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Background/Introduction: Few data is currently available on neutropenia and agranulocytosis related to drug intake. Aim: We report here data on 203 patients with established idiosyncratic drug-induced agranulocytosis, followed up in a referral centre within a university hospital. Design: Data from 203 patients with idiosyncratic drug-induced agranulocytosis were retrospectively reviewed. Methods: All cases were extracted from a cohort study on agranulocytosis in the Strasbourg University Hospital (Strasbourg, France). Results: The mean age was 61.6 years old (range: 18-95), the gender ratio (F/M) was 1.3. Several comorbidities were present in 63.5%. The most frequent causative drugs were: antibiotics (49.3%), especially b-lactams and cotrimoxazole; antithyroid drugs (16.7%); neuroleptic and anti-epileptic agents (11.8%); antiviral agents (7.9%); and platelet aggregation inhibitors as ticlopidine and acid acetylsalicylic (6.9%). The main primary clinical manifestations during hospitalization included: isolated fever (26.3%); septicaemia (13.9%); documented pneumonia (13.4%); sore throat and acute tonsillitis (9.3%); and septic shock (6.7%). The mean neutrophil count at nadir was 0.148 × 109/L (range: 0-0.48). All febrile patients were treated with broad-spectrum antibiotics and 107 (52.7%) with hematopoietic growth factors. The mean duration of haematological recovery (neutrophil count ⩾1.5 × 109/L) was 7.8 (range: 2-20). This mean duration was reduced to 2.1 days (range: 2-16) (p=0.057) with hematopoietic growth factors. Outcome was favourable in 91.6% of patients; seventeen died. Thirty-seven patients (18.2%) required intensive care. Discussion/Conclusion: The present study demonstrated that idiosyncratic drug-induced agranulocytosis is a relative rare events; that antibiotics, antithyroid, neuroleptic and anti-epileptic agents, and platelet aggregation inhibitors are the main incriminated drug classes; that agranulocytosis typically serious, with at least 50% exhibiting severe sepsis and a mortality rate <10%; and that modern management of such disorder may reduce the infection-related mortality. [ABSTRACT FROM AUTHOR]

Background: In a phase 3 study, the authors assessed the effects of dasatinib at doses of 140 mg once daily and 70 mg twice daily in patients who had either chronic myeloid leukemia (CML) in advanced phases or Philadelphia chromosome-positive acute lymphoblastic leukemia and were resistant or intolerant to imatinib. In the current report, the results for patients with CML in blast phase after 2 years of follow-up are reported.Methods: Patients were stratified according to whether they had CML in myeloid blast phase (MBP-CML) or in lymphoid blast phase (LBP-CML) and were randomized (1:1) within each stratum to receive either oral dasatinib 140 mg once daily or 70 mg twice daily.Results: In patients with MBP-CML, the major hematologic response rate was 28% for both regimens; and, in patients with LBP-CML, the major hematologic response rate was 42% for once-daily dasatinib and 32% for twice-daily dasatinib. The major cytogenetic response rates were 25% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective rates in patients with LBP-CML were 50% and 40%. The overall survival rate at 24 months was 24% for once-daily dasatinib and 28% for twice-daily dasatinib in patients with MBP-CML, and the respective values in patients with LBP-CML were 21% and 16%. Adverse events indicated a trend toward improved tolerability for the once-daily regimen.Conclusions: The current results suggested that dasatinib 140 mg once daily had similar efficacy and improved tolerability relative to the 70-mg twice-daily regimen in patients with imatinib-resistant, blast phase CML. [ABSTRACT FROM AUTHOR]

Vitamin B12 or cobalamin deficiency occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%-20% of all cases), insufficient dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency. [ABSTRACT FROM AUTHOR]

