Mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)): evaluating mediators of psychological and physical outcomes in a large randomized controlled trial.

MBSR(BC) is known to have a positive impact on psychological and physical symptoms among breast cancer survivors (BCS). The cognitive mechanisms of "how" MBSR(BC) works was addressed in a recent study that found that there was strong consistent evidence that reduced emotional reactivity is a mediator and moderate consistent evidence that mindfulness, rumination, and worry were mediators. The purpose of this study, as part of a larger R01 trial, was to test whether positive effects achieved from the MBSR(BC) program were mediated through changes in increased mindfulness, decreased fear of breast cancer recurrence, and perceived stress. Female BCS > 21 years diagnosed with Stage 0-III breast cancer were randomly assigned to a 6-week MBSR(BC) or a Usual Care (UC)regimen. Potential mediators of 6- and 12-week outcomes were identified by analysis of covariance (ANCOVA), followed by formal mediational analyses of main effects of MBSR(BC) on 6- and 12-week outcomes, including percentage of total effects explained. Among 322 BCS (167 MBSR(BC) and 155 UC), fear of recurrence and perceived stress, but not mindfulness, mediated reductions in anxiety and fatigue at weeks 6 and 12, partially supporting our hypothesis of cognitive mechanisms of MBSR(BC). TRIAL REGISTRATION: Registration Number: NCT01177124 http://www.ClinicalTrials.gov.

Prospective international validation of the Quality of Life in Myelodysplasia Scale (QUALMS).

Disease-specific measures of quality of life can improve assessment of disease-related symptoms and psychosocial sequelae. We report on the development and validation of the Quality of Life in Myelodysplasia Scale (QUALMS), a 38-item assessment tool for patients with myelodysplastic syndromes (MDS). In 2014-2015, a multi-center cohort of patients with myelodysplasia completed the QUALMS, as well as the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the Functional Assessment of Cancer Therapy Anemia Scale (FACT-An); a second administration was undertaken three to six months later. A total of 255 patients from the United States, Canada and Italy participated. Median age was 72 years, 56.1% were men, and the International Prognostic Scoring System distribution was 40.4% low, 42.0% intermediate-1, 13.3% intermediate-2 and 2.3% high. QUALMS scores ranged from 24 to 99 (higher scores are better), with a mean of 67.2 [standard deviation (SD)=15.2]. The measure was internally consistent (α=0.92), and moderately correlated with the multi-item QLQ-C30 scales and the FACT-An (r=-0.65 to 0.79; all P<0.001). Patients with hemoglobin of 8 g/dL or under scored lower than those with hemoglobin over 10 g/dL (61.8 vs 71.1; P<0.001), and transfusion-dependent patients scored lower than transfusion-independent patients (62.4 vs 69.7; P<0.01). Principal components analysis revealed "physical burden", "benefit-finding", and "emotional burden" subscales. There was good overall test-retest reliability among those with stable hemoglobin (r=0.81), and significant changes for patients hospitalized or with infections between administrations (both P<0.01). These data suggest the QUALMS is a valuable tool for assessing MDS-specific quality of life in the modern treatment era.

Phase II clinical study of erlotinib for treatment of myelodysplastic syndromes.

Outcome in patients with myelodysplastic syndrome (MDS) after azanucleoside failure is poor with unmet need for active novel agents. Preclinical data have suggested that erlotinib has in vivo and in vitro off epidermal growth factor receptor (EGFR)-target activity in MDS. We conducted a phase II study with single-agent erlotinib 150 mg/day orally in MDS patients following azanucleoside failure. All intermediate-2 or high-risk MDS patients by International Prognostic Scoring System and only those low/intermediate-1 patients with transfusion-dependent anemia or platelet counts <50 × 10(9) /L or a significant clinical hemorrhage requiring platelet transfusion or ANC <1 × 10(9) /L were eligible, with most of our patients being at high risk. In 35 eligible patients, overall best response was 14% (3 patients having marrow complete response and 2 hematological improvement). Four deaths occurred on study (sepsis, intracranial hemorrhage, sudden death, and acute myeloid leukemia (AML)). The most common observed grade 3/4 toxicities according to CTCAE v3 were diarrhea (17.1%), rash (17.1%), and infection (11.6%), accompanied by fatigue, thrombocytopenia, and anorexia at 5.7% each. Median overall survival was 6.8 months (95% CI 4.9-13.2), and leukemia-free survival was 5 months (95% CI 3.4-7.3). Erlotinib was generally well tolerated, with modest single-agent activity. Given these results and preclinical data suggesting synergistic effect with azanucleosides, the combination should be further explored.

