Alloimmune-mediated lung syndromes (allo-LSs) are life-threatening complications after hematopoietic cell transplantation (HCT). Respiratory virus (RV) has been suggested to play a role in the ...pathogenesis.
We studied the relation between RV DNA/RNA detection in the upper/lower airways before HCT and the occurrence of allo-LSs.
We retrospectively analyzed all HCT recipients between 2004 and 2014, in whom real-time PCR for RV was performed in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL) fluid before HCT. The main outcome of interest was the presence of an allo-LS, which was defined as idiopathic pneumonia syndrome or bronchiolitis obliterans syndrome. Other outcomes were overall survival and treatment-related mortality. We used Cox proportional hazard models, logistic regression models, and Fine-Gray competing risk regression for analyses.
One hundred seventy-nine children (median age, 6.8 years) were included. RVs were found in 61% (41% in BAL fluid/NPAs and 20% in NPAs only). Rhinovirus was the most frequently detected RV (42%). Allo-LSs occurred in 13%. RV positivity in BAL fluid was a predictor for allo-LSs (hazard ratio, 3.8; 95% CI, 1.4-10.7; P = .01), whereas RV positivity in NPAs only was not. No other predictors were found. Grade II to IV acute graft-versus-host disease related to steroid treatment shows a trend toward a protective effect (odds ratio, 0.16; 95% CI, 0.0-1.3; P = .08). Allo-LSs significantly increased treatment-related mortality (52% ± 10% in allo-LSs and 20% ± 4% in non–allo-LSs, P = .007).
These results show that pre-HCT BAL fluid RV positivity was a predictor for allo-LSs. Screening for RVs before HCT might identify patients at risk for allo-LSs. This could have implications for prevention and treatment and might subsequently influence the outcomes of HCT.
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Abstract Purpose Splenectomy might be a risk factor for valvular heart disease (VHD) in adult Hodgkin lymphoma survivors. As this risk is still unclear for childhood cancer survivors (CCS), the aim ...of this study is to evaluate the association between treatments affecting splenic function (splenectomy and radiotherapy involving the spleen) and VHD in CCS. Methods CCS were enrolled from the DCCSS‐LATER cohort, consisting of 6,165 five‐year CCS diagnosed between 1963 and 2002. Symptomatic VHD, defined as symptoms combined with a diagnostic test indicating VHD, was assessed from questionnaires and validated using medical records. Differences in the cumulative incidence of VHD between CCS who received treatments affecting splenic function and CCS who did not were assessed using the Gray test. Risk factors were analyzed in a multivariable Cox proportional hazards model. Results The study population consisted of 5,286 CCS, with a median follow‐up of 22 years (5‐50 years), of whom 59 (1.1%) had a splenectomy and 489 (9.2%) radiotherapy involving the spleen. VHD was present in 21 CCS (0.4%). The cumulative incidence of VHD at the age of 40 years was significantly higher in CCS who received treatments affecting splenic function (2.7%, 95% confidence interval (CI) 0.4%‐4.9%) compared with CCS without (0.4%, 95% CI 0.1%‐0.7%) (Gray's test, p = 0.003). Splenectomy was significantly associated with VHD in a multivariable analysis (hazard ratio 8.6, 95% CI 3.1‐24.1). Conclusions and implications Splenectomy was associated with VHD. Future research is needed to determine if CCS who had a splenectomy as part of cancer treatment might benefit from screening for VHD.
