Marcia K. Liepman

Trimethoprim/sulfamethoxazole prophylaxis in neutropenic patients: Reduction of infections and effect on bacterial and fungal flora

Abstract A prospective, randomized study was undertaken in neutropenic patients to evaluate the efficacy of prophylactic trimethoprim/sulfamethoxazole in reducing infections and to assess the effect of prophylaxis on bacterial and fungal flora. Fifty-five patients with leukemia, lymphoma, or solid tumors randomly received either one single-strength trimethoprim/sulfamethoxazole tablet twice daily or no drug for the period of expected neutropenia. Trimethoprim/ sulfamethoxazole prophylaxis did not significantly reduce the mean number of febrile days per patient, but did decrease the number of documented infections. The control group experienced 28 infections, including 11 bacteremias and seven infection-associated deaths; the group that received trimethoprim/sulfamethoxazole had seven infections, including two bacteremias and no infection-related deaths. Patients treated with trimethoprim/sulfamethoxazole had no enteric gram-negative bacillary infections compared with 12 infections in the control group. Fungal infections occurred in four control patients but only in one patient who received trimethoprim/sulfamethoxazole. Surveillance cultures revealed that trimethoprim/sulfamethoxazole prophylaxis did not lead to colonization with trimethoprim/sulfamethoxazole-resistant Enterobacteriaceae, Pseudomonas, or fungi. Colonization with filamentous fungi was common in both groups and was related to season of the year rather than prophylactic antibiotic therapy. In conclusion, trimethoprim/ sulfamethoxazole prophylaxis reduced infectious episodes in neutropenic patients without increasing the risk of fungal and trimethoprim/sulfamethoxazole-resistant gram-negative bacillary infections.

The treatment of chronic lymphocytic leukemia with COP chemotherapy

Since single drug therapy of chronic lymphocytic leukemia (CLL) has not resulted in prolonged remissions of advanced disease, we initiated a program of combination chemotherapy, COP (cycloposphamide, vincristine sulfate, prednisone) for CLL patients with increasing adenopathy, splenomegaly, and/or signs of marrow failure defined as either anemia or thrombocytopenia. Thirty‐six patients received COP either as initial therapy or following progression of disease on single agent therapy. The response rate was 72% with 26 patients responding (16 complete remissions, and 10 good partial remissions). The responses lasted from 8 to 50+ months. Sixteen of the responding patients remain in remission, 2 have active disease and 8 have died. Median survival has not yet been reached but the two‐year survival from initiation of COP of the responding patients (complete and good partial response) is 90%. Ten patients had either poor partial or no response with median survival of 18 months. The median survival of the entire group of 36 patients is 35 months. COP is an effective and well tolerated therapy for advanced chronic lymphocytic leukemia.

Meningeal leukemia complicating chronic lymphocytic leukemia

Two patients with classic chronic lymphocytic leukemia had meningeal leukemia as a complication of their disease. Intrathecal chemotherapy was successful in eradicating signs and symptoms of meningeal involvement. One of these patients is alive without evidence of central nervous system leukemia 30 months after diagnosis of meningeal leukemia, and 5½ years after the diagnosis of chronic lymphocytic leukemia. Although uncommon, meningeal involvement in chronic lymphocytic leukemia may occur at various times in the course of the disease, it responds to conventional therapy.

Endocarditis as a complication of indwelling right atrial catheters in leukemic patients

Three patients with acute leukemia who had chronic indwelling right atrial catheters developed endocarditis. In all cases, the infection was cured with antibiotics only after removal of the infected catheter. Although infective endocarditis has been rarely noted in leukemic patients, the use of chronic indwelling catheters may lead to an increased incidence of this infection in these patients.

Combination chemotherapy of refractory lymphoma with cis‐dichlorodiamineplatinum, vinblastine, and bleomycin

Therapy of advanced lymphomas after failure of chemotherapy with cytoxan and adriamycin containing combinations remains poor. We have treated 17 patients with refractory lymphomas of various histologies with an intensive regimen of cisplatin, vinblastine and bleomycin. There were three complete clinical responses (6, 10+, 8 months, respectively) and five partial responses (2.5, 3, 4, 7, 18 months, respectively) for a total of 8/17 responders. Four of the eight responders had bone or bone marrow involvement. In addition, three patients had dramatic shrinkage of measurable lesions, but the duration (<1 month) was too short to allow classification as a response. Toxicity included severe myelosuppression requiring that patients be hospitalized in the majority of cases, mild to moderate rise in serum creatinine levels in 41% of patients and one case of fatal pulmonary fibrosis. This regimen may be useful in patients with refractory or relapsing lymphoma; alternatively, it may be useful as part of an initial treatment protocol utilizing non‐cross‐resistant regimens for the management of patients with poor prognosis lymphomas.