Efficacy of Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC)) a Treatment for Cancer-related Cognitive Impairment (CRCI): A Randomized Controlled Trial.

Introduction: The Mindfulness-Based Stress Reduction (MBSR) Program for breast cancer survivors (BCS) is designed to enhance cognitive training through formal and informal meditational practices. This randomized clinical trial (RCT) aimed to evaluate if BCS assigned to either the MBSR(BC), Breast Cancer Education Support (BCES), or Usual Care (UC) regimens experienced greater improvements at 6, 12, and 26 weeks on objective and subjective cognitive performance. Methods: BCS (n = 212) randomized to a three-group RCT: MBSR(BC) (n = 91), BCES (n = 90), or UC (n = 31) were assessed on cognitive performance and symptoms at baseline, 6, 12, and 26 weeks. Linear mixed models were fit to evaluate the effects of the MBSR(BC) program, hypothesizing ordered effect improvements: (MBSR[BC] highest, BCES intermediate, UC lowest) along with baseline characteristics evaluated as moderators. Results: Of the BCS (mean age of 57), 73% were White, and non-Hispanic, and 77% received both chemotherapy (CT) and radiation. Cognitive performance improved in all groups. Although there were no statistically significant between-group differences in cognitive outcomes, significant symptom reductions occurred for the MBSR(BC) group (p = 0.003). Within-group effect size analysis at 26 weeks showed substantial improvements in all three groups (effect sizes >0.50) in subjective impairments and quality of life (effect size >0.50) and objective measures of cognitive performance. MBSR(BC) showed the largest within-group effect size in the reduction of fatigue (effect size = 0.81). Effect sizes occurred in the hypothesized direction for 10 of the 18 outcomes. Discussion: Although the MBSR(BC) program did not show significant differences in cognitive performance compared with BCES and UC, all groups improved and reductions in fatigue were beneficial for MBSR(BC). Results suggest that cognitive performance may improve after CT over time considering one's natural history. Furthermore, BCS enrolled in RCTs may be more motivated to improve their health status (NCT02786797).

Defining and Addressing Research Priorities in Cancer Cachexia through Transdisciplinary Collaboration.

For many patients, the cancer continuum includes a syndrome known as cancer-associated cachexia (CAC), which encompasses the unintended loss of body weight and muscle mass, and is often associated with fat loss, decreased appetite, lower tolerance and poorer response to treatment, poor quality of life, and reduced survival. Unfortunately, there are no effective therapeutic interventions to completely reverse cancer cachexia and no FDA-approved pharmacologic agents; hence, new approaches are urgently needed. In May of 2022, researchers and clinicians from Moffitt Cancer Center held an inaugural retreat on CAC that aimed to review the state of the science, identify knowledge gaps and research priorities, and foster transdisciplinary collaborative research projects. This review summarizes research priorities that emerged from the retreat, examples of ongoing collaborations, and opportunities to move science forward. The highest priorities identified include the need to (1) evaluate patient-reported outcome (PRO) measures obtained in clinical practice and assess their use in improving CAC-related outcomes; (2) identify biomarkers (imaging, molecular, and/or behavioral) and novel analytic approaches to accurately predict the early onset of CAC and its progression; and (3) develop and test interventions (pharmacologic, nutritional, exercise-based, and through mathematical modeling) to prevent CAC progression and improve associated symptoms and outcomes.

The Moderating Role of Genetics on the Effectiveness of the Mindfulness-Based Stress Reduction for Breast Cancer (MBSR(BC)) Program on Cognitive Impairment.

