Reproductive outcomes and reproductive health care utilization among male survivors of childhood cancer: A DCCSS-LATER study.

BACKGROUND: Treatment-related gonadal dysfunction leading to fertility problems is a frequently encountered late effect in childhood cancer survivors (CCSs). This study evaluated reproductive outcomes and reproductive health care utilization among male CCSs compared with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor LATER study part 1, a questionnaire and linkage study. A questionnaire addressing reproductive outcomes and reproductive health care was completed by 1317 male CCSs and 407 male siblings. A total of 491 CCSs and 185 siblings had a previous or current desire for children and were included in this study. RESULTS: Fewer CCSs had biological children compared with siblings (65% vs. 88%; p < .001). The type of conception by men who fathered a child was comparable between CCSs and siblings (spontaneous conception of 90% of both groups; p = .86). The percentage of men who had consulted a reproductive specialist because of not siring a pregnancy was higher in CCSs compared with siblings (34% vs. 12%; p < .001). Following consultation, fewer CCSs underwent assisted reproductive techniques (ART) compared with siblings (41% vs. 77%; p = .001). After ART, fewer CCSs fathered a child compared with siblings (49% vs. 94%; p = .001). CONCLUSIONS: More male survivors consult a reproductive specialist, but fewer survivors undergo ART and father a child after ART compared with siblings. This insight is important for understanding potential problems faced by survivors regarding family planning and emphasizes the importance of collaboration between oncologists and reproductive specialists.

Unhealthy lifestyle behaviors, overweight, and obesity among childhood cancer survivors in the Netherlands: A DCCSS LATER study.

BACKGROUND: The objective of this study was to examine the prevalence of unhealthy lifestyle behaviors, overweight, and obesity in Dutch childhood cancer survivors (CCSs) compared with sibling controls and the Dutch general population. Other aims were to assess associated factors of unhealthy lifestyle behaviors, overweight, and obesity and to identify subgroups of CCSs at risk for these unhealthy statuses. METHODS: The authors included 2253 CCSs and 906 siblings from the Dutch Childhood Cancer Survivor Study-Late Effects After Childhood Cancer cohort, part 1, and added data from the Dutch general population. Questionnaire data were collected on overweight and obesity (body mass index >25.0 kg/m2), meeting physical activity guidelines (>150 minutes per week of moderate or vigorous exercises), excessive alcohol consumption (>14 and >21 alcoholic consumptions per week for women and men, respectively), daily smoking, and monthly drug use. Multivariable logistic regression analyses and two-step cluster analyses were performed to examine sociodemographic-related, health-related, cancer-related, and treatment-related associated factors of unhealthy lifestyle behaviors and to identify subgroups of CCSs at risk for multiple unhealthy behaviors. RESULTS: CCSs more often did not meet physical activity guidelines than their siblings (30.0% vs. 19.3%; p < .001). Married as marital status, lower education level, nonstudent status, and comorbidities were common associated factors for a body mass index ≥25.0 kg/m2 and insufficient physical activity, whereas male sex and lower education were shared associated factors for excessive alcohol consumption, daily smoking, and monthly drug use. A subgroup of CCSs was identified as excessive alcohol consumers, daily smokers, and monthly drug users. CONCLUSIONS: The current results emphasize the factors associated with unhealthy behaviors and the potential identification of CCSs who exhibit multiple unhealthy lifestyle behaviors.

Engineering of CD34+ progenitor-derived natural killer cells with higher-affinity CD16a for enhanced antibody-dependent cellular cytotoxicity.

