Ganciclovir-induced ataxia and encephalopathy.

BACKGROUND: Ganciclovir can be used to treat a primary cytomegalovirus (CMV) infection, however it can cause side effects. CASE DESCRIPTION: We describe a 60-year-old immunocompromised woman with a primary CMV infection who was treated with ganciclovir. She developed an encephalopathy which resolved after discontinuation of ganciclovir. CONCLUSION: A reversible encephalopathy as a side effect of ganciclovir.

Acute renal haemodynamic effects of glucagon-like peptide-1 receptor agonist exenatide in healthy overweight men.

AIMS: To determine the acute effect of glucagon-like peptide-1 (GLP-1) receptor agonist exenatide and the involvement of nitric oxide (NO) on renal haemodynamics and tubular function, in healthy overweight men. METHODS: Renal haemodynamics and tubular electrolyte handling were measured in 10 healthy overweight men (aged 20-27 years; BMI 26-31 kg/m(2)) during intravenous administration of placebo (saline 0.9%), exenatide, and exenatide combined with the NO-synthase inhibitor L-N(G)-monomethyl arginine (L-NMMA). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance techniques, respectively, based on timed urine sampling. Glomerular hydrostatic pressure and vascular resistance of afferent and efferent renal arterioles were calculated using the Gomez formulae. Urinary electrolytes, osmolality and pH were also measured. RESULTS: GFR increased by a mean of 18 ± 20 (+20%; p = 0.021) and ERPF increased by a median (interquartile range) of 68 (26; 197) ml/min/1.73 m(2) (+14%; p = 0.015) during exenatide infusion versus placebo. During L-NMMA infusion, exenatide increased GFR by mean 8 ± 12 ml/min/1.73 m(2) (+9%; p = 0.049). Exenatide increased estimated glomerular pressure by +6% (p = 0.015) and reduced afferent renal vascular resistance by -33% (p = 0.038), whereas these effects were blunted during L-NMMA infusion. Exenatide increased absolute and fractional sodium excretion, urinary osmolality and urinary pH. The tubular effects of exenatide were not altered by concomitant L-NMMA infusion. CONCLUSIONS: Exenatide infusion in healthy overweight men acutely increases GFR, ERPF and glomerular pressure, probably by reducing afferent renal vascular resistance, and at least partially in an NO-dependent manner. As baseline renal haemodynamics in patients with type 2 diabetes differ from those in healthy individuals, clinical studies on the renal effects of GLP-1 receptor agonists are warranted.

Glucagon-like peptide-1 receptor agonist exenatide has no acute effect on MRI-measured exocrine pancreatic function in patients with type 2 diabetes: a randomized trial.

AIMS: To investigate the effect of infusion of the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide on exocrine pancreatic function. METHODS: This was a randomized, placebo-controlled, double-blind, crossover study in 12 male patients with type 2 diabetes, treated with oral glucose-lowering agents. On two separate occasions, exenatide or placebo (saline 0.9%) were administered intravenously, in randomized order. Exocrine pancreatic function was measured using secretin-enhanced magnetic resonance cholangiopancreatography. The primary outcome measure was defined as secretin-stimulated pancreatic excretion volume. Secondary outcome measures were maximum secretion speed and the time to reach this maximum. In addition, changes in pancreatic duct (PD) diameter were measured. RESULTS: Exenatide did not change secretin-stimulated pancreatic excretion volume, as compared with placebo (mean ± standard error of the mean 142.2 ± 15.6 ml vs 142.6 ± 8.5 ml, respectively; p = 0.590). Also, exenatide did not change the maximum secretion speed (33.1 ± 1.4 vs 36.9 ± 2.2; p = 0.221), nor the time to reach this maximum (both 4 min 30 s). No differences in PD diameter were observed between the two groups. CONCLUSIONS: Infusion of exenatide did not directly influence MRI-measured exocrine pancreatic excretion in patients with type 2 diabetes. Although long-term studies are warranted, these findings suggest that potential adverse pancreatic effects of GLP-1 receptor agonists are not mediated by changes in exocrine pancreatic secretion.

An observational cohort study on geriatric patient profile in an emergency department in the Netherlands.

