Treosulfan/fludarabine: a new conditioning regimen in allogeneic transplantation.

Recently, the water-soluble bifunctional alkylating agent treosulfan demonstrated broad stem cell toxicity, immunosuppressive as well as antileukemic activity. Due to its well known low non-hematologic toxicity profile, treosulfan was considered an alternative agent for conditioning prior to allogeneic transplantation. A first clinical study, combining 3 x 10 g/m2 of treosulfan with 5 x 30 mg/m2 of fludarabine, demonstrated the feasibility of this conditioning. A fast, reliable and complete development of the donor hematopoiesis was evident as well as a low non-hematologic toxicity, transplantation-related mortality and relapse rate. In a second study treosulfan was escalated from 3 x 10 to 3 x 12 and 3 x 14 g/m2. In this protocol, 55 pts (patients) not amenable to standard conditioning suffering from various hematological malignancies were included. Complete donor chimerism was reached by day 28 in 80% of the pts. So far, 8 pts (11%) died without disease progression and 11 pts (20%) relapsed. Treosulfan was very well tolerated. Especially no hepatic VOD, severe cardiac or pulmonary toxicity was noted. Acute GvHD (degrees 11-IV) occurred in 44% and chronic GvHD in 45% of pts. Considering the poor prognosis of these study populations, treosulfan-based conditioning is considered to be safe and efficient. New phase 11 clinical protocols in AML and MDS will be initiated.

Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.

Do cancer patients with chemotherapy-induced leukopenia benefit from an antiseptic chlorhexidine-based oral rinse? A double-blind, block-randomized, controlled study.

Patients undergoing cancer chemotherapy frequently suffer from mucositis, particularly if they become leukopenic (leucocytes <1000/microL). To identify a possible benefit from antiseptic rinsing of the oral cavity, 47 patients were randomized to rinse either with a chlorhexidine-based product (chlorhexidine concentration 0.3%; N=24) or with an amine-stannous fluoride combination (control group; N=23). Patients were asked to rinse three times a day for 30s from the beginning of chemotherapy until the end of leukopenia. Before rinsing, as well as during and after leukopenia, aerobic and anaerobic bacteria in the oral cavity were counted. At the same time, the patients were assessed for mucositis. In the chlorhexidine-based group, a significant decrease of the aerobic (P=0.042) and anaerobic (P=0.008) bacterial flora was identified. In the control group, the numbers of aerobic and anaerobic bacteria remained unchanged (P>0.05). Fifteen patients in the chlorhexidine-based group had a C-reactive protein (CRP) increase >50mg/L, compared with only eight patients in the control group [odds ratio: 3.13, confidence interval (CI) 0.82-12.39]. Nine patients in the chlorhexidine-based group but only two patients in the control group developed severe mucositis. This difference was statistically significant with an odds ratio of 6.30 (CI: 1.02-49.67). As not all of the 47 patients developed severe leukopenia, a separate analysis was carried out for patients with <1000 leucocytes/microL for a minimum of three days. The results of the microbial counts were very similar, with a clear reduction in the chlorhexidine group and no major alterations in the control group. Twelve of 15 patients in the chlorhexidine-based group had a CRP >50mg/L whereas only eight of 15 patients did so in the control group, which can be regarded as a slightly elevated risk for a CRP increase in the former group. Seven of 15 patients developed severe mucositis in the chlorhexidine-based group, but only two of 15 patients in the control group. These differences were not significant, but patients treated with chlorhexidine-based product seemed to have more problems with inflammation of the oral mucous membranes, resulting in an elevated mucositis score and a CRP increase. Other parameters such as body temperature or application of antibiotics did not differ between the two groups. We conclude that treatment with the chlorhexidine-based product did not provide a clinical benefit for cancer chemotherapy patients. On the contrary, the risk of mucositis and clinical sequelae seems to be enhanced, although the counts of micro-organisms on the oral mucous membranes are significantly reduced.

DNA in Lennert's lymphoma. Report of a case with cytophotometric studies.

We present the first case of Lennert's Lymphoma in which cytophotometric determinations for DNA contents are undertaken. DNA Histograms of lymphoid cells, Immunoblasts, and epitheloid cells are evaluated for their euploid or aneuploid DNA contents. The aneuploid DNA stem line pattern found in the case under discussion testifies to the malignant nature of Lennert's Lyphoma.