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To date, bone marrow transplantation affords the only successful means of achieving full immunologic reconstitution of patients with severe combined immunodeficiency disease (SCID). We have achieved immunologic reconstitution in 6 of 7 SCID patients using marrow transplants from compatible sib donors. One child died of Pneumocystis carinii pneumonia following early immunologic reconstitution. A second child died of sepsis without evidence of engraftment, despite 3 marrow grafts, and a third died unexpectedly from massive aspiration pneumonia following complete immunologic reconstititon. Thus, in 4 of 7 children with SCID full and long-lasting immunologic reconstitution has been achieved by transplantation of marrow from matched sib donors. From these initial efforts, much has been learned, and it is clear that several factors, some of which remain poorly understood, may influence the outcome of marrow grafting. However, despite the difficulties encountered, bone marrow transplantation continues to hold real promise for correction of this otherwise fatal disease.
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PMID:Compatible bone marrow transplantation and immunologic reconstitution of combined immunodeficiency disease. 23 81

In order to determine the nature of infectious complications in hairy-cell leukemia we studied 20 consecutive patients seen at UCLA and analyzed the available literature. The incidence of serious infection in our series was 40%, and pneumonia and septicemia due to Pseudomonas and E. coli organisms were the leading types of infections. Fungal infections with Cryptococci and Histoplasma organisms were documented, and a single case of Pneumocystis carinii pneumonia was observed. Noninfectious fever occurred in 30% of our patients. There was a clear relationship between fungal disease and corticosteroid therapy, and the overall incidence of infection was correlated with the degree of neutropenia and corticosteroid treatment. No relationship was found between age, duration of disease, or the use of cytotoxic chemotherapy and infectious complications. Of the 13 infectious episodes, 11 occurred in patients prior to splenectomy. Only two episodes were seen in splenectomized patients, both occurring in the immediate postoperative period. We conclude that splenectomy has a beneficial effect in reducing the incidence of infections in hairy-cell leukemia and that corticosteroids should be used cautiously, since they predispose to opportunistic infection in this disease.
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PMID:Infections in hairy-cell leukemia. 41 62

The purpose of this study was to determine the prevalence of fever of unknown origin (FUO) in a cohort of HIV positive patients and to describe their evolution and the final diagnosis. The clinical records of 412 patients followed from January 1987 to December 1990 at our HIV outpatient clinic were reviewed: in 151 patients 255 episodes of fever had been observed of which 22 (in 21 patients) met the criteria for FUO. 19 patients (90%) presented with a CDC/WHO stage IV HIV infection and the mean CD4+ lymphocyte count was 0.160 G/l. The etiology was ultimately determined in 13/22 episodes (3 Pneumocystis carinii pneumonia, 3 invasive infections due to atypical mycobacteria, 2 bacterial pneumonia, 1 Cytomegalovirus colitis, 1 Isospora belli enteritis, 1 visceral leishmania, 1 candida septicemia and 1 lymphoma). In 6/22 episodes, the fever subsided after zidovudine was started and was therefore attributed to HIV itself. In 3/22 episodes no etiology was found. In conclusion, this series shows that FUO is usually seen in advanced HIV infection and that it often represents an early sign of opportunistic infection. This observation underlines the importance of follow-up, since it finally served to detect the etiology of FUO in 86% of cases. Trial treatment with zidovudine can be useful where no pathology has been discovered despite 3 weeks' follow-up and appropriate investigations.
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PMID:[Fever of unknown origin in a cohort of HIV-positive patients]. 144 86

In this project, we examined the spectrum of AIDS-related conditions and variations in associated inpatient mortality for AIDS patients treated in a national sample of hospitals. We identified 10,538 adult discharges with a diagnosis indicating AIDS from 258 hospitals from a national sample of 438 acute-care hospitals with 6 million discharges in 1986-1987. Opportunistic and other infections occurred in 55.9 and 37.9%, respectively, of AIDS discharges, and inpatient fatality rates varied considerably depending on complication type(s) and comorbidities. Clinical conditions were more important predictors of inpatient death than demographic or treatment site characteristics. Among opportunistic infections, odds of inpatient death were significantly increased for progressive multifocal leukoencephalopathy (odds ratio [OR] = 2.8), Pneumocystis carinii pneumonia (OR = 2.4), cryptococcosis (OR = 1.6), atypical mycobacterial infections (OR = 1.6), and toxoplasmosis (OR = 1.3). Odds of inpatient death were also significantly increased by non-AIDS-defining infections causing septicemia (OR = 3.1) or CNS involvement (OR = 1.6) or pulmonary involvement (OR = 1.5). After controlling for clinical conditions, significant differences in odds of death persisted across regions, age, and ethnic groups. Increases in hospitals' AIDS treatment experience were associated with a significant decrease in odds of inpatient death. These analyses provide a national perspective on the diversity of AIDS-related clinical conditions and their relative effects on inpatient mortality.
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PMID:Variations in inpatient mortality for AIDS in a national sample of hospitals. 145 27

