Pseudohyperkalemia in chronic lymphocytic leukemia: Prevalence, impact, and management challenges.

The term pseudohyperkalemia refers to a false elevation in serum potassium levels due to potassium release from cells in vitro. Falsely elevated potassium levels have been reported in patients with thrombocytosis, leukocytosis, and hematologic malignancies. This phenomenon has been particularly described in chronic lymphocytic leukemia (CLL). Leukocyte fragility, extremely high leukocyte counts, mechanical stress, higher cell membrane permeability related to an interaction with lithium heparin in plasma blood samples, and metabolite depletion due to a high leukocyte burden have been reported to contribute to pseudohyperkalemia in CLL. The prevalence of pseudohyperkalemia is up to 40%, particularly in the presence of a high leukocyte count (>50 × 109/L). The diagnosis of pseudohyperkalemia is often overlooked, which may result in unnecessary and potentially harmful treatment. The use of whole blood testing and point-of-care blood gas analysis, along with thorough clinical evaluation, may help differentiate between true and pseudohyperkalemic episodes.

Risk of Hematologic Malignancies in Elderly Patients With Ankylosing Spondylitis: A Cohort Study and Systematic Review.

OBJECTIVE: To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS). PATIENTS AND METHODS: We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015. RESULTS: We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS. CONCLUSION: The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.

Validation of a modified pre-lysis sample preparation technique for flow cytometric minimal residual disease assessment in multiple myeloma, chronic lymphocytic leukemia, and B-non Hodgkin lymphoma.

BACKGROUND: Minimal residual disease (MRD) assessment of hematopoietic neoplasia below 10-4 requires more leukocytes than is usually attainable by post-lysis preparation. However, not all laboratories are resourced for consensus Euroflow pre-lysis methodology. Our study aim was to validate a modified pre-lysis protocol against our standard post-lysis method for MRD detection of multiple myeloma (MM), chronic lymphocytic leukemia (CLL), and B-non Hodgkin lymphoma (B-NHL), to meet demand for deeper MRD assessment by flow cytometry. METHOD: Clinical samples for MRD assessment of MM, CLL, and B-NHL (50, 30, and 30 cases, respectively) were prepared in parallel by pre and post-lysis methods for the initial validation. Total leukocytes, MRD, and median fluorescence intensity of antigen expression were compared as measures of sensitivity and antigen stability. Lymphocyte and granulocyte composition were compared, assessing relative sample processing stability. Sensitivity of the pre-lysis assay was monitored post validation for a further 18 months. RESULTS: Pre-lysis achieved at least 10-4 sensitivity in 85% MM, 81% CLL, and 90% B-NHL samples versus 24%, 48%, and 26% by post-lysis, respectively, with stable antigen expression and leukocyte composition. Post validation over 18 months with technical expertise improving, pre-lysis permitted 10-5 MRD assessment in 69%, 86%, and 82% of the respective patient groups. CONCLUSION: This modified pre-lysis procedure provides a sensitive, robust, time efficient, and relatively cost-effective alternative for MRD testing by MFC at 10-5 , facilitating clinically meaningful deeper response assessment for MM, CLL, and B-NHL. This method adaptation may facilitate more widespread adoption of highly sensitive flow cytometry-based MRD assessment.

Incidence and management of toxicity associated with ibrutinib and idelalisib: a practical approach.

The use of novel B-cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B-cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinemia. Ibrutinib, the first-in-class inhibitor of Bruton tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ, have recently been approved for the treatment of several indolent B-cell malignancies. These drugs are especially being used for previously unmet needs, i.e., for patients with relapsed or refractory disease, high-risk cytogenetic or molecular abnormalities, or with comorbidities. Treatment with ibrutinib and idelalisib is generally well tolerated, even by elderly patients. However, the use of these drugs may come with toxicities that are distinct from the side effects of immunochemotherapy. In this review we discuss the most commonly reported and/or most clinically relevant adverse events associated with these B-cell receptor inhibitors, with special emphasis on recommendations for their management.

Prevalence, characteristics and management of occult hepatitis B virus infection in patients with chronic lymphocytic leukemia: a single center experience.

Several reports have emphasized the risk of hepatitis B virus (HBV) reactivation in patients with lymphoproliferative disorders undergoing cytotoxic treatment. To determine the prevalence of occult B infection (OBI) in a population with chronic lymphocytic leukemia (CLL) and management with universal prophylaxis (UP) in all patients undergoing chemoimmunotherapy or targeted prophylaxis (TP) in patients experiencing seroreversion during therapy, we analyzed 397 patients with CLL from our database. The prevalence of OBI in our patients with CLL was 8.6% (34 patients). When comparing patients with OBI/CLL with those with CLL, we did not find any statistical difference among clinical-biological parameters and time dependent endpoints except for a lower peripheral blood lymphocyte count in the OBI/CLL group (p = 0.036). From 2000 to 2010 careful follow-up and TP were adopted; two out of 10 patients (20%) showed seroreversion. From June 2010 we adopted UP during and 12 months after immunosuppressive treatment in all patients with CLL with OBI; no evidence of seroreversion was detected.

Epidemiology and management of infectious complications of contemporary management of chronic leukemias.

