Phase I/II evaluation of pentostatin (2'-deoxycoformycin) in a five day schedule for the treatment of relapsed/refractory B-cell chronic lymphocytic leukaemia.

The purpose of this study was to determine the efficacy and toxicity of pentostatin (2'-deoxycoformycin) administered in a five day schedule every 28 days to patients with B-cell chronic lymphocytic leukaemia (B-CLL) relapsed from or refractory to at least one line of prior chemotherapy. The initial dose level of 2 mg/m2/day was adjusted up or down by 0.5 mg/m2 in subsequent cycles on the basis of haematological and non-haematological toxicities. The five day schedule was selected because published pharmacokinetic studies had indicated that although pentostatin had an elimination half-life of approximately six hours and could inhibit plasma adenosine deaminase activity for 24 hours, recovery of enzyme activity rapidly took place and accumulation of dATP which has a toxic effect on non-replicating lymphoid cells could be increased by repeated dosing. Twenty-nine patients were entered into the study and dose-escalation was possible in nine, while dose reductions were required for five patients. Of the 24 patients evaluable for response, complete responses were achieved in two and partial responses in five for an overall response rate of 29.2%. Toxicity consisted of myelosuppression, infection, nausea and vomiting and hepatotoxicity but was experienced at acceptable levels considering the heavily pre-treated nature of the patient population. Pentostatin in this schedule has salvage activity in previously treated or resistant patients with B-CLL.

CD23 expression in non-Hodgkin lymphoma: immunohistochemical demonstration using the antibody BU38 on paraffin sections.

The leucocyte antigen CD23 is upregulated in the early stages of B-cell activation by Interleukin-4 (IL-4), and functions as an IgE receptor and lymphocyte growth factor. We have studied the expression of CD23 in 68 cases of non-Hodgkin lymphoma (NHL) using the antibody BU38. This new antibody has the great advantage of being applicable to routinely-processed paraffin sections. CD23 was expressed in tumour cells in 27 out of 36 cases of low grade NHL and 3 out of 32 cases of high grade NHL. Follicular dendritic cells were strongly positive and were seen in follicular lymphomas. Macrophages were also positive and were numerous in high grade lesions.

Pharmacokinetics of imipenem/cilastatin in neutropenic patients with haematological malignancies.

The pharmacokinetics of imipenem/cilastatin were studied in febrile neutropenic patients with haematological malignancies. The peak plasma concentrations (36.4 +/- 4.96 mg/l), plasma half-life (60 min), volume of distribution (0.28 +/- 0.02 l/kg) and plasma clearance (3.23 +/- 0.38 ml/min/kg) were comparable with those in normal healthy volunteers suggesting that the drug handling is not appreciably altered in this group of patients. The administration of 12.5 mg/kg (max 1 g), 6-hourly achieved levels that were up to 3.5 times MICs of most relevant bacteria. The drug therefore has a potential use as empirical monotherapy in febrile neutropenic patients.

Sequential demonstration of nucleolar organizer regions and Ki67 immunolabelling in non-Hodgkin's lymphomas.

In order to investigate the relationship between the numbers of interphase silver-stained nucleolar organizer regions (AgNORs) and cell proliferation, we have studied prospectively a small series of non-Hodgkin's lymphomas (NHL). We applied the recently described double staining technique for sequential immunostaining and the AgNOR reaction to the same sections of tumour from each case. The immunostaining was performed with the antibody Ki67, known to demonstrate the nuclei of proliferating cells. A significant difference was found between the AgNOR scores in Ki67+ and Ki67- cells, the counts being much higher in the former than the latter. This was the case for both high- and low-grade NHL and is further evidence that interphase AgNOR counts reflect cell proliferation level, at least in lymphomas.