Biomedical subjects

A Stein

Publications and source records attributed to A Stein.

At least 73 records · Page 4Linked to original sources

PubMed2000

Predictors of therapy-related leukemia and myelodysplasia following autologous transplantation for lymphoma: an assessment of risk factors.

We analyzed data on 612 patients who had undergone high-dose chemoradiotherapy (HDT) with autologous stem cell rescue for Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the City of Hope National Medical Center, to evaluate the incidence of therapy-related myelodysplasia (t-MDS) or therapy-related acute myeloid leukemia (t-AML) and associated risk factors. A retrospective cohort and a nested case-control study design were used to evaluate the role of pretransplant therapeutic exposures and transplant conditioning regimens. Twenty-two patients developed morphologic evidence of t-MDS/t-AML. The estimated cumulative probability of developing morphologic t-MDS/t-AML was 8.6% +/- 2.1% at 6 years. Multivariate analysis of the entire cohort revealed stem cell priming with VP-16 (RR = 7.7, P = 0.002) to be independently associated with an increased risk of t-MDS/t-AML. The influence of pretransplant therapy on subsequent t-MDS/t-AML risk was determined by a case-control study. Multivariate analysis revealed an association between pretransplant radiation and the risk of t-MDS/t-AML, but failed to reveal any association with pretransplant chemotherapy or conditioning regimens. However, patients who had been primed with VP-16 for stem cell mobilization were at a 12. 3-fold increased risk of developing t-AML with 11q23/21q22 abnormalities (P = 0.006). Patients undergoing HDT with stem cell rescue are at an increased risk of t-MDS/t-AML, especially those receiving priming with VP-16 for peripheral stem cell collection. (Blood. 2000;95:1588-1593)

Adolescent↗

PubMed2000

A rare simultaneous presentation of testicular mixed germ cell tumor with a contralateral testis torsion.

We report a rare case of a 27-year-old man presenting with an acute scrotum with simultaneous occurrence of testicular tumor and contralateral torsion. Preoperative imaging demonstrated the testicular missed torsion, yet findings were equivocal with regard to the testicular tumor. On scrotal exploration the left testis was found to be ischemic due to threefold rotation. The right testis was not identifiable, being composed of numerous necrotic lesions. Frozen section suggested malignancy, hence high right orchiectomy was performed. Histologic examination of the right testis showed mixed germ cell tumor, containing all the subtypes. To our knowledge no similar case has been reported.

Adult↗

PubMed2000

Marked weight reduction lowers resting and exercise blood pressure in morbidly obese subjects.

Obesity and high blood pressure (BP) often coexist. Weight reduction lowers resting BP but its effect on BP during exercise (a predictor of target organ damage) has not been evaluated. Blood pressure was measured at rest and during cycling, before and after weight reduction induced by gastric restriction. Nineteen subjects (4 male), 41 +/-2 (SEM) years of age and body mass index (BMI) of 43 +/- 0.9 kg/m2, were studied. On each occasion BP was measured at rest, at a steady state of 0 and 25 watts, at peak exercise and 1 min into recovery. Body weight was reduced by 28% +/- 6% and BMI decreased from 43.3 +/- 0.9 to 31.5 +/- 0.7 kg/m2 (P < .01). Both BP and heart rate, at rest and at all exercise intensities, were significantly lower after weight reduction. Resting BP decreased from 133 +/-4/87 +/- 3 mm Hg to 115 +/- 4/77 +/- 2 mm Hg (P < .001), and BP at peak exercise decreased from 181 +/- 8/98 +/- 4 to 162 +/- 6/83 +/- 5 mm Hg (P < .001). The change in resting systolic BP did not correlate with the change in body weight or with the change in heart rate, but it correlated with the baseline systolic BP (R = 0.61; P < .005). It is concluded that marked weight reduction reduces BP at rest and at all exercise intensities. Gastroplasty should be considered as an option in morbidly obese hypertensive patients who are not well controlled with conventional treatment, and who fail to lose or to maintain a reduced weight by calorie restriction alone.

Adult↗

PubMed2000

Using the Baldrige management system framework in health care: the Veterans Health Administration experience.