BACKGROUND: Genetics may influence symptoms experienced by breast cancer survivors (BCS) by moderating the effects of stress-reducing interventions, including the Mindfulness-Based Stress Reduction (MBSR(BC)) program, to reduce symptom severity. As part of a larger clinical trial, the aim of this study was to evaluate genetic variants as moderators of MBSR(BC) on improvements among BCS in cognitive functioning and symptoms. METHODS: BCS (n = 128) were randomized to MBSR(BC) or the Breast Cancer Education Support Program. Objective neuropsychological and subjective measures of cognitive performance, and psychological and physical symptoms were collected at baseline, 6, 12, and 26 weeks. Linear mixed models were implemented to identify MBSR(BC)'s effects over time. A total of 22 single nucleotide polymorphisms (SNPs) from 20 genes known to be related to these symptoms were investigated using genomic DNA. These SNPs were tested as moderators of MBSR(BC) program effects. RESULTS: Results showed MBSR(BC) participants experienced significantly greater benefits in cognitive functioning, however, the level of benefit varied based on one's genetic profile. Effects sizes, consistency across similar measures were investigated. Among 22 candidate SNPs, rs4680 in COMT, rs1800497 in ANKK1, and rs6277 in DRD2 demonstrated the strongest, most consistent positive effects in moderating MBSR(BC)'s impact on cognitive outcomes. CONCLUSIONS: Although the effects were small, this translational research may potentially identify BCS with genotypes that would be most influenced by the MBSR(BC) program. These results may be used to develop personalized intervention programs tailored to the genetic profile of each breast cancer survivor who received chemotherapy or chemotherapy and radiation. TRIAL REGISTRATION: ClinicalTrials.gov, https://www.ClinicalTrials.gov Registration Number: NCT02786797.

Quality of life outcomes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: a controlled comparison.

PURPOSE: Tyrosine kinase inhibitors (TKIs) are now standard treatment for chronic myeloid leukemia (CML). While TKIs have less toxicity than previous treatments, they have side effects that can impact quality of life (QOL). METHODS: This study compared CML patients taking a TKI for an average of 4.01 years (range 0.50-9.79 years) to age- and gender-matched controls with no history of cancer on measures of symptom burden, depression, fatigue, sleep, and health-related QOL. RESULTS: Compared to controls (n = 62), CML patients (n = 62) taking a TKI (imatinib 55 %, nilotinib 31 %, and dasatinib 14 %) reported significantly worse fatigue severity (p < .001), fatigue interference (p < .001), depression (p = .007), symptom burden (p < .001), and physical QOL (p < .001). TKI patients were also more likely meet established cutoffs for clinically meaningful fatigue (p values < .001) and depression (p = .004). There were no differences in mental QOL or sleep (p values > .010). Regarding specific symptoms, TKI patients were more likely to report nausea, diarrhea, itching, skin changes, swelling of arms or legs, and not looking like themselves (p values < .001). CONCLUSIONS: These data suggest the need for interventions to address QOL in CML patients taking TKIs.

Clinical characteristics and outcomes of EZH2-mutant myelodysplastic syndrome: A large single institution analysis of 1774 patients.

EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p < 0.001). Patients with EZH2mut MDS had lower response rates to hypomethylating agents compared to EZH2wt MDS (26% vs. 39%; p = 0.050). Median OS of patients with EZH2mut MDS was 30.8 months, with a significantly worse OS than EZH2wt group (35.5 vs. 61.2 months, p = 0.003) in the lower-risk IPSS-R categories. Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS.

Cardiovascular Adverse Events and Mitigation Strategies for Chronic Myeloid Leukemia Patients Receiving Tyrosine Kinase Inhibitor Therapy.

Cardiovascular (CV) risk mitigation is an important consideration in the management of chronic myeloid leukemia (CML) patients. Although BCR-ABL1 inhibition by tyrosine kinase inhibitors (TKI) has led to a significant improvement in prognosis, the majority of CML patients will require indefinite TKI therapy. Given the success of therapy, there has been a shift in focus to include CV care as part of routine patient management. To optimize outcomes, both patient-specific comorbidities and a detailed understanding of the cardiotoxicity safety profiles imparted by each TKI should be considered during agent selection. Clinicians face the challenge of early detection and management of these cardiotoxicities while balancing the risk-benefit ratios of maintaining life-saving cancer therapy. Advanced practitioners play a critical role in CML patient management that extends to the recognition and management of TKI-associated side effects. They should be cognizant of the potential for TKI-associated cardiotoxicities along with appropriate baseline risk assessments, active surveillance, and mitigation strategies as part of a collaborative team effort with cardio-oncologists.

Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

Safety profiles of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.

