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The treatment of hairy cell leukemia with alpha 2b-interferon: experience with 27 patients treated more than one year.

Thirty-six patients with progressive hairy cell leukemia were treated with recombinant alpha 2b-interferon injected subcutaneously 2 X 10(6) IU/m2, three times a week. Twenty-seven patients completed 12 months of therapy and were randomized either to receive 6 months of continued interferon or to go off treatment. At the time of randomization, two patients had achieved a complete response, 22 a partial response, and three a minimal response. Three patients have relapsed, one while receiving interferon during the randomization period and two who were off therapy for 6 months. The outpatient regimen of interferon administration was well tolerated, with the principal acute toxicities being fever and an influenza-like syndrome and the major long-term toxicity being mild-moderate fatigue.

Humans↗

[Study of the association of histocompatibility antigens with rheumatism].

Study of histocompatibility antigens of the HIA system in 86 patients with rheumatic fever has demonstrated the high rate of the antigens AII, B27, Cw2, 3, Dr5, 7 as compared with control (600 healthy persons). It is therefore necessary to point to the involvement of the HIA system in the formation of proneness to rheumatic fever and its clinical varieties. Special attention should be drawn to the locus HIA C. Histocompatibility antigens associated with rheumatic fever can be viewed as risk factors which should necessarily be taken into account during the conduction of the primary prophylaxis, especially in children coming from the families whose members are afflicted with rheumatic fever as well as in predicting the character of the disease progress and heart disease formation. The presence in the phenotype of A2, AII, B13, 27, Cw2, 3 is associated with a continuously relapsing disease. A10 occurs only in an acute disease marked by a high degree of activity. Mitral diseases are associated with A9, B27, Cw2, 3 whereas aortal distress with AII, B7, 27 and Cw2. B13, Bw35, Cw2 and Dr7 are mostly demonstrable in patients without any heart disease, Dr4 occurs in diseases characterized by minimal activity.

Aortic Valve↗

Etoposide plus carboplatin or cisplatin in good-risk patients with germ cell tumors: a randomized comparison.

Two hundred sixty-five evaluable patients were randomized to receive either carboplatin/etoposide (131 patients) or cisplatin/etoposide (134 patients). Among the carboplatin-treated patients, 115 (88%) achieved a complete remission, compared with 121 (90%) of patients receiving cisplatin. In the carboplatin group, however, 16 patients (12%) relapsed following complete remission, in contrast to four (3%) of those receiving cisplatin. Thus, the total number of unfavorable events (incomplete response + relapse) was 32 (24%) in the carboplatin arm, compared with 17 (13%) in the cisplatin arm (P = .02). In addition, patients receiving carboplatin had a greater likelihood of being hospitalized for neutropenia and fever (P = .016) and had lower platelet nadirs (P < .001). It was concluded that carboplatin administered at the dose and schedule used in this clinical trial resulted in an inferior event-free survival rate and worse toxicity than cisplatin, and is not recommended for use in general practice.

Adolescent↗

Long-lasting complete remission in patients with hairy cell leukemia treated with 2-CdA: a 5-year survey.

Between January 1991 and January 1994, 40 patients with hairy-cell leukemia (HCL), 30 males and 10 females, with a median age of 54 years, were treated with a single course of 2-chlorodeoxyadenosine (2-CdA) at a dose of 0.1 mg/kg/day continuous infusion for 7 days. Thirteen patients were untreated and 27 had previously received alpha-interferon. Thirty out of 40 patients (75%) achieved complete remission (CR) and 10 (25%) partial remission (PR). The median follow-up duration for patients in CR has been 48 months (range 30-66). Five of the complete responders (17%) relapsed at 12, 24, 26, 30 and 36 months after treatment as documented by the increase of hairy cells (Hc) in the bone marrow and two of them, who were retreated with 2-CdA after showing an initial impairment of peripheral blood values, obtained a second CR. The remaining three relapsed patients were never retreated and still show normal peripheral counts after 30, 38 and 40 months. Twelve of the continuous complete responder patients are still in CR after more than 5 years. In contrast, 8 out of 10 partial responders progressed after 8-36 months and all of them were retreated with 2-CdA at a dose of 0.15 mg/kg/day for 5 days i.v. Four of them (50%) achieved a CR, three a better PR and one patient died 6 months after the second 2-CdA course because of infectious complications. Two additional patients, both in CR, died after 28 and 37 months because of a second neoplasm. Toxic side-effects consisted of febrile episodes recorded in 16 patients: in seven of them, fever lasted only 24-48 h after the end of treatment and was apparently not infection-related. In the remaining nine patients, showing in addition severe neutropenia (neutrophils less than 1.0 x 10(9)/l), fever was related to bacterial infection requiring systemic antibiotics in all of them and G-CSF in three cases. In conclusion, 2-CdA induces a very high proportion of complete and long-lasting remissions in patients with HCL. In a number of cases relapse at bone marrow level may not affect peripheral blood values for prolonged time. However, in those patients with initial pancytopenia a retreatment with 2-CdA is still effective in inducing a durable second CR.