Agranulocytosis is a life-threatening disorder in any age, but particularly so in elderly patients who are receiving, on average, a larger number of drugs than younger patients. Drug-induced agranulocytosis still remains a rare event, with an annual incidence rate of approximately 3-12 cases per million population. This disorder frequently occurs as an adverse reaction to drugs, particularly antibacterials, antiplatelet agents, antithyroid drugs, antipsychotics or antiepileptic drugs, and NSAIDs. Although patients experiencing drug-induced agranulocytosis may initially be asymptomatic, the severity of the neutropenia usually translates into the onset of severe sepsis that requires intravenous broad-spectrum antibacterial therapy. In this setting, haematopoietic growth factors have been shown to shorten the duration of neutropenia. Thus, with appropriate management, the mortality rate of idiosyncratic drug-induced agranulocytosis is now 5-10%. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To review the influence of age on the response of patients with idiopathic thrombocytopenic purpura (ITP) to corticosteroids, splenectomy and danazol. METHODS: We retrospectively reviewed a cohort of 139 consecutively treated patients with ITP diagnosed between 1985 and 1994. In particular, we analysed the therapies used, their response rates, prognostic indicators of response and adverse effects. Furthermore, we compared the efficacy and tolerability of the various therapies between younger and older patients (<60 and > or =60 years old). RESULTS: Corticosteroids were used as first-line treatment in 118 patients with an initial response rate of 83%. Age did not affect the outcome of corticosteroid therapy, but all the patients aged > or =60 years reported adverse effects. A splenectomy was performed in 55 patients with an initial response rate of 87%. Older patients had significantly poorer outcomes from splenectomy with higher postoperative morbidity. Finally, danazol was given in 33 patients with a favourable response in 72% of cases. Compared with younger patients, older patients had a significantly better outcome with danazol. CONCLUSIONS: Age may have significant effects on the response to and adverse effects of therapy in ITP, and this should be considered when choosing the treatment modality for the elderly. [ABSTRACT FROM AUTHOR]

Cytarabine ocfosfate (YNK01) is a prodrug analogue of cytarabine which is resistant to systemic deamination after oral administration. Following initial studies indicating significant anti-tumour activity of YNK01 a phase II trial was initiated in order to assess the tolerability and efficacy of a combination of this agent with interferon alpha-2b (IFN-alpha2b) in recently diagnosed chronic phase CML patients (n = 98). The treatment was subdivided into cycles consisting of 4 weeks of continuous administration of IFN-alpha-2b (3 MU/m(2)/day 1st week and then 5 MU/m(2)/day) and 14 days of oral YNK01 (600 mg/day 1st cycle). At the end of each cycle the dose of YNK01 was adjusted according to the blood count observed during the previous 4 weeks. The median time from diagnosis to inclusion in the trial was 2 months (range 6 days to 7.5 months). At 12 weeks, 62 patients (63%; 95% CI, 54-73) achieved a complete hematological response. At 24 weeks, of 98 patients, two achieved a complete cytogenetic response, 14 a partial response (16% major cytogenetic response rate; 95% CI, 9-24) and 34 a minor response; 19 patients were not evaluable for cytogenetic response. During the trial, 20 patients progressed to accelerated (6) or blastic phases (14). The median time to progression was 15 months (range 2-38 months). At 3 years the overall survival was 79% (95% CI, 70-88). Although the complete hematological response rate compared favorably with the 40% response rate previously obtained with the subcutaneous formulation of Ara-c, the cytogenetic response rate was less than expected. Most of the patients experienced side-effects and all permanently stopped YNK01. Although the combination seems attractive the initial dose of 600 mg per day is probably too high and should be reconsidered in further trials. [ABSTRACT FROM AUTHOR]

