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Biomedical subjects

J Amess

Publications and source records attributed to J Amess.

At least 19 recordsLinked to original sources
PubMed2004

Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma.

PURPOSE: An open-label phase II study was conducted at two centers to establish the efficacy and safety of tositumomab and iodine I 131 tositumomab at first or second recurrence of indolent or transformed indolent B-cell lymphoma. PATIENTS AND METHODS: A single dosimetric dose was followed at 7 to 14 days by the patient-specific administered radioactivity required to deliver a total body dose of 0.75 Gy (reduced to 0.65 Gy for patients with platelets counts of 100 to 149 x 10(9)/L). Forty of 41 patients received both infusions. RESULTS: Thirty-one of 41 patients (76%) responded, with 20 patients (49%) achieving either a complete (CR) or unconfirmed complete remission [CR(u)] and 11 patients (27%) achieving a partial remission. Response rates were similar in both indolent (76%) and transformed disease (71%). The overall median duration of remission was 1.3 years. The median duration of remission has not yet been reached for those patients who achieved a CR or CR(u). Eleven patients continue in CR or CR(u) between 2.6+ and 5.2+ years after therapy. Therapy was well tolerated; hematologic toxicity was the principal adverse event. Grade 3 or 4 anemia, neutropenia, and thrombocytopenia were observed in 5%, 45%, and 32% of patients, respectively. Secondary myelodysplasia has occurred in one patient. Four patients developed human antimouse antibodies after therapy. Five of 38 assessable patients have developed an elevated thyroid-stimulating hormone; treatment with thyroxine has been initiated in one patient. CONCLUSION: High overall and CR rates were observed after a single dose of tositumomab and iodine I 131 tositumomab in this patient group. Toxicity was modest and easily managed.

Adult↗
PubMed2001

Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis.

BACKGROUND: Certain infections can trigger chronic fatigue syndromes (CFS) in a minority of people infected, but the reason is unknown. We describe some factors that predict or are associated with prolonged fatigue after infectious mononucleosis and contrast these factors with those that predicted mood disorders after the same infection. METHODS: We prospectively studied a cohort of 250 primary-care patients with infectious mononucleosis or ordinary upper-respiratory-tract infections until 6 months after clinical onset. We sought predictors of both acute and chronic fatigue syndromes and mood disorders from clinical, laboratory, and psychosocial measures. FINDINGS: An empirically defined fatigue syndrome 6 months after onset, which excluded comorbid psychiatric disorders, was most reliably predicted by a positive Monospot test at onset (odds ratio 2.1 [95% CI 1.4-3.3]) and lower physical fitness (0.35 [0.15-0.8]). Cervical lymphadenopathy and initial bed rest were associated with, or predicted, a fatigue syndrome up to 2 months after onset. By contrast, mood disorders were predicted by a premorbid psychiatric history (2.3 [1.4-3.9]), an emotional personality score (1.21 [1.11-1.35]), and social adversity (1.7 [1.0-2.9]). Definitions of CFS that included comorbid mood disorders were predicted by a mixture of those factors that predicted either the empirically defined fatigue syndrome or mood disorders. INTERPRETATION: The predictors of a prolonged fatigue syndrome after an infection differ with both definition and time, depending particularly on the presence or absence of comorbid mood disorders. The particular infection and its consequent immune reaction may have an early role, but physical deconditioning may also be important. By contrast, mood disorders are predicted by factors that predict mood disorders in general.

Chi-Square Distribution↗
PubMed1999

Acute promyelocytic leukaemia: a retrospective analysis of patients treated at St. Bartholomew's Hospital 1969-1995.

