A randomised evaluation of low-dose cytosine arabinoside plus lenalidomide versus single-agent low-dose cytosine arabinoside in older patients with acute myeloid leukaemia: Results from the LI-1 trial.

Improving outcomes for older patients with acute myeloid leukaemia remains an unmet need. As part of the LI-1 trial, we evaluated lenalidomide (LEN) in combination with low-dose cytosine arabinoside (LDAC) in patients aged >60 years unfit for intensive therapy and compared this to LDAC alone. Two hundred and two patients, randomised 1:1, were evaluable. Overall response rate (CR + CRi) was higher for LDAC + LEN versus LDAC (26% and 13.7% respectively p = 0.031). However, there was no difference in overall survival between the arms (14% and 11.5% at 2 years for LDAC + LEN and LDAC respectively). The addition of LEN was associated with increased toxicity and supportive care requirements.

Treatment intensification with FLAG-Ida may improve disease control in younger patients with secondary acute myeloid leukaemia: long-term follow up of the MRC AML15 trial.

Secondary acute myeloid leukaemia (AML) has a poor outcome following "3 + 7-like" chemotherapy. While CPX-351 has been approved for patients aged 60-75, the optimal treatment, or comparator, in younger patients is less clear. The MRC AML15 trial randomised younger patients between daunorubicin and ara-C (DA) and DA plus etoposide (ADE) and ADE and fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) induction. Overall results failed to show an overall survival benefit for FLAG-Ida despite a reduction in relapse, the outcome of patients <60 years with secondary AML compared to DA/ADE was not reported. In this group (n = 115) response to induction was not different [complete remission/complete remission with incomplete haematological response 81% vs. 79%), however, 5-year overall survival and relapse free survival was superior for FLAG-Ida [37% vs. 27%, stratified hazard ratio (HR) 0·45 (0·33-0·90) P = 0·02 and 41% vs. 22%; stratified HR 0·54 (0·31-0·96) P = 0·04] respectively, suggesting that younger patients with secondary AML may benefit from treatment intensification and that "3 + 7" may not be the optimal comparator in trials for this group of patients.

A randomised comparison of FLAG-Ida versus daunorubicin combined with clofarabine in relapsed or refractory acute myeloid leukaemia: Results from the UK NCRI AML17 trial.

The prognosis for younger patients with relapsed acute myeloid leukaemia (AML) is generally dismal. Allogeneic stem cell transplantation is the preferred therapy for these patients. As part of the UK NCRI AML17 trial, daunorubicin/clofarabine (DClo) was compared with fludarabine, cytarabine, granulocyte colony-stimulating factor with idarubicin (FLAG-Ida) in 311 patients designated high-risk following course one of induction therapy, which has previously been reported. We now report the results of the same randomisation in patients who were refractory to two induction courses or subsequently relapsed. A total of 94 relapsed or refractory AML patients, usually less than 60 years of age and with mainly favourable or intermediate-risk cytogenetics, were randomised to receive up to three courses of DClo or FLAG-Ida, with the aim of proceeding to transplant. Complete remission was achieved in 74% of patients with no difference between the arms. Overall, 57% of patients received a transplant with no difference between the arms, likewise overall survival at five years showed no significant difference (21% for DClo vs. 22% for FLAG-Ida). No patient who did not receive a transplant survived beyond 21months. A stratified analysis including the 311 post course 1 high-risk patients who underwent the same randomisation showed a consistent treatment benefit for FLAG-Ida.

Outcomes of older patients aged 60 to 70 years undergoing reduced intensity transplant for acute myeloblastic leukemia: results of the NCRI acute myeloid leukemia 16 trial.

