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The relationships among thrombocytosis, abnormal platelet aggregation and altered hemostasis in primary thrombocythemia remain poorly understood. Consequently, the appropriate management of asymptomatic patients is controversial and needs to be individualized. For symptomatic patients, conventional therapy, usually hydroxyurea, is directed primarily at lowering the platelet count by suppression of megakaryocyte activity. Recombinant interferon alpha can selectively lower platelet counts and may offer a reasonable alternative. Recent experience with anagrelide is also most promising in both symptomatic and asymptomatic patients. Current thoughts on the pathogenesis and management guidelines are presented here.

Interferon-alpha has not been used previously in hemodialysis patients with chronic hepatitis B and C. This uncontrolled report evaluates the biochemical and/or histologic profile resulting from the administration of interferon-alpha in seven hemodialysis patients, two with chronic hepatitis B and five with hepatitis C. Biochemical improvement was noted in all patients. Histologic progression did not occur in the two cases in which such assessment was made, and five of them were subsequently transplanted without recurrence of disease.

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.

A phase II study using a combination of Ondansetron and Lorazepam to treat patients receiving either highly or moderately emetogenic chemotherapy regimens has recently been completed. A total of 56 patients were enrolled and data from 53 is amenable to analysis. The overall response rates were 100% and 91% for the highly and moderately emetogenic regimens respectively, with 16 out of 20 patients (80%) and 18 out of 33 patients (54.5%) achieving a complete or major response respectively. Toxicity was mild and no dose modifications were necessary.

The optimal approach for curing patients with chronic myeloid leukemia (CML) in chronic phase (CP) is an allogeneic bone marrow transplant (BMT). However, this approach is not available to the majority of patients. Autografting, using either purged or unpurged bone marrow or peripheral blood stem cells (PBSC), could be beneficial for patients who are not eligible for BMT. Between 1984 and 1992, 21 patients with CML in CP were autografted using unmanipulated PBSC harvested either at diagnosis or thereafter. Ten of 21 patients survived at a median of 84 months following autografting (range: 12-108 months). Eleven patients died, seven of blast transformation and four from other causes. The timing of the autograft or the harvest does not appear to have a bearing on survival.

Late relapse of leukaemia is rare in patients with chronic myeloid leukaemia (CML) subjected to allogeneic bone marrow transplantation in chronic phase. Herein, we report a patient who presented with acute lymphoblastic leukaemia who after chemotherapy developed a picture consistent with CML in chronic phase. He then received an allograft from an HLA-identical sister and remained in complete remission for 4 years, before he eventually relapsed with features of myeloid transformation of CML. We speculate that the same population of already transformed leukaemic progenitor cells may have given rise to the original lymphoid blast cells and the myeloid blast cells that characterized the terminal relapse.

A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM.

Sixteen patients with advanced (stage III) malignant melanoma were treated with escalating doses of intravenous BCNU and melphalan starting at 400 and 35 mg/m2, respectively, and escalating to 1,000 and 110 mg/m2, respectively, combined with autologous marrow transplantation. The duration of granulocytopenia and time to granulocyte recovery was similar in all groups regardless of chemotherapy dose. Platelet recovery was delayed in patients receiving the highest doses of chemotherapy. This study showed that bone marrow colony-forming units in culture took as long as 6 months to recover. This was adequate to bring peripheral blood counts to normal but not to pretreatment levels. These studies indicate that autologous bone marrow transplantation is beneficial in enhancing short-term recovery, but may not be beneficial in the long-term hematopoietic recovery.

Chronic myeloid leukaemia, a clonal myeloproliferative disorder with a biphasic nature, is characterised by a specific chromosomal aberration, the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a reciprocal translocation between chromosomes 9 and 22 and involves the ABL and BCR genes resulting in a chimeric mRNA encoding a specific protein, termed P210. At present, there is no convincing evidence that to maintain the leucocyte count within the normal range prolongs the duration of the stable chronic phase or of survival, and the objectives of treatment are simply to alleviate symptoms or to delay their onset. It has, however, become clear that bone marrow transplantation performed during the chronic phase using an HLA-identical sibling donor offers the best chance of a cure.

Although bony involvement by transitional cell carcinoma of the bladder occurs frequently, its presentation as a symptomatic solitary bony metastasis is rare. Furthermore, presentation as a solitary distal metastasis with osteolytic and osteoblastic components is almost a novelty. We present such a case, which is additionally unusual in that the primary lesion in the bladder and the metastasis were resectable.

Following recent reports suggesting that the addition of cimetidine to interferon may enhance response rates in patients with metastatic malignant melanoma, we have completed a Phase II study of the use of recombinant alpha 2 interferon and cimetidine in patients with advanced malignant melanoma and who had progressive disease following interferon therapy alone. We observed two partial responses, no complete responses, and two patients had stable disease. Toxicity encountered was analogous to that of interferon alone. We conclude that the additional of cimetidine to alpha interferon is not beneficial in the treatment of advanced metastatic malignant melanoma.

