 0·001), and increased with current age and age at diagnosis (by 3–4% per year, P ≤ 0·001) but decreased with longer follow‐up (by 2%/year, P = 0·005). Patients on anti‐depressants and those reporting cancer‐related body change/appearance concerns more frequently reported a negative impact (P < 0·04 and P < 0·03 respectively). These self‐reported outcomes confirm literature findings, suggest improvement over time, but highlight a need for involvement of support services.     

Risk factor analysis of non‐Hodgkin lymphoma‐associated haemophagocytic syndromes: a multicentre study

Haemophagocytic syndrome is often associated with malignant lymphoma; however, few studies have examined lymphoma‐associated haemophagocytic syndrome (LAHS). A total of 1239 patients with non‐Hodgkin lymphoma were analysed at 12 institutions in Hokkaido prefecture between January 2007 and December 2011 to assess the incidence, prognosis and risk factors of LAHS. The cumulative incidence rate of LAHS was 2·8% (35/1239). Overall survival (OS) in patients with LAHS was significantly inferior to those without LAHS (3‐year OS: 35·6 vs. 59·0% respectively, P < 0·0001). The cumulative incidence of LAHS was higher in patients with T/Natural Killer (NK)‐cell lymphoma than in those with B‐cell lymphoma (8·2 vs. 1·8% respectively, P < 0·0001). The characteristics of patients with and without early death (within the first 120 d after developing LAHS) were subsequently compared to evaluate the prognostic factor of LAHS. The results obtained showed that the rate of early death after developing LAHS was higher in patients with T/NK‐cell lymphoma than in those with B‐cell lymphoma (62·5 vs. 10·5%, P = 0·0033). In conclusion, the complication and mortality rates of LAHS were higher in patients with T/NK‐cell lymphoma after they developed LAHS than in those with B‐cell lymphoma.     

Laboratory detection of strongyloidiasis: IgG‐, IgG4‐ and IgE‐ELISAs and cross‐reactivity with lymphatic filariasis

Enzyme‐linked immunosorbent assays (ELISAs) were developed for the detection of IgG, IgG₄ and IgE antibodies against Strongyloides stercoralis. A commercial ELISA (IVD Research, USA) was also used, and the sensitivities and specificities of the four assays were determined. Serum samples from 26 patients with S. stercoralis infection and 55 patients with other infections or no infection were analysed. Sensitivities of the IgG₄, IgG, IgE and IgG (IVD) assays were 76·9%, 84·6%, 7·7% and 84·6%, respectively, while the specificities were 92·7%, 81·8%, 100% and 83·6%, respectively. If filariasis samples were excluded, the specificities of the IgG₄‐ELISA and both IgG‐ELISAs increased to 100% and 98%, respectively. A significant positive correlation was observed between IgG‐ and IgG₄‐ELISAs (r = 0·4828; P = 0·0125). IgG‐ and IgG‐ (IVD) ELISAs (r = 0·309) were positively correlated, but was not significant (P = 0·124). Meanwhile there was no correlation between IgG₄‐ and IgG‐ (IVD) ELISAs (r = 0·0042; P = 0·8294). Sera from brugian filariasis patients showed weak, positive correlation between the titres of antifilarial IgG₄ and the optical densities of anti‐Strongyloides IgG₄‐ELISA (r = 0·4544, P = 0·0294). In conclusion, the detection of both anti‐Strongyloides IgG₄ and IgG antibodies could improve the serodiagnosis of human strongyloidiasis. Furthermore, patients from lymphatic filariasis endemic areas who are serologically diagnosed with strongyloidiasis should also be tested for filariasis.     

Neurotoxic side effects in children with refractory or relapsed T‐cell malignancies treated with nelarabine based therapy

The prognosis in children with refractory or relapsed (r/r) T‐cell acute lymphoblastic leukaemia (T‐ALL) or lymphoblastic lymphoma (T‐LBL) is poor. Nelarabine (Ara‐G) has successfully been used as salvage therapy in these children, but has been associated with significant, even fatal, neurotoxicities. We retrospectively analysed 52 patients with r/r T‐ALL/T‐LBL aged ≤19 years who were treated with Ara‐G alone (n = 25) or in combination with cyclophosphamide and etoposide (n = 27). The majority of patients (45/52) received 1–2 cycles of Ara‐G. Seventeen patients (32·7%) had refractory disease, 28 (53·8%) were in first relapse and 7 (13·5%) were in second relapse. A response to Ara‐G was achieved in 20 patients and 15 (28·8%) were in remission at last follow‐up. Twelve patients (23·1%) had neurotoxic adverse effects (neuro‐AE) of any grade, of whom 7 (13·5%) developed neurotoxicity ≥ grade III. The most frequent neuro‐AEs were peripheral motor neuropathy (19·2%), peripheral sensory neuropathy (11·5%) and seizures (9·6%). Three patients died of central neuro‐AE after 1–2 cycles of combination therapy. Patients with neurotoxicity were significantly older (median 15·17 years) than those without (10·34 years, P = 0·017). No differences were observed between mono‐ and combination therapy concerning outcome and neuro‐AE. The incidence of neuro‐AE was not associated with concurrent intrathecal therapy or prior central nervous system irradiation.     

Machine‐learning algorithms for predicting hospital re‐admissions in sickle cell disease

Reducing preventable hospital re‐admissions in Sickle Cell Disease (SCD) could potentially improve outcomes and decrease healthcare costs. In a retrospective study of electronic health records, we hypothesized Machine‐Learning (ML) algorithms may outperform standard re‐admission scoring systems (LACE and HOSPITAL indices). Participants (n = 446) included patients with SCD with at least one unplanned inpatient encounter between January 1, 2013, and November 1, 2018. Patients were randomly partitioned into training and testing groups. Unplanned hospital admissions (n = 3299) were stratified to training and testing samples. Potential predictors (n = 486), measured from the last unplanned inpatient discharge to the current unplanned inpatient visit, were obtained via both data‐driven methods and clinical knowledge. Three standard ML algorithms, Logistic Regression (LR), Support‐Vector Machine (SVM), and Random Forest (RF) were applied. Prediction performance was assessed using the C‐statistic, sensitivity, and specificity. In addition, we reported the most important predictors in our best models. In this dataset, ML algorithms outperformed LACE [C‐statistic 0·6, 95% Confidence Interval (CI) 0·57–0·64] and HOSPITAL (C‐statistic 0·69, 95% CI 0·66–0·72), with the RF (C‐statistic 0·77, 95% CI 0·73–0·79) and LR (C‐statistic 0·77, 95% CI 0·73–0·8) performing the best. ML algorithms can be powerful tools in predicting re‐admission in high‐risk patient groups.