Challenges in management of older patients with chronic myeloid leukemia.

Tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with chronic myeloid leukemia (CML), however, older patients are often underrepresented in pivotal trials. Approximately 20% of older adults never start treatment and face significant barriers to accomplish favorable outcomes. The treatment goal is to improve survival, prevent progression, and preserve quality of life. This is achieved through optimizing TKI doses and employing discontinuation strategies to attain treatment-free remission (TFR), a goal increasingly pursued by older patients. Imatinib may be favored as the front-line option for older individuals due to its side effect profile and cost. Bosutinib's favorable cardiovascular tolerability makes it a suitable second-line agent, but lower-dose dasatinib may likewise be an attractive option. The prevalence of comorbidities can preclude the use of second generation TKIs in some older patients. Optimal care for older patients with CML centers on personalized treatment, close monitoring, and proactive support.

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia.

BACKGROUND: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. METHODS: We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. RESULTS: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups. CONCLUSIONS: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms.

ABSTRACT: Myelodysplastic syndromes/neoplasms (MDS) are heterogeneous, clonal myeloid neoplasms characterized by ineffective hematopoiesis, progressive cytopenias, and an increased risk of progression to acute myeloid leukemia. The diversity in disease severity, morphology, and genetic landscape challenges not only novel drug development but also therapeutic response assessment. The MDS International Working Group (IWG) response criteria were first published in the year 2000 focusing on measures of blast burden reduction and hematologic recovery. Despite revision of the IWG criteria in 2006, correlation between IWG-defined responses and patient-focused outcomes, including long-term benefits, remains limited and has potentially contributed to failures of several phase III clinical trials. Several IWG 2006 criteria also lacked clear definitions leading to problems in practical applications and interobserver and intraobserver consistency of response reporting. Although the 2018 revision addressed lower-risk MDS, the most recent update in 2023 redefined responses for higher-risk MDS and has set out to provide clear definitions to enhance consistency while focusing on clinically meaningful outcomes and patient-centered responses. In this review, we analyze the evolution of the MDS response criteria, limitations, and areas of improvement.

Supportive Care for Patients With Myelodysplastic Syndromes.

ABSTRACT: Myelodysplastic syndromes are a heterogeneous group of bone marrow disorders characterized by ineffective hematopoiesis, progressive cytopenias, and an innate capability of progressing to acute myeloid leukemia. The most common causes of morbidity and mortality are complications related to myelodysplastic syndromes rather than progression to acute myeloid leukemia. Although supportive care measures are applicable to all patients with myelodysplastic syndromes, they are especially essential in patients with lower-risk disease who have a better prognosis compared with their higher-risk counterparts and require longer-term monitoring of disease and treatment-related complications. In this review, we will address the most frequent complications and supportive care interventions used in patients with myelodysplastic syndromes, including transfusion support, management of iron overload, antimicrobial prophylaxis, important considerations in the era of COVID-19 (coronavirus infectious disease 2019), role of routine immunizations, and palliative care in the myelodysplastic syndrome population.

Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence.

Tyrosine kinase inhibitor (TKI) use is critical in the care of patients with chronic myeloid leukemia (CML). Quantitative polymerase chain reaction (qPCR) testing for BCR-ABL1 every 3 months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1192 patients aged ≥66 years (median age, 74 years) with newly diagnosed CML who were followed up for ≥13 months from TKI initiation. In total, 965 patients (81.0%) had ≥1 test, with 425 (35.7%) and 540 (45.3%) of the patients tested during 1, 2, and ≥3 quarters (optimal monitoring) of the first year from TKI initiation, respectively. In multivariable analysis, diagnosis in later years and influenza vaccination before diagnosis, a proxy for health care access, were associated with optimal qPCR monitoring. Use of low-income subsidy and residing in census tracts with the lowest socioeconomic status were associated with less optimal monitoring. Patients with optimal monitoring were 60% more likely to be TKI adherent (odds ratio, 1.60; 95% CI, 1.11-2.31; P = .01) and had improved 5-year survival (hazard ratio, 0.66; 95% CI, 0.49-0.90; P < .01) than those without such monitoring. In this large, real-world study of CML management patterns, many older patients had suboptimal molecular monitoring, which was associated with decreased TKI adherence and worse survival.

Second malignancies among older patients with classical myeloproliferative neoplasms treated with hydroxyurea.

Patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF), are known to have an increased risk of second malignancies (SMs). Hydroxyurea (HU) is a guideline-recommended cytoreductive therapy for patients at high risk for MPNs. Controversy exists as to whether HU use is associated with a higher risk of SMs, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We conducted a retrospective cohort study of older patients diagnosed with MPN (age ≥66 years) between 2010 and 2017 and included the data in the Surveillance, Epidemiology, and End Results Medicare-linked database. Multivariable competing risk analyses adjusting for patient characteristics were used to assess the impact of HU on the development of SM. We identified 4023 patients (1688 with PV, 1976 with ET, and 359 with MF) with a median age of 77 (interquartile range [IQR], 71-83) years at the time of MPN diagnosis. After a median follow-up of 3.25 (IQR, 2.10-5.00) years, 489 patients developed an SM (346 solid, 73 lymphoid, and 70 myeloid malignancies). The cumulative incidence probability of SM was 19.88% (95% confidence interval [CI], 17.16%-22.75%) among 2683 HU users and 22.31% (95% CI, 17.51%-27.47%) among 1340 nonusers, respectively (Gray's test, P < .01). We did not identify significant differences in the incidence of solid or hematologic SMs, including AML/MDS (hazard ratio, 1.33; 95% CI, 0.77-2.29; P = .30), between HU users and nonusers. Our results suggest that the use of HU does not increase the risk of SM in older patients with MPN.

Bicarbonate use and mortality outcome among critically ill patients with metabolic acidosis: A meta analysis.

BACKGROUND: The use of sodium bicarbonate in the treatment of metabolic acidosis in critically ill subjects has long been a subject of debate. Despite empiric use in the setting of severe acidemia in critically ill patients, there is little data looking into the role of sodium bicarbonate in the treatment of severe metabolic acidosis in the intensive care unit (ICU) setting. METHODS: We conducted a comprehensive search of Pubmed and Cochrane Central Register of Controlled Trials addressing bicarbonate use in the metabolic acidosis in the intensive care unit (ICU) setting. We examined mortality as end point. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated for all outcomes using a random-effect model. RESULTS: The final search yielded 202 articles of which all were screened individually. A total of 11 studies were identified but 6 studies were excluded due to irrelevance in mortality outcome and methodology. Analysis was done separately for observational studies and randomized controlled trials. The pooled OR [95% CI] for mortality with bicarbonate use in the observational studies was 1.5 [0.62-3.67] with heterogeneity of 67%, while pooled OR for mortality in the randomized trials was 0.72 [0.49-1.05] (figure 2). In combining all studies, the pooled odds ratio was 0.93 95% [0.69-1.25] but with heterogeneity of 63%. After sensitivity analysis with removing the study done by Kim et al. 2013, heterogeneity was 0% with OR 0.8 [0.59-1.10]. CONCLUSION: There is no significant difference in mortality in the use of bicarbonate among critically ill patients with high anion gap metabolic acidosis predominantly driven by lactic acidosis.

False positive fourth generation HIV test in a patient with severe malaria.

Severe malaria is an uncommon diagnosis in the United States. However, awareness of signs, symptoms, and treatment options is imperative in order to promptly initiate optimal therapy. False positive human immunodeficiency virus (HIV) results are rare in the setting of acute malaria infection and with the introduction of newer fourth-generation immunoassays. The Centers for Disease Control algorithms assist in confirming true HIV infection (Branson et al. 2014).

Granulomatous response to invasive pulmonary aspergillosis in an immunotherapy-naive host, a maladaptive response?

Pulmonary aspergillosis causes a wide spectrum of disease, ranging from asymptomatic airway colonization to severe invasive disease, contingent on the host's immune status and underlying pulmonary anatomy. The invasive form of aspergillosis is a rare occurrence in the immunocompetent population. Nevertheless, patients with a compromised innate immune response are at greatest risk. We present a case of a patient with known Crohn's disease who developed invasive pulmonary aspergillosis. His clinical picture was further complicated by an uncommon immune response characterized by the development of granulomas encasing the Aspergillus forms found on his lung biopsy, likely representing a maladaptive response, possibly related to the effects of his granulomatous disease in the lungs. He was successfully treated with antifungal therapy and video assisted thoracoscopic surgery with placement of thoracostomy tube drainage for a parapneumonic effusion. We will discuss the factors leading to his atypical presentation and clinical outcome.

Trends and Outcomes of Venous Thromboembolism in Hospitalized Patients With Ovarian Cancer: Results From Nationwide Inpatient Sample Database 2003 to 2011.

