Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04). Among treated patients, 39 relapsed during the follow-up period. These patients were characterized before treatment by a higher incidence of trisomy 12 (38 vs 11%, P < .001) and TP53 disruption (31 vs 4%, P = .0002). A significantly shorter 5-year overall survival was found for treated patients with CK (72.4 vs 85.8%; P = .007), unmutated IGHV (70 vs 100%; P = .04), or TP53 disruption (55.7 vs 82.7%; P < .0001). Three risk groups were defined based on the status of TP53 disruption or unmutated IGVH, which differed significantly in terms of 5-year overall survival. Moreover, the presence of CK impacted pejoratively 5-year overall survival and progression-free survival in all these 3 groups. Conventional karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required.

[Severe hypoglycemias in a diabetic man by surreptitious self-injections of an insulin analogue]. / Hypoglycémies répétées et inexpliquées chez un patient diabétique traité par analogue de l'insuline.

A 44 years-old diabetic male patient was admitted several times to the emergency department of Albi Hospital (France) for nocturnal hypoglycemias with losses of consciousness. The initial blood analysis, performed on a Cobas(®) analyzer, retrieved low levels of insulinemia. This patient was treated by analogues of insulin and did not present any comorbidities. Moreover, an extensive check-up did not retrieve any evident cause for these hypoglycemias. After a severe hypoglycemic coma that occurred during the last hospitalization when insulinotherapy was interrupted, the staff suggested the possibility of a factice hypoglycemia by surreptitious administration of insulin. Hormonal assays were then performed on a Centaur(®) analyzer, which is able to recognize insulin aspart and glargine. They revealed elevated concentrations of insulin along with low levels of C-peptide. Such a blood profile is consistent with an exogenous administration of insulin or its analogues. On the basis of this biological clue, the patient was questioned again and he finally admitted self-injection of insulin aspart. This case gives us the opportunity to review the diabetic hypoglycemia, to point out the particularities of the blood assays of insulin analogues and to confirm the need of a close collaboration between clinic and laboratory staffs in the difficult cases of factice hypoglycemias.

Bortezomib and heart failure: case-report and review of the French Pharmacovigilance database.

Bortezomib is a proteasome inhibitor commonly indicated for the treatment of multiple myeloma and non Hodgkin lymphoma. Cardiac adverse drug reactions of this drug are not clearly established. We report case where direct involvement of bortezomib in the occurrence of heart failure is strongly suspected and 22 other cases spontaneously reported to the French Pharmacovigilance System. This report should increase cardiologist awareness about the risk of heart failure related to this drug. Moreover, these cases underline the need for a systematic cardiac screening in patients exposed to bortezomib.