Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies

The feasibility of combining cladribine with cyclophosphamide and prednisone in the management of indolent lymphoid malignancies was determined. Nineteen patients [nine chronic lymphocytic leukaemia (CLL), seven non-Hodgkin's lymphoma (NHL) and three macroglobulinaemia (M))] received cladribine 0.1 mg kg−1 per day as a subcutaneous bolus injection on days 1–3 (up to 5 injections) with intravenous cyclophosphamide 500 mg m−2 on day 1 and oral prednisone 40 mg m−2 on days 1–5 at 4-weekly intervals up to a maximum of six courses. A total of 80 courses were given. Overall response rate was 88%, with four patients achieving a complete clinical and haematological response and 12 achieving a partial response. Neutropenia WHO grade 4 in two patients and WHO grade 3 infection in one patient were the limiting toxicities on treatment. During the follow-up, WHO grade ≥3 haematological complications occurred in five patients and WHO grade ≥3 non-haematological complications in five patients. There were no treatment-related deaths. This study demonstrates the feasibility of the cladribine/cyclophosphamide/prednisone (CCP) combination that appears highly active and safe in the management of indolent lymphoid malignancies. © 1999 Cancer Research Campaig

Assessment of long-term quality of life in patients with anal carcinomas treated by radiotherapy with or without chemotherapy

This study was conducted to assess long-term Quality of Life (QOL) in patients treated by radiotherapy with or without chemotherapy for anal carcinomas. Patients with a maximum age of 80 years, and who were alive at least 3 years following completion of treatment with a functioning anal sphincter and without active disease, were selected for this study. Of 52 such patients identified, 41 (79%) were evaluable. There were 35 females and six males with a median age of 71 years (55-80). The median follow-up interval was 116 months (range 37-218). QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer: one for cancer-specific QOL (EORTC QLQ-C30) and one for site-specific QOL (EORTC QLQ-CR38). For the function scales a higher score represents a higher level of functioning (100 being the best score), whereas for the symptom scales a higher score indicates a higher level of symptomatology/problems (0 being the best score). For the QLQ-C30, the functional scale scores ranged from 71 (global quality of life) to 85 (role function) and the symptom scale scores from 6 (nausea-vomiting) to 28 (diarrhoea). For the QLQ-CR38 module the functional scale scores ranged from 13 (sexual functioning) to 74 (body image) and for the symptom scale scores from 5 (weight loss) to 66 (sexual dysfunction in males). None of the functional and symptom scale scores seemed to be better in patients with longer follow-up. In patients treated with sphincter conservation for anal carcinomas, long-term QOL as measured by the EORTC QLQ-C30 and QLQ-CR38 appears to be acceptable, with the exception of diarrhoea and perhaps sexual function. Moreover, the subset of patients who presented with severe complications and/or anal dysfunction showed poorer scores in most scale

Treatment of anal carcinoma in the elderly: feasibility and outcome of radical radiotherapy with or without concomitant chemotherapy

For most cancers, information on treatment tolerance and results for elderly patients is quite limited. This study was conducted to investigate the feasibility and results of curative nonsurgical treatment of patients age 75 years or older with anal carcinoma

The multicenter trial SAKK 37/95 of cladribine, cyclophosphamide and prednisone in the treatment of chronic lymphocytic leukemias and low-grade non-Hodgkin's lymphomas

A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1-5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned

Polysomy 8 defines a clinico-cytogenetic entity representing a subset of myeloid hematologic malignancies associated with a poor prognosis: report on a cohort of 12 patients and review of 105 published cases.

Tetrasomy, pentasomy, and hexasomy 8 (polysomy 8) are relatively rare compared to trisomy 8. Here we report on a series of 12 patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative disorder (MPD) associated with polysomy 8 as detected by conventional cytogenetics and fluorescence in situ hybridization (FISH). In an attempt to better characterize the clinical and hematological profile of this cytogenetic entity, our data were combined with those of 105 published patients. Tetrasomy 8 was the most common presentation of polysomy 8. In 60.7% of patients, polysomy 8 occurred as part of complex changes (16.2% with 11q23 rearrangements). No cryptic MLL rearrangements were found in cases in which polysomy 8 was the only karyotypic change. Our study demonstrates the existence of a polysomy 8 syndrome, which represents a subtype of AML, MDS, and MPD characterized by a high incidence of secondary diseases, myelomonocytic or monocytic involvement in AML and poor overall survival (6 months). Age significantly reduced median survival, but associated cytogenetic abnormalities did not modify it. Cytogenetic results further demonstrate an in vitro preferential growth of the cells with a high level of aneuploidy suggesting a selective advantage for polysomy 8 cells