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Phase-II trial of idarubicin, fludarabine, cytosine arabinoside, and filgrastim (Ida-FLAG) for treatment of refractory, relapsed, and secondary AML.

The current phase-II trial was initiated to assess the efficacy and toxicity of the Ida-FLAG regimen in patients with poor-risk acute myeloid leukemia (AML). Three subgroups of patients with AML were eligible for the study: (a) refractory, (b) first relapse, or (c) secondary AML (i.e., signs of trilineage myelodysplasia at diagnosis or the history of a myelodysplasia or myeloproliferative disorder). Fifty-seven fully evaluable patients were included in the study. Twenty patients received a second course of Ida-FLAG. Complete remission was achieved by 1/14 patients with refractory AML, 12/15 patients with relapsed AML, and 17/28 patients with secondary AML. The median duration of ANC <1000/microl was 17 days (10-36); of platelets <30,000/microl 23 days (9-65); of days with fever >38.0 degrees C 6 days (1-33). Thirteen patients (22.8%) died within 42 days of severe infection or hemorrhage. Overall survival at 20 weeks in the subgroups was 24% for patients with refractory, 78% for patients with relapsed, and 55% for patients with secondary AML. The toxicity of the first cycle of Ida-FLAG is moderate. The feasibility and subjective tolerance of the Ida-FLAG regimen are acceptable. There is no evidence for an increase of atypical infections. The efficacy for patients with secondary AML and especially those with first relapse of AML is good, with a high rate of complete remissions. Remission duration seems to be short. Therefore, an intensified post-remission therapy seems necessary.

Acute Disease↗

Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors.

PURPOSE: Two options cure nearly all patients with pathologic stage II nonseminomatous germ cell tumors (NSGCTs): two cycles of adjuvant chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) or cisplatin, vinblastine, bleomycin, cyclophosphamide, and dactinomycin (VAB-6); or close observation with full treatment at relapse. Two cycles of etoposide plus cisplatin (EP) were given to selected patients with pathologic stage II NSGCT and high-volume nodal metastases. PATIENTS AND METHODS: All patients had pathologic stage II NSGCT with one or more of the following features found at retroperitoneal lymph node dissection (RPLND), suggesting a greater than 50% likelihood of relapse after observation alone: (1) any lymph node involved by tumor greater than 2 cm (stage N2b); (2) > or = six nodes involved with tumor (stage N2b); and (3) extranodal extension (stage N3). Two cycles of therapy were given at 21-day intervals; each cycle consisted of etoposide 100 mg/m2 plus cisplatin 20 mg/m2 per day given on days 1 to 5. RESULTS: Fifty patients were treated with two cycles of EP. Treatment was well tolerated; five patients (10%) were admitted for nadir fever and none had grade II or greater neurologic, renal, or pulmonary toxicity. All 50 patients are alive and relapse-free at a median follow-up time of 35 months (range, 12 to 72). The follow-up duration has been > or = 2 years for 42 patients. CONCLUSION: A treatment program that consists of two cycles of EP is effective in preventing relapses in patients with completely resected pathologic stage N2b and N3 NSGCT. The likelihood of relapse without adjuvant cisplatin-containing chemotherapy in this group has been shown to be greater than 50%. As has been demonstrated in patients with disseminated germ cell tumor (GCT), EP can be considered a therapeutic option in the adjuvant setting for completely resected N2b and N3 NSGCT.

Adolescent↗

Calcinosis cutis and intestinal pseudoobstruction in a patient with adult onset Still's disease associated with recurrent relapses of disordered coagulopathy.

Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown origin, characterized by a typical spiking fever, evanescent salmon-colored rash, polyarthralgia, and myalgia. Calcinosis cutis and gastrointestinal involvement have rarely been noted in AOSD. We herein describe a 54-year-old woman who demonstrated repeated disseminated intravascular coagulation (DIC), and adult respiratory distress syndrome (ARDS), associated with AOSD. The patient also revealed a remarkable degree of digital calcinosis cutis and intestinal pseudoobstruction. A connective tissue disease, such as systemic sclerosis, might have been the underlying factor in the latter two symptoms.

Anticoagulants↗

[Remission and relapse of acute eosinophilic pneumonia].