2-Chloroadenosine↗

Prospective, multicenter evaluation of risk factors associated with invasive bacterial infection in children with cancer, neutropenia, and fever.

PURPOSE: To identify clinical and laboratory parameters present at the time of a first evaluation that could help predict which children with cancer, fever, and neutropenia were at high risk or low risk for an invasive bacterial infection. PATIENTS AND METHODS: Over a 17-month period, all children with cancer, fever, and neutropenia admitted to five hospitals in Santiago, Chile, were enrolled onto a prospective protocol. Associations between admission parameters and risk for invasive bacterial infection were assessed by univariate and logistic regression analyses. RESULTS: A total of 447 febrile neutropenic episodes occurred in 257 children. Five parameters were statistically independent risk factors for an invasive bacterial infection. Ranked by order of significance, they were as follows: C-reactive protein levels of 90 mg/L or higher (relative risk [RR], 4.2; 95% confidence interval [CI], 3.6 to 4.8); presence of hypotension (RR, 2.7; 95% CI, 2.3 to 3.2); relapse of leukemia as cancer type (RR, 1.8, 95% CI, 1.7 to 2.3); platelet count less than or equal to 50,000/mm(3) (RR, 1.7; 95% CI, 1.4 to 2.2); and recent (< or = 7 days) chemotherapy (RR, 1.3; 95% CI, 1.1 to 1.6). Other previously postulated risk factors (magnitude of fever, monocyte count) were not independent risk factors in this study population. CONCLUSION: In a large population of children, common clinical and laboratory admission parameters were identified that can help predict the risk for an invasive bacterial infection. These results encourage the possibility of a more selective management strategy for these children.

Adolescent↗

[Bacteremia caused by Salmonella non-typhi in patients infected with HIV].

All the cases of HIV infected patients diagnosed in our department during 1987 of Salmonella bacteremia are included in this report. Out of a total of 10 patients with both conditions, six were diagnosed of AIDS, three of AIDS related complex, and one presented an asymptomatic HIV infection. The mean age was 32.9 years (range 22 to 56). Eight of them were males, seven were intravenous drug addicts, and three were homosexual. Fever was observed in all cases and diarrhea in four of them. Salmonella enteritidis was isolated from the blood culture of nine patients and salmonella typhimurium from one. Salmonella enteritidis was isolated from the stool culture of 5 patients and Salmonella typhimurium and Campylobacter from the stool culture of one patient. Of the 10 patients 6 have died, 4 of them within the three weeks after the diagnosis of Salmonella non-typhi bacteremia, 2 have not relapsed and two patients were lost during follow up.

Acquired Immunodeficiency Syndrome↗

Relapsing polychondritis in an adolescent.