Twenty-one patients (median age = 34, range = 10-49; F:M = 7:14) received a preparative regimen consisting of busulfan 4 mg/kg/day x 4, cytosine arabinoside 2 g/m2/12 h x 4 and cyclophosphamide 60 mg/kg/day x 2 ('BAC' regimen) for allogeneic bone marrow transplantation. Out of 12 patients with acute myeloid leukemia (AML), two were in first remission, six were in second remission and four had resistant, relapsed disease or prolonged marrow aplasia after induction chemotherapy. Five of the 12 patients with AML had secondary AML. Four patients had transfusion-dependent myelodysplastic syndrome. Three patients with chronic myeloid leukemia were in the accelerated phase and two were in the blastic phase. Organ toxicities related to the preparative regimen were graded. Liver toxicity occurred in 11 patients, two of these were fatal veno-occlusive disease (VOD) (10%). Nineteen of the 21 patients had grade 2 or less diarrhea, and 13 also had mucositis. One patient developed grade 3 cardiac toxicity, and one other patient had grade 1 skin toxicity. Four patients had gross hematuria related to treatment (19%). No renal, pulmonary or CNS toxicities were encountered. Ten patients have died, two from regimen-related hepatic VOD. Of the remaining eight deaths, four were from respiratory failure in four patients (one case each of Pneumocystis pneumonia, CMV pneumonia, bronchiolitis obliterans associated with chronic graft-versus-host disease, and interstitial pneumonitis complicated pulmonary emboli), and one patient each from GI bleeding, cardiac arrhythmia, sepsis and CNS bleeding. Thus far, only one patient transplanted for secondary AML in second remission relapsed at day 230.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allogeneic bone marrow transplantation in high-risk myeloid disorders using busulfan, cytosine arabinoside and cyclophosphamide (BAC). 154 49

During 1983-1988, hospitalizations of patients with a diagnosis of human immunodeficiency virus (HIV) infection increased from 1.3 to 33.7 per 100,000 persons. We used the National Hospital Discharge Survey, which is based on a representative sample of discharges from nonfederal short-stay hospitals, to describe illnesses among hospitalized patients with HIV infection. Of 222,200 such hospitalizations during 1983-1988, most occurred among persons who were 25-44 years of age (79%), white (66%), and male (90%). Among men 25-44 years of age, HIV admissions increased from 8.5 to 148.6 per 100,000 persons during 1983-1988; among black men 25-44 years of age, HIV hospitalizations increased from 43.1 to 387.4 per 100,000 persons. Among women, hospitalizations increased 3.4-fold. Frequently listed illnesses in the Centers for Disease Control (CDC) AIDS case definition were Pneumocystis carinii pneumonia (30%), candidiasis (20%), and Kaposi's sarcoma (13%). Other frequently listed illnesses included infections (39%) such as pneumonia, sepsis, and urinary tract infections; blood dyscrasias (30%) such as anemia, thrombocytopenia, and agranulocytosis; metabolic (17%), gastrointestinal (16%), and respiratory disorders (12%); and drug abuse (9%). These data provide a minimum estimate of HIV hospitalizations because for some patients HIV infection may not be specified on the discharge record. HIV hospitalizations are increasing markedly and are associated with a broad spectrum of severe morbidity.
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PMID:Increasing impact of HIV infection on hospitalizations in the United States, 1983-1988. 156 Mar 47

In a pilot study of the combination of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL), 10 patients with advanced or progressive disease were treated in four centres. Up to a total of 15 courses in individual patients were given. Toxicity was relatively mild with nausea due to epirubicin being the most commonly reported side-effect. One patient developed a probable septicemia during a period of neutropenia. In another patient who died from probable Pneumocystis carinii pneumonia (PCP) after only one course of therapy, death could not be regarded as necessarily treatment-related. In seven previously untreated patients, one complete response and four partial remissions were seen. All three previously treated patients showed partial remissions.
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PMID:A pilot study of epirubicin and chlorambucil in the treatment of chronic lymphocytic leukemia (CLL). 174 98