Reduced intensity conditioning (RIC) transplantation is increasingly offered to older patients with acute myeloblastic leukemia. We have previously shown that a RIC allograft, particularly from a sibling donor, is beneficial in intermediate-risk patients aged 35-65 years. We here present analyses from the NCRI AML16 trial extending this experience to older patients aged 60-70 inclusive lacking favorable-risk cytogenetics. Nine hundred thirty-two patients were studied, with RIC transplant in first remission given to 144 (sibling n=52, matched unrelated donor n=92) with a median follow-up for survival from complete remission of 60 months. Comparisons of outcomes of patients transplanted versus those not were carried out using Mantel-Byar analysis. Among the 144 allografted patients, 93 had intermediate-risk cytogenetics, 18 had adverse risk and cytogenetic risk group was unknown for 33. In transplanted patients survival was 37% at 5 years, and while the survival for recipients of grafts from siblings (44%) was better than that for recipients of grafts from matched unrelated donors (34%), this difference was not statistically significant (P=0.2). When comparing RIC versus chemotherapy, survival of patients treated with the former was significantly improved (37% versus 20%, hazard ratio = 0.67 [0.53-0.84]; P<0.001). When stratified by Wheatley risk group into good, standard and poor risk there was consistent benefit for RIC across risk groups. When stratified by minimal residual disease status after course 1, there was consistent benefit for allografting. The benefit for RIC was seen in patients with a FLT3 ITD or NPM1 mutation with no evidence of a differential effect by genotype. We conclude that RIC transplantation is an attractive option for older patients with acute myeloblastic leukemia lacking favorable-risk cytogenetics and, in this study, we could not find a group that did not benefit.

Family caregiver ambassador support for caregivers of patients with newly diagnosed hematological cancer: a feasibility study.

PURPOSE: This study investigated the feasibility of a one-on-one peer support intervention in family caregivers of newly diagnosed patients with a hematological cancer during initial treatment. METHODS: The study was a one-arm feasibility study including family caregivers of newly diagnosed patients with hematological cancer (n = 26) and caregiver ambassadors who were family caregivers of previously treated patients as peer supporters (n = 17). The one-on-one peer support intervention consisted of three components: a caregiver ambassador preparatory course; 12 weeks of one-on-one peer support, and caregiver ambassador network meetings. RESULTS: Family caregivers reported high satisfaction with the delivery and flexibility of one-on-one peer support and improved in most psychosocial outcomes over time. Telephone and text messages were the most used form of contact between the peers. Caregiver ambassadors reported high satisfaction with the preparatory course and used the available support from the network meetings. No adverse events were reported. CONCLUSION: One-on-one peer support provided by a caregiver ambassador is feasible and safe in family caregivers of newly diagnosed hematological cancer patients during their initial treatment. Utilizing volunteer caregiver ambassadors has the potential to be a new support model in family caregivers of hematological cancer patients across diagnostic groups within a clinical setting. CLINICAL TRIAL REGISTRATION NUMBER: NCT04039100, July 29, 2019.

Patient ambassador support in newly diagnosed patients with acute leukemia during treatment: a feasibility study.

PURPOSE: This study investigated the feasibility of patient ambassador support in newly diagnosed patients with acute leukemia during treatment. METHODS: A multicenter single-arm feasibility study that included patients newly diagnosed with acute leukemia (n = 36) and patient ambassadors previously treated for acute leukemia (n = 25). Prior to the intervention, all patient ambassadors attended a 6-h group training program. In the intervention, patient ambassadors provided 12 weeks of support for patients within 2 weeks of being diagnosed. Outcome measures included feasibility (primary outcome), safety, anxiety, and depression measured by the Hospital Anxiety and Depression Scale, quality of life by the Functional Assessment of Cancer Therapy-Leukemia and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and symptom burden by MD Anderson Symptom Inventory, the Patient Activation Measure, and the General Self-Efficacy Scale. RESULTS: Patient ambassador support was feasible and safe in this population. Patients and patient ambassadors reported high satisfaction with the individually adjusted support, and patients improved in psychosocial outcomes over time. Patient ambassadors maintained their psychosocial baseline level, with no adverse events, and used the available support to exchange experiences with other patient ambassadors and to manage challenges. CONCLUSION: The patient ambassador support program is feasible and has the potential to be a new model of care incorporated in the hematology clinical care setting, creating an active partnership between patients and former patients. This may strengthen the existing supportive care services for patients with acute leukemia. TRIAL REGISTRATION: NCT03493906.