Seventy-two patients with acute promyelocytic leukemia (APML) were treated at St.Bartholomew's Hospital (SBH) over a 25-year period. Improvements in supportive care and the use of more intensive chemotherapy have led to an increase in the complete remission rate from 14 to 58%. Similarly, the median survival has increased from 3 weeks to 2 years; the median duration of remission, which was 7 months in 1974, has not yet been reached. There was also a significant difference in survival from first recurrence, compared with that of patients with other subtypes of acute myeloid leukemia. RT-PCR analysis on bone marrow samples from 14 patients confirmed the presence of the PML/RARA fusion; 13 of the 14 patients achieved 'molecular remission' after therapy. The one patient who remained persistently positive experienced recurrence within 4 months. In seven of the eight patients in whom the disease recurred, the translocation was identified by RT-PCR at the time of relapse, whilst in one patient it was noted 4 months prior to morphological recurrence. These results illustrate the improvement in prognosis that occurred over a 25-year period in patients with APML treated at a single centre.

Adult↗
PubMed1999

Patterns of outcome following recurrence after myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma.

PURPOSE: To assess the patterns of recurrence, management, and survival following recurrence after myeloablative therapy with autologous bone marrow transplantation (ABMT) in patients with follicular lymphoma (FL). PATIENTS AND METHODS: Between June 1985 and October 1995, 99 patients with FL received cyclophosphamide and total-body irradiation with ABMT as consolidation of second or subsequent remission. RESULTS: Median length of follow-up was 5 1/2 years, and 33 patients developed recurrent lymphoma a median of 14 months after ABMT. In 26 patients, the recurrence was overt; in seven, it was detected on surveillance investigation. Twenty-six patients presented with recurrence at previous sites of disease. Twenty-two patients (67%) had FL at the time of recurrence; in 11 (33%), there was evidence of transformation to diffuse large B-cell lymphoma. Eight patients were managed expectantly; five were alive 21 to 53 months later. Twenty-five patients have required treatment to date; eight remained alive 6 months to 10 years later, and five were in remission. The Kaplan-Meier estimate of patients alive 5 years after recurrence is 45% (95% confidence interval, 27% to 62%). In univariate and multivariate analyses, survival after recurrence and overall survival after diagnosis were similar to those of a historical control group who received conventional treatment, before the introduction of myeloablative therapy (adjusted hazard ratio [HR], 1.56, P = .3, and HR, 1.34, P = .4, respectively). CONCLUSION: The survival pattern of patients with FL following recurrence after myeloablative therapy and ABMT suggests that this treatment does not compromise outcome in patients in whom it fails, reflecting the survival pattern of the disease when treated conventionally.

Adult↗
PubMed1998

Incidence, risk and prognosis of acute and chronic fatigue syndromes and psychiatric disorders after glandular fever.

BACKGROUND: The role of viruses in the aetiology of both chronic fatigue syndrome (CFS) and depressive illness is uncertain. METHOD: A prospective cohort study of 250 primary care patients, presenting with glandular fever or an ordinary upper respiratory tract infection (URTI). RESULTS: The incidence of an acute fatigue syndrome was 47% at onset, after glandular fever, compared with 20% with an ordinary URTI (relative risk 2.3, 95% CI 1.3-4.1). The acute fatigue syndrome lasted a median (interquartile range) of eight weeks (4-16) after glandular fever, but only three weeks (2-4) after an URTI. The prevalence of CFS was 9-22% six months after glandular fever, compared with 0-6% following an ordinary URTI, with relative risks of 2.7-5.1. The most conservative measure of the incidence of CFS was 9% after glandular fever, compared with no cases after an URTI. A conservative estimate is that glandular fever accounts for 3113 (95% CI 1698-4528) new cases of CFS per annum in England and Wales. New episodes of major depressive disorder were triggered by infection, especially the Epstein-Barr virus, but lasted a median of only three weeks. No psychiatric disorder was significantly more prevalent six months after onset than before. CONCLUSIONS: Glandular fever is a significant risk factor for both acute and chronic fatigue syndromes. Transient new major depressive disorders occur close to onset, but are not related to any particular infection if they last more than a month.

Acute Disease↗
PubMed1996

Intensive chemotherapy for adult acute lymphoblastic leukaemia given with or without granulocyte-macrophage colony stimulating factor.

