Doxorubicin in lymphoma: association between pharmacokinetic variability and clinical response.

Despite many years of clinical use in Hodgkin lymphoma, no previous studies have evaluated the relationship between doxorubicin pharmacokinetics and clinical response. In a pilot study, we associated the area under the curve of doxorubicin with successful remission. Patients with successful remission (n = 14) had a trend toward a higher median area under the curve than those who failed remission (n = 4; 36,390 versus 19,350 ng/mL x minute, P = 0.08, respectively). Median peak serum concentrations were 73 ng/mL among failures and 280 ng/mL in those who achieved remission (P = 0.06). The 2 groups did not differ regarding demographic and clinical parameters or doxorubicin dose. If corroborated by further studies, therapeutic drug monitoring of doxorubicin may be warranted in patients with Hodgkin lymphoma.

der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL) - detected by spectral karyotyping (SKY).

Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.