Longitudinal symptom burden in adult patients with acute leukaemia participating in the PACE-AL randomised controlled exercise trial-an explorative analysis.

OBJECTIVE: Patients with acute leukaemia undergoing chemotherapy experience multiple symptoms that interfere with activities of daily living. Exercise-based interventions have been used to remedy disease and treatment-related symptoms in patients with cancer. We explored the impact of exercise and health counselling on symptom prevalence, severity and longitudinal patterns. METHODS: Explorative analysis of M.D. Anderson Symptom Inventory and Brief Fatigue Inventory completed weekly in a randomized controlled trial of patients with acute leukaemia undergoing consolidation chemotherapy. Seventy patients were consecutively recruited and randomly allocated to usual care (n = 36) or 12-week supervised exercise and health counselling (n = 34) at Copenhagen University Hospital, 2011-2014. RESULTS: There was no difference in symptom prevalence between groups, but we found a significant increase in symptom and fatigue severity in the intervention group during the study period. However, the symptom burden reduced significantly in both groups at 12 weeks. Longitudinally, the symptom cluster; 'drowsiness, fatigue, disturbed sleep, difficulty remembering' was significantly more severe in the intervention group. CONCLUSION: Intervention and control group participants had substantial symptom and fatigue burden during 12-week moderate exercise and health counselling in patients with acute leukaemia undergoing chemotherapy. A greater symptom burden was found in the intervention group during the 12 weeks, though reducing in both groups at 12 weeks. Studies are needed to examine the link between exercise and symptom severity.

Patient ambassador support: Experiences of the mentorship between newly diagnosed patients with acute leukaemia and their patient ambassadors.

OBJECTIVE: The study explores how newly diagnosed patients with acute leukaemia and their patient ambassadors experience the mentorship during the patient ambassador support programme. METHODS: Explorative semi-structured individual interviews (n = 28) were carried out in patients with acute leukaemia (n = 15) and their patient ambassadors (n = 13). Interpretive description was the methodological framework used for the thematic analysis of the qualitative interview data. RESULTS: Identified themes were as follows: (a) exchanging life experiences (subthemes: individualised support and a meaningful return); (b) existential cohesion; (c) interreflection; and (d) terms and conditions (subtheme: break in journey). Patients experienced a feeling of being understood, the cohesion leading to hope and a feeling of being able to cope with their situation. Patient ambassadors experienced a sense of meaningfulness and gratitude for life. CONCLUSIONS: Patients and patient ambassadors experienced benefits from the individualised support. Their shared experiences created a connection and mutual mirroring, which led to a sense of hope and gratitude for life. Initiatives that introduce peer-to-peer support in newly diagnosed patients with acute leukaemia as part of treatment and in daily clinical practice are crucial. Future studies should further examine the feasibility of peer-to-peer support interventions along the trajectory of acute leukaemia.

A randomized assessment of adding the kinase inhibitor lestaurtinib to first-line chemotherapy for FLT3-mutated AML.