BACKGROUND: Currently, Dutch emergency care systems focus on rapid emergency department (ED) patient management with short completion times, which may not meet specific geriatric care needs. METHODS: Six-week observational study in patients aged ≥70 years, attending the ED of VU University Medical Center (VUmc, Amsterdam, the Netherlands) during weekday peak presentation times (10 AM - 10 PM). RESULTS: During six weeks, a total of 183 patients aged ≥70 years attended the ED, of which 117 (63.9%) presented during weekday peak hours. One hundred patients with a median age of 81 (min-max; 70-97 years) were prospectively observed. The majority presented with fall-related complaints (30%), multiple comorbidities (≥3 in 50.0%) and polymedication (≥5 in 53.7%). Mean ED length of stay was 175.8 (range 20-399) minutes (n=98). Of the patients discharged to their usual residence prior to the ED visit (n=58), 36.2% returned to our ED within 30 days; one in five of these patients had initially presented with a fall. CONCLUSION: In this study, fall-related injuries were the most frequent presenting complaint during weekday peak presentation times in 70-plus patients. Of these, one in five discharged from the ED returned within 30 days. Our emergency care system may not adequately cover comprehensive ED geriatric assessment, or provide sufficient outpatient care after ED home discharge. We believe that EPs should be more aware of the complex problems encountered in acute geriatric patients and address follow-up care pathways such as geriatric outpatient services, more often in frail elderly patients discharged home.

Women with silicone breast implants and unexplained systemic symptoms: a descriptive cohort study.

BACKGROUND: Since their introduction, the safety of silicone breast implants has been under debate. Although an association with systemic diseases was never established, women continuously blamed implants for their unexplained systemic symptoms. In 2011, a pattern of symptoms caused by systemic reactions to adjuvants (e.g. vaccines, silicone) was identified: 'autoimmune syndrome induced by adjuvants' (ASIA). Our aim was to collect a cohort of women with silicone breast implants and unexplained systemic symptoms to identify a possible pattern and compare this with ASIA. METHODS: Women with silicone breast implants and unexplained systemic symptoms were invited through national media to visit a special outpatient clinic in Amsterdam. All were examined by experienced consultant physicians and interviewed. Chest X-ray and laboratory tests were performed. RESULTS: Between March 2012 and 2013, 80 women were included, of which 75% reported pre-existent allergies. After a symptom-free period of years, a pattern of systemic symptoms developed, which included fatique, neurasthenia, myalgia, arthralgia and morning stiffness in more than 65% of women. All had at least two major ASIA criteria and 79% fulfilled ≥ 3 typical clinical ASIA manifestations. After explantation, 36 out of 52 women experienced a significant reduction of symptoms. CONCLUSIONS: After excluding alternative explanations, a clear pattern of signs and symptoms was recognised. Most women had pre-existent allergies, suggesting that intolerance to silicone or other substances in the implants might cause their symptoms. In 69% of women, explantation of implants reduced symptoms. Therefore, physicians should recognise this pattern and consider referring patients for explantation.

Primary lymphoma of bone: extranodal lymphoma with favourable survival independent of germinal centre, post-germinal centre or indeterminate phenotype.

AIMS: To determine prognostic significance of immunohistochemical markers and investigate possible germinal centre (GC) derivation in primary lymphoma of bone (PLB). METHODS: Immunohistochemical expression of BCL-6, CD10, BCL-2, p53, CD30, CD44 and MUM-1 was studied in 36 patients with PLB. All cases were clinically staged and cases of secondary bone involvement of primary nodal lymphomas were excluded, prior to immunostaining. Clinical charts were reviewed for clinical symptoms and therapy given; survival post-biopsy was calculated. RESULTS: All patients presented with pain and a palpable mass. The majority showed centroblastic-multilobated morphology; half of the cases (19/36) had a GC phenotype (CD10+BCL-6+ or CD10-BCL-6+MUM-1-), whereas 8/36 cases had a non-GC phenotype (CD10-BCL-6- or CD10-BCL-6+MUM-1+). Nine cases were of indeterminate phenotype (CD10-BCL-6+; MUM-1 not available). Eight of 22 evaluated patient samples showed immunoreactivity for MUM-1. Most patients (31/36) received combination therapy in the form of polychemotherapy and radiotherapy. The five-year overall survival was 75%. No significant difference in survival was found between the three different tumour phenotypes, or for the tested antigens individually. Age at presentation and stage of disease had a significant influence on five-year overall survival. Survival rates were 90% for the patients <60 years of age and 40% for those > or =60 years. Survival rates were 90% for stage I and 41% for stage IV. CONCLUSION: This study illustrates the homogeneity of PLB. The majority of cases are of the GC phenotype which has a favourable prognosis.