BACKGROUND: In 1998 the Veterans Health Administration (VHA) developed the Quality Achievement Recognition Grant, a competitive grant application open to all Veterans Integrated Service Networks (VISNs) within the VHA system and based on the Baldrige management framework. Eight of the 22 VISNs attended the educational programs and initiated the grant application process; 7 completed applications. Team award experts from VHA and external sources reviewed, scored, and wrote feedback reports to all applicants and conducted four site visits. IDENTIFICATION OF BEST PRACTICES AND RECOMMENDATIONS FOR FUTURE APPLICANTS: Each application was compared to examples of ideal applications to identify areas of excellence and areas for improvement. In general, the best applicants identified and described key processes and articulated the methods used to evaluate and improve processes. For example, they were able to identify the process used to incorporate key constituents into the strategy development process. One applicant developed a series of management advisory committees, the membership of which includes veterans' service organizations, academic affiliates, community members, and congressional delegates, which were tapped to develop a strategic plan. Leading applicants in the future are likely to be able to demonstrate evidence of deployment and constant review of the strategy and to emphasize the human resources plan into the strategic planning and deployment. CONCLUSIONS: The Baldrige management framework is a useful tool for identification of areas of achievement and areas for improvement within the VHA. Potential applicants for the award could benefit from ensuring coherence across the application, placing a greater emphasis on work systems, and incorporating more extensive analysis of market conditions.

Awards and Prizes↗

PubMed2000

Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial.

We have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.

Acute Disease↗

PubMed2000

Effects of allogeneic bone marrow transplantation on recipient bone mineral density: A prospective study.

Allogeneic bone marrow transplant (BMT) recipients have many known risk factors for developing decreased bone mineral density (BMD) after transplantation. We performed a prospective sequential evaluation of BMD in the lumbar spine and nondominant hip using dual-energy x-ray absorptiometry (DEXA) in a cohort of 47 adult patients (median age, 43 years) who were undergoing radiation-based BMT for hematologic malignancies. Baseline DEXA studies were performed before BMT and repeated at 3 to 4 months, 6 to 8 months, and 12 to 14 months after BMT. The majority of patients (60%) had been minimally treated with combination cytotoxic chemotherapy, having received no more than 1 treatment regimen before BMT. Graft-versus-host disease prophylaxis consisted of cyclosporine in combination with either methotrexate or prednisone, or both. Mean lumbar spine and hip BMD were normal before BMT (spine: 1.01 g/cm2, z score = 96%; hip: 0.86 g/cm2, z score = 100%) and gradually decreased (spine: 0.98 g/cm2, z score = 94%; hip: 0.76 g/cm2, z score = 91%) at 12 to 14 months. These declines were statistically significant (P < .006 and < .002 for lumbar spine; P < .001 and < .001 for hip). In addition, the sharpest decline occurred during the first 6 months after BMT and was more marked in the hip than the lumbar spine. These data suggest that BMT adversely affects BMD in this patient population.

Absorptiometry, Photon↗

PubMed2000

Field research for the authorisation of pesticides.

On request of the Dutch government a committee of the Health Council of the Netherlands has reviewed the role that results of field research in its broadest sense (i.e., including multi-species toxicity tests in the laboratory, research on model ecosystems et cetera) can play in ecotoxicological risk assessment for the authorisation of pesticides. The Committee believes that field research can provide valuable additional data about the exposure of non-target organisms and the resultant effects at population, community and ecosystem level. However, it frequently is unclear how these data might be used in reaching a decision about authorisation. To solve this problem, it is necessary to specify what is understood by "unacceptable damage". Both more clearly formulated protection goals of the government and a better understanding of the ecological significance of effects are needed to clarify this. Furthermore, the Committee points out that the statistical power of field trials must be sufficient to allow for the detection of changes that might be regarded as ecologically relevant. Finally, it recommends keeping a finger on the pulse in relation to authorised pesticides by monitoring their presence in environmental compartments and by investigating their role in suddenly occurring mortality among conspicuous animal species, such as birds, fish and honeybees. This kind of research forms a safety net for substances that have been wrongly authorised.

Ecosystem↗

PubMed2000

Peripartum general anasthesia without tracheal intubation: incidence of aspiration pneumonia.