AIMS AND OBJECTIVES: To review the use of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia (CML) and provide recommendations for managing adverse events (AEs) to maximise patient benefit. BACKGROUND: Treatment of CML has been revolutionised with the advent of tyrosine kinase inhibitors (TKIs) that target the breakpoint cluster region-Abelson (BCR-ABL) kinase. Imatinib is the only first-line TKI currently available for the treatment of CML; however, intolerance and resistance remain significant clinical challenges. The approved second-line treatment options for CML are dasatinib, nilotinib or escalated-dose imatinib. DESIGN: Review article. METHODS: Searches of PubMed, ASCO and ASH electronic databases for relevant search terms were performed between July 2008-January 2009. FINDINGS: Dasatinib has no cross-intolerance with imatinib, and the most frequent AEs (cytopenias and pleural and pericardial effusions) can generally be managed by dose interruption and reduction. Nilotinib has a high degree of haematologic cross-intolerance with first-line imatinib. As might be expected, high-dose imatinib has the potential for more severe AEs than standard-dose imatinib. CONCLUSIONS: There are known safety issues inherent to each TKI and close monitoring by nursing staff is necessary to identify and effectively manage AEs. RELEVANCE TO CLINICAL PRACTICE: All three TKIs have demonstrated potential for fluid retention and cardiotoxicity. Nurses should be aware of how these AEs manifest and intervene appropriately. The safety profiles of these TKIs clearly differs and it is important to consider factors such as comorbidities when making treatment decisions.

Growth and Change in the Journal of Human Lactation: A Content Analysis 1985-2018.

BACKGROUND: A professional association journal should reflect the needs of its organization, its readers, and the field it represents. Evaluating the needs that the Journal of Human Lactation has met, and those it has not, is essential if it is to remain relevant to its readers. AIMS: (1) Describe the characteristics of articles published from 1985 through 2018. (2) Describe content intended to educate lactation support providers and clinicians. (3) Explore the ways the content has illustrated the growth and development of lactation knowledge, and (4) identify the reoccurring content threads consistent throughout the 34 years. METHODS: A prospective mixed methods approach incorporating a quantitative content analysis and a qualitative thematic analysis was used. Frequency distributions were done on all the variables extracted from published articles (N = 1586). The second level of analysis identified themes using an iterative and consensus approach. RESULTS: Mirroring the growth in the lactation field, the volume of research articles published each year has increased along with the percent of research articles per issue. Research methods have become more diverse. The international scope and relevance, while always present, has been steadily increasing. Threads identified were; striving for international scope, advancing lactation education, developing a body of knowledge that informs clinical practice in lactation, and creating a centralized place for multidisciplinary research about lactation. CONCLUSION: The body of work published in the Journal of Human Lactation parallels the development of the lactation specialty. We have highlighted areas for improvement and possible further study.

Lenalidomide and Prednisone in Low and Intermediate-1 IPSS Risk, Non-Del(5q) Patients With Myelodysplastic Syndromes: Phase 2 Clinical Trial.

PURPOSE: To test the hypothesis that combination treatment with lenalidomide and prednisone will yield a higher erythroid response rate in patients with non-del(5q) lower-risk myelodysplastic syndromes compared to the historical clinical trial data with lenalidomide monotherapy, which reported a 26% transfusion independence rate. PATIENTS AND METHODS: The study enrolled 25 patients with lower-risk myelodysplastic syndromes by the International Prognostic Scoring System who were transfusion dependent or who had symptomatic anemia and prior erythroid stimulating agent failure or low chance of response. The planned dose of lenalidomide was 10 mg per day. Prednisone dose was 30 mg by mouth, daily cycle 1 tapered by 10 mg after each cycle to 5 mg by mouth every other day for those with response beyond cycle 6. The primary objective was best response (hematologic improvement-erythroid, HI-E) by International Working Group 2006 criteria within 24 weeks. RESULTS: The HI-E rate was 20% (5/25) and was 22% (5/23) for patients with evaluable data. All those with response became red blood cell-transfusion independent (5/23). The median time to response was 57 days. The median duration of response was 80 days (95% confidence interval, 69-91). Three of 5 of those with response did not have prior hypomethylating agent, while 14 of 20 those without response received a hypomethylating agent. CONCLUSION: The combination was relatively well tolerated, with no additional observed toxicity to single-agent lenalidomide.

A Phase II Study to Determine the Safety and Efficacy of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase (IDO) Enzyme INCB024360 in Patients with Myelodysplastic Syndromes.