Abstract Platinum-containing chemotherapeutics are efficacious for a variety of pediatric malignancies, nevertheless these drugs can induce ototoxicity. However, ototoxicity data on large cohorts of ...childhood cancer survivors (CCSs) who received platinum agents, but not cranial irradiation are scarce. Therefore, we have studied the frequency and determinants of ototoxicity in a cross-sectional multicenter CCS cohort, including the role of co-medication since it has been suggested that these play a role in ototoxicity. We have collected treatment data and audiograms from the medical records of CCS treated in the seven pediatric oncology centres in The Netherlands. Ototoxicity was defined as Münster grade ≥2b (>20 dB at ≥4–8 kHz). Four-hundred-fifty-one CCS who received platinum agents, but not cranial irradiation (median age at diagnosis: 4.9 years, range: 0.01–19 years) were included. The overall frequency of ototoxicity was 42%. Ototoxicity was observed in 45% of the cisplatin-treated CCS, in 17% of the carboplatin-treated CCS and in 75% of the CCS that had received both agents. Multivariate analysis showed that younger age at diagnosis (odds ratio OR: 0.6, 95% confidence interval CI: 0.5–0.6 per 5 years increase); higher total cumulative dose cisplatin (OR: 1.2, 95% CI: 1.2–1.5 per 100 mg/m2 increase); and co-treatment with furosemide (OR: 2.3, 95% CI: 1.4–3.9) were associated with ototoxicity. We conclude that treatment with (higher total cumulative dose of) cisplatin, young age and furosemide co-medication independently are associated with an increased risk of ototoxicity in CCS. Future prospective studies are necessary to confirm the additive risk of co-medication on the development of ototoxicity.
Purpose
Childhood cancer survivors (CCS) are in need of specialized information about late effects of treatment. In the current study, we assessed the perceived usability and satisfaction with the ...content of a national website with information on late effects and analyzed possible determinants related to website usability and content satisfaction.
Methods
CCS and their parents were contacted through our local follow-up program and via online media to complete an online questionnaire regarding their baseline characteristics, medical decision style, and the usability and content of the website. Usability was evaluated using the System Usability Scale (SUS), a validated questionnaire resulting in a score from 0 to 100. For the content rating, we constructed a six-item scale resulting in a score from 1 to 5 (Cronbach's
α
, 0.83). Comments were analyzed qualitatively.
Results
Fifty-five survivors and forty-three parents of survivors completed the questionnaire. Median age of respondents was 41 years (range, 17–58). Respondents rated the website's usability with a mean SUS score of 72.5 (95 % CI, 69.2–74.9). The mean content rating was 3.7 (95 % CI, 3.5–3.8). No determinants were significantly related to the perceived usability or content satisfaction in multivariate analyses. Qualitative analysis revealed respondents' preference for more detailed and even scientific information on late effects.
Conclusion
Respondents were satisfied with the usability and the contents of a website that targeted at their information needs. As knowledge about late effects is still limited among survivors, a website can be a valuable resource to improve their knowledge, promote healthy behavior, and in the end, improve their quality of life.
Heparin fulfills its anticoagulant action through activation of antithrombin (AT), and thus thrombosis secondary to AT deficiency can be associated with heparin resistance.
A 12-year-old girl with ...severe venous thrombosis was referred to us because of undetectable anti-Xa levels despite low-molecular-weight heparin therapy. Laboratory investigations revealed a homozygous AT mutation in the heparin binding site (AT Budapest III). She was subsequently treated with rivaroxaban successfully.
Heparin resistance warrants evaluation for AT deficiency. Rivaroxaban may be considered a valid anticoagulant alternative to low-molecular-weight heparin in these patients.
The purpose of this study was to develop a simple semiquantitative high-resolution CT (HRCT) scoring system to differentiate alloimmune-mediated lung syndromes (allo-LS) from other lung diseases ...early after hematopoietic cell transplantation. Allo-LS should be differentiated from other abnormalities, such as infections and toxicity, because they are life threatening and require prompt and specific treatment.
In 52 pediatric hematopoietic cell transplant recipients with early symptoms of pulmonary disease, a clinical diagnosis was made by an expert physician. HRCT studies were scored by two independent radiologists for various airway and parenchyma abnormalities. HRCT scores were compared with the final clinical diagnoses.
Patients with allo-LS had significantly higher HRCT severity scores for ground-glass pattern and airtrapping compared with patients with nonalloimmune disease. A combined score was constructed (the "allo-score") that appeared to have good predictive capacity for clinical allo-LS (AUC = 0.82). HRCT scoring was reproducible for all items except airway wall thickening and septal thickening.
A simple HRCT severity score can be helpful to differentiate allo-LS from other pulmonary complications early after hematopoietic cell transplantation.