The clinical benefit of adding FMS-like tyrosine kinase-3 (FLT3)-directed small molecule therapy to standard first-line treatment of acute myeloid leukemia (AML) has not yet been established. As part of the UK AML15 and AML17 trials, patients with previously untreated AML and confirmed FLT3-activating mutations, mostly younger than 60 years, were randomly assigned either to receive oral lestaurtinib (CEP701) or not after each of 4 cycles of induction and consolidation chemotherapy. Lestaurtinib was commenced 2 days after completing chemotherapy and administered in cycles of up to 28 days. The trials ran consecutively. Primary endpoints were overall survival in AML15 and relapse-free survival in AML17; outcome data were meta-analyzed. Five hundred patients were randomly assigned between lestaurtinib and control: 74% had FLT3-internal tandem duplication mutations, 23% FLT3-tyrosine kinase domain point mutations, and 2% both types. No significant differences were seen in either 5-year overall survival (lestaurtinib 46% vs control 45%; hazard ratio, 0.90; 95% CI 0.70-1.15; P = .3) or 5-year relapse-free survival (40% vs 36%; hazard ratio, 0.88; 95% CI 0.69-1.12; P = .3). Exploratory subgroup analysis suggested survival benefit with lestaurtinib in patients receiving concomitant azole antifungal prophylaxis and gemtuzumab ozogamicin with the first course of chemotherapy. Correlative studies included analysis of in vivo FLT3 inhibition by plasma inhibitory activity assay and indicated improved overall survival and significantly reduced rates of relapse in lestaurtinib-treated patients who achieved sustained greater than 85% FLT3 inhibition. In conclusion, combining lestaurtinib with intensive chemotherapy proved feasible in younger patients with newly diagnosed FLT3-mutated AML, but yielded no overall clinical benefit. The improved clinical outcomes seen in patients achieving sustained FLT3 inhibition encourage continued evaluation of FLT3-directed therapy alongside front-line AML treatment. The UK AML15 and AML17 trials are registered at www.isrctn.com/ISRCTN17161961 and www.isrctn.com/ISRCTN55675535 respectively.

Systematic patient involvement for homebased outpatient administration of complex chemotherapy in acute leukemia and lymphoma.

Based on experience with comprehensive patient involvement, we present data from implementation of portable, programmable infusion pumps (PPP) for home-based chemotherapy administration in patients with acute leukaemia and in lymphoma patients receiving (carmustine, etoposide, cytarabine, melphalan) BEAM regimen. Data from 84 patients, receiving 177 cycles of PPP administered chemotherapy, showed convincing safety with minor equipment errors encountered and with high patient satisfaction. In-hospital days could be reduced with 52% out of a total of 1197 treatment days. Homebased PPP has several advantages from a patient perspective and furthermore frees up in-hospital beds for patients in need of them.

Addition of the mammalian target of rapamycin inhibitor, everolimus, to consolidation therapy in acute myeloid leukemia: experience from the UK NCRI AML17 trial.

As part of the UK NCRI AML17 trial, adult patients with acute myeloid leukemia in remission could be randomized to receive the mammalian target of rapamycin inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse-free survival. At 5 years there was no difference in relapse-free survival [29% versus 40%; odds ratio 1.19 (0.9-1.59) P=0.2], cumulative incidence of relapse [60% versus 54%: odds ratio 1.12 (0.82-1.52): P=0.5] or overall survival [45% versus 58%: odds ratio 1.3 (0.94-1.81): P=0.11]. The independent Data Monitoring Committee advised study termination after randomization of 339 of the intended 600 patients because of excess mortality in the everolimus arm without any evidence of beneficial disease control. The delivery of the everolimus dose was variable, but there was no evidence of clinical benefit in patients with adequate dose delivery compared with no treatment. This study suggests that the addition of mammalian target of rapamycin inhibition to chemotherapy provides no benefit.

A randomized comparison of daunorubicin 90 mg/m2 vs 60 mg/m2 in AML induction: results from the UK NCRI AML17 trial in 1206 patients.

Modifying induction therapy in acute myeloid leukemia (AML) may improve the remission rate and reduce the risk of relapse, thereby improving survival. Escalation of the daunorubicin dose to 90 mg/m(2) has shown benefit for some patient subgroups when compared with a dose of 45 mg/m(2), and has been recommended as a standard of care. However, 60 mg/m(2) is widely used and has never been directly compared with 90 mg/m(2). As part of the UK National Cancer Research Institute (NCRI) AML17 trial, 1206 adults with untreated AML or high-risk myelodysplastic syndrome, mostly younger than 60 years of age, were randomized to a first-induction course of chemotherapy, which delivered either 90 mg/m(2) or 60 mg/m(2) on days 1, 3, and 5 combined with cytosine arabinoside. All patients then received a second course that included daunorubicin 50 mg/m(2) on days 1, 3, and 5. There was no overall difference in complete remission rate (73% vs 75%; odds ratio, 1.07 [0.83-1.39]; P = .6) or in any recognized subgroup. The 60-day mortality was increased in the 90 mg/m(2) arm (10% vs 5% (hazard ratio [HR] 1.98 [1.30-3.02]; P = .001), which resulted in no difference in overall 2-year survival (59% vs 60%; HR, 1.16 [0.95-1.43]; P = .15). In an exploratory subgroup analysis, there was no subgroup that showed significant benefit, although there was a significant interaction by FLT3 ITD mutation. This trial is registered at http://www.isrctn.com as #ISRCTN55675535.