Relapsing polychondritis (RP) is an uncommon systemic disorder with a highly variable course. A 17-year-old woman recently presented with a 1-month history of depression, weight loss, chest wall tenderness, hoarseness, and dysphagia. Physical examination revealed cachexia, low-grade fever, pharyngeal erythema, and tenderness of the right auricle, anterior chest, cricothyroid cartilage, and both knees. Laboratory studies included a hematocrit of 34% and a sedimentation rate of 50 mm/hr. Initial improvement on oral corticosteroids was followed by respiratory distress. At that time calcified tracheal cartilage, subglottic stricture, and a saddle nose deformity were present. Despite therapy with steroids, dapsone, and pulse cyclophosphamide, the respiratory distress reoccurred, eventually necessitating tracheostomy. Tracheal cartilage biopsy confirmed the presumptive diagnosis of RP. Bilateral auricular chondritis developed after initial presentation, as did acute vertigo. Although seen in all age groups, less than 10% of cases of RP are seen in children and adolescents. Auricular chondritis (89% of all cases), inflammatory asymetric arthritis (81% of all cases), nasal chondritis (72% of all cases), respiratory tract chondritis (56% of all cases), and audiovestibular abnormalities (46% of all cases) were present in our patient. Relapsing polychondritis may follow a slowly evolving or rapidly progressive course. Appropriate diagnosis and aggressive therapy are recommended to lessen the morbidity and mortality.

Adolescent↗

High dose melphalan and total body irradiation with autologous marrow rescue in childhood acute lymphoblastic leukaemia after relapse.

High dose melphalan (HDM 110-140 mg/m2) and total body irradiation (TBI, 10.5 Gy, single fraction) followed by infusion of autologous bone marrow (ABMT) was evaluated for toxicity and efficacy in 24 children with acute lymphoblastic leukaemia (ALL) in second (CR2) or third remission (CR3). Marrow was purged with Campath 1 in six children (four were children in CR3). All children had engraftment with a median of 30 days (range 18-70 days) to neutrophil count greater than 0.5 x 10(9)/l. Four children (16%) died from toxicity 1-4 months after autograft, two from pneumonitis, one from an intracerebral haemorrhage and one from sepsis. Apart from fever and mucositis the procedure was well tolerated. Nine of 17 children treated in CR2 remain in complete remission 6-72 months after ABMT (median 25 months). Seven of these have a follow-up of greater than 12 months. Three of the seven children treated in CR3 are alive 17, 22 and 29 months post ABMT. Seven children relapsed within 10 months (median 4 months) of the autograft. Only one relapse has occurred beyond 10 months. HDM and TBI followed by ABMT is a relatively well tolerated regimen and may contribute to survival in children with relapsed ALL.

Adolescent↗

[Studies on the relation between the production of anti-O and anti-H agglutinins and the specific treatment of typhoid fever].

The AA, studied the behaviour of anti-O and anti-H agglutinins in patients with typhoid fever treated with CAF or with CAF+ corticosteroides. They have shown that, during the treatment with antibiotics, the O-agglutinins, which appeared extremely quickly, can be present at a high level and for a long time in the serum; on the other hand the H-agglutinins are usually present at a lower level and tend to decrease more rapidly. In patients treated with CAF+ corticosteroides the agglutinins behaviour was not substancially different from that in patients treated with antibiotic only. These modifications in humoral immunity are notable only when treatment is begun early. On the basis of the results and of data in the most recent literature, the AA. also discuss the problem of typhoid relapses, the pathogenesis of which cannot depend from the modifications of humoral immunity only.

Adolescent↗

Doxycycline and rifampicin for mild scrub-typhus infections in northern Thailand: a randomised trial.

BACKGROUND: Some strains of scrub typhus in northern Thailand are poorly responsive to standard antirickettsial drugs. We therefore did a masked, randomised trial to compare rifampicin with standard doxycycline therapy for patients with scrub typhus. METHODS: Adult patients with strictly defined, mild scrub typhus were initially randomly assigned 1 week of daily oral treatment with 200 mg doxycycline (n=40), 600 mg rifampicin (n=38), or doxycycline with rifampicin (n=11). During the first year of treatment, the combined regimen was withdrawn because of lack of efficacy and the regimen was replaced with 900 mg rifampicin (n=37). Treatment outcome was assessed by fever clearance time (the time for oral temperature to fall below 37.3 degrees C). FINDINGS: About 12,800 fever patients were screened during the 3-year study to recruit 126 patients with confirmed scrub typhus and no other infection, of whom 86 completed therapy. Eight individuals received the combined regimen that was discontinued after 1 year. The median duration of pyrexia was significantly shorter (p=0.01) in the 24 patients treated with 900 mg daily rifampicin (fever clearance time 22.5 h) and in the 26 patients who received 600 mg rifampicin (fever clearance time 27.5 h) than in the 28 patients given doxycycline monotherapy (fever clearance time 52 h). Fever resolved in a significantly higher proportion of patients within 48 h of starting rifampicin (900 mg=79% [19 of 24], 600 mg=77% [20 of 26]) than in patients treated with doxycycline (46% [13 of 28]; p=0.02). Severe gastrointestinal events warranted exclusion of two patients on doxycyline. There were two relapses after doxycycline therapy, but none after rifampicin therapy. INTERPRETATION: Rifampicin is more effective than doxycycline against scrub-typhus infections acquired in northern Thailand, where strains with reduced susceptibility to antibiotics can occur.

