Biomedical subjects
Publications and source records attributed to S Bolam.
Each year at the Annual Scientific Meeting of the British Society for Haematology, there is a slide session in which microscopic slides of six patients with haematological disorders are discussed by two experts. Further data and the final diagnosis are then provided. The slide session is presented here, as it occurred at the meeting.
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PURPOSE: We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination. PATIENTS AND METHODS: In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM which comprised idarubicin 10 mg/m(2) i.v., days 1 and 2; dexamethasone 100 mg, 12-h infusion, days 1, 2 and 3; cytosine arabinoside (ARA-C) 1.0 g/m(2), 1-h infusion, days 1 and 2; methotrexate 2.0 g/m(2), 6-h infusion, day 3 (with folinic acid rescue); and cytosine arabinoside 70 mg plus methotrexate 12 mg, intrathecally, days 1 and 8. Two cycles were delivered at 3-weekly intervals. After response assessment, patients received adjuvant cranial radiotherapy (40 Gy over 20 fractions). RESULTS: The series comprised 24 patients, 11 male and 13 female. Their median age was 53 years (range 21 to 73 years). Grade 4 neutropenia and thrombocytopenia occurred in the majority of patients treated. Of the eight PCNSL patients, seven achieved complete remission (CR). Four remained in CR at the time of this report with a median duration of follow-up of 25 months (range 11 to 42 months). Of the 16 SCNSL patients, 12 achieved CR. Seven patients remained in CR at the time of this report with a median duration of follow-up of 24 months (range 18 to 57 months). CONCLUSION: This study suggests that IDARAM is an effective regimen in both PCNSL and SCNSL and is suitable for further development and evaluation.
The treatment of acute myelogenous leukaemia (AML) in the elderly is a difficult and increasing problem. The elderly are generally less able to tolerate the intensive chemotherapy required to achieve a sustained remission, and there is an increased incidence of resistant disease in this age group. Granulocyte- and granulocyte-macrophage colony-stimulating factors have been demonstrated to shorten the duration of severe neutropenia following chemotherapy for solid tumours and after bone marrow/peripheral blood stem cell transplantation, and the effect of these growth factors in the treatment of AML has been investigated in a number of trials using 2 distinct strategies. Growth factors may be administered following chemotherapy in an attempt to accelerate neutrophil recovery, and they may be given before and during chemotherapy with the aim to increase the number of leukaemic blast cells in cell cycle and enhance their responsiveness to chemotherapy. Both of these approaches have proved safe despite initial theoretical concerns regarding the expression of receptors for these growth factors on leukaemic cells. The results of trials using these growth factors in the treatment of AML in the elderly generally show a significant reduction in the duration of neutropenia following induction chemotherapy. However, consistent benefits with respect to morbidity and early mortality together with improvements in long term disease outcome have not been observed. The 'priming' approach using growth factors before and during induction chemotherapy has proved equally disappointing in failing to improve response rates or survival. The routine use of these growth factors in the treatment of AML in the elderly population as a whole would, therefore, not seem to be cost effective.
We describe the occurrence of myelodysplastic changes (hypogranular myeloid series and Pelger cells, dyserythropoiesis with ring sideroblasts) in five of 31 patients with chronic lymphoproliferative disorders after treatment with purine analogues. The bone marrows of 31 patients with chronic lymphoproliferative disorders before and after treatment with purine analogues were reviewed. The majority of patients had received extensive prior treatment, but none had dysplastic changes prior to treatment with purine analogues. We suggest that a purine analogue may have been responsible for dysplastic change and that further follow-up of this phenomenon is warranted.
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The term "thrombopoietin" (TPO) was first coined in 1958 but, despite several cytokines having thrombopoietic effects, the major megakaryocytic growth and development factor was not cloned until 1994. Wendling and colleagues (Virol, 1986; 149: 242-246) recognised a novel murine viral oncogene, v-mpl, responsible for a myeloproliferative syndrome. The corresponding human proto-oncogene, c-mpl, codes for a member of the haemopoietic cytokine receptor family. Its ligand is TPO. The structure and function of TPO, together with its action in stimulating proliferation and maturation of megakaryocytes, are discussed in detail in this review which also details the pre-clinical usage and clinical potential of TPO as a platelet sparing agent in haemato-oncological practice.
We report on the use of fludarabine in four patients with splenic lymphoma with villous lymphocytes (SLVL). All four had relapsed after, or failed to respond to, recommended first-line therapies. In each case fludarabine resulted in a complete clinico-haematological response with minimal toxicity, which, in the two patients with long-term follow-up, proved durable. Fludarabine is effective in the treatment of SLVL and should be considered as both a first-line therapeutic option as well as salvage therapy in this condition.
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