Vosaroxin and vosaroxin plus low-dose Ara-C (LDAC) vs low-dose Ara-C alone in older patients with acute myeloid leukemia.

The development of new treatments for older patients with acute myeloid leukemia is an active area, but has met with limited success. Vosaroxin, a quinolone-derived intercalating agent has several properties that could prove beneficial. Initial clinical studies showed it to be well-tolerated in older patients with relapsed/refractory disease. In vitro data suggested synergy with cytarabine (Ara-C). To evaluate vosaroxin, we performed 2 randomized comparisons within the "Pick a Winner" program. A total of 104 patients were randomized to vosaroxin vs low-dose Ara-C (LDAC) and 104 to vosaroxin + LDAC vs LDAC. When comparing vosaroxin with LDAC, neither response rate (complete recovery [CR]/complete recovery with incomplete count recovery [CRi], 26% vs 30%; odds ratio [OR], 1.16 (0.49-2.72); P = .7) nor 12-month survival (12% vs 31%; hazard ratio [HR], 1.94 [1.26-3.00]; P = .003) showed benefit for vosaroxin. Likewise, in the vosaroxin + LDAC vs LDAC comparison, neither response rate (CR/CRi, 38% vs 34%; OR, 0.83 [0.37-1.84]; P = .6) nor survival (33% vs 37%; HR, 1.30 [0.81-2.07]; P = .3) was improved. A major reason for this lack of benefit was excess early mortality in the vosaroxin + LDAC arm, most obviously in the second month following randomization. At its first interim analysis, the Data Monitoring and Ethics Committee recommended closure of the vosaroxin-containing trial arms because a clinically relevant benefit was unlikely.

An operational definition of primary refractory acute myeloid leukemia allowing early identification of patients who may benefit from allogeneic stem cell transplantation.

Up to 30% of adults with acute myeloid leukemia fail to achieve a complete remission after induction chemotherapy - termed primary refractory acute myeloid leukemia. There is no universally agreed definition of primary refractory disease, nor have the optimal treatment modalities been defined. We studied 8907 patients with newly diagnosed acute myeloid leukemia, and examined outcomes in patients with refractory disease defined using differing criteria which have previously been proposed. These included failure to achieve complete remission after one cycle of induction chemotherapy (RES), less than a 50% reduction in blast numbers with >15% residual blasts after one cycle of induction chemotherapy (REF1) and failure to achieve complete remission after two courses of induction chemotherapy (REF2). 5-year overall survival was decreased in patients fulfilling any criteria for refractory disease, compared with patients achieving a complete remission after one cycle of induction chemotherapy: 9% and 8% in patients with REF1 and REF2 versus 40% (P<0.0001). Allogeneic stem cell transplantation improved survival in the REF1 (HR 0.58 (0.46-0.74), P=0.00001) and REF2 (HR 0.55 (0.41-0.74), P=0.0001) cohorts. The utilization of REF1 criteria permits the early identification of patients whose outcome after one course of induction chemotherapy is very poor, and informs a novel definition of primary refractory acute myeloid leukemia. Furthermore, these data demonstrate that allogeneic stem cell transplantation represents an effective therapeutic modality in selected patients with primary refractory acute myeloid leukemia.

Early warning and prevention of pneumonia in acute leukemia by patient education, spirometry, and positive expiratory pressure: A randomized controlled trial.