Imatinib-induced pseudoporphyria.

Imatinib, a synthetic tyrosine kinase inhibitor, is used as first-line therapy for chronic myeloid leukaemia. Imatinib treatment is associated with a variety of adverse effects, most of which are mild to moderate and generally abate after the first months of treatment. Cutaneous adverse reactions are often encountered in patients using imatinib. Pseudoporphyria is regularly associated with the use of medication, especially naproxen and other nonsteroidal anti-inflammatory drugs, but the list of culprits is expanding. We present a patient with imatinib-induced pseudoporphyria. Taking into account the rapidly growing use of imatinib, physicians should be aware of the possibility of imatinib-induced pseudoporphyria. Adequate photoprotection can improve treatment compliance.

A case of cocaine-induced panhypopituitarism with human neutrophil elastase-specific anti-neutrophil cytoplasmic antibodies.

OBJECTIVE: To describe a patient with cocaine-induced panhypopituitarism associated with human neutrophil elastase-anti-neutrophil cytoplasmic antibodies (HNE-ANCA). CASE: A 41-year-old man presented with extreme fatigue, cold intolerance and anorexia with 20 kg weight loss in the last 6 months. His medical history was unremarkable. He snorted cocaine twice a week during the last 6 years. On examination, we saw a pale and skinny man, with a normal blood pressure. Because of the severity of symptoms central hypothyroidism was suspected and very low values of TSH, free thyroxine and free triiodothyronine were measured. His FSH, LH, ACTH, cortisol, prolactin and testosterone levels were also low. Magnetic resonance imaging and computed tomography scan showed a normal-sized pituitary gland entirely embedded in a dense, oedematous, contrast-enhancing mass, and a total destruction of the nasal septum with the absence of conchae and severely impaired sinus walls. A transnasal biopsy showed an acute necrotising, non-specific and non-granulomatous inflammation. Although cocaine-induced panhypopituitarism was suspected, Wegener's granulomatosis could not be excluded. Serology on ANCA showed a strongly positive C-ANCA titre (320 U/l) with specificity for HNE. A cocaine-induced HNE-ANCA-associated panhypopituitarism was diagnosed. Our patient was advised to quit using cocaine immediately and was initially treated with glucocorticoids and testosterone, followed by thyroxine. This led to a dramatic clinical response with an increase of appetite, weight gain and regained energy. After 2 years, the patient is well and his ANCA titre is no longer positive. CONCLUSION: We describe the first documented case of cocaine-induced panhypopituitarism associated with HNE-specific ANCA.

Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis.

BACKGROUND: Post-thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). OBJECTIVES: To determine the risk of PTS after DVT and to assess risk factors for PTS. METHODS: Patients were recruited from the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Consecutive patients who suffered a first DVT of the leg were included in a follow-up study. All patients completed a questionnaire and DNA was obtained. PTS was ascertained in a structured interview using a clinical classification score. RESULTS: The 1-year cumulative incidence of PTS was 25% and 7% for severe PTS. Elastic compression stockings were prescribed in 1412 (85%) patients. The majority used their stockings every day. Women were at an increased risk compared with men [risk ratio (RR) 1.5, 95% confidence interval (CI) 1.3-1.8]. Similarly, obese patients had a 1.5-fold increased risk of PTS compared with normal weight patients (RR 1.5, 95% CI 1.2-1.9), with a 1-year cumulative incidence of 34% compared with 22%. Patients who already had varicose veins had an increased risk (RR 1.5, 95% CI 1.2-1.8) of PTS. DVT in the femoral and iliac vein was associated with a 1.3-fold increased risk of PTS compared with popliteal vein thrombosis (RR 1.3, 95% CI 1.1-1.6). Patients over 60 years were less likely to develop PTS than patients below the age of 30 (RR 0.6, 95% CI 0.4-0.9). Malignancy, surgery, minor injury, plaster cast, pregnancy or hormone use did not influence the risk of PTS neither did factor (F)V Leiden nor the prothrombin 20210A mutation. CONCLUSIONS: PTS is a frequent complication of DVT, despite the widespread use of elastic compression stockings. Women, obese patients, patients with proximal DVT and those with varicose veins have an increased risk of PTS, whereas the elderly appeared to have a decreased risk.