Systemic chemotherapy has been of limited benefit in the treatment of intracranial neoplasms, due, in part, to the inability to deliver effective drug doses to the neoplasm without systemic toxicity. We have completed a clinical trial of intracarotid BCNU and FUDR using an implantable pump in patients with unilateral malignant astrocytomas (Grade III and IV) in the hope of obtaining better tumor control with less systemic toxicity. Six patients had in-dwelling catheters placed in the internal carotid artery attached to a percutaneous refillable pump (Infusaid 400). The treatment program consisted of bolus BCNU 400 mg every 6 weeks and FUDR by continuous infusion at dosages ranging from 0.5 mg/24 h to 2.5 mg/24 h. The maximum tolerable dose of FUDR was 1 mg/24 h with ipsilateral mucositis and conjunctivitis being dose limiting factors. Flow studies demonstrated significant perfusion of the ipsilateral eye and surrounding face secondary to ophthalmic artery collaterals. No patient had systemic toxicity and the lowest WBC encountered was 2 400 with normal differential and platelets.

Despite improved understanding of the chronic lymphoid leukaemias, the long-term outcome for the majority of patients remains dismal. An alkylating agent, usually chlorambucil, with or without prednisone, remains the standard palliative treatment for chronic lymphocytic leukaemia. More recently, two new drugs have emerged, 2'deoxycoformycin and alpha-interferon, which appear to offer substantial benefit to patients with hairy cell leukaemia.

Nausea and vomiting may be the most distressing part of cytotoxic chemotherapy for malignant disease and frequently leads to default from treatment. Furthermore, in some patients, anxiety associated with chemotherapy precipitates anticipatory vomiting. 24 patients with refractory vomiting associated with chemotherapy were selected from a homogeneous group of malignancies. 25% of these also had anticipatory vomiting. Lorazepam, a benzodiazepine, in a dose of 3 mg/m2, was given by mouth in conjunction with a standard centrally acting antiemetic 30 min before chemotherapy. Vomiting was totally abolished in 70% of patients; in only 4% two vomiting episodes occurred. In addition, 17% of patients had complete amnesia of the events of chemotherapy. This pilot study suggests that lorazepam in conjunction with standard antiemetic therapy may be an effective means of controlling refractory nausea and vomiting.

Hodgkin's disease (HD) has variable clinical and pathologic features in different geographic regions. The reasons behind this are not completely clear. We reviewed 81 cases of adult HD who presented to the Adult Oncology Unit of the King Faisal Specialist Hospital, Riyadh, Saudi Arabia between 1975 and 1982. Fifty-seven (70.4%) were males and 24 (29.6%) were females with median ages of 29.9 and 23 years, respectively. The male:female ratio was 2.38:1. Two distinct age peaks at 18 and 48 years were seen in both sexes, with bimodality being more striking in females. The most common histologic subtype encountered was mixed cellularity (59.3%). Most of the patients (67.9%) were either Stage III or Stage IV at the time of diagnosis. These patterns differ significantly from those seen in reported Western series, but are similar to those reported from other areas in the Middle East.

Cutaneous malignant melanoma is occurring in epidemic proportions in the United States. To provide a profile of persons at risk and the epidemiologic features of malignant melanoma, we reviewed the records of 325 patients with cutaneous malignant melanoma seen at the University of Colorado Health Sciences Center between 1973 and 1983. Most patients had fair skin, brown or blonde hair, blue or green eyes, and had difficulty in suntanning. The majority of melanomas (72%) developed in preexisting nevi. In women, melanomas were most common on the extremities, and in men they occurred most frequently on the trunk, head or neck. The most frequently noted depth of invasion was Clark's level IV. At diagnosis, most of the patients (77%) were at stage I. We conclude that malignant melanoma constitutes a major disease problem in the western United States that is largely preventable with appropriate physician and patient education.

Fifty-nine patients with metastatic malignant melanoma were entered into a phase II trial of recombinant alpha-2 interferon given in a dosage of 10 million IU/M2 subcutaneously three times per week for one year. Forty-five of these were evaluable for response. Of five evaluable patients with ocular primaries, none responded to interferon treatment. Four of 40 patients (10%) with cutaneous primaries achieved complete remission, and 6 further patients (15%) had partial remissions for a combined response rate of 25%. Two patients remain in complete remission 15+ and 32+ months after starting treatment. Responses were limited to subcutaneous, lymph node and lung metastases. The treatment schedule was well tolerated with the majority of patients receiving more than 70% of their predicted doses. Flu-like symptoms were the most common side effect. No evidence of cumulative toxicity was seen. We conclude that interferon is an active agent in metastatic malignant melanoma of cutaneous origin and that further trials are indicated.