Long-lasting neutropenia associated with acute myeloid leukemia (AML) and its treatment gives rise to a high risk of pneumonia. The use of broad-spectrum antibiotic prophylaxis during outpatient management has not completely protected patients against admission due to infections and neutropenic fever, emphasizing the need to approach infection protection with complementary efforts. In a randomized controlled design, we examined the applicability of patient-performed daily spirometry [forced expiratory volume in one second (FEV1)] as an early warning tool and explored the effectiveness of positive expiratory pressure (PEP) in preventing pneumonia among 80 AML patients. Twenty-five incidences of pneumonia were detected among 23 patients (6 interventions, 17 controls), giving a prevalence of 28.75% during 5420 days of observation. We found a significant difference in incidence between intervention versus control group (2.17 per 1000 days vs. 6.52 per 1000 days, P = 0.021, respectively). A cross point at 80-76% of the personal FEV1 reference value showed high sensitivity and specificity on pneumonia development. Our data demonstrate the feasibility of educating AML patients in their continuous daily measurement of FEV1 and use of PEP. Daily measures of FEV1 may be an important early warning tool for assessment of pulmonary deterioration during critical phases of neutropenia. We suggest that strategic patient education in the use of spirometry and PEP should be part of standard of care for AML patients undergoing induction chemotherapy.

Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia.

In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007) in the rituximab + dexamethasone group. There was an increased incidence of grade 3 to 4 adverse events in the rituximab + dexamethasone group (P = .04). In conclusion, rituximab + dexamethasone induced higher response rates and longer time to relapse than dexamethasone alone. This study is registered at http://clinicaltrials.gov as NCT00909077.

Optimized patient-trajectory for patients undergoing treatment with high-dose chemotherapy and autologous stem cell transplantation.

PURPOSE: Before, during and after autologous hematopoietic stem cell transplantation (HD-ASCT) patients suffer from significant loss of physical function, and experience multiple complications during and after hospitalization. Studies regarding safety and feasibility of physical exercise interventions for patients undergoing treatment with HD-ASCT are missing. METHODS: Forty patients referred to HD-ASCT treatment, suffering from multiple myeloma, lymphoma or amyloidosis aged 23-70 years were enrolled in a prospective longitudinal study. The study consisted of a home-based exercise program for use in the ambulatory setting and supervised exercise sessions Monday to Friday for 30-40 minutes during admission. Safety of the exercise program and physical tests were assessed by using a weekly questionnaire and report of inadvertent incidences. Adherence to the home-based exercise program was reported by using a patient diary, weekly questionnaire and count of daily attendance in supervised sessions during hospital stay. Data collection was scheduled shortly after diagnosis, admission, discharge and eight weeks after discharge. Success criteria were: no severe adverse events in relation to exercise program and assessments; performance of three days of physical exercises during ambulatory period and hospital stay and 150 minutes of weekly physical activity. RESULTS: Of the 25 patients who completed the exercise program during the ambulatory period prior to HD-ASCT a mean weekly attendance to home exercises of 5.3 (± 2.8) days and a median weekly physical activity of 240 (± 153.8) minutes was found. During hospital stay the median attendance was 9 (± 3.9) days of 10 (± 6.9) possible. Two months after discharge the patients reported a median weekly physical activity of 360 (2745.5) minutes. No severe adverse events in relation to the exercise program or assessments were reported. CONCLUSION: Based on the enrolled number of patients the physical exercise intervention for patients undergoing HD-ASCT seems promising regarding feasibility and safety.

Allelic methylation levels of the noncoding VTRNA2-1 located on chromosome 5q31.1 predict outcome in AML.