BACKGROUND AIMS: Natural killer (NK) cell transfer is a promising cellular immunotherapy for cancer. Previously, we developed a robust method to generate large NK cell numbers from CD34+ hematopoietic stem and progenitor cells (HSPCs), which exhibit strong anti-tumor activity. However, since these cells express low levels of the Fc receptor CD16a in vitro, antibody-dependent cellular cytotoxicity (ADCC) by these cells is limited. To broaden clinical applicability of our HSPC-NK cells toward less NK-sensitive malignancies, we aimed to improve ADCC through CD16a transduction. METHODS: Using wildtype and S197P mutant greater-affinity (both with V158) CD16a retroviral transgenes (i.e., a cleavable and noncleavable CD16a upon stimulation), we generated CD16a HSPC-transduced NK cells, with CD34+ cells isolated from umbilical cord blood (UCB) or peripheral blood after G-CSF stem cell mobilization (MPB). CD16a expressing NK cells were enriched using flow cytometry-based cell sorting. Subsequently, phenotypic analyses and functional assays were performed to investigate natural cytotoxicity and ADCC activity. RESULTS: Mean transduction efficiency was 34% for UCB-derived HSPCs and 20% for MPB-derived HSPCs, which was enriched by flow cytometry-based cell sorting to >90% for both conditions. Expression of the transgene remained stable during the entire NK expansion cell generation process. Proliferation and differentiation of HSPCs were not hampered by the transduction process, resulting in effectively differentiated CD56+ NK cells after 5 weeks. Activation of the HSPC-derived NK cells resulted in significant shedding of wildtype CD16a transcribed from the endogenous gene, but not of the noncleavable mutant CD16a protein expressed from the transduced construct. The mean increase of CD107+IFNγ+ expressing NK cells after inducing ADCC was tenfold in enriched noncleavable CD16a HSPC-NK cells. Killing capacity of CD16a-transduced NK cells was significantly improved after addition of a tumor-targeting antibody in tumor cell lines and primary B-cell leukemia and lymphoma cells compared to unmodified HSPC-NK cells. CONCLUSIONS: Together, these data demonstrate that the applicability of adoptive NK cell immunotherapy may be broadened to less NK-sensitive malignancies by upregulation of CD16a expression in combination with the use of tumor-targeting monoclonal antibodies.

Feasibility and potential effectiveness of nurse-led video-coaching interventions for childhood, adolescent, and young adult cancer survivors: the REVIVER study.

BACKGROUND: Childhood, adolescent, and young adult (CAYA) cancer survivors, at risk for late effects, including cancer-related fatigue, cardiovascular issues, and psychosocial challenges, may benefit from interventions stimulating behaviour adjustments. Three nurse-led eHealth interventions (REVIVER) delivered via video calls and elaborating on person-centred care, cognitive behaviour therapy and/or motivational interviewing were developed. These interventions target: 1) fatigue management, 2) healthier lifestyle behaviours, and 3) self-efficacy and self-management. This study aimed to assess the feasibility and potential effectiveness of the REVIVER interventions for CAYA cancer survivors and healthcare professionals. METHODS: In a single-group mixed methods design, CAYA cancer survivors aged 16-54, more than five years post-treatment, were enrolled. Feasibility, assessed via Bowen's outcomes for feasibility studies, included acceptability, practicality, integration and implementation, demand and adherence. Qualitative data from semi-structured interviews and a focus group interview with survivors and healthcare professionals supplemented the evaluation. Paired sample t-tests assessed changes in self-reported quality of life, fatigue, lifestyle, self-management, and self-efficacy at baseline (T0), post-intervention (T1), and 6-month follow-up (T2). RESULTS: The interventions and video consults were generally acceptable, practical, and successfully integrated and implemented. Success factors included the nurse consultant (i.e., communication, approach, and attitude) and the personalised approach. Barriers included sustainability concerns, technical issues, and short intervention duration. Regarding demand, 71.4%, 65.4%, and 100% of eligible CAYA cancer survivors engaged in the fatigue (N = 15), lifestyle (N = 17) and empowerment (N = 3) intervention, respectively, with 5, 5 and 2 participants interviewed, correspondingly. Low interest (demand) in the empowerment intervention (N = 3) and dropout rates of one-third for both fatigue and empowerment interventions were noted (adherence). Improvements in quality of life, fatigue (fatigue intervention), lifestyle (lifestyle intervention), self-efficacy, and self-management were evident among survivors who completed the fatigue and lifestyle interventions, with medium and large effect sizes observed immediately after the intervention and six months post-intervention. CONCLUSIONS: Our study demonstrates the feasibility of nurse-led video coaching (REVIVER interventions) despite lower demand for the empowerment intervention and lower adherence to the fatigue and empowerment interventions. The medium and high effect sizes found for those who completed the interventions hold potential clinical significance for future studies investigating the effectiveness of the REVIVER interventions.