BACKGROUND: INCB024360 is an oral inhibitor of the enzyme indoleamine 2,3-dioxygenase (IDO), which catalyzes the degradation of tryptophan to kynurenine. Preclinical data suggest that IDO1 inhibition by INCB024360 will increase T cell proliferation, and decrease T regulatory cells and myeloid derived suppressor cells suppressive activity. We conducted a phase II study to explore activity and pharmacodynamics of INCB024360 in patients with myelodysplastic syndromes. PATIENTS AND METHODS: All patients were treated with INCB024360 600 mg orally twice a day for at least 16 weeks. Fifteen patients were enrolled. The median age was 72 years. The International Prognostic Scoring System risk was low in 27% (n = 4), intermediate-1 in 47% (n = 7), and intermediate-2 in 27% (n = 4). All patients had prior azacitidine. RESULTS: The best response was stable disease in 12 (80%) patients and progressive disease in 3 (20%) patients. The treatment was relatively well-tolerated. One patient developed hypothyroidism and adrenal insufficiency (grade 2), and 1 patient had low testosterone level. The mean IDO expression was 39% at baseline and 26% after treatment (n = 9; P = .4). The mean burst forming unit-erythroid changed from 72 to 191 colonies/106 (n = 5; P = .036), and the mean colony forming unit-granulocye, monocyte from 62 to 180 colonies/106 (n = 6; P = .5). The mean myeloid derived suppressor cell % (CD33Lin-HLA cells) was 29.5% at baseline compared with 27.6% after treatment (n = 9; P = .7). The mean T-regulatory effector memory cell % changed from 9.6% at screening to 7.4% at end of treatment (n = 14; P = .8). The mean kynurenine/tryptophan ratio decreased from 45 at baseline to 26 (42% reduction) at cycle 2, day 1 (P < .005). CONCLUSION: Future directions may include testing INCB024360 early in the course of the disease.

Transitioning Patients With Iron Overload From Exjade to Jadenu.

Iron overload is a concern for patients who require chronic transfusions as a result of inherited or acquired anemias, including sickle cell disease, thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the primary treatment for iron overload in these patients. The ICT deferasirox, which has been available as an oral dispersible tablet for liquid suspension, is now also available as a once-daily, film-coated tablet (FCT). Deferasirox FCT allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. Dose adjustment increments, determined by titration monitoring, are lower for the FCT because of greater bioavailability.

Potential of Biosimilars to Increase Access to Biologics: Considerations for Advanced Practice Providers in Oncology.

Biosimilars are biologic products that are highly similar, but not identical, to a licensed reference (or "originator") biologic product. These agents have the potential to provide efficiencies and improve access to treatment for patients. Biosimilars are currently available for use in clinical practice, including oncology indications, and several more are in clinical development. Due to several key differences in their fundamental properties, production and manufacturing of biosimilars is more complex compared with that of small-molecule generic drugs. Accordingly, the generic drug approval process is not suitable or transferable to biosimilars, the approval of which involves extensive and thorough comparison with the originator biologic. Advanced practice providers play an important role in evaluating treatment options available to patients, prescribing, patient education, and product monitoring. In order to perform these tasks effectively, advanced practice providers should understand the concepts related to biosimilars in clinical practice, particularly regarding extrapolation to other indications, product labeling, interchangeability between products, and routine pharmacovigilance, among other clinical considerations. However, many health-care providers have limited awareness and minimal experience regarding biosimilars. Thus, the purpose of this review is to provide an overview of biosimilars and discuss the clinical considerations for oncology advanced practice providers concerning these therapies.

Practical Guide to Bone Marrow Sampling for Suspected Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) comprise a group of diverse clonal hematopoietic stem cell malignancies that are characterized by ineffective hematopoiesis and progressive bone marrow failure. Clinical symptoms are generally nonspecific. The diagnosis, classification, and risk stratification of MDS rely on the evaluation of peripheral blood and bone marrow sampling using the Revised International Prognostic Scoring System tool. Accurate diagnosis and risk stratification require a good-quality bone marrow sample. Bone marrow samples are obtained using two complementary techniques: bone marrow aspiration and bone marrow biopsy. Knowledge of what constitutes an adequate bone marrow sample and a proper bone marrow sampling technique may help advanced practitioners obtain quality samples while minimizing patient discomfort and risk. Patient preparation and positioning, site selection, sampling equipment, and sampling technique can help lead to the collection of high-quality bone marrow samples. Postprocedural care and knowledge of potential complications can reduce a patient's pain and optimize recovery.