This study estimated the incidence of pulmonary aspiration during general anasthesia for obstetric procedures performed in the peripartum period (Caesarean sections were not studied). The records of 1870 patients anasthetised without tracheal intubation were reviewed retrospectively. The diagnosis of aspiration was based on the anasthetist's written remarks and the postoperative course. Eighty per cent of patients received ketamine and a benzodiazepine, and the remaining 20% received methohexital or thiopental and fentanyl. No cricoid pressure or tracheal intubation was performed. A single case of mild aspiration was detected in a woman anasthetised with methohexital (an incidence of 0.053%). These results suggest that the risk of aspiration during general anasthesia without tracheal intubation, during and immediately after delivery, may not be higher in obstetric patients in the peripartum period, as has been reported previously.

Adult↗

PubMed2000

[Foreign body granuloma after lower eyelid avulsion and surgical revision with silicone tube splint].

BACKGROUND: Foreign-body-reactions with granulomas after use of silicone-containing biomaterials are of clinical importance [4]. HISTORY AND SIGNS: A 4-year old patient entered our hospital with a reddish vascularised tumor. The tumor's origin was in the conjunctiva of the nasal lid-angle of the right eye. THERAPY AND OUTCOME: After a traumatic disconnection of the canaliculus lacrimalis inferior, a bicanalicular silicon-tube intubation had been performed with the patient in the age of one year. Only 3 years after this intervention a secondary clinical examination could be performed. At this time, an extended solid conjunctival-tumor appeared at the operated eye. After removal and histological examination it could be classified as a foreign body granuloma. CONCLUSIONS: The blood- and tissue compatibility of silicone is only insufficiently guaranteed on the basis of the hydrophobic material-surface. After reconstructive lacrimal surgery postoperative care and the removal of the stabilizing silicone material is necessary.

Child, Preschool↗

PubMed2000

[Doppler sonography of the short posterior ciliary artery in patients with primary open angle glaucoma].

AIM: The area of primary damage in glaucomas is the optic nerve head. This region is directly supplied by the peripapillary choroid and the short posterior ciliary arteries (SPCA). This study was designed to evaluate the choroidal and SPCA haemodynamics in high tension (HTG) and normal tension (NTG) primary open angle glaucoma patients, as well as in healthy controls (CTL). METHODS: 20 HTG, 12 NTG, and 32 age matched volunteers (CTL) without clinically relevant extracranial stenosis of the carotid arteries were evaluated for ocular pulse amplitude (OPA; OBF-System OBF Labs, UK) and for temporal SPCA peak systolic flow (PSV), enddiastolic flow (EDV), pulsatility (PI) and resistance indices (RI) using a 9 MHz phased array (Elegra Advanced System; Siemens, Germany). RESULTS: (mean +/- SD): In the control group the PSV (cm/s) of the SPCA was 10.90 +/- 1.53; EDV (cm/s) was 3.24 +/- 0.24, PI was 1.30 +/- 0.39, RI was 0.69 +/- 0.11, OPA (mm Hg) was 2.2 +/- 0.25; IOP (mmHg) was 14.6 +/- 1.5. When compared to CTL matched for age, sex, and refraction, NTG-patients showed the following results: OPA was significantly (p < 0.05) reduced, dopplersonography showed a significant (p < 0.05) reduction in diastolic flow patterns and a significant (p < 0.05) increase in PI and RI. In HTG-patients the parameters investigated where not significantly (p > 0.05) altered. CONCLUSION: These data suggest reduced haemodynamics in the choroid and in the SPCA of NTG patients, which may contribute to progression of the optic neuropathy. In HTG the Doppler parameters and the OPA are not altered compared with the control group.

Ciliary Arteries↗

PubMed2000

Repeated pregnancies in BALB/c mice infected with Coxiella burnetii cause disseminated infection, resulting in stillbirth and endocarditis.