Adolescent↗

Aggressive combination chemotherapy of bone marrow relapse in childhood acute lymphoblastic leukemia containing aclacinomycin-A: a multicentric trial.

An intensive 7-day combination chemotherapy protocol was designed to reinduce children with early bone marrow relapse of acute lymphoblastic leukemia (less than 6 months after the end of or during preceding treatment). This aggressive approach seemed to be justified for a group of patients who were at the highest risk for ultimate treatment failure. In all, 38 children were enrolled for study. The ratio of male (median age, 10 years) to female (median age, 13 years) subjects was 27:11. Thirty patients were treated for their first relapse and eight for their second or subsequent relapse. Isolated bone marrow involvement was present in 24 cases. All patients had received heavy pretreatment including anthracyclines with cumulative doses of between 120 and 240 mg/m2. 22 of these patients, achieved complete remission, ten did not respond to therapy, and six died from the toxicity of the protocol. Cardiac failure was the cause of death in one child (after additional radiotherapy for a mediastinal mass). No further clinical manifestation of cardiomyopathy could be observed. The other five patients died from hemorrhages or infectious complications. The main side effects were fever, gastrointestinal problems, stomatitis, and severe bone marrow aplasia lasting for about 2 weeks with nadirs of platelets and white blood count around days 10-14. The remission rate of 60% was acceptable, though not satisfactory. Only four children survived disease-free for 13+, 14+, 20+, and 22+ months after diagnosis of relapse.

Aclarubicin↗

[Severe withdrawal symptoms with fever during paroxetine tapering off].

A 30-year-old man with depression who was treated with paroxetine (Seroxat) developed severe withdrawal symptoms when the medication was gradually diminished and stopped: agitation, irritability, vertigo, lightheadedness and fever up to 40 degrees C. The symptoms disappeared after the medication was reintroduced but recurred after rediscontinuation. When the dosage was diminished very gradually the symptoms were mild. The depression did not recur. Such withdrawal symptoms are most prevalent after discontinuation of paroxetine but can occur after use of all selective serotonin reuptake inhibitors. The withdrawal syndrome includes both physical and psychiatric symptoms and needs to be distinguished from a relapse of the psychiatric disorder. Good information and gradual discontinuation of the antidepressant after long-term use are adequate measures to prevent severe withdrawal symptoms.

Adult↗

Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse.

OBJECTIVE: To study the characteristics of catheter-related, gram-negative bacteremia (GNB) and the role of central venous catheter (CVC) removal. DESIGN: This retrospective study involved a search of the microbiological department records of CVC and blood cultures and patients' medical records. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Patients with cancer who had catheter-related GNB, defined as (1) a positive catheter tip culture with at least 15 colony-forming units semiquantitatively, (2) isolation of the same organism from the tip and peripheral blood cultures, (3) no other source for bacteremia except the CVC, and (4) clinical manifestations of infection (fever or chills). RESULTS: Between January 1990 and December 1996, 72 cases of catheter-related GNB were available for review. Most of the patients (67; 93%) had their CVCs removed in response to the bacteremia. Few patients (5; 7%) retained their CVCs and were treated with appropriate antibiotics. When CVCs were removed, only 1 patient (1%) relapsed with the same organism, whereas all 5 patients with retained CVCs relapsed after having responded (P < .001). The most commonly isolated organisms were Enterobacter, Klebsiella, Stenotrophomonas, Pseudomonas, and Acinetobacter species. Catheter removal within 72 hours of the onset of the catheter-related GNB was the only independent protective factor against relapse of the infection (odds ratio, 0.13; 95% confidence interval, 0.02-0.75; P = .02). CONCLUSION: In patients with documented catheter-related GNB, CVCs should be removed within 48 to 72 hours to prevent relapse.