Twenty-six patients with newly diagnosed ALL (age range 15-49 years, median 32 years) received treatment comprising: cycles 1 and 2: adriamycin 30 mg/m2 days 1-3, vincristine: 2 mg days 1, 8, and 15, with prednisolone 40 mg daily, given until complete remission (CR). L-asparaginase 10000 units/m2, days 1-14, was given only with the first cycle. Cycle 3 consisted of 100 mg/m2 etoposide orally, days 1-5, and 1 gm/m2 bd cytosine arabinoside (ara-C) days 1-5. Cycles 1-3 were then repeated. Intrathecal methotrexate (MTX) 12.5 mg was given on day 1 of each treatment cycle. The first 12 consecutive patients received this chemotherapy alone, the subsequent 14 received, in addition, 3 micrograms/kg GM-CSF subcutaneously, from day 4 of cycles 1,2,4 and 5 (and from day 6 of cycles 3 and 6) until the absolute neutrophil count had reached 0.5 x 10(9)/1. All patients in whom CR was achieved then received prophylactic cranial irradiation. With the exception of those with T-ALL, this was followed by oral maintenance therapy consisting of 6-mercaptopurine, MTX, and cyclophosphamide for 3 years. Patients receiving GM-CSF did not have shorter intercycle times or a lower incidence of documented infections than those who did not receive it. The CR rate was 89% overall-uninfluenced by GM-CSF, but higher than that achieved previously at St Bartholomew's Hospital in an equivalent age-group.

Adolescent↗
PubMed1995

The existence of a fatigue syndrome after glandular fever.

This prospective cohort study was designed to test whether a distinct fatigue syndrome existed after the onset of glandular fever. Two hundred and fifty primary care patients, with either glandular fever or an ordinary upper respiratory tract infection (URTI) were interviewed three times in the 6 months after the clinical onset of their infection. At each interview a standardized psychiatric interview was given and physical symptoms were assessed. There were 108 subjects with and Epstein-Barr virus (EBV) infection; 83 subjects had glandular fever not caused by EBV and 54 subjects had an ordinary URTI. Five subjects were excluded because they had no evidence of an infection. Principal components analyses of symptoms supported the existence of a fatigue syndrome, particularly in the two glandular fever groups. The addition of symptoms not elicited by the standard interviews gave the full syndrome. This included physical and mental fatigue, excessive sleep, psychomotor retardation, poor concentration, anhedonia, irritability, social withdrawal, emotional lability, and transient sore throat and neck gland swelling with pain. A fatigue syndrome probably exists after glandular fever.

Animals↗
PubMed1995

The validity and reliability of the fatigue syndrome that follows glandular fever.

The validity and reliability of an empirically defined fatigue syndrome were tested in a prospective cohort study of 245 primary care patients, with glandular fever or an upper respiratory tract infection. Subjects were interviewed three times in the 6 months after onset. Subjects with the empirically defined fatigue syndrome were compared with those who were well and those who had a psychiatric disorder. The validity of the fatigue syndrome was supported, separate from psychiatric disorders in general and depressive disorders in particular. Only 16% of subjects with the principal component derived fatigue factor also met criteria for a psychiatric disorder (excluding pre-morbid phobias). Compared with subjects with psychiatric disorders, subjects with the operationally defined fatigue syndrome reported more severe physical fatigue, especially after exertion, were just as socially incapacitated, had fewer mental state abnormalities, and showed little overlap on independent questionnaires. A more mild fatigue state also existed. Both fatigue syndrome and state were more reliable diagnoses over time than depressive disorders. The empirically defined syndrome probably is a valid and reliable condition in the six months following glandular fever.

Cohort Studies↗
PubMed1994

Prevalence and clinical correlations of MLL gene rearrangements in AML-M4/5.

Rearrangements of the human trithorax gene (MLL, HRX, Htrx-1, All-1) were studied by Southern blotting in blast cells stored at presentation from 65 adults with de novo acute myelomonocytic (AML-M4) and acute monocytic leukemia (AML-M5). MLL rearrangements were demonstrated in 15 (23%) cases, including eight patients in whom karyotype analysis had failed to detect abnormalities of chromosome band 11q23. The patients with MLL rearrangements did not differ significantly from those with germline configurations in terms of the sex and age of the patients, the presence of lymphadenopathy, hepatosplenomegaly, or central nervous system involvement, and the absolute blast count at diagnosis. Kaplan-Meier analysis of the treated patients demonstrated no difference in survival for patients with MLL rearrangements compared with those without rearrangements. Therefore, in contrast to infantile acute leukemia, in adults with AML-M4 and AML-M5, MLL rearrangements do not identify a subgroup of patients with different clinical features or prognosis.