Development of a target concentration intervention to individualize paroxysmal nocturnal hemoglobinuria treatment with pegcetacoplan.

Pegcetacoplan (Aspaveli®/Empaveli™) is a factor C3 inhibitor that is approved for the treatment of paroxysmal nocturnal hemoglobinuria. An individualized dosing strategy might be useful to improve patient-friendliness and cost-effectiveness of this very expensive drug. Therefore, the aim of this study was to develop an individualized treatment regimen for pegcetacoplan based on the pharmacokinetic-pharmacodynamic data of the manufacturer. We conducted a clinical trial simulation with the approved dosing regimen of 1080 mg twice-weekly and a target concentration intervention-based dosing regimen in patients with and without prior eculizumab use. For eculizumab-naïve patients, the target concentration intervention-based dosing regimen resulted in a comparable fraction of patients with LDH normalization (LDH < 226 U/L) and hemoglobulin normalization (> 12 g/dL) compared to the approved regimen (LDH 50.2% and 50.0% respectively and hemoglobulin 45.6% and 44.4%). A modest dose reduction of ~ 5% was possible with target concentration intervention-based dosing. An intensified dosing interval was necessary in 2.3% of the patients however an interval prolongation was possible in 28.2% of the patients. Similar results were obtained for patients prior treated with eculizumab. In this study we show the potential of an individualized dosing regimen of pegcetacoplan with can improve patient friendliness in approximately 30% of the patients and improve therapy in approximately 2% of the patients at slightly reduced costs.

Impact of tyrosine kinase inhibitors on glucose control and insulin regulation in patients with chronic myeloid leukemia.

Treatment with tyrosine kinase inhibitors (TKIs), especially nilotinib, often results in hyperglycemia, which may further increase cardiovascular disease risk in patients with chronic myeloid leukemia (CML). The mechanism underlying the TKI-induced glucose dysregulation is not clear. TKIs are suggested to affect insulin secretion but also insulin sensitivity of peripheral tissue has been proposed to play a role in the pathogenesis of TKI-induced hyperglycemia. Here, we aimed to assess whether skeletal muscle glucose uptake and insulin responses are altered in nondiabetic patients with CML receiving TKI treatment. After a glycogen-depleted exercise bout, an intravenous glucose bolus (0.3 g/kg body weight) was administered to monitor 2-h glucose tolerance and insulin response in 14 patients with CML receiving nilotinib, 14 patients with CML receiving imatinib, and 14 non-CML age- and gender-matched controls. A dynamic [18F]-FDG PET scan during a hyperinsulinemic-euglycemic clamp was performed in a subgroup of 12 male patients with CML to assess m. quadriceps glucose uptake. We showed that patients with CML treated with nilotinib have an increased insulin response to intravenous glucose administration after muscle glycogen-depleted exercise. Despite the increased insulin response to glucose administration in patients with CML receiving nilotinib, glucose disappearance rates were significantly slower in nilotinib-treated patients when compared with controls in the first 15 min after glucose administration. Although [18F]-FDG uptake in m. quadriceps was not different, patients receiving nilotinib showed a trend toward decreased glucose infusion rates during euglycemic clamping when compared with patients receiving imatinib. Together, these findings indicate disturbed skeletal muscle glucose handling in patients with CML receiving nilotinib therapy.NEW & NOTEWORTHY In this study, we have shown that non-diabetic patients with CML receiving nilotinib therapy show early signs of disturbed skeletal muscle glucose handling, which was not observed in imatinib-treated patients. These observations in nilotinib users may reflect decreased muscle insulin sensitivity, which could serve as a potential target to counteract glycemic dysregulation, and is of clinical importance since these patients have an increased cardiovascular disease risk.