Practical Strategies for Management of Lenalidomide-Associated Cytopenias in Myelodysplastic Syndromes With del(5q).

CASE STUDY A male patient aged 67 years with a 2-year history of refractory anemia and myelodysplastic syndromes (MDS) with del(5q) started lenalidomide (Revlimid) treatment as a participant in the MDS-001 trial (List et al., 2005). At the time of the study, this patient had been transfusion-dependent since 2001, and at study entry he had received a total of 12 units of red blood cells (RBCs). The patient started lenalidomide at 25 mg daily for 21 days of each 28-day cycle on April 2, 2002. (Please note that as a result of subsequent trials, the approved starting dose for lenalidomide in patients with del[5q] MDS is 10 mg.) The patient developed treatment-related pancytopenia in the first 3 weeks of treatment (see Figure on next page). On day 24, lenalidomide was withheld. Platelet and white blood cell (WBC) counts were recovered during a 21-day period, and treatment was resumed with lenalidomide at 10 mg daily. During this initial dose interruption, the patient's hemoglobin level improved. He achieved RBC-transfusion independence (TI) during week 5 of treatment-his last RBC transfusion was on April 22, 2002. Bone marrow (BM) analysis, including fluorescence in situ hybridization, after 3 months of therapy, did not show the del(5q) abnormality. A repeat BM analysis after 57 months of treatment revealed minimal residual dyspoiesis, normal metaphase cytogenetics, and normal cell morphology. Subsequent BM biopsies showed transient trisomy 8 abnormalities but no del(5q) abnormality. The patient required one additional dose reduction during the first year of treatment. The patient did not require hospitalization during lenalidomide treatment but did have a history of seasonal allergies and a propensity for acute sinusitis. He received a single dose of pegfilgrastim (Neulasta) and a short course of antibiotics for active infections, generally one course of antibiotics per year. This patient continued on lenalidomide at 5 mg daily for 21 days of every 28-day cycle without further dose reduction. The patient achieved durable RBC-TI and continued to receive treatment for more than 11 years. The levels of hemoglobin, platelets, and WBCs for an 11-year period in this patient are shown in the Figure. This patient had one normal platelet count in 11 years of lenalidomide treatment but no bleeding episodes. The average platelet count in the 11-year period was 67 × 1,000/∝L (normal range, 150-425 × 1,000/∝L). Similarly, the WBC count remained below normal, with an average of 3.1 × 1,000/∝L (normal range, 3.4-10.4 × 1,000/∝L). He remained active and continued working as an aerospace engineer until age 75. This case demonstrates how effective management of cytopenias, through dose interruptions and modifications in the early weeks of treatment, helps to enable long-term lenalidomide treatment and a high quality of life. Despite the persistence of moderate, asymptomatic cytopenias, the patient was able to remain on lenalidomide therapy and maintained RBC-TI for more than 11 years. The patient died on October 4, 2014, at age 79.5, due to coronary artery disease and heart failure.

Treatment Choices: A Quality of Life Comparison in Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome.

BACKGROUND: In the present exploratory, observational study, we compared the effect of intensive versus nonintensive treatment on quality of life for patients aged ≥ 60 years diagnosed with acute myeloid leukemia or high-risk myelodysplastic syndrome at 1 month after treatment. PATIENTS AND METHODS: A total of 73 patients with acute myeloid leukemia or high-risk myelodysplastic syndrome who had been treated at the inpatient and outpatient malignant hematology at Moffitt Cancer Center, a National Cancer Institute-designated comprehensive cancer center, were included. Two paired measurements of self-reported quality of life were used, 1 before treatment and 1 at 1 month after treatment to compare intensive versus nonintensive treatment. Patients completed the Functional Assessment of Cancer Therapy-Leukemia version for the quality-of-life measurement. Repeated measures analysis of variance was used to compare the effect of treatment and time and the interaction of treatment and time. The main research variables were intensive versus nonintensive treatment as the independent variable and quality of life measured using the Functional Assessment of Cancer Therapy-Leukemia version as the dependent variable. RESULTS: Physical function and leukemia symptoms improved for patients treated with intensive chemotherapy. A trend was found for improved quality of life for the intensive treatment compared with nonintensive treatment, for which the quality of life was stable at 1 month. CONCLUSION: The study participants treated with inpatient, induction chemotherapy experienced statistically significant improvement in their quality of life at 1 month. The outpatient, nonintensive study participants had stable quality of life at 1 month.