This is a review of the epidemiology and management of infectious complications of contemporary management of chronic leukemias. Patients with chronic leukemias typically are affected by nuisance infections due to the underlying hematologic condition, particularly hypogammaglobulinemia in CLL patients. With active treatment, particularly those agents that cause defects in cell-mediated immunity, the incidence of opportunistic infections increases although endogenous bacterial, mycobacterial, and fungal infections also occur. Exogenous treatment with immunoglobulin and antimicrobial prophylaxis, particularly anti-Pneumocystis prophylaxis, may be indicated in select patients. Routine vaccinations should be maintained in these patients and vaccination early in the course of treatment may result in improve protection.

Patients' experience of chronic lymphocytic leukaemia: baseline health-related quality of life results from the LRF CLL4 trial.

We examined the effects of active untreated chronic lymphocytic leukaemia (CLL) on health-related quality of life (HRQoL), measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) at randomisation into the Leukaemia Research Fund CLL4 trial. Patients were scored 0-100 within each of 15 domains. A difference between groups of > or = 10 points was deemed clinically significant (asterisked * below). 431 valid baseline questionnaires were returned. Compared with population norms, patients had impaired HRQoL in 13/15 domains. The greatest differences were in fatigue*, sleep disturbance*, role functioning and global HRQoL. Fatigue was reported by 81% of patients, compared with the next most common symptoms: sleep disturbance (56%) and dyspnoea (49%). There was no association between spleen, liver or lymph node enlargement, or lymphocytosis and any HRQoL domain. Older age (> or =70 years) was associated with poorer physical functioning (P < 0.001) but fewer financial difficulties (P < 0.001*). Impairment of HRQoL at baseline was most apparent in stage A-progressive patients with B-symptoms and stage C patients with haemoglobin <120 g/l: compared with all others, these patients had poorer physical, role and social functioning, more fatigue and dyspnoea and poorer global HRQoL (all P < or = 0.001*). These findings support the recommendation to begin treatment when patients experience symptomatic disease, to improve HRQoL.

Caring for patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed form of leukemia in the Western world, accounting for approximately 20%-30% of all cases of leukemia. Despite recent medical and scientific advances, the literature on the subjective experience and nursing care of patients diagnosed with CLL remains scarce and sporadic. This article provides a brief overview on the pathophysiology, clinical characteristics, and treatment options of CLL with focus placed on implications for nursing care. Fatigue, the most common symptom reported by patients, and infection, the leading cause of disease-related deaths, also will be addressed. Emerging data examining quality of life and the incidence of anxiety and depression in this patient population will be reviewed, and strategies aimed at addressing the educational needs of patients and family members will be discussed.

Randomized trial of intravenous immunoglobulin prophylaxis for patients with chronic lymphocytic leukaemia and secondary hypogammaglobulinaemia.

Forty-two patients with chronic lymphocytic leukaemia (CLL), serum IgG levels < 5.5 milligrams and a history of two or more recent infections, were randomized to receive infusions of 18 g human intravenous immunoglobulin (IVIg) or human albumin placebo every three weeks. During the 12 month study 122 infections were documented but only four were associated with neutropenia. Ten patients (24%) with IgG levels < 3.0 milligrams experienced 65% of the infections. In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections. If three further infections occurred, placebo patients were commenced on 18 g IVIg, and IVIg patients were increased to 24 g IVIg. Approximately 50% of these cases subsequently remained infection free. The study shows the usefulness of prophylactic Sandoglobulin in CLL patients with hypogammaglobulinaemia, and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams.

Cost effectiveness of prophylactic intravenous immune globulin in chronic lymphocytic leukemia.

BACKGROUND: A recent randomized controlled trial of intravenous immune globulin in patients with chronic lymphocytic leukemia and hypogammaglobulinemia demonstrated a statistically significant reduction in the rate of bacterial infections among patients who received intravenous immune globulin. We used decision-analysis techniques to determine whether prophylactic intravenous immune globulin is likely to result in an overall clinical benefit to patients who receive this treatment and to examine its cost effectiveness. METHODS: We constructed a model to compare two strategies: treatment with intravenous immune globulin at a dose of 400 mg per kilogram of body weight every three weeks and no immune globulin therapy. Baseline estimates of the efficacy of intravenous immune globulin were derived from the published results of the randomized trial. The costs of treatment, complications, and infections were estimated on the basis of component costs. Health outcomes were measured in terms of gains in quality-adjusted life expectancy. RESULTS: Intravenous immune globulin therapy can result in a loss of quality-adjusted life expectancy when the inconvenience of treatment is taken into account. If the inconvenience of treatment is not considered, therapy results in a gain of 0.8 quality-adjusted days per patient per year of therapy at a cost of $6 million per quality-adjusted life-year gained. CONCLUSIONS: Decision-analysis modeling may be applied to the results of randomized controlled trials to assess the potential clinical and financial effects of adopting the intervention in medical practice. In the case of intravenous immune globulin therapy in patients with chronic lymphocytic leukemia and hypogammaglobulinemia, this type of analysis suggests that treatment might not result in improved quality or length of life and that it is extraordinarily expensive in comparison with other treatments generally accepted as cost effective.