Desire for children among male survivors of childhood cancer: A DCCSS LATER study.

BACKGROUND: Knowledge of the desire for children among childhood cancer survivors (CCSs) is scarce. This study evaluated the desire for children in male CCSs in comparison with male siblings. METHODS: A nationwide cohort study was conducted as part of the Dutch Childhood Cancer Survivor Study LATER study: 1317 male CCSs and 407 male sibling controls completed a questionnaire addressing the desire for children. Logistic regression analyses were used to explore the independent association between survivorship status and the desire for children. Furthermore, additional analyses were performed to identify which cancer-related factors were associated with the desire for children in male CCSs. RESULTS: After adjustments for the age at assessment, the percentage of men who had a desire for children was significantly lower among CCSs compared with the siblings (74% vs. 82%; odds ratio [OR], 0.61; 95% CI, 0.46-0.82; p = .001). The association between survivorship status and the desire for children was attenuated after adjustments for marital status, level of education, and employment status (OR, 0.83; 95% CI, 0.61-1.14; p = .250). The percentage of men who had an unfulfilled desire for children remained significantly higher among CCSs compared with the siblings after adjustments for sociodemographic factors (25% vs. 7%; OR, 5.14; 95% CI, 2.48-10.64; p < .001). CONCLUSIONS: The majority of male CCSs have a desire for children. The likelihood of having to deal with an unfulfilled desire for children is 5 times higher among CCSs compared with their siblings. This insight is important for understanding the needs and experienced problems of CCSs regarding family planning and fertility issues.

Switching from imatinib to nilotinib plus pegylated interferon-α2b in chronic phase CML failing to achieve deep molecular response: clinical and immunological effects.

In order to improve molecular response for a discontinuation attempt in chronic myeloid leukemia (CML) patients in chronic phase, who had not achieved at least a molecular response <0.01% BCR-ABL1IS (MR4.0) after at least 2 years of imatinib therapy, we prospectively evaluated whether they could attain MR4.0 after a switch to a combination of nilotinib and 9 months of pegylated interferon-α2b (PegIFN). The primary endpoint of confirmed MR4.0 at month 12 (a BCR-ABL1IS level ≤ 0.01% both at 12 and 15 months) was reached by 44% (7/16 patients, 95% confidence interval (CI): 23- 67%) of patients, with 81% (13/16 patients, 95% CI: 57-93%) of patients achieving an unconfirmed MR4.0. The scheduled combination was completed by 56% of the patients, with premature discontinuations, mainly due to mood disturbances after the introduction of PegIFN, questioning the feasibility of the combination of nilotinib and PegIFN for this patient population and treatment goal. A comprehensive clinical substudy program was implemented to characterize the impact of the treatment changes on the immunological profile. This trial was registered at www.clinicaltrials.gov as #NCT01866553.

Nationwide study of eculizumab in paroxysmal nocturnal hemoglobinuria: Evaluation of treatment indications and outcomes.

Eculizumab is an effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). However, considering the risk of life-threatening meningococcal disease, life-long duration and costs, there are strict criteria for initiation of therapy. To evaluate the application and real-world effectiveness of eculizumab in the Netherlands, a multicenter retrospective cohort study was conducted: indications and treatment outcomes were collected for 105 Dutch PNH patients. In all patients, eculizumab was initiated conforming to indications as formulated in the Dutch PNH guideline. According to recently published response criteria, 23.4% of the patients had reached a complete hematological response, 53.2% a good or partial response, and 23.4% a minor response after 12 months of therapy. In the majority of patients the response remained stable during long-term follow-up. The degree and relevance of extravascular hemolysis significantly differed between response groups (p = 0.002). Improvements of EORTC-QLQc30 and FACIT-fatigue scores were observed, however patients reported lower scores than the general population. A detailed evaluation of 18 pregnancies during eculizumab showed no maternal or fetal deaths, and no thromboembolic events during pregnancy. This study demonstrates that the majority of patients benefit from eculizumab when adhering to the indications as formulated in the Dutch PNH guideline. However, novel therapies are needed to further improve real-world outcomes, such as hematological responses and quality of life.

