ABSTRACT
Headache is frequently reported as one of the neurological manifestations of essential thrombocythaemia (ET) and other myeloproliferative neoplasms. It is associated with considerable morbidity; yet, it is a frequently under-recognised symptom. In patients with ET, headaches may be attributable to the disease, to the prescribed ET treatment, or unrelated to ET. The majority of headaches in ET are self-limiting and can be managed with standard headache therapies such as paracetamol, but it is vital that the clinician managing these conditions is able to recognise the headaches with a more sinister pathology. In this article, we will review the incidence and management of headaches in ET, whether they are primarily related to the disease or a result of its treatment. Identification of specific headache types in patients with ET may enable physicians to employ the most effective headache medication. This would enhance the patient-physician relationship, increasing patient compliance and thus reducing the risk of adverse outcomes.
Subject(s)
Headache Disorders/etiology , Thrombocythemia, Essential/complications , Alkylating Agents/therapeutic use , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Aspirin/therapeutic use , Humans , Hydroxyurea/adverse effects , Immunologic Factors/adverse effects , Interferon-alpha/adverse effects , Phosphorus Radioisotopes/therapeutic use , Platelet Aggregation Inhibitors/adverse effects , Quinazolines/adverse effects , Radiopharmaceuticals/therapeutic use , Risk Factors , Thrombocythemia, Essential/drug therapyABSTRACT
Cytosine arabinoside plays a pivotal role in the therapy of acute myeloid leukemias with the concentration of its active metabolite, ara-CTP, being positively correlated with improved clinical outcome. Both in vitro studies and ex vivo studies have confirmed the ability of the purine analogues to enhance ara-CTP accumulation within leukemic cells via the stimulation of deoxycytidine kinase. Clinical studies have confirmed the efficacy of these combination regimes in the treatment of acute leukemias. The basis of the biochemical rationale for the development of combination chemotherapy regimes with purine analogues for acute leukemias is reviewed along with clinical studies of their effectiveness and toxicity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytarabine/therapeutic use , Leukemia/drug therapy , Purines/therapeutic use , Acute Disease , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cytarabine/pharmacology , Drug Synergism , Humans , Purines/pharmacologyABSTRACT
In vitro sensitivity to ara-G of peripheral blood B-CLL lymphocytes from 23 patients was assessed using the flow cytometric TdT assay. All patients had typical B-CLL, according to immunophenotype and morphology, and none had received treatment within 1 year of testing. A wide range of spontaneous apoptosis was recorded. Exposure of the cells to a concentration of ara-G, comparable to plasma levels achieved in a phase I trial, produced significant increases in the rate of apoptosis in 21 out of 23 patients. Prior treatment, stage or lymphocyte doubling time did not influence the effect of ara-G. Ten patients' samples tested, in parallel, for sensitivity to fludarabine demonstrated a good correlation of response to both drugs. This in vitro evidence of activity against B-CLL suggests that the spectrum of clinically useful action may be broader than previously demonstrated.
Subject(s)
Antineoplastic Agents/pharmacology , Arabinonucleosides/pharmacology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Lymphocytes/drug effects , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Flow Cytometry , Humans , Lymphocytes/pathologyABSTRACT
Seventeen patients (aged 50-85 years) with relapsed or refractory non-Hodgkin's lymphoma (NHL, 10 patients) or chronic lymphocytic leukaemia (CLL, seven patients) were treated with a combination of fludarabine 25 mg/m2/d and cyclophosphamide 250 mg/m2/d for 3 d repeated every 4 weeks. 12 patients had previously received purine analogue therapy of which four had progressive disease during treatment. The overall response rate of patients with CLL was 71% (28% CR, 43% PR) and for NHL was 50% (0% CR, 50% PR). Toxicity consisted of nausea and vomiting which was maximal in the 3 d after therapy, infections and haematological suppression which was prolonged in some patients. This combination, which is based on a rational prediction of synergistic activity, is highly effective but associated with significant problems with tolerance.
Subject(s)
Antineoplastic Agents/therapeutic use , Lymphoproliferative Disorders/drug therapy , Aged , Aged, 80 and over , Cyclophosphamide/administration & dosage , Female , Humans , Male , Middle Aged , Salvage Therapy , Treatment Outcome , Vidarabine/administration & dosage , Vidarabine/analogs & derivativesSubject(s)
Anticoagulants/adverse effects , Heart Valve Prosthesis , Heparin/adverse effects , Pregnancy Complications, Hematologic/prevention & control , Warfarin/adverse effects , Female , Humans , Partial Thromboplastin Time , Pregnancy , Pregnancy Complications, Cardiovascular , Pregnancy, High-RiskABSTRACT
The purine analogue, fludarabine, is of proven efficacy in the treatment of lymphoid malignancies. The drug appears to be well tolerated with minimal side-effects, and few toxicities have been observed. A case of myelodysplasia occurring after therapy with fludarabine is presented and its implications are discussed.