OBJECTIVE: Venous thromboembolism (VTE) is a major cause of mortality and morbidity in hospitalized patients with malignancy. Nationwide Inpatient Sample database was analyzed to determine the trends in the rate of hospitalization and mortality from VTE in hospitalized ovarian cancer patients and assess its economic impact and resource utilization. METHOD: We queried the 2003 to 2011 Nationwide Inpatient Sample database from Healthcare Cost and Utilization project (Agency of Healthcare Research and Quality) to identify all adults (age ≥18 years) ovarian cancer. Patients hospitalized with VTE as one of the top 3 discharge diagnoses were also identified. Demographic characteristics and in-hospital outcomes of this population were compared with ovarian cancer patients without VTE. Binary logistic regression analysis was used to obtain adjusted odds ratios (ORs). RESULTS: A total of 34,249 (3.5%) of a total of 981,386 hospitalized ovarian cancer patients had an accompanying diagnosis of VTE. Mean age of the study population was 64 years. After adjusting for potential confounders, compared with those without VTE, ovarian cancer patients with VTE had significantly higher inpatient mortality (6.2% vs 4.3%; OR, 1.12 [confidence interval (CI), 1.06-1.17]; P < .001), longer length of stay (5 vs 4 days; OR, 1.40 [CI, 1.36-1.43]; P < .001), higher average cost of hospitalization (US $26,000 vs US $22,000; OR, 1.10 [CI, 1.07-1.13]; P < .001), and greater disability at discharge (OR, 1.34 [CI, 1.31-1.38]; P < .001). Although the annual number of VTE admissions in ovarian cancer patients increased, in-hospital mortality declined from 10.9% in 2003 to 5.3% in 2011. CONCLUSIONS: Venous thromboembolism in hospitalized patients with ovarian cancer is associated with higher inpatient mortality, length of stay, higher cost of hospitalization, and disability at discharge. The hospitalization rate has increased, but the inpatient mortality rate has declined over study period.

Erdheim-Chester disease, moving away from the orphan diseases: A case report.

With approximately 750 cases reported, Erdheim-Chester disease is an exceedingly rare histiocyte cell disorder. Affected sites typically include long bones, large vessels and central nervous system. However, cutaneous and pulmonary involvement can also occur. The diagnosis is ascertained by identification of foamy histiocytes positive for CD68, CD163, and factor XIIIa on immunoperoxidase staining. Recently published literature have described an association between Erdheim-Chester disease and BRAF V600E mutation. This finding prompted the investigation of therapeutic possibilities with BRAF inhibitors, successful agents against other BRAF mutation-positive diseases. Vemurafenib, a BRAF kinase inhibitor, has been shown to be effective in BRAF V600E mutation-positive malignancies, such as NSCLC and melanoma, as well as in several case reports of Erdheim-Chester disease. We report a case of Erdheim-Chester disease diagnosed at our institution, treated with vemurafenib.

Time-to-reporting of blood culture positivity and central venous catheter-associated Candida glabrata fungemia in cancer patients.

Among cancer patients with Candida glabrata (the Candida species with the slowest in-vitro growth) fungemia, time-to-positive blood culture reporting (TTR) was shorter in catheter-associated candidemia (mean±standard deviation: 67±35 h) than in candidemia from other sources (79±31, P<.01). TTR<48 h was 92% specific for catheter-associated C. glabrata fungemia.

Invasive Fusariosis in the Voriconazole Era: Single-Center 13-Year Experience.

Background. Invasive fusariosis remains an aggressive, albeit infrequent infection in immunocompromised patients. Methods. We identified all cases of invasive fusariosis between January 2002 and December 2014. We recorded patient characteristics including clinical presentation, treatment, and outcomes at 6 and 12 weeks after diagnosis, as well as species identification and antifungal drug susceptibilities. Results. Fifteen patients were diagnosed with proven (12, 80%) or probable (3, 20%) fusariosis. Median age was 60 years (range, 26-78), and 10 patients were male. Underlying conditions included hematological malignancies (13, 87%), juvenile idiopathic arthritis (1, 7%), and third-degree burns (1, 7%). Five patients underwent hematopoietic stem-cell transplantation before diagnosis. Six patients (40%) received systemic glucocorticoids, and 11 patients (73%) had prolonged neutropenia at the time of diagnosis. Clinical presentations included the following: skin/soft tissue infection (8, 53%), febrile neutropenia (4, 27%), respiratory tract infection (2, 13%), and septic arthritis (1, 7%). Twelve patients were treated with voriconazole: 6 (40%) with voriconazole alone, 4 (27%) with voriconazole and terbinafine, and 2 (13%) with voriconazole, terbinafine, and amphotericin. One patient (7%) was treated with terbinafine alone, and another with micafungin alone. Four patients underwent surgical debridement (4, 27%). Susceptibility testing was performed on 9 isolates; 8 demonstrated voriconazole minimum inhibitory concentrations ≥4 µg/mL. The cumulative probability of survival was 66.7% and 53.3% at 6 and 12 weeks after diagnosis. Conclusions. Mortality associated with invasive fusariosis remains high. Cumulative mortality at our center was lower than previous reports despite elevated voriconazole minimum inhibitory concentrations. Combination therapy should be studied systematically for fusariosis.