Severe bleeding complications in HIV-positive haemophiliac patients treated with protease inhibitors.

The availability of more potent drugs for the treatment of human immunodeficiency virus (HIV) infection has led to the development of aggressive drug regimens, including the widespread use of HIV protease inhibitors. Several reports have indicated increased bleeding complications in haemophiliac patients after starting treatment with protease inhibitors. We present two cases of exceptionally severe hemorrhagic events in HIV-positive patients with haemophilia A after starting HIV protease inhibitors, resulting in significant morbidity and mortality. One patient developed a progressive paranephric pseudotumor becoming symptomatic only one month after the start of ritonavir. The second patient presented with an intracranial bleed, resulting in his death within forty-eight hours, nineteen weeks after he was started on nelfinavir. Both patients showed an excellent antiviral response to the HIV-protease inhibitors with significant decrease in their HIV-RNA titers. Potentially serious hemorrhagic complications that require emergent intervention may occur in HIV-positive haemophiliac patients undergoing therapy with protease inhibitors. Clinicians should be alert to these complications.

A case of biliary carcinoid presenting with pancreatitis and obstructive jaundice.

A 43-yr-old man presented to the clinic with abdominal pain, jaundice, nausea, and vomiting and weight loss over a 6-month period. Physical exam was unrevealing other than mild epigastric tenderness. A computed tomographic scan of the abdomen revealed a mass in the head of the pancreas, which was resected at laparotomy by a Whipple's procedure. The histology showed a biliary tract carcinoid tumor. The patient had normal hydroxy-indole-acetic acid (HIAA) levels throughout. There has been no evidence of disease or tumor recurrence at 3.5 yr of follow up.

Testicular lymphoma.

Non-Hodgkin's lymphoma of the testis is an uncommon disease. It accounts for approximately 9% of testicular neoplasms. Despite this low overall incidence, however, it is the most common testicular malignancy in the elderly. Testicular lymphoma has a rather high incidence of bilateral involvement and a propensity for extranodal spread to the skin, subcutaneous tissue, CNS, lung, and Waldeyer's ring. Although intermediate-grade diffuse large B-cell lymphoma is the most common histologic pattern among primary testicular lymphoma, secondary infiltration of the testis, especially in high-grade Burkitt's lymphoma, is more prevalent. Although excellent results with a doxorubicin-containing chemotherapy regimen have been achieved in early-stage disease, patients with advanced disease have a grave prognosis.

Treatment with low-dose oral etoposide in patients with myelodysplastic syndromes.

Forty-three patients with myelodysplastic syndromes (MDS) received treatment with oral etoposide 50 mg/day for 21 consecutive days every 4 weeks. Eighteen patients (42%) experienced hematological responses, including 12 of 17 (70%) patients with chronic myelomonocytic leukemia (CMML). Three of five CMML patients who failed treatment with hydroxyurea experienced major hematological responses with oral etoposide. Median response duration exceeded 9 months (range: 4-49 + months), and one patient remains in an unmaintained complete remission for 4 years. Toxicity included nausea/vomiting in five patients, fever (four patients), infection (three patients), mucositis (two patients), and anorexia (two patients). Two patients had grade 4 neutropenia with sepsis necessitating treatment withdrawal. We conclude that low-dose oral etoposide has remitting activity in MDS and is an effective treatment alternative for patients with CMML.

Acute cardiac tamponade associated with pericardial extramedullary hematopoiesis in agnogenic myeloid metaplasia.

A 67-year-old man was diagnosed with agnogenic myeloid metaplasia. Several months later, he presented with dyspnea, malaise and chest pain. A pericardial effusion was evident and a pericardial biopsy was consistent with extramedullary hematopoiesis.

Vascular toxicity associated with chemotherapy and hormonotherapy.

Vascular complications associated with chemotherapy and hormonotherapy are being reported with increasing frequency. Such vascular toxicity is clinically heterogenous, ranging from asymptomatic venous lesions to fatal hepatic venoocclusive disease of the liver. Putative mechanisms for such toxicity include drug-induced endothelial cell damage, perturbation of the clotting cascade, platelet activation and aggregation, alteration of thromboxane-prostacyclin homeostasis, and dysregulation of cytokines. Better documentation of the incidence and types of vascular toxicity and studies to help elucidate the pathogenesis and management of such toxicity are needed.

Peripheral T-cell lymphoma of the scrotum.

Primary lymphoma of the scrotum is rare. We report a case of primary immunoblastic lymphoma of the scrotum in a homosexual who was negative for antibodies to human immunodeficiency virus. Immunoperoxidase stains of paraffin-embedded tissue were consistent with a T-cell phenotype. Although complete remission was initially induced with surgical extirpation of the tumor and combination chemotherapy, isolated skin relapse developed which again responded to chemotherapy.