High D-dimer levels increase the likelihood of pulmonary embolism.

Objective. To determine the utility of high quantitative D-dimer levels in the diagnosis of pulmonary embolism. Methods. D-dimer testing was performed in consecutive patients with suspected pulmonary embolism. We included patients with suspected pulmonary embolism with a high risk for venous thromboembolism, i.e. hospitalized patients, patients older than 80 years, with malignancy or previous surgery. Presence of pulmonary embolism was based on a diagnostic management strategy using a clinical decision rule (CDR), D-dimer testing and computed tomography. Results. A total of 1515 patients were included with an overall pulmonary embolism prevalence of 21%. The pulmonary embolism prevalence was strongly associated with the height of the D-dimer level, and increased fourfold with D-dimer levels greater than 4000 ng mL(-1) compared to levels between 500 and 1000 ng mL(-1). Patients with D-dimer levels higher than 2000 ng mL(-1) and an unlikely CDR had a pulmonary embolism prevalence of 36%. This prevalence is comparable to the pulmonary embolism likely CDR group. When D-dimer levels were above 4000 ng mL(-1), the observed pulmonary embolism prevalence was very high, independent of CDR score. Conclusion. Strongly elevated D-dimer levels substantially increase the likelihood of pulmonary embolism. Whether this should translate into more intensive diagnostic and therapeutic measures in patients with high D-dimer levels irrespective of CDR remains to be studied.

High D-dimer level is associated with increased 15-d and 3 months mortality through a more central localization of pulmonary emboli and serious comorbidity.

High D-dimer levels are predictors of death in patients with pulmonary embolism (PE), as are more proximally located, larger emboli. The direct link between these three has not yet been described. A cohort of 674 consecutive patients with confirmed PE was studied. Patients were followed up for 3 months. D-dimer levels were measured only in patients with an unlikely clinical probability (n = 262). The odds ratio (OR) for death of all variables was calculated. Multivariate analysis was performed to identify independent risk factors for mortality. The best predictive D-dimer cut-off point for mortality was a concentration >3000 ng/ml FEU (OR 7.29). High D-dimer levels were correlated with active malignancy and age over 65 years, both being indicators of 3-month mortality. High D-dimer levels were also correlated with centrally located pulmonary emboli and 15-d mortality. The combination of high D-dimer levels and central emboli increased early mortality risk by 2.2. High D-dimer levels in patients with an unlikely clinical probability were associated with fatal outcome after PE. Centrally located pulmonary emboli were associated with higher D-dimer levels and worse 15-d mortality. Active malignancy, being an inpatient at time of diagnosis and age over 65 years were associated with higher D-dimer levels and worse 3-month survival.

Vaccination responses and lymphocyte subsets after autologous stem cell transplantation.

Twenty autologous stem cell transplant recipients were vaccinated with three doses of Diphtheria-Tetanus-Poliomyelitis vaccine and conjugated Haemophilus influenzae type b (Hib) vaccine. Pneumococcal vaccination consisted of two doses of conjugated vaccine followed by a single dose of polysaccharide vaccine, at 6, 8 and 14 months after transplantation, respectively. Mean anti-tetanus, anti-Hib and anti-pneumococcal IgG antibodies significantly increased after each vaccination. Response rates after the full vaccination schedule were 94%, 78% and 61% for Hib, conjugated 7-valent pneumococcal vaccine and non-conjugated 23-valent pneumococcal vaccine, respectively. Three months after transplantation, CD16(+)CD56(+) NK cells were in the normal range and remained so. The total number of T lymphocytes at 3 months was and remained in the normal range. The mean CD4/CD8 ratio was 0.43 at 3 months post aSCT and, while gradually increasing, remained subnormal. The mean number of CD19(+) B lymphocytes significantly increased during the study period. Patients with CD19 counts <0.10 x 10(9)L(-1) required at least two Hib vaccinations to show a response, while the majority of patients with CD19 counts > or = 0.20 x 10(9)L(-1) showed a response to Hib after one vaccination only. Thus, a minimum threshold level of CD19(+) cells appears to be required for adequate responses to vaccination.

Extreme leucocytosis: not always leukaemia.