BCR::ABL1 kinase domain mutation testing and clinical outcome in a nationwide chronic myeloid leukemia patient population.

OBJECTIVES: Acquired missense mutations in the BCR::ABL1 kinase domain (KD) may cause tyrosine kinase inhibitor (TKI) treatment failure. Based on mutation-specific in vitro derived IC50-values, alternative TKI may be selected. We assessed clinical practice of BCR::ABL1 KD mutation testing, clinical response in relation to IC50-values, and clinical outcome of tested patients. METHODS: Patients from six Dutch CML reference centers and a national registry were included once a mutational analysis was performed. Reasons for testing were categorized as suboptimal TKI response, and primary or secondary TKI resistance. RESULTS: Four hundred twenty analyses were performed in 275 patients. Sixty-nine patients harbored at least one mutation. Most analyses were performed because of suboptimal TKI response but with low mutation incidence (4%), while most mutations were found in primary and secondary resistant patients (21% and 51%, respectively). Harboring a BCR::ABL1 mutation was associated with inferior overall survival (HR 3.2 [95% CI, 1.7-6.1; p < .001]). Clinically observed responses to TKI usually corresponded with the predicted TKI sensitivity based on the IC50-values, but a high IC50-value did not preclude a good clinical response per se. CONCLUSIONS: We recommend BCR::ABL1 KD mutation testing in particular in the context of primary or secondary resistance. IC50-values can direct the TKI choice for CML patients, but clinical efficacy can be seen despite adverse in vitro resistance.

Dose optimalization of subcutaneous ravulizumab is predicted to yield significant savings and to improve patient friendliness.

Ravulizumab is an expensive complement C5-inhibitor for the treatment of paroxysmal nocturnal haemoglobinuria. Recently, a subcutaneous formulation has entered the market, for which the approved dosing regimen results in supratherapeutic ravulizumab concentrations in the majority of patients in the registration studies. Therefore, we explored alternative dosing regimens in silico based on the registration data of the manufacturer. Extending the interval from 1 to 2 weeks or individualized dosing based on therapeutic drug monitoring resulted in therapeutic ravulizumab concentrations and comparable predicted efficacy in terms of lactate dehydrogenase normalization, with dose reductions up to 64%. We here show that with an individualized dose, a substantial dose reduction for subcutaneous ravulizumab might be possible with improved patient-friendliness.

Effect of invasive aspergillosis on risk for different causes of death in older patients with acute myeloid leukaemia or high-risk myelodysplastic syndrome.

PURPOSE: Study objectives were to estimate the cumulative incidence of death due to different causes of death (CODs) and investigate the effect of invasive aspergillosis (IA) on each separate COD in a cohort of older patients with acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS) included in the Haemato-Oncology Foundation for Adults in the Netherlands (HOVON) 43 randomized controlled trial. METHODS: Pre-collected data from the trial was obtained from the HOVON data center and relevant clinical information was extracted. The cumulative incidence of death due to different CODs was estimated with a competing risk model and the association between each COD and prognostic factors, including IA, were investigated with a cause-specific hazard Cox regression model. RESULTS: In total 806 patients were included, mean age of 70 years and 55% were male. The cumulative incidences of death due to leukaemia or infection at 3, 6, 12 and 36 months were 0.06, 0.11, 0.23, 0.42 and 0.17, 0.19, 0.22, 0.25 respectively. Incidence of IA was 21% and diagnosis of IA up until the final chemotherapy cycle was associated with an increased risk of dying from leukaemia (cause-specific hazard ratio (CSHR): 1.75, 95% CI 1.34-2.28) and a trend was seen for infection (CSHR: 1.36, 95% CI 0.96-1.91). CONCLUSION: Leukaemia was the most likely cause of death over time, however in the first year after diagnosis of AML or high-risk MDS infection was the most likely cause of death. Patients with IA had a relatively increased risk of dying from leukaemia or infection.