Vascular toxicity associated with antineoplastic agents.

It is apparent that a variety of vascular disorders have been reported after the administration of antineoplastic agents. However, it is not clear whether all of these entities are related to cytotoxic drugs, the malignancy itself, or some other unrelated factor. Nonetheless, there does appear to be a cause-effect relationship between cisplatin, bleomycin, velban chemotherapy, and Raynaud's phenomenon. In addition, painful acral erythema may occur in association with several drugs, especially protracted infusions of 5-fluorouracil and high-dose cytosine arabinoside. Mitomycin is the most common cause of the thrombotic microangiopathic syndrome, and in the majority of cases it is a lethal event. Unfortunately, HVOD is a major toxic effect of many preparatory bone marrow transplantation protocols and ways to prevent this potentially life-threatening complication should be avidly pursued. In this regard, pentoxifylline and low-dose heparin have recently been reported to be effective in preventing HVOD. Although recent reports have documented thromboses and thromboembolic events in patients with breast cancer treated with cytoxan, methotrexate, and 5-fluorouracil-based protocols, only one study had a no-treatment control arm. Future breast cancer studies should evaluate this problem prospectively. More studies are needed to help elucidate the pathogenesis of vascular toxicity associated with chemotherapy.

Carboplatin in non-small cell lung cancer: an update on the Cancer and Leukemia Group B experience.

Since 1984, the Respiratory Committee of the Cancer and Leukemia Group B (CALGB) has evaluated carboplatin, either alone or in combination, in five separate phase II studies for patients with inoperable non-small cell lung cancer (NSCLC). All patients had an Eastern Cooperative Oncology Group performance status of 0 to 2 and had not received previous treatment with chemotherapy. In 70 patients with stage IIIB or IV disease, carboplatin 400 mg/m2 administered intravenously once every 4 weeks produced a 16% overall response rate and an acceptable toxicity profile. Subsequently, combinations of carboplatin/cisplatin, carboplatin/etoposide, and carboplatin/vinblastine have been evaluated in similar patient groups. Response rates of 11%, 12%, and 20%, respectively, were obtained. Myelosuppressive toxicity was substantially greater with carboplatin/etoposide and carboplatin/vinblastine than with carboplatin alone. Carboplatin/vinblastine demonstrated efficacy similar to that of the cisplatin/vinblastine combination previously evaluated by CALGB for treatment of similar patients with advanced NSCLC; ease of administration and lack of significant nephrotoxicity also compared favorably with cisplatin-based therapy. In regional NSCLC patients, carboplatin 100 mg/m2/wk can be administered intravenously concurrently with 60 Gy thoracic radiotherapy given over 6 weeks. The impact of concurrent carboplatin added to a sequential chemotherapy-radiotherapy program for patients with regional NSCLC is currently under study by the CALGB Respiratory Committee.

Expression of the multidrug resistance gene product (P-glycoprotein) in myelodysplasia is associated with a stem cell phenotype.

Previous studies have indicated relative resistance to chemotherapy in the myelodysplastic syndromes (MDS) and associated acute leukaemia. To determine if multidrug resistance may contribute to chemoresistance in these disorders, we studied bone marrow specimens for P-glycoprotein expression (P-GP) by immunocytochemical staining with monoclonal antibodies reactive with cytoplasmic (C219) or surface epitopes (MRK16) of P-GP. Forty-five case specimens from 43 patients were studied, including 32 cases of primary MDS, seven cases of acute myeloid leukaemia (AML) following MDS, and six therapy-related haematological disorders. Cytogenetic analysis was available on 36 specimens. Two staining patterns were detected: (1) cytoplasm and plasma membrane, and (2) staining restricted primarily to the nuclear-cytoplasmic junction. P-GP was detected in seven (22%) cases of primary MDS, four (57%) cases of AML evolving from MDS, and five (83%) cases of therapy-related haematological disorders. Expression of P-GP was restricted to blasts and leukaemic monocytes, and was otherwise absent from terminally differentiated blood cells. Analysis of the relation between P-GP expression and reactivity with the human progenitor cell antigen CD34, revealed a highly significant association (P = 0.001). P-GP reactivity was distributed equally among normal and abnormal karyotypes and did not correlate with specific cytogenetic abnormalities. These findings indicate that multidrug resistance in MDS and karyotypically-related haematological disorders is closely linked to a stem cell phenotype and may contribute to chemoresistance in these disorders.