A 46-year-old man presented with progressive dyspnea of acute onset, nonproductive coughing, and a high fever. He had been in his usual good health until symptoms began on the previous day. The chest roentgenogram revealed Kerley A and B lines, perivascular cuffing, hilar haze, and bilateral pleural effusins. Body temperature was 37 degrees C and PaO2 was 42 Torr. All clinical and radiographic signs improved. On the 12th hospital day, dyspnea and diffuse infiltration shadows on the chest roentgenogram suddenly occurred again. Acute eosinophilic pneumonia was strongly suspected because of increasing peripheral eosinophilia, and from the results of histologic examination of a specimen obtained by transbronchial lung biopsy. Without steroid treatment, the patient's condition gradually improved. Most cases of eosinophilic pneumonia have been diagnosed as pulmonary infiltration with eosinophilia (PIE). However, this patient did not have PIE syndrome, but instead was given a diagnosis of acute eosinophilic pneumonia, which was first described in 1990. This case may help establish criteria for the diagnosis and steroid treatment of acute eosinophilic pneumonia.

Acute Disease↗

Chloramphenicol combined with ampicillin in treatment of typhoid.

Fifty out of 100 patients with typhoid fever, matched for age, stage of illness, and degree of fever, were treated with chloramphenicol and the other 50 were treated with chloramphenicol combined with ampicillin. The febrile period was shortened by up to 29% in patients treated with the combined drugs compared with those given only chloramphenicol. Moreover, no patient on combined therapy had a febrile relapse, whereas two relapses occurred among patients treated with chloramphenicol only. We conclude that chloramphenicol and ampicillin together are better than chloramphenicol alone in the treatment of typhoid fever.

Adolescent↗

[Malignant peritoneal mesothelioma occurring in periodic disease: apropos of a case].

INTRODUCTION: Peritoneal mesothelioma is a rare malignant neoplasm that might be linked to chronic peritoneal inflammation. As well, the association peritoneal mesothelioma-familial Mediterranean fever is uncommon. EXEGESIS: We report the case of a 60-year-old man who presented for 30 years with standard periodic familial Mediterranean fever accompanied by acute abdominal episodes, sensitive to colchicine. Between 1988 and 1995, acute abdominal episodes were accompanied by more and more profuse recurrent ascites, partially resolving under colchicine treatment. In 1995, the last episode was severe (with loss of weight and inability to tolerate feeding) and conducted to the patient's death due to peritoneal mesothelioma, as confirmed by the biopsy. CONCLUSION: Profuse and recurrent ascites is unusual in standard periodic familial Mediterranean fever. Asbestos exposure at the origin of peritoneal mesothelioma is not well documented. Furthermore, the disease clinical and paraclinical features are misleading, and the diagnosis is based on histology. The prognosis is severe, and treatment is usually disappointing. Our observation clearly demonstrates the interconnection between an unusual form of profuse and relapsing ascites that occurred in the course of a periodic disease and peritoneal mesothelioma. The potential role of recurrent peritonitis related to familial Mediterranean fever in the pathogenesis of the tumor is discussed.

Abdominal Pain↗

Comparison of a 6-month course peginterferon alpha-2b plus ribavirin and interferon alpha-2b plus ribavirin in treating Chinese patients with chronic hepatitis C in Taiwan.

Previous studies in Caucasian patients showed treatment of chronic hepatitis C with pegylated interferon/ribavirin was well tolerated, and produced a higher response rate especially in genotype 1 infections. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. A total of 153 patients with biopsy-proven chronic hepatitis C were randomly assigned to receive either weekly injection of peginterferon alpha-2b 1.5 mcg/kg plus oral ribavirin (1000 or 1200 mg/day, depending on body weight) (PEG group, n = 76) or 3 MU of interferon alpha-2b t.i.w. plus ribavirin (IFN group, n = 77) for 24 weeks. Sustained virological response (SVR) was defined as the sustained disappearance of serum hepatitis C virus (HCV) RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Baseline demographic, viral and histological characteristics were comparable between the two groups. Using an intent-to-treat analysis, HCV genotype 1 patients showed a significantly higher SVR in patients receiving PEG-IFN rather than IFN (65.8%vs 41.0%, P = 0.019), but no difference was found in genotype non-1 patients (PEG vs IFN: 68.4%vs 86.8%, P = 0.060). Genotype 1 patients (28.6%) in the PEG-IFN group relapsed, as compared with 52.9% in the IFN group (P = 0.040). Multivariate analyses showed early virological response at week 12 of therapy and genotype non-1 were significant predictors to SVR. As compared with the IFN group, patients receiving PEG-IFN had a significantly higher rate of discontinuation, dose reduction, fever, headache, insomnia, leucopenia and thrombocytopenia. In genotype 1 chronic hepatitis C Chinese patient, PEG-IFNalpha2b ribavirin had significantly better SVR and lower relapse rate when compared to IFN/ribavirin. Both regimens can be recommended for genotype non-1 chronic hepatitis C Chinese patients. However, a higher rate of adverse events and discontinuance of therapy were noted in patients treated with PEG-IFNalpha2b ribavirin.