Adolescent↗
PubMed1994

Human trithorax gene rearrangements in therapy-related acute leukaemia after etoposide treatment.

Molecular analysis of leukaemic blasts from 9 patients with secondary myeloid leukaemia reveals rearrangements of the human trithorax gene (Htrx-1) in three patients, including one in whom abnormalities of chromosome 11 band q23 were not detected by conventional cytogenetics. All three patients had been treated with epipodophyllotoxins, whilst none of the six without rearrangements had received these agents. The patients with rearrangements also presented with different clinical features. These findings support the separation of secondary leukaemia into two classes, and correlate rearrangements of the Htrx-1 gene with a group of secondary leukaemias that follow specific cancer treatment regimens.

Adult↗
PubMed1993

Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas.

beta-2 microglobulin levels were measured in stored serum taken at presentation from 262 patients treated with combination chemotherapy for Kiel classification high-grade lymphoma at a single centre over a 15 year period. A significant association was found between elevated levels and advanced (Ann Arbor stage III or IV) disease or hepatic infiltration, but not with other sites of extranodal involvement or bulky disease. Patients with normal levels at presentation had a 70% remission rate with treatment compared to 37% of those with elevated levels (P < 0.001). With median follow up of 6 years duration of remission was significantly greater in patients with normal beta-2 microglobulin at presentation (plateau at 70%, compared to median remission of 19 months in those with raised levels, P < 0.001). Survival overall was also better in the group with normal levels (actuarial median 9 years compared to 1 year, P < 0.001). Multivariate analyses including treatment type, age, sex, B symptoms, stage, bulk, albumin, sodium, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and beta-2 microglobulin, placed beta-2 microglobulin among the three most influential independent variables for prediction of response rate, duration of remission and overall survival.

Adolescent↗
PubMed1993

Patterns of survival in patients with Hodgkin's disease: long follow up in a single centre.

BACKGROUND: Prolonged remission can now be induced in the majority of patients with Hodgkin's disease with chemotherapy and/or irradiation. However, there is a significant proportion of patients in whom this approach fails, either at presentation or subsequently. Survival is the definitive endpoint to assess treatment efficacy. In this study, the survival patterns of a large group of consecutive patients treated in a single institution are presented. RESULTS: The overall median survival was 18.3 years. Clinical remission (complete remission plus good partial remission) was induced in 443 (85%); the median survival of patients in remission has not been reached. Fifty-eight patients achieved responses less than clinical remission with initial therapy (partial response) or had progressive disease, the median survival of this group being 1.4 years. With further therapy, remission was subsequently induced in 10; 5 are still alive, 5 have died between 1.9 years and 14.3 years. Twenty patients died before completion of therapy. Recurrence has been documented in 147 of the patients in remission (following initial therapy) over a median follow up period of 13 years (minimum 5 years). One hundred forty-three of these patients were retreated following recurrence (105 chemotherapy, 28 radiotherapy, 6 combined modality treatment and 4 surgery). Second remission was induced in 109/143 (76%). There was a trend towards better second remission induction in patients whose first remission was longer than 1 year (p = 0.06). The median duration of second remission was inferior to first remission duration (p < 0.001). There was no correlation between duration of first remission and survival following recurrence (p = 0.8) or with duration of second remission (p = 0.54). There was no significant difference in duration of second remission between patients who were initially treated with radiotherapy or chemotherapy (p = 0.3). The median survival following second remission was 12.0 years, being the same for patients with initially localized disease (stages I and II) treated with radiation alone and for patients with advanced Hodgkin's disease (stages III and IV) treated with chemotherapy. Survival after recurrence is significantly better for patients under 50 years at the time of recurrence (p < 0.001). Second recurrence was documented in 46 patients, third remission being reinduced in 22, the median survival of the latter being 5.1 years. CONCLUSION: These results illustrate the importance of prolonged follow up in defining the clinical course of patients with HD and are vital for planning experimental chemotherapy at the time of treatment failure or recurrence.