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Introduction Peu de données sont actuellement disponibles dans la littérature sur la neutropénie et l’agranulocytose du sujet âgé. À notre connaissance, il n’existe pas de données factuelles sur les agranulocytoses médicamenteuses idiosyncratiques dans cette population. Nous décrivons ici le tableau clinique et le devenir des sujets âgés présentant un tel accident hématologique. Patients et méthodes Les données de 61 patients âgés de 75 ans ou plus, avec une agranulocytose idiosyncratique induite par un médicament, ont été rétrospectivement revues. Tous les cas ont été extraits d’une banque de données sur les agranulocytoses médicamenteuses ( n = 203), hospitalisées aux hôpitaux universitaires de Strasbourg. Cette banque inclus toutes les observations de neutropénies sévères (neutrophiles ≤ 0,5 × 109/L) et aiguës répondant aux critères de Bénichou (Rev Franç d’Hématol 1976) depuis janvier 1984 à ce jour. Résultats L’âge moyen des patients était 84,9 ans (extrêmes : 75–95), le rapport F/M de 2,4. Des affections sous-jacentes étaient présentes dans 74 %. Les médicaments responsables les plus fréquents d’agranulocytose étaient : les antibiotiques (43,8 %), les antithyroïdiens (15,8 %), les neuroleptiques et les antiépileptiques (12,3 %), et des antiagrégants plaquettaires (10,5 %). Le tableau clinique pendant l’hospitalisation consistait en : une fièvre isolée (27,6 %), une septicémie ou un choc septique (24,1 %), et une pneumonie (20,7 %). Le nombre moyen de neutrophiles était au nadir de 0,15 × 109/L (extrêmes : 0–0,4). Tous les patients fébriles ont été traités avec des antibiotiques à large spectre et 36 avec des facteurs de croissance hématopoïétiques (FCH). L’évolution a été favorable dans 85,3 % des patients. Neuf décès ont néanmoins étaient enregistrés. Toutefois, seul 2 patients âgés (3,3 %) sont décédés d’un choc septique non contrôlé, en rapport directement avec la profondeur de la neutropénie. Une comparaison de la mortalité entre les patients de < 75 ans (gr 1) ( n = 142), ≥ 75 ans (gr 2) ( n = 62) et ≥ 85 ans (gr 3) ( n = 19) a révélé une différence significative sur le plan statistique avec respectivement une mortalité de : 4,2 % ( n = 6), 14,8 % ( n = 9), et 23,1 % ( n = 4) ( p < 0,05). À noter que les 3 décès survenus dans le gr 3 étaient en rapport avec une comorbidité sous-jacente. Conclusion À notre connaissance, cette étude est la première consacrée aux sujets âgés de plus de 75 ans. Elle documente le fait que 30 % des agranulocytoses médicamentes concernent des sujets âgés fragiles. Dans cette population, les médicaments les plus souvent incriminés sont comme classiquement décrit chez l’adulte : les antibiotiques, les antithyroïdiens, les neuroleptiques, les antiépileptiques et les antiagrégants plaquettaires. Le tableau clinique est souvent sévère (moitié d’infections profondes ou généralisées et de chocs septiques) avec une mortalité proche de 15 %. Toutefois, la prise en charge optimale de cet accident (hospitalisation, antibiothérapie, FCH) permet de réduire la mortalité liée à l’infection (3,3 %). [ABSTRACT FROM AUTHOR]

Examines the treatment with fludarabine in a patient with Waldenström's macroglobulinemia (WM). Benefits of the purine analogs for the patient; Characteristics of WM; Results of the study.

Abstract: Purpose: The aim of this study is to report personal experience of pancytopenia related to low-dose methotrexate and to review the literature. Methods: We included retrospectively all cases of pancytopenia related to low-dose methotrexate (<25 mg/week), followed between January 1997 and December 2006, in the university hospital of Strasbourg, France. Results: Five women, mean age 75.6 years, were included in the present study. Clinical manifestations included: symptomatic anemia (n =4), infection (n =3) and hemorrhagic manifestations (n =2); one patient had no feature. Mean hemoglobin concentration was 8,8 g/dl; mean white cell and platelet counts were 1500 /mm3 and 16000 /mm3, respectively. Potential risk factors were identified in all patients: renal failure and low serum albumin levels (n =5), anti-inflammatory drug intake (n =2), folate deficiency (n =4) and cobalamin deficiency (n =1). One patient died of septic and hemorrhagic cerebral complications. Conclusion: Pancytopenia related to tow-dose methotrexate is a rare but life-threatening disorder. Search and prevention of potential risk factors are required in all patients; determination of MTHFR genotype may be of several interests as folate supplementation. [Copyright &y& Elsevier]