The effect of hematopoietic stem cell transplantation on patient-reported subjective oral dryness: a systematic review focusing on prevalence, severity and distress.

OBJECTIVE: The aim of the present systematic review is to assess the prevalence and severity of and distress caused by xerostomia over time in adult hematopoietic stem cell transplantation (HSCT) recipients. METHODS: PubMed, Embase, and the Cochrane Library were searched for papers published between January 2000 and May 2022. Clinical studies were included if patient-reported subjective oral dryness was reported in adult autologous or allogeneic HSCT recipients. Risk of bias was assessed according to a quality grading strategy published by the oral care study group of the MASCC/ISOO, resulting in a score between 0 (highest risk of bias) and 10 (lowest risk of bias). Separate analysis focused on autologous HSCT recipients, allogeneic HSCT recipients receiving a myeloablative conditioning (MAC), and those receiving a reduced intensity conditioning (RIC). RESULTS: Searches yielded 1792 unique records; 22 studies met the inclusion criteria. The quality scores ranged between 1 and 7, with a median score of 4. The prevalence, severity, and distress of xerostomia increased shortly after HSCT. Severity of xerostomia in allogeneic MAC recipients was higher compared to allogeneic RIC recipients 2-5 months post-HSCT (mean difference: 18 points on 0-100 scale, 95% CI: 9-27); after 1-2 years, there was no significant difference anymore. CONCLUSION: The prevalence of xerostomia in HSCT recipients is high in comparison to the general population. The severity of complaints is raised during the first year post-HSCT. The intensity of the conditioning plays a key role in the short-term development of xerostomia, while factors affecting the recovery in the long term remain largely unknown.

Caries, periodontitis and tooth loss after haematopoietic stem cell transplantation: A systematic review.

OBJECTIVE: A systematic review was conducted to assess scientific knowledge concerning the effect of haematopoietic stem cell transplantation (HSCT) on the occurrence of caries, periodontal conditions and tooth loss, and to evaluate the prevalence of these diseases in adult HSCT survivors (PROSPERO 152906). METHODS: PubMed and Embase were searched for papers, published from January 2000 until November 2020 without language restriction, assessing prevalence, incidence or parameters of caries, periodontal conditions and tooth loss in HSCT recipients (≥80% transplanted in adulthood). Bias risk was assessed with checklists from Joanna Briggs Institute, and data synthesis was performed by narrative summary. RESULTS: Eighteen papers were included (1618 subjects). Half were considered at high risk of bias. Longitudinal studies did not show caries progression, decline in periodontal health or tooth loss after HSCT. The prevalence in HSCT survivors ranged from 19% to 43% for caries, 11% to 67% for periodontitis, and 2% to 5% for edentulism. Certainty in the body of evidence was very low. CONCLUSIONS: Haematopoietic stem cell transplantation, on the short term, may have little to no effect on caries, periodontal conditions and tooth loss. Caries and periodontitis may be more common in HSCT survivors compared with the general population, whereas edentulism may be comparable. However, the evidence for all conclusions is very uncertain.

Effectiveness of digital care platform CMyLife for patients with chronic myeloid leukemia: results of a patient-preference trial.