Adolescent↗
PubMed1993

The management of recurrent acute myelogenous leukaemia at a single centre over a fifteen-year period.

One hundred and sixty-two patients initially treated at St Bartholomew's Hospital between 1974 and 1988 developed recurrent acute myelogenous leukaemia (AML). In the majority, the intention was to administer intensive chemotherapy again; 22/162 were re-treated palliatively. A second complete remission (CR) was achieved in 50/126 (40%) evaluable patients. Several different regimens were employed over this time period; the treatment used was the only factor that correlated with achievement of second CR (P = 0.04). Ten of the 50 patients received myeloablative therapy with either allogeneic or autologous bone marrow transplantation in second CR. The median duration of second CR for those patients who did not proceed to intensive consolidation with bone marrow transplantation was 7 months. There was no correlation between second remission duration and age, or with the administration of either intensive or conventional consolidation therapy. The median survival from first recurrence for all patients was 4 months, increasing to only 5 1/2 months for those re-treated with chemotherapy and to 12 months for those patients in whom a second CR was achieved, confirming the very poor prognosis of these patients.

Adolescent↗
PubMed1993

Fludarabine in low-grade lymphoma.

During the last 4 years, 88 patients with low-grade non-Hodgkin's lymphoma have received fludarabine, 25 mg/m2 daily for 5 days, repeated every 3 to 4 weeks. Fifty-one patients received fludarabine at recurrence or when the disease was deemed resistant to conventional treatment, 21 patients received the drug in the context of "minimal residual disease" in the hope of complete remission being achieved with a view to proceeding to myeloablative therapy (cyclophosphamide and total body irradiation) with autologous bone marrow transplantation, and 16 newly diagnosed patients received fludarabine as first-line therapy. Myelosuppression was the predominant toxicity, with 55% and 31% of previously treated and newly diagnosed patents, respectively, becoming neutropenic (neutrophils < or = 1.0 X 10(9)/L). The response rate (complete and partial response) was 44% for both patients with recurrent/resistant disease (20 of 45 evaluable patients) and for those with "minimal residual disease" (nine of 20 evaluable patients). In newly diagnosed patients, the response rate was 69% (11 of 16 patients). Five patients died of infection while neutropenic. These results confirm the activity of fludarabine in low-grade non-Hodgkin's lymphoma. Its precise role remains to be determined.

Adult↗
PubMed1992

Treatment of adult acute lymphoblastic leukaemia (ALL) over a 16 year period.

Between 1972 and 1988 269 newly diagnosed adolescents and adults (age range 14-78 years) with ALL were managed with three protocols of increasing intensity (OPAL, HEAV'D, OPAL-HDAraC). The complete remission (CR) rate in 212 patients treated with OPAL and HEAV'D was 151/212 (71%), the median CR duration was 1.9 years. With a median follow-up of 9 years, 49 patients remain free of disease. On multivariate analysis age, blast cell count, and immunophenotype were found to correlate significantly with CR rate, remission duration and survival. CR was achieved in 38/57 (67%) patients subsequently treated with OPAL-HDAraC; however, although remission duration was longer in 'high risk' patients (T, B and Null phenotype irrespective of blast cout, cALLA+ve with blast count greater than 10 x 10(9)/l) as compared to the results achieved in similar patients with OPAL/HEAV'D, overall, the results were no better than those achieved previously. Indeed, patients in the 'standard risk' category (cALLA+ve, blast count less than 10 x 10(9)/l) fared better previously. Subsequently, neither treatment according to prognostic variables, or the addition of different pairs of drugs in rotation, to HEAV'D, have improved outcome in 63 other patients. Currently, further intensification of the early treatment is being evaluated.

Adolescent↗