Adolescent↗

[Hepatic resection plus hepatic artery infusion with implantable port for colorectal metastases].

Hepatic resection of metastatic colorectal carcinoma offers a chance for long term survival and is being performed with increasing frequency. The aim of this study is to reduce the re relapse in the residual liver after curative hepatectomy. Nineteen patients with hepatic metastases from colorectal carcinoma who underwent hepatic resection plus hepatic artery infusion therapy using an implantable port (HR-HAI) were analyzed. As hepatic resection, lobectomies were performed in 6 patients, segmentectomies in 8 patients and wedge resection in 5 patients. As chemotherapeutic agents, adriamycin in 8 patients, mitomycin C in 7 patients and OK-432 in 4 patients were used. The drugs were administered through hepatic artery via a port every one month for one year at the out patient clinic. Eight out of 19 patients had no complication by HR-HAI therapy, but 3 patients had catheter obstruction within one year, 4 had gastrointestinal discomfort, 3 fever up and 1 liver tissue necrosis. The serious hepatotoxicity such as sclerosing cholangitis was not observed. Re-relapses were appeared in 15 patients and the sites were the residual liver in 10 patients, and 5 in the other organs. The 3-year survival rate of 19 treated patients was 40.0% higher than 33.3% of 52 patients undergone hepatic resection alone, but the difference was not statistically significant.

Antineoplastic Agents↗

Prospective randomized comparative trial of pefloxacin versus cotrimoxazole in the treatment of typhoid fever in adults.

Pefloxacin, which has been shown to have a high in vitro activity against Salmonella spp., was compared to cotrimoxazole in the treatment of typhoid fever in adults. In a prospective, randomized trial, 42 patients with bacteriologically documented typhoid fever received either 400 mg pefloxacin b.i.d. or 160/800 mg cotrimoxazole b.i.d. Duration of treatment was 14 days in both groups. All patients were cured without experiencing a relapse or becoming a salmonella carrier. Apyrexia and resolution of digestive and neurological symptoms were obtained in a significantly shorter time with pefloxacin than with cotrimoxazole. Pefloxacin was well tolerated and more effective than cotrimoxazole in the treatment of typhoid fever.

Adult↗

Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with a high-dose doxorubicin-containing regimen.

Forty-seven previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with four courses of a regimen that consisted of high-dose (120 mg/m2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine (2 mg), cytarabine (3 gm/m2), and dexamethasone (50 mg intravenously [IV] on day 1 and 20 mg/day orally on days 2 to 5) (AVAD), which was administered every 3 to 4 weeks. The median age of the patients was 58 years; 72% were Ann Arbor stage IV, 49% had "B" symptoms, 62% had masses larger than 7 cm, 40% had masses at least 10 cm in diameter, and 49% had serum lactate dehydrogenase (LDH) greater than 250 U/L. Overall, 72% of the patients (89% of diffuse large-cell lymphoma [DLCL] patients) attained complete (CR) or probable complete responses (PCR), and relapses occurred in 32%. There were no episodes of clinical congestive heart failure, but one patient developed recurrent ventricular arrhythmias. Fever during neutropenia occurred with 65% of treatment courses. Three deaths were attributed primarily to complications of therapy. The lymphoma-free survival of all entered patients is 51% (24 of 47), with a follow-up of 30 to 67 months (median, 58 months). These results confirm that high CR/PCR and long-term survival rates can be achieved in patients with aggressive histologies of non-Hodgkin's lymphomas, even in groups with poor prognostic factors, using high-dose anthracycline-containing chemotherapy regimens delivered over a short period of time. However, the apparently higher relapse rate in comparison to our previous study leads us to speculate that consolidation with noncross-resistant agents may be helpful in increasing even further the cure rate in this group of patients.

Adult↗

Lomustine (CCNU) for the treatment of resistant lymphoma in dogs.