The clinical presentation of chronic myeloid leukemia (CML) at diagnosis differs in children compared to adults. At younger age, anemia appears to be frequent at diagnosis, but its prevalence and its ...impact on prognosis are not well known. In the International Registry of Childhood CML, we selected children and adolescents in chronic phase at diagnosis of CML and treated upfront with imatinib. We examined their hemoglobin level at diagnosis according to the WHO grades to assess the prevalence of anemia and its impact on response to tyrosine kinase inhibitors (TKIs). Data on 430 patients were included. Anemia at diagnosis was observed in 350 patients (81%), with a mean hemoglobin level of 96.4 g/l (SD 23.6). Among them, 182 patients (52%) presented with moderate anemia and 110 (31%) with severe anemia while 58 (17%) had mild anemia. Compared with mild and no anemia, moderate and severe forms were significantly associated with younger age at diagnosis, asthenia, splenomegaly, and increased leukocyte and basophil counts. Delays in achieving major and deep molecular responses were significantly increased for patients with moderate and severe anemia, and also failure of imatinib treatment was more frequent in these two sub-cohorts. However, hemoglobin level was not significantly associated with survival. Anemia at diagnosis of pediatric CML was frequent and may be considered as a prognostic factor.
Summary
Outcome of 333 children with acute myeloid leukaemia relapsing after a first allogeneic haematopoietic stem cell transplantation was analyzed. Four‐year probability of overall survival ...(4y‐pOS) was 14%. 4y‐pOS for 122 children receiving a second haematopoietic stem cell transplantation was 31% and 3% for those that did not (P = <0·0001). Achievement of a subsequent remission impacted survival (P = <0·0001). For patients receiving a second transplant survival with or without achieving a subsequent remission was comparable. Graft source (bone marrow vs. peripheral blood stem cells, P = 0·046) and donor choice (matched family vs. matched unrelated donor, P = 0·029) positively impacted survival after relapse. Disease recurrence and non‐relapse mortality at four years reached 45% and 22%.
Barth syndrome (BTHS) is an X-linked disease characterized by defective remodeling of phospholipid side chains in mitochondrial membranes. Major features include neutropenia, dilated cardiomyopathy, ...motor delay and proximal myopathy, feeding problems, and constitutional growth delay. We conducted this review of neutropenia in BTHS to aid in the diagnosis of this disease, and to improve understanding of both the consequences of neutropenia and the benefits of treatment with granulocyte colony-stimulating factor (G-CSF).
In 88 patients with BTHS, neutropenia, that is, at least one count below 1.5 × 10/l, was detected in 74 (84%) and 44% had severe chronic neutropenia, with multiple counts below 0.5 × 10/l. The pattern of neutropenia varied between intermittent and unpredictable, chronic and severe, or cyclical with mathematically regular oscillations. Monocytosis, that is, monocytes more than 1.0 × 10/l, was observed at least once in 64 of 85 (75%) patients. G-CSF was administered to 39 of 88 patients (44%). Weekly average G-CSF doses ranged from 0.12 to 10.92 μg/kg/day (mean 1.16 μg/kg/day, median 1.16 μg/kg/day). Antibiotic prophylaxis was additionally employed in 21 of 26 neutropenic patients. Pretreatment bone marrow evaluations predominantly showed reduced myeloid maturation which normalized on G-CSF therapy in seven of 13 examined. Consistent clinical improvement, with reduced signs and symptoms of infections, was observed in response to prophylactic G-CSF ± prophylactic antibiotics. However, despite G-CSF and antibiotics, one adult patient died with multiple infections related to indwelling medical devices and gastrostomy site infection after 15.5 years on G-CSF and a pediatric patient required gastrostomy removal for recurrent abdominal wall cellulitis.
BTHS should be considered in any men with neutropenia accompanied by any of the characteristic features of this syndrome. Prophylaxis with G-CSF ± antibiotics prevents serious bacterial infections in the more severe neutropenic patients although infections remain a threat even in patients who are very compliant with therapy, especially in those with indwelling devices.
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