Q fever is a widespread zoonosis caused by the obligate intracellular bacterium Coxiella burnetii. Although this highly virulent organism is most concentrated in mammals during parturition, there are few reports on the manifestations of perinatal Q fever in the human and animal host. The affinity of C. burnetii to pregnancy and its abortifacient potential were investigated in a murine animal model. Intraperitoneal infection of female BALB/c mice with C. burnetii, followed by repeated pregnancies over a 2-year period, resulted in persistent infection associated with abortion and perinatal death, with a statistically significant decrease in viable offspring. In addition, endocarditis occurred in 2 of the adult animals, and C. burnetii antigen and DNA were detected in their heart valves. Taken together, these results demonstrate the abortifacient potential of C. burnetii and the increased risk of persistent infection and endocarditis in pregnant mice, probably related to a decline in cellular immunity during pregnancy.

Animals↗

PubMed2000

Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections.

In order to describe the clinical features and the epidemiologic findings of 1,383 patients hospitalized in France for acute or chronic Q fever, we conducted a retrospective analysis based on 74,702 sera tested in our diagnostic center, National Reference Center and World Health Organization Collaborative Center for Rickettsial Diseases. The physicians in charge of all patients with evidence of acute Q fever (seroconversion and/or presence of IgM) or chronic Q fever (prolonged disease and/or IgG antibody titer to phase I of Coxiella burnetii > or = 800) were asked to complete a questionnaire, which was computerized. A total of 1,070 cases of acute Q fever was recorded. Males were more frequently diagnosed, and most cases were identified in the spring. Cases were observed more frequently in patients between the ages of 30 and 69 years. We classified patients according to the different clinical forms of acute Q fever, hepatitis (40%), pneumonia and hepatitis (20%), pneumonia (17%), isolated fever (17%), meningoencephalitis (1%), myocarditis (1%), pericarditis (1%), and meningitis (0.7%). We showed for the first time, to our knowledge, that different clinical forms of acute Q fever are associated with significantly different patient status. Hepatitis occurred in younger patients, pneumonia in older and more immunocompromised patients, and isolated fever was more common in female patients. Risk factors were not specifically associated with a clinical form except meningoencephalitis and contact with animals. The prognosis was usually good except for those with myocarditis or meningoencephalitis as 13 patients died who were significantly older than others. For chronic Q fever, antibody titers to C. burnetii phase I above 800 and IgA above 50 were predictive in 94% of cases. Among 313 patients with chronic Q fever, 259 had endocarditis, mainly patients with previous valvulopathy; 25 had an infection of vascular aneurysm or prosthesis. Patients with endocarditis or vascular infection were more frequently immunocompromised and older than those with acute Q fever. Fifteen women were infected during pregnancy; they were significantly more exposed to animals and gave birth to only 5 babies, only 2 with a normal birth weight. More rare manifestations observed were chronic hepatitis (8 cases), osteoarticular infection (7 cases), and chronic pericarditis (3 cases). Nineteen patients were observed who experienced first a documented acute infection, then, due to underlying conditions, a chronic infection. To our knowledge, we report the largest series of Q fever to date. Our results indicate that Q fever is a protean disease, grossly underestimated, with some of the clinical manifestations being only recently reported, such as Q fever during pregnancy, chronic vascular infection, osteomyelitis, pericarditis, and myocarditis. Our data confirm that chronic Q fever is mainly determined by host factors and demonstrate for the first time that host factors may also play a role in the clinical expression of acute Q fever.

Age Distribution↗

PubMed2000

4.0 Tesla magnetic resonance imaging of brainstem lesions with ocular motility deficits.

The authors studied six patients with brainstem ocular motility deficits with 4.0 Tesla (T) magnetic resonance imaging to investigate whether a higher field strength would produce superior images compared with 1.5T. In four patients whose lesions were evident on 1.5T, the increased signal-to-noise achieved with 4.0T allowed for better resolution at 1-mm slice thickness than was achieved at the standard 5-mm slice thickness with 1.5T. In the two patients with unremarkable 1.5T scan results, 4.0T also failed to demonstrate a lesion. Therefore, 4.0T imaging has superior resolution to 1.5T imaging and can provide more detailed images of lesions identified by 1.5T.

Adolescent↗

PubMed2000

Probable identification of a membrane-associated repressor of Bacillus subtilis DNA replication as the E2 subunit of the pyruvate dehydrogenase complex.