Forty-three dogs with lymphoma that had relapsed or had failed to achieve complete remission to previous chemotherapy were treated with lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea [CCNU]) at a dosage of 90-100 mg/m2 body surface area p.o. every 3 weeks. Durable complete or partial responses occurred in 11 dogs for a median of 86 days. The acutely dose-limiting toxicosis was neutropenia 7 days after administration, resulting in a recommended dosage of 90 mg/m2. Cumulative thrombocytopenia occurred in dogs receiving continued CCNU treatment, and a dose interval of 3 weeks may be too short for continued administration of this drug. Toxicoses evident as fever or central nervous system signs or renal damage were uncommon or rare. CCNU is effective in the treatment of relapsed lymphoma.

Animals↗

Herpes simplex encephalitis: diagnostic problems and late relapse.

A 5-year-old female presented with prolonged afebrile right-sided focal seizures, right brachio-facial paralysis, and dysarthria; consciousness was not altered. Fever appeared 20 hours after onset of neurological symptoms. At admission (day 1) cerebral computerized tomography and cerebrospinal fluid (CSF) analyses were normal including undetectable alpha-interferon (alpha-IFN) and negative herpes simplex virus (HSV) polymerase chain reaction (PCR). Acyclovir was started at a dosage of 60mg/kg/day for 21 days and neurological symptoms improved. Cerebral magnetic resonance imaging (MRI) showed lesions in the left thalamus and left parietal lobe. On day 8, CSF contained an elevated leukocyte count with a predominance of lymphocytes, but alpha-IFN and HSV DNA were still undetectable. Delayed intrathecal synthesis of specific anti-HSV antibodies was found on day 26 and confirmed herpes simplex encephalitis (HSE) diagnosis. Twenty months after this episode, the patient presented with a febrile meningeal syndrome. PCR detected HSV DNA in CSF and cerebral imaging showed a new left temporal lesion. At relapse onset, intrathecal synthesis of specific anti-HSV antibodies had disappeared. Acyclovir was started at a dosage of 60mg/kg/day for 21 days and neurological status improved. At discharge, neurological examination showed right hemiparesis and bucco-facial dyspraxia. Diagnostic problems of HSE diagnosis in children are highlighted. It is suggested that the premature disappearance of intrathecal synthesis of a specific anti-HSV antibody might play a permissive role in the resurgence of cerebral viral replication.

Acyclovir↗

Prophylactic treatment of Rocky Mountain spotted fever.

Prophylactic treatment of Rocky Mountain spotted fever with a single dose of oxytetracycline was investigated in guinea pigs. Disease was prevented when treatment was administered shortly before expected onset. Relapses occurred when treatment preceded expected onset by 48 h or more.

Agglutination Tests↗

Early response to alpha interferon in a patient affected by hairy cell leukemia.

A 61-year-old splenectomized male patient affected by hairy cell leukemia (HCL) in relapse was treated with interferon (IFN) at a dosage of 3 x 10(6) U/day. After only 11 days of treatment, IFN was stopped because the patient developed fever, jaundice and respiratory distress. Upon recovery from this infectious episode, the patient was judged to be in complete remission of HCL on the basis of clinical and laboratory findings, and he remained off-therapy for 2 years. When an overt relapse occurred, the patient was again treated with IFN and, after a very short time, he achieved a new, good partial remission that is maintained 28 months later without treatment. This observation remains speculative for understanding the mechanism of action of IFN in other comparable HCL cases.

Combined Modality Therapy↗

[Episodic angioedema associated with eosinophilia in relapsing erythema and swelling of the right thigh].

On March 16, 2000, a 37-year-old male was admitted to another hospital for fever, erythema of the limbs, and swelling of the right lower leg. The leukocyte count was 19,800/microliter, and the ratio of eosinophils was 61%, suggesting marked eosinophilia. Thoracic computed tomography (CT) revealed pneumonia in the left lung. However, the patient was negative for autoantibodies or parasitic antibodies. Administration of prednisolone at 80 mg/day resulted in a marked improvement of the symptoms and the eosinophilia. For diagnosis, detailed examination, and treatment, the patient was referred and admitted to our department on March 28. The dose of prednisolone was gradually decreased. On April 15, the agent was discontinued. Eosinophilia was not observed, however erythema of the limbs and swelling of the right lower leg recurred. Skin biopsy revealed in mild edema of the corium and eosinophilic infiltration, suggesting episodic angioedema associated with eosinophilia (EAE). In 1984, Greich et al. reported 4 patients with repeated angioedema, hives, and marked eosinophilia, and proposed the term EAE. Since then, more than 50 patients have been reported in Japan. Only 4 of these patients were males. We report on the present male patient together with the pathological findings.

Adult↗