BACKGROUND: Two most important factors determining treatment success in chronic myeloid leukemia (CML) are adequate medication compliance and molecular monitoring albeit still being suboptimal. The CMyLife platform is an eHealth innovation, co-created with and for CML patients, aiming to improve their care, leading to an increased quality of life and the opportunity of hospital-free care. OBJECTIVE: To explore the effectiveness of CMyLife in terms of information provision, patient empowerment, medication compliance, molecular monitoring, and quality of life. METHODS: Effectiveness of CMyLife was explored using a patient-preference trial. Upon completion of the baseline questionnaire, participants actively used (intervention group) or did not actively use (questionnaire group) the CMyLife platform for at least 6 months, after which they completed the post-intervention questionnaire. Scores between the intervention group and the questionnaire group were compared with regard to the within-subject change between baseline and post-measurement using Generalized Estimating Equation models. RESULTS: At baseline, 33 patients were enrolled in the questionnaire group and 75 in the intervention group. Online health information knowledge improved significantly when actively using CMyLife and patients felt more empowered. No significant improvements were found regarding medication compliance and molecular monitoring, which were already outstanding. Self-reported effectiveness showed that patients experienced that using CMyLife improved their medication compliance and helped them to oversee their molecular monitoring. Patients using CMyLife reported more symptoms but were better able to manage these. CONCLUSIONS: Since hospital-free care has shown to be feasible in time of the COVID-19 pandemic, eHealth-based innovations such as CMyLife could be a solution to maintain the quality of care and make current oncological health care services more sustainable. TRIAL REGISTRATION: ClinicalTrials.gov NCT04595955 , 22/10/2020.

Improvement, Implementation, and Evaluation of the CMyLife Digital Care Platform: Participatory Action Research Approach.

BACKGROUND: The evaluation of a continuously evolving eHealth tool in terms of improvement and implementation in daily practice is unclear. The CMyLife digital care platform provides patient-centered care by empowering patients with chronic myeloid leukemia, with a focus on making medication compliance insightful, discussable, and optimal, and achieving optimal control of the biomarker BCR-ABL1. OBJECTIVE: The aim of this study was to investigate to what extent the participatory action research approach is suitable for the improvement and scientific evaluation of eHealth innovations in daily clinical practice (measured by user experiences) combined with the promotion of patient empowerment. METHODS: The study used iterative cycles of planning, action, and reflection, whereby participants' experiences (patients, health care providers, the CMyLife team, and app suppliers) with the platform determined next actions. Co-design workshops were the foundation of this cyclic process. Moreover, patients filled in 2 sets of questionnaires for assessing experiences with CMyLife, the actual use of the platform, and the influence of the platform after 3 and at least 6 months. Data collected during the workshops were analyzed using content analysis, which is often used for making a practical guide to action. Descriptive statistics were used to characterize the study population in terms of information related to chronic myeloid leukemia and sociodemographics, and to describe experiences with the CMyLife digital care platform and the actual use of this platform. RESULTS: The co-design workshops provided insights that contributed to the improvement, implementation, and evaluation of CMyLife and empowered patients with chronic myeloid leukemia (for example, simplification of language, and improvement of the user friendliness of functionalities). The results of the questionnaires indicated that (1) the platform improved information provision on chronic myeloid leukemia in 67% (33/49) of patients, (2) the use of the medication app improved medication compliance in 42% (16/38) of patients, (3) the use of the guideline app improved guideline adherence in 44% (11/25) of patients, and (4) the use of the platform caused patients to feel more empowered. CONCLUSIONS: A participatory action research approach is suited to scientifically evaluate digital care platforms in daily clinical practice in terms of improvement, implementation, and patient empowerment. Systematic iterative evaluation of users' needs and wishes is needed to keep care centered on patients and keep the innovation up-to-date and valuable for users.

The effect of conditioning regimen and prescribed medications on hyposalivation in haematopoietic cell transplantation (HCT) patients: an 18-month prospective longitudinal study.