Two Bacillus subtilis lysogenic libraries were probed by an antibody specific for a previously described membrane-associated inhibitor of B. subtilis DNA replication (J. Laffan and W. Firshein, Proc. Natl. Acad. Sci. USA 85:7452-7456, 1988). Three clones that reacted strongly with the antibody contained an entire open reading frame. Sequencing identified one of the clones (R1-2) as containing the E2 subunit of the pyruvate dehydrogenase complex, dihydrolipoamide acetyltransferase. An AT-rich sequence in the origin region was identified initially as the site to which extracts from the R1-2 clone were bound. This sequence was almost identical to one detected in Bacillus thuringiensis that also bound the E2 subunit but which was involved in activating the Cry1 protoxin gene of the organism, not in inhibiting DNA replication (T. Walter and A. Aronson, J. Biol. Chem., 274:7901-7906, 1999). However, the exact sequence was not as important in B. subtilis as the AT-rich core region. Binding would occur as long as most of the AT character of the core remained. Purified E2 protein obtained by use of PCR and an expression vector reacted strongly with antibody prepared against the repressor protein and the protein in the R1-2 clone, but its specificity for the AT-rich region was altered. The purified E2 protein was capable of inhibiting membrane-associated DNA replication in vitro, but anti-E2 antibody was variable in its ability to rescue repression when added to the assay.

Acetyltransferases↗

PubMed2000

Qualitative interview study of communication between parents and children about maternal breast cancer.

OBJECTIVE: To examine parents' communication with their children about the diagnosis and initial treatment of breast cancer in the mother. DESIGN: Qualitative interview study within a cross-sectional cohort. SETTING: Two breast cancer treatment centers. PARTICIPANTS: 32 women with stage I or stage II breast cancer with 56 school-aged children. Main outcome measures Semistructured interview regarding timing and extent of communication with children about the diagnosis and initial treatment of the mother's illness, reasons for talking to children or withholding information, and help available and requested from health professionals. RESULTS: Women were most likely to begin talking to their children after their diagnosis had been confirmed by biopsy, but a few waited until after surgery or said nothing at all. Family discussion did not necessarily include mention of cancer. There was considerable consistency in the reasons given for either discussing or not discussing the diagnosis. The most common reason for not communicating was to avoid children's questions, particularly those about death. Although most women had helpful discussion with a physician concerning their illness, few were offered help with talking to their children; many would have liked help, particularly the opportunity for both parents to talk to a health professional with experience in understanding and talking to children. CONCLUSION: Parents diagnosed with cancer or other serious illnesses should be offered help to think about whether, what, and how to tell their children and about what children can understand, especially as they may well be struggling themselves to come to terms with their illness.

Adolescent↗

PubMed2000

Urinary cytokeratin 20 as a marker for transitional cell carcinoma.

OBJECTIVES: To determine if detection of cytokeratin 20 (CK20) gene expression, by reverse transcriptase-polymerase chain reaction (RT-PCR) in urine from transitional cell carcinoma (TCC) patients, can provide a new noninvasive tool for the follow-up of patients with urothelial carcinoma of the bladder. METHODS: Urine was collected from 95 patients previously diagnosed as TCC during their follow-up, and from 27 healthy volunteers. All patients had a transurethal resection of tumor or biopsies obtained from 'suspicious' areas in the bladder. RNA was extracted from cells collected from the urine and RT-PCR was performed with specific primers for the amplification of cytokeratin 8, a general marker for epithelial cells, and of CK 20, a marker for TCC urothelium. RESULTS: CK20 expression was detected in 86.7% of TCC patients, and only in 3.3% of healthy volunteers (specificity 96.7%). Strong correlation was found between tumor grade and expression of CK20 in urine. All grade III and IV tumors demonstrated positive CK20 expression (100% sensitivity), whereas the sensitivity for lower grades was between 71 and 80%. Among 11 patients with a previous biopsy-proven diagnosis of TCC and a current negative biopsy, in 9 patients CK20 expression was detected. Further follow-up of these patients for a period of 6 months revealed recurrence of TCC in 4 patients. CONCLUSION: CK20 detection in urine cells is a simple, noninvasive method with a high potential to become the marker of choice for monitoring and follow-up of TCC patients. More information is needed regarding CK20 expression in nonmalignant urological disease, to evaluate its use for routine screening purposes.