Effect of Prophylactic Ketoconazole and Nystatin on Fungal Flora

Summary: The effect of prophylactic antifungal drugs on oropharyngeal and anterior nares fungal colonization was studied in 20 patients receiving nystatin and 19 patients receiving ketoconazole. Surveillance cultures were obtained weekly for a mean of 27.1 ± 4.8 days in the nystatin group and 44.0 ±6.7 days in the ketoconazole group. Initially, 63.2% of nystatin patients and 77.8% of ketoconazole patients had yeasts in their oropharynx. Neither drug eliminated oropharyngeal yeast colonization; by the end of the first four weeks of surveillance, 66.7% of the nystatin group and 63.6% of the ketoconazole group still had yeasts in the oropharynx. However, both drugs caused a reduction in the quantity of yeasts grown on successive cultures. Filamentous fungi were isolated in baseline cultures in 42.1% of the nystatin patients and 33.3% of the ketoconazole patients. Prophylaxis did not appear to alter carriage of filamentous fungi in the upper airways. Pathogenic filamentous fungi were only rarely isolated, and this rate did not increase with prophylaxis. Resistance to polyene antifungals (nystatin, amphotericin B) or to ketoconazole did not occur as a result of prophylaxis.

The Chronic Leukemias

Chronic granulocytic leukemia, chronic lymphocytic leukemia and its variants, and hairy cell leukemia are characterized by prominent organ infiltration and marrow replacement, with a course consisting of years. Although treatment is effective in ameliorating symptoms, little has been gained in terms of increased survival.

Altered isozyme patterns of leucocyte alkaline phosphatase in disease states

Summary. Leucocyte alkaline phosphatase (LAP) is a granulocyte enzyme whose concentration varies in disease states. In order to determine whether the pattern of expression is altered in leukaemic granulocytes, we have analysed the LAP isozyme pattern of a series of normal subjects and patients with various haematological diseases.

Cisplatin, VP-16-213 and MGBG (Methylglyoxal bis guanylhydrazone) combination chemotherapy in refractory lymphoma, a phase II study

SummaryIn an effort to improve the treatment of patients with refractory or recurrent lymphoma, we developed a protocol using cis-platinum combined with two other agents of known efficacy in these disorders but with differing side effects: VP-16 and MGBG. Twenty-six eligible patients were treated with this regimen. There were 15 men and 11 women with a median age of 54 years (22–73), and performance status of 1 (0–3). Their diagnoses were Hodgkins disease 5 and non-Hodgkins lymphoma [NHL] 21 which included 11 with diffuse histocytic lymphoma [DHL]. The median number of chemotherapy regimens was 2 (1–5); 12 also received radiotherapy. Twenty patients are evaluable for response: 15 NHL and 5 Hodgkins disease. Three patients, all of whom had DHL entered complete remission (20%) with a median time to treatment failure of 7 1/2 months. Six NHL (40%) and one Hodgkins disease (20%) patients entered a partial remission. There were three early deaths: one due to progressive disease, one to acute respiratory failure, and one with disease status undocumented. Toxicity included leukopenia, thrombocytopenia, anorexia, nausea, vomiting, stomatitis, alopecia, renal failure, profound peripheral neuropathy, and hypersensitivity vasculitis. Treatment was stopped because of the latter two. These agents are non-crossresistant with doxorubicin-containing regimens. The drugs are possibly synergistic and modestly active with moderate to severe toxicity.

Pseudolymphoma masquerading as colonic malignancy

The case of a patient with a constricting lesion of the hepatic flexure is presented. Radiographic and endoscopic findings in this patient could not conclusively distinguish a benign from a malignant process. The patient eventually underwent operation, at which time hemicolectomy and ileotransverse colostomy were performed. The final pathologic diagnosis of the resected lesion was pseudolymphoma. The definition and significance of this diagnosis are discussed.