[Allergies to betalactam-antibiotics: when and how to evaluate?]. / Allergien auf beta-laktam-antibiotika: wann und wie abklären?

When there is the suspicion of an allergic reaction to betalactam-antibiotics, the allergological evaluation is an important tool to confirm the allergy and to test alternative medicaments. As all the testing methods for the allergologic evaluation (cutaneous tests and in-vitro tests) don't have a high sensitivity, a broad case report and the former documentation of the symptoms and diagnostic findings are essential, to enable a high significance of the examination and to assess the indication for the provocation test which is the gold standard in many cases. The documentation of the time flow is basic, to differentiate between immediate reactions (hours after intake) and nonimmediate reactions (several days after intake). The diagnostic evaluation not later than after six months increases the prospects for a successful allergic evaluation.

En cas de suspicion d'une réaction allergique aux antibiotiques bêta-lactames, l'investigation allergique est un moyen important pour confirmer l'allergie et pour évaluer des médicaments alternatifs. Comme cependant toutes les méthodes des tests de l'évaluation allergique (tests cutanés et in-vitro-tests) n'ont pas de sensibilité élevée, une anamnèse détaillée et la documentation des symptômes sont cruciaux pour rendre hautement significative l'évaluation et pour pouvoir poser l'indication pour le test de provocation qui est souvent la méthode de référence. La documentation du déroulement de l'allergie est capitale pour différencier entre une réponse immédiate (quelques heures après la prise de l'agent) et une réponse retardée (quelques jours après la prise de l'agent). L'investigation au plus tard après six mois augmente les chances de succès d'une évaluation allergique.

Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS).

This study examines the prognostic significance of early molecular response using an expanded dataset in chronic myeloid leukemia patients enrolled in the International Randomized Study of Interferon and STI571 (IRIS). Serial molecular studies demonstrate decreases in BCR-ABL transcripts over time. Analyses of event-free survival (EFS) and time to progression to accelerated phase/blast crisis (AP/BC) at 7 years were based on molecular responses using the international scale (IS) at 6-, 12-, and 18-month landmarks. Patients with BCR-ABL transcripts > 10% at 6 months and > 1% at 12 months had inferior EFS and higher rate of progression to AP/BC compared with all other molecular response groups. Conversely, patients who achieved major molecular response [MMR: BCR-ABL (IS) ≤ 0.1%] by 18 months enjoyed remarkably durable responses, with no progression to AP/BC and 95% EFS at 7 years. The probability of loss of complete cytogenetic response by 7 years was only 3% for patients in MMR at 18 months versus 26% for patients with complete cytogenetic response but not MMR (P < .001). This study shows a strong association between the degree to which BCR-ABL transcript numbers are reduced by therapy and long-term clinical outcome, supporting the use of time-dependent molecular measures to determine optimal response to therapy. This study is registered at www.clinicaltrials.gov as NCT00006343.

Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors.

PURPOSE To study the pharmacokinetics (PK) of imatinib (IM) in patients with advanced GI stromal tumors (GISTs) treated in a randomized phase II study and to explore the potential relationship between IM plasma levels and long-term clinical outcomes. PATIENTS AND METHODS Patients were randomly assigned to receive IM at 400 mg versus 600 mg daily. IM plasma levels were analyzed in a subset of patients (n = 73) for whom PK data on day 1 and at steady-state (SS, day 29) were available. IM PK was evaluated using a population PK approach. The relationship between IM plasma exposure and clinical outcome was explored by grouping patients into quartiles according to IM trough concentration (C(min)). The clinical outcome parameters evaluated include overall objective benefit rate (OOBR; complete response plus partial response plus stable disease) time to progression (TTP), and KIT genotyping. Results IM PK exposure showed a high inter-patient variability, and clinical outcomes were correlated with IM trough levels at SS. The median TTP was 11.3 months for patients in the lowest C(min) quartile (Q1, < 1,110 ng/mL) compared with more than 30 months for Q2 to Q4 (P = .0029). OOBR was also inferior in Q1 patients. In patients with GIST with KIT exon 11 mutations (n = 39), the OOBR was 67% for Q1 patients versus 100% for all others (P = .001). CONCLUSION In patients with advanced GIST, IM trough levels at SS were associated with clinical benefit. Patients with IM C(min) below 1,100 ng/mL showed a shorter TTP and lower rate of clinical benefit (OOBR). Further studies are justified to test whether monitoring IM plasma levels might optimize clinical outcomes for patients with GIST.