Biomarkers, Tumor↗

PubMed2000

Sonographic detection of a foreign body in the urethra and urinary bladder.

Reported herein is a 41-year-old male who presented for ultrasound due to two episodes of lower urinary tract infections within a period of 5 months. The sonographic examination revealed an elongated foreign body in the urethra extending into the urinary bladder. Self-insertion of foreign bodies into the urethra is usually done for erotic stimulation. However, foreign bodies can be inserted by children due to curiosity and by mentally retarded people, patients with psychiatric disorders as well as by intoxicated patients and in confusional states. Due to embarrassment, the patients seek medical help only when they are symptomatic and hence some of the foreign bodies are removed only several months after insertion. Detection might be either by plain abdominal films when the foreign bodies are radiopaque or by the use of contrast media. In the case presented by us, this was done by sonography. Endoscopic removal of these foreign bodies is considered the treatment of choice. Recurrent or chronic unexplained urinary tract infections should raise a high index of suspicion to the possible existence of a foreign body in the urethra and/or urinary bladder.

Adult↗

PubMed2000

Autologous stem-cell transplantation for poor-risk and relapsed intermediate- and high-grade non-Hodgkin's lymphoma.

The primary objective of this study was to evaluate the outcome of patients treated with high-dose chemo-/radiotherapy or high-dose chemotherapy and autologous stem-cell transplant (ASCT) for relapsed, refractory, or poor-risk intermediate-grade (IG) and high-grade (HG) non-Hodgkin's lymphoma (NHL). The secondary objectives were to determine prognostic factors for relapse and survival. Between February 1987 and August 1998, 264 patients, 169 (64%) IG and 95 (36%) HG, underwent high-dose therapy and ASCT at City of Hope National Medical Center (COHNMC). There were 157 (59%) males and 107 (41%) females with a median age of 44 years (range, 5-69 years). The median number of prior chemotherapy regimens was 2 (range, 1-4), and 71 (27%) had received prior radiation as part of induction or as salvage therapy. The median time from diagnosis to ASCT was 10.8 months (range, 3-158 months). Ninety-four patients (36%) underwent transplantation in first complete/partial remission (CR/PR), 40 (15%) in induction failure, and 130 (49%) in relapse or subsequent remission. Two preparative regimens were used: total body irradiation/high-dose etoposide/cyclophosphamide (TBI/VP/CY) in 208 patients (79%) and carmustine/etoposide/cyclophosphamide (BCNU/VP/CY) in 56 patients (21%). One hundred sixty-three patients (62%) received peripheral blood stem cells (PBSC) and 101 (38%) received bone marrow (BM) alone or BM plus PBSC. At a median follow-up of 4.43 years for surviving patients (range, 1-12.8 years), the 5-year Kaplan-Meier estimates of probability of overall survival (OS), progression-free survival (PFS), and relapse for all patients are 55% (95% confidence interval [CI]: 49%-61%), 47% (95% CI: 40%-53%), and 47% (95% CI: 40%-54%), respectively. There were 27 deaths (10%) from nonrelapse mortality, including seven (3%) patients who developed second malignancies (five with myelodysplasia/acute myelogenous leukemia and two with solid tumors). By stepwise Cox regression analysis, disease status at ASCT was the only prognostic factor that predicted for both relapse and survival. The 5-year probability of PFS for patients transplanted in first CR/PR was 73% (95% CI: 62%-81%) as compared to 30% (95% CI: 16%-45%) for induction failure and 34% (95% CI: 26%-42%) for relapsed patients. Our results further support the role of high-dose therapy and ASCT during first CR/PR for patients with poor-risk intermediate- and high-grade NHL. Early transplant is recommended for patients failing initial induction therapy or relapsing after chemotherapy-induced remission. Relapse continues to be the most common cause of treatment failure. An alternative approach to prevent relapse, the incorporation of radioimmunotherapy into the high-dose regimen, is being investigated. The development of a second malignancy is a serious complication of high-dose therapy, which requires close surveillance.

Adolescent↗