Anti-Bacterial Agents↗

Fludarabine combination therapy for the treatment of chronic lymphocytic leukemia.

Fludarabine combination therapies have attained an increased popularity in the treatment of chronic lymphocytic leukemia (CLL). Among them, the combination of fludarabine/cyclophosphamide (FC) is by far the best regimen studied. Patients receiving FC at relapse show response rates (RRs) of 70%-94% with 11%-34% complete remission (CR) rates. In previously untreated patients with CLL, RRs of 64%-88% with 21%-46% CR rates were observed. The main side effects of FC are myelotoxicity and infections; most complications are reported as fever of unknown origin, infections of the upper respiratory tract, or herpes virus infection. There is probably a correlation between the higher dose of cyclophosphamide (> 750 mg/m2 per treatment course) and an increase in the number of severe infectious complications. Similar results were reported regarding the RRs and side effects of the combination of fludarabine/epirubicin. The triple combination of fludarabine/cyclophosphamide/mitoxantrone and fludarabine combinations with anti-CD20 (rituximab) or anti-CD52 (Campath-1H) antibody, might be even be more promising, since a relevant number of complete molecular remissions are achieved with these drugs. The precise role of fludarabine combinations within the overall treatment strategy remains to be determined. Our current recommendation is to use these combinations at relapse, while their use in first-line therapy should be investigated in clinical protocols. It remains to be shown whether patients with CLL achieve improved overall survival with these combination chemotherapies.

Adolescent↗

Typhoid fever in Singapore: a review of 370 cases.

The medical records of 370 patients treated for typhoid fever between 1986 and 1988 at the Communicable Disease Centre, Singapore, were reviewed. The disease was generally mild. There was no mortality. Fever was found in 98.4% of patients on admission and diarrhoea in 21%. Cough was predominantly a symptom of children and occurred in 7.1% of patients aged below 15 years. Other symptoms were uncommon. Hepatomegaly was found in 71% and splenomegaly in 47%. Leucopenia was not a helpful diagnostic marker. Chloramphenicol was the drug of choice. The relapse rate was 5.4% and the convalescent and temporary carrier rates 11.6%. The risk of developing the carrier state was significantly higher among patients who were afebrile on admission compared with those who were febrile (P less than 0.001); it was also higher in patients treated with ampicillin as compared to those treated with chloramphenicol (P less than 0.001, chi 2 = 22.7, odds ratio = 5.25, 95% confidence limits: 2.46 and 11.29). The role of ampicillin as a first line treatment for acute typhoid fever may need further re-evaluation.

Adolescent↗

High-dose chemoradiotherapy with syngeneic bone marrow transplantation for multiple myeloma: a case report and literature review.

We had the opportunity to treat a patient with progressive heavily pretreated multiple myeloma with high-dose chemoradiotherapy with hematopoietic rescue by syngeneic bone marrow transplantation. The patient was a 53-year-old male who had previously received melphalan, prednisone, 1,3-bis (2-chloroethyl)-l-nitrosourea (BCNU), vincristine, and standard radiation therapy. At the time of bone marrow transplantation, he had increasing bone pain, increasing M-protein (IgG kappa), and a bone marrow diagnostic of myeloma. The transplant regimen consisted of cyclophosphamide, 60 mg/kg intravenously for 2 days, and total body irradiation--1,200 rads given as 200-rad fractions, twice daily for three days. The transplant course was complicated by confusion, herpes simplex mucositis, fever, and two episodes of idiopathic diffuse interstitial pneumonia. Over the next 2 years the patient did well and was in immunologic and bone marrow complete remission. Unfortunately, 3 years after treatment, the myeloma relapsed with detectable M-protein. Three and one-half years after transplant, clinical relapse occurred with bone pain and lytic lesions necessitating additional radiation and chemotherapy. Salvage therapy has produced clinical improvement and the patient is alive almost 4 years from transplant and almost 7 years from diagnosis. Although intense chemoradiotherapy did not cure this patient, substantial control of a refractory tumor was observed. This case, together with other cases of intense therapy for myeloma which are reviewed in this paper, support the concept of high-dose therapy and should foster further investigation of high-dose therapy.

Bone Marrow Transplantation↗