OBJECTIVES: Haematopoietic cell transplantation (HCT) preceded by a conditioning regimen is an established treatment option for (non)malignant haematologic disorders. We aim to describe the development of hyposalivation over time in HCT recipients, and determine risk indicators. MATERIALS AND METHODS: A multi-centre prospective longitudinal observational study was conducted. Unstimulated (UWS) and stimulated (SWS) whole saliva was collected before HCT, early post-HCT, and after 3, 6, 12, and 18 months. The effect of type of transplantation (allogeneic vs autologous) and intensity (full vs reduced) of the conditioning regimen on hyposalivation (UWS < 0.2 mL/min; SWS < 0.7 mL/min) was explored. RESULTS: A total of 125 HCT recipients were included. More than half of the patients had hyposalivation early post-HCT; a quarter still had hyposalivation after 12 months. The conditioning intensity was a risk indicator in the development of hyposalivation of both UWS (OR: 3.9, 95% CI: 1.6-10.6) and SWS (OR: 8.2, 95% CI: 2.9-24.6). After 3 and 12 months, this effect was not statistically significant anymore. CONCLUSIONS: Hyposalivation affects the majority of patients early post-HCT. The conditioning intensity and the type of transplantation were significant risk indicators in the development of hyposalivation. The number of prescribed medications, total body irradiation as part of the conditioning regimen and oral mucosal graft-versus-host disease did not influence hyposalivation significantly. CLINICAL RELEVANCE: Because of the high prevalence of hyposalivation, HCT recipients will have an increased risk of oral complications. It might be reasonable to plan additional check-ups in the dental practice and consider additional preventive strategies.

Mucositis and Infection in Hematology Patients.

Survival in patients with hematological malignancies has improved over the years, both due to major developments in anticancer treatment, as well as in supportive care. Nevertheless, important and debilitating complications of intensive treatment regimens still frequently occur, including mucositis, fever and bloodstream infections. Exploring potential interacting mechanisms and directed therapies to counteract mucosal barrier injury is of the utmost importance if we are to continue to improve care for this increasingly growing patient population. In this perspective, I highlight recent advances in our understanding of the relation of mucositis and infection.

Prevalence and risk factors of cancer-related fatigue in childhood cancer survivors: A DCCSS LATER study.

BACKGROUND: Cancer-related fatigue is a debilitating late effect after treatment for childhood cancer. The prevalence of fatigue in childhood cancer survivors (CCSs) and associated factors for fatigue has varied widely in previous studies. Two important aspects of cancer-related fatigue, its severity and chronicity, are often not assessed. This study investigated the prevalence of, and risk factors for, severe chronic fatigue (CF) in a national cohort of Dutch CCSs. METHODS: In this study, 2810 CCSs (5-year survivors of all childhood malignancies diagnosed between 1963 and 2001 with a current age of 12-65 years) and 1040 sibling controls were included. CF was assessed with the Short Fatigue Questionnaire and was defined as a score ≥ 18 and persistence of fatigue for ≥6 months. Cancer- and treatment-related characteristics, current health problems, and demographic and lifestyle variables were assessed as potential risk factors for CF via multivariable logistic regression analyses. RESULTS: In adult CCSs and sibling controls (≥18 years old), the prevalence of CF was 26.1% and 14.1%, respectively (P < .001). In adolescent CCSs and sibling controls (<18 years old), the prevalence of CF was 10.9% and 3.2%, respectively. Female gender (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.73-2.62), unemployment (OR, 2.18; 95% CI, 1.67-2.85), having 1 or more health problems (OR for 1-2, 1.48; 95% CI, 1.18-1.87; OR for >2, 2.20; 95% CI, 1.50-3.21), and a central nervous system diagnosis (OR, 1.74; 95% CI, 1.17-2.60) were significantly associated with CF in adult CCSs. CONCLUSIONS: This study shows that CCSs, regardless of their cancer diagnosis, report CF more often than sibling controls. This study provides new evidence for the prevalence of fatigue in CCSs.

The evolution of the loss of life expectancy in patients with chronic myeloid leukaemia: a population-based study in the Netherlands, 1989-2018.

Studies on the conditional life expectancy of patients with chronic myeloid leukaemia (CML) are lacking. Using data from the Netherlands Cancer Registry, we examined the life expectancy of patients with CML in the Netherlands diagnosed during 1989-2018. As of the early 2010s, the life expectancy of patients with CML who survived several years after diagnosis came narrowly close to the general population's life expectancy, regardless of age. This finding can essentially be ascribed to the introduction and broader application of tyrosine kinase inhibitors (TKIs) and provide optimism to patients with CML who can look forward to a near-normal life expectancy in a modern TKI era.