Deletions of chromosome 5q are associated with poor outcomes in acute myeloid leukemia (AML) suggesting the presence of tumor suppressor(s) at the locus. However, definitive identification of putative tumor suppressor genes remains controversial. Here we show that a 106-nucleotide noncoding RNA vault RNA2-1 (vtRNA2-1), previously misannotated as miR886, could potentially play a role in the biology and prognosis of AML. vtRNA2-1 is transcribed by polymerase III and is monoallelically methylated in 75% of healthy individuals whereas the remaining 25% of the population have biallelic hypomethylation. AML patients without methylation of VTRNA2-1 have a considerably better outcome than those with monoallelic or biallelic methylation (n = 101, P = .001). We show that methylation is inversely correlated with vtRNA2-1 expression, and that 5-azanucleosides induce vtRNA2-1 and down-regulate the phosphorylated RNA-dependent protein kinase (pPKR), whose activity has been shown to be modulated by vtRNA2-1. Because pPKR promotes cell survival in AML, the data are consistent with vtRNA2-1 being a tumor suppressor in AML. This is the first study to show that vtRNA2-1 might play a significant role in AML, that it is either mono- or biallelically expressed in the blood cells of healthy individuals, and that its methylation state predicts outcome in AML.

It is feasible and safe to stop specialized follow-up of asymptomatic lower risk chronic lymphocytic leukemia.

Approximately half of patients with chronic lymphocytic leukemia (CLL) will never require treatment, still they are recommended life-long specialized follow-up (sFU). To prioritize health care resources, local hospital management implemented ending sFU in asymptomatic patients with CLL international prognostic index (CLL-IPI) and CLL without need of treatment (CLL-WONT) low to intermediate risk, who were covered by universal health care. To evaluate the feasibility and safety of ending sFU, we investigated 3-year clinical outcomes among 112 patients selected by clinical assessment to end sFU as compared with 88 patients continuing sFU. Patients who ended sFU were older but otherwise lower risk compared with patients continuing sFU. Overall survival (OS) was similar in patients ending and continuing sFU (3-year OS 87% and 80%, respectively; P=0.16). Hospital visits per patient-year were lower (median 0.7 vs 4.3, P<0.0001) and time to first infection was longer (P=0.035) in patients ending sFU as compared with those who continued sFU: this included fewer COVID infections (8 [7%] vs 17 [18%]; P=0.029) and shorter in-hospital antimicrobial treatment (median 4 vs 12 days, respectively; P=0.026). Finally, one in six patients got re-referred including 4 patients meeting iwCLL criteria for need of treatment. This also resulted in a lower 3-year first treatment rate for patients ending sFU compared with patients continuing sFU (4% vs 23%, respectively; P<0.0001). In conclusion, it is feasible and safe to end sFU for patients with CLL who have low to intermediate risk CLL-IPI and CLL-WONT scores upon thorough clinical evaluation prior to ending specialized follow-up.

Family caregiver quality of life and symptom burden in patients with hematological cancer: A Danish nationwide cross-sectional study.

OBJECTIVE: To investigate the quality of life (QoL) and the impact of caregiving in family caregivers of hematological cancer patients and its association with patient symptom burden. METHODS: A cross-sectional study including Danish patients (n = 375) and caregivers (n = 140). Caregivers completed scales for anxiety and depression using the Hospital Anxiety and Depression Scale, sleep quality using the Pittsburgh Sleep Quality Index, health related QoL using the 12-item Short-Form Health Survey, and caregiver roles using the Caregiver Roles and Responsibilities Scale. Patients reported symptoms using the MD Anderson Symptom Inventory. Analysis of covariance was used to examine associations between patient symptom burden and caregivers' QoL outcomes. RESULTS: The results show that caregivers experience sleep difficulties, moderate anxiety, and reduced QoL. Patient symptom burden was significantly associated with caregiver anxiety (p = 0.009), and mental well-being (p = 0.002), while patient treatment status was a significant factor associated with caregiver anxiety (p = 0.016), depression (p = 0.009), emotional well-being (p = 0.002), and sleep (p = 0.01). CONCLUSION: Caregivers of patients with hematological cancers undergoing active treatment face a high symptom burden, which significantly impacts their QoL, including sleep, psychological well-being, and emotional health. Patients reported a high symptom burden, and patient symptom burden was significantly associated with caregiver QoL. Adequate patient and caregiver support is needed to promote their well-being and mitigate adverse health effects in caregivers, and this should be acknowledged in the context of caring for patients with hematological cancer.