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Biomedical subjects

S O'Brien

Publications and source records attributed to S O'Brien.

At least 217 records · Page 12Linked to original sources
PubMed1995

Advances in the biology and treatment of B-cell chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in the western hemisphere. Diagnosis and staging of CLL are usually straightforward, but predicting an individual patient's prognosis is still a challenge. Cytogenetic abnormalities provide important prognostic information in CLL and may show its molecular heterogeneity. A search for oncogene abnormalities continues, although no consistent defects have been identified. New agents such as fludarabine produce high complete remission rates and have generated interest in earlier treatment as a first step in a potential cure. Fludarabine also makes autologous bone marrow transplant feasible as a consolidation therapy. Immunologic abnormalities and minimal residual disease persist in most patients in remission. Combining fludarabine with other active agents and devising effective postremission strategies may change the natural history of CLL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Collection and transfusion of granulocyte concentrates from donors primed with granulocyte stimulating factor and response of myelosuppressed patients with established infection.

Fifteen patients with prolonged neutropenia (a median of 23 days with granulocyte [PMN] < or = 500/microliters) and established fungal infections that had not responded to adequate antifungal therapy were transfused with PMN concentrates collected from 35 cytokine-primed granulocyte colony-stimulating factor (GCSF) donors. Patients received a median of six transfusions. Leukocytosis and granulocytosis were observed within 24 hours of the first GCSF injection, which yielded concentrates averaging 55 x 10(9) white blood cells and 41 x 10(9) PMN. Data analysis suggested that response might be related to the duration of neutropenia and known infection, as patients given PMN tx earlier in the infectious course tended to have a better response. No significant toxicity was observed in donors.

Blood Component Transfusion↗
PubMed1995

A three year follow up of self expanding metal stents in the endoscopic palliation of longterm survivors with malignant biliary obstruction.

Effective palliation of malignant biliary obstruction with conventional 10 or 12 French gauge straight polyethylene endoprostheses is limited by stent occlusion, which typically occurs four to five months after insertion. Short term follow up studies of self expanding metal stents (Wallstent, Schneider, UK) in the treatment of patients with malignant biliary obstruction have shown that their use is associated with fewer episodes of stent occlusion compared with plastic stents. There are few data, however, on the longterm patency and durability of metal stents in malignant disease. Between May 1989 and May 1992, metal stents were inserted in 28 patients with malignant bile duct strictures secondary to ampullary tumour (n = 10), pancreatic carcinoma (n = 10), cholangiocarcinoma (n = 7), and porta hepatis nodes from colorectal carcinoma (n = 1). The follow up of these patients until May 1993 is reported with a median follow up of 14.6 months. Twenty two of 28 (78.6%) patients remained free of jaundice or cholangitis. The median period of stent patency was 8.2 months (range 1.0-32.5). Thirteen patients represented with jaundice or cholangitis and endoscopic retrograde cholangiopancreatography showed evidence of stent occlusion due to tumour ingrowth. Successful clearance of metal stents was achieved by balloon trawling, or insertion of a polyethylene stent. In conclusion, metal stents provide improved longterm palliation for patients with malignant biliary strictures with fewer episodes of occlusion compared with conventional stents.

Adult↗
PubMed1995

Idarubicin cardiotoxicity: a retrospective study in acute myeloid leukemia and myelodysplasia.

PURPOSE: To estimate the incidence of idarubicin (IDA)-related cardiomyopathy in acute myeloid leukemia (AML) and myelodysplasia (MDS). PATIENTS AND METHODS: We analyzed a group of 127 AML/MDS patients who received IDA-based induction and postremission or salvage therapy and achieved a complete remission (CR) that lasted > or = 12 weeks for the development of IDA-related congestive heart failure (CHF). CHF was defined as definite if a resting left ventricular ejection fraction (LVEF) of < or = 45% measured by radionuclide ventriculogram (RV) accompanied the clinical diagnosis of CHF, which had to be made during or within 6 months of receiving IDA and for which no other cause was apparent; without RV confirmation, the diagnosis was considered probable. Patients who had RVs performed were evaluated for decreasing LVEF. Older age (> or = 70 years), prior/sequential anthracycline/mitoxantrone (anthraquinone) therapy, and cardiac disease/hypertension were evaluated as risk factors for the development of CHF. RESULTS: One hundred fifteen patients were assessable (median age, 40 years; median dose, 96 mg/m2). Sixty-five had RVs performed during therapy; 43 had risk factors. The probability of IDA-related cardiomyopathy was 5% at a cumulative IDA dose of 150 to 290 mg/m2, with 18 patients receiving doses greater than 150 mg/m2. At a cumulative IDA dose of 150 mg/m2, the probability of a mild or greater asymptomatic decrease probability of a mild or greater asymptomatic decrease in LVEF (> or = 10% to a level < or = 50%) was 18%, whereas the probability of a moderate or greater asymptomatic decrease in LVEF (> or = 15% to a level < or = 45%) was 7%. No patient with asymptomatic LVEF decreases developed CHF. CHF was more frequent in patients with prior/sequential exposure to anthracyclines/mitoxantrone (P = .01). CONCLUSION: In this patient group, IDA-related cardiomyopathy was uncommon with cumulative IDA doses of up to 290 mg/m2. Asymptomatic LVEF decreases were more frequent, but their predictive value for the development of CHF is unclear.

Adolescent↗
PubMed1995

Immune-mediated and unusual complications during interferon alfa therapy in chronic myelogenous leukemia.

PURPOSE: Long-term treatment with interferon alfa (IFN alpha) can produce or exacerbate immune-mediated complications (IMC). The purpose of this study was to analyze the experience with IMC and unusual complications in patients with chronic myelogenous leukemia (CML) undergoing IFN alpha treatment. PATIENTS AND METHODS: The occurrence of IMC and unusual complications was evaluated in patients with Philadelphia chromosome (Ph)-positive CML. RESULTS: Well-documented and clinically evident complications developed in 35 patients after a median of 14 months of IFN alpha treatment. These included 28 (5%) of 581 patients with Ph-positive CML treated with IFN alpha-containing regimens at M.D. Anderson Cancer Center (MDACC) and seven patients referred for opinion or problems who were on other studies. Hypothyroidism occurred in 11 patients (2%), immune-mediated hemolysis in seven (1%), and connective tissue diseases in 11 (2%). Other unusual occurrences included congestive heart failure (CHF; n = 4), porphyria cutanea tarda (PCT; n = 3), membranous glomerulonephritis (MGN; n = 1), and vitiligo (n = 1). IFN treatment was discontinued in 19 patients and the dose was reduced in five. Ten of 11 patients (91%) with immune-mediated hypothyroidism and eight of 11 (73%) with connective tissue diseases had some degree of cytogenetic response at the time of the event. CONCLUSION: Although the frequency of IMC is low, patients treated with IFN