Three patients were analysed for an extreme leucocytosis (>50x10(9)/l) because leukaemia was suspected. In all three patients the leucocytosis proved to be caused by a leukaemoid reaction. This reaction was associated with a hepatic angiosarcoma in the first patient, with a Salmonella infection in the second patient and with a necrotic leg abscess in the third patient. Retrospectively, 25 patients with a leukaemoid reaction were identified in our hospital during a four-year period. Besides leukaemia, a leukaemoid reaction, which often has a dismal prognosis, should be considered in patients with an extreme leucocytosis.

Blue rubber bleb nevus syndrome co-existing with celiac disease.

BACKGROUND: Anaemia caused by iron deficiency is one of the most common disorders in the world. We describe a patient with iron deficiency anaemia in whom absorption was limited due to celiac disease, superimposed to chronic blood loss due to the blue rubber bleb nevus syndrome, a rare syndrome characterised by multiple cutaneous venous malformations in association with visceral lesions. CASE REPORT: A 54-year-old patient with severe iron deficiency anaemia showed marked rubbery cutaneous lesions on the body surface, extremities, under and on the left side of the tongue as well as in the stomach and duodenum. The appearance and pathological examination of the lesions were consistent with the diagnosis of blue rubber bleb nevus syndrome (BRBNS). Biopsy of the mucosa of the duodenum showed celiac disease. No association between celiac disease and BRBNS has been previously described. CONCLUSION: Combined loss of iron and malabsorption from the gastrointestinal tract can lead to severe iron deficiency. Early recognition of both diseases can result in early treatment. Patients can recover completely with iron suppletion and a gluten-free diet. Recognising typical BRBNS skin lesions would provide a potential diagnosis and could prevent unnecessary procedures or invasive surgery.

[The value of integrated PET-CT images in 2 lymphoma patients with skeletal localisations]. / De waarde van gefuseerde PET-CT-beelden bij 2 lymfoompatiënten met skeletlokalisaties.

In two women with Hodgkin's disease, 36 and 34 years of age, the PET-scan showed increased FDG-uptake in regions where the CT-scan did not reveal any abnormalities. Integration of the PET-CT images visualised bone marrow localisations in both patients. One patient underwent a CT-guided bone biopsy that confirmed this localisation. In both cases, the results of the integrated PET-CT images altered the therapy that would have been given on the basis ofthe standard staging technique. Both patients underwent radiotherapy. After 6 months, one patient had no visible lesions. The other patient died due to progression ofthe disease. Integrated PET-CT images can play an important role, not only in the precise classification and staging of lymphoma but also at the start of therapy, as an initial scan, in the evaluation of the response to treatment, and in the early detection of recurrence.

Short intensive sequential therapy followed by autologous stem cell transplantation in adult Burkitt, Burkitt-like and lymphoblastic lymphoma.

The feasibility and efficacy of up-front high-dose sequential chemotherapy followed by autologous stem cell transplantation (ASCT) in previously untreated adults (median age 33 years; range 15-64) with Burkitt lymphoma (BL), Burkitt-like lymphoma (BLL) or lymphoblastic lymphoma (LyLy), both without central nervous system or extensive bone marrow involvement was investigated in a multicenter phase II study. Treatment consisted of two sequential high-dose chemotherapy induction courses incorporating prednisone, cyclophosphamide, doxorubicin, etoposide and mitoxantrone, without high-dose methotrexate or high-dose cytarabine. Patients with at least PR went on with BEAM and ASCT. Protocol treatment was completed by 23/27 (85%) BL/BLL and 13/15 (87%) LyLy patients. Median treatment duration until BEAM was 70 (range: 50-116) days. No toxic deaths occurred. Response to treatment was complete response (CR) 81% and partial response (PR) 11% for BL/BLL, CR 73% and PR 20% for LyLy. At a median follow-up of 61 months of patients still alive, six BL/BLL and eight LyLy patients have died. The actuarial 5-year overall and event-free survival estimates are 81 and 73% for BL/BLL vs 46 and 40% for LyLy patients. In conclusion, this short up-front high-dose sequential chemotherapy regimen, followed by ASCT is highly effective in adults with BL/BLL with limited bone marrow involvement, but less so in patients with LyLy.

Chronic lymphocytic leukemia cells display p53-dependent drug-induced Puma upregulation.