Twenty-five pediatric orthotopic liver transplantations (OLTs) performed in 22 patients at Sainte-Justine Hospital were reviewed for infections complications. One patient died within 12 hours posttransplantation and is excluded. The patients had an average age of 6.1 years (range, 1.25 to 19 years) and an average weight of 20.4 kg (range, 11 to 55 kg). Two patients (9%) were cytomegalovirus (CMV) seropositive and 9 of 19 patients (48%) were Epstein-Barr virus (EBV) seropositive preoperatively. Five of the donors (20%) were CMV seropositive. The most common indications for OLT were biliary atresia (8) and tyrosinemia (7). There were 4 deaths, for an overall mortality rate of 19%. In 3 patients, deaths were related to infection (CMV hepatitis and duodenitis with aortoduodenal fistula, adult respiratory distress syndrome [ARDS] with Streptococcus viridans pneumonia, Escherichia coli cholangitis with progressive hepatic failure). Fifteen patients (72%) had 41 major infections, most of them bacterial, during the first month posttransplantation. These include pneumonia (25%), line sepsis (17%), cholangitis (14%), and tracheitis (14%). There was only one major viral infection, a CMV hepatitis that occurred in the first month posttransplantation. Three patients had fungal infections (8%) associated with hepatic artery thrombosis and recurrent cholangitis. All three patients required retransplantation. There was only one protozoal infection (Pneumocystis carinii pneumonia) causing life-threatening respiratory failure, from which patient recovered without sequelae. Infection still remains a serious complication of OLT. Bacterial infection is common and is usually associated with technical complications. The low rate of CMV infection is related to low incidence of CMV in the donor pool and the minimal use of strong immunosuppressants.
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PMID:Infectious complications of pediatric liver transplantation. 191 82

To assess the effect of the human immunodeficiency virus (HIV) epidemic on mortality in US children younger than 15 years of age and to identify associated causes of death, the authors examined final national mortality statistics for 1988, the most recent year for which such data are available. In 1988, there were 249 deaths attributed to HIV/acquired immunodeficiency syndrome (AIDS) in children younger than 15 years of age. Associated causes of death listed most frequently on 270 death certificates with any mention of HIV/AIDS included conditions within the AIDS surveillance case definition (30%), pneumonia (excluding Pneumocystis carinii pneumonia) (17%), septicemia (10%), and noninfectious respiratory diseases (8%). The impact of HIV/AIDS as a cause of death was most striking in the 1-through 4-year-old age group and in black and Hispanic children, particularly in the Northeast. By 1988 in New York State, HIV/AIDS was the first and second leading cause of death in Hispanic and black children 1 through 4 years of age, accounting for 15% and 16%, respectively, of all deaths in these age-race groups. With an estimated 1500 to 2000 HIV-infected children born in 1989, the impact of HIV on mortality in children will become more severe.
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PMID:Impact of the human immunodeficiency virus epidemic on mortality in children, United States. 203 83

Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD-II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5-fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT). The best response rate (complete and partial remissions combined) was 73% in IESS-MD-I and 70% in IESS-MD-II, so there was no statistical evidence of a difference in response rates (P = 0.62). The length of best response also was similar between studies (P = 0.79), with approximately 30% of the patients on both studies remaining in remission at 3 years. The percentage of patients surviving 5 years or more was 30 on the first study and 28 on the second study (P = 0.49). The major sites of relapse after a response were lung and bone, each occurring with nearly equal frequency. The age of the patient was related to both best response rate and survival: patients 10 years of age or younger had substantially higher response and survival rates than patients 11 years of age or older. The favorable prognosis for younger patients might be explained by a more favorable distribution of primary sites at diagnosis; 39% of patients 10 years of age or younger had rib primary sites, compared with only 16% for patients older than 10 years of age (P = 0.05). The frequency of life-threatening toxicity was substantially higher in IESS-MD-I (30%) than in IESS-MD-II (9%), but the frequency of fatal toxicity was similar (6% to 7%). Fatal complications included Adriamycin-induced cardiomyopathy, Pneumocystis carinii pneumonia, unspecified pneumonitis, and sepsis. The most common toxicity and complications were leukopenia and infections.
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PMID:Ewing's sarcoma metastatic at diagnosis. Results and comparisons of two intergroup Ewing's sarcoma studies. 220 33


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