We investigated the apoptosis gene expression profile of chronic lymphocytic leukemia (CLL) cells in relation to (1) normal peripheral and tonsillar B-cell subsets, (2) IgV(H) mutation status, and (3) effects of cytotoxic drugs. In accord with their noncycling, antiapoptotic status in vivo, CLL cells displayed high constitutive expression of Bcl-2 and Flip mRNA, while Survivin, Bid and Bik were absent. Paradoxically, along with these antiapoptotic genes CLL cells had high-level expression of proapoptotic BH3-only proteins Bmf and Noxa. Treatment of CLL cells with fludarabine induced only the proapoptotic genes Bax and Puma in a p53-dependent manner. Interestingly, the degree of Puma induction was more pronounced in cells with mutated IgVH genes. Thus, disturbed apoptosis in CLL is the net result of both protective and sensitizing aberrations. This delicate balance can be tipped via induction of Puma in a p53-dependent matter, the level of which may vary between groups of patients with a different tendency for disease progression.

Lack of prognostic significance of BCL2 and p53 protein overexpression in elderly patients with diffuse large B-cell non-Hodgkin's lymphoma: results from a population-based non-Hodgkin's lymphoma registry.

The prognostic significance of age was studied in 372 patients with diffuse large B-cell non-Hodgkin's lymphoma, in relation to the prognostic factors of overexpressed BCL2 and p53 oncoprotein. Overexpression of BCL2 and p53 oncoprotein was defined when more than 50% of the tumor cells showed positive staining. The data were analyzed with respect to the age groups < 65 and > or = 65 years of age. There was a trend for BCL2 overexpression to occur significantly more often among patients older than 65 years of age (P = 0.065). Patients with BCL2 overexpression showed significantly inferior disease free survival rate, but only for patients younger than 65 years (log-rank test P = 0.0002), and the overexpression showed also an independent prognostic significance (P < 0.001). With respect to overexpressed p53 a significant difference was reached for complete remission rate (P = 0.01) and 5-year survival rate (log-rank test P = 0.04), again only for the younger age group. When the analyses were repeated for the older patients who had been treated adequately, the same lack of significance was found, both for BCL2 and p53. This study demonstrates that the negative prognostic value of overexpressed BCL2 and p53 protein is not of concern for patients older than 65 years of age. Among elderly patients the International Prognostic Index score seems the predominant risk factor for inferior prognosis.

Efficacy and safety of oral fludarabine phosphate in previously untreated patients with chronic lymphocytic leukemia.

PURPOSE: A prospective, multicenter, open-label, phase II clinical trial to assess oral fludarabine phosphate treatment in terms of safety, efficacy, and quality of life. Reference to a historical group of patients treated with the intravenous (IV) formulation allowed the two formulations to be compared. PATIENTS AND METHODS: Patients with previously untreated B-cell chronic lymphocytic leukemia received 10-mg tablets of fludarabine phosphate to a dose of 40 mg/m(2)/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles. Efficacy was assessed using International Workshop on Chronic Lymphocytic Leukemia and National Cancer Institute criteria for response. Safety monitoring included WHO toxicity grading for adverse events. Quality of life was also assessed. RESULTS: Eighty-one patients received treatment. According to International Workshop on Chronic Lymphocytic Leukemia criteria, the overall response rate was 71.6% (complete remission, 37.0%; partial remission, 34.6%). The response rate using National Cancer Institute criteria was 80.2% (complete remission, 12.3%; partial remission, 67.9%). Median time to progression was 841 days (range, 28 to 1,146 days). The most frequently reported grade 3/4 toxicity was myelosuppression. WHO grade 3/4 hematological toxicities included granulocytopenia (32.1%), anemia (9.9%), and thrombocytopenia (4.9%). Gastrointestinal toxicity was more common with the oral formulation than with IV fludarabine phosphate, but was generally mild to moderate and did not require treatment. Statistically significant improvements in mean emotional and insomnia quality-of-life scores were seen after treatment. CONCLUSION: This study demonstrates that oral fludarabine phosphate is clinically effective and generally well tolerated by patients with previously untreated B-cell chronic lymphocytic leukemia. Oral fludarabine phosphate has a similar clinical efficacy and safety profile to the IV formulation. Oral fludarabine phosphate does not adversely affect quality of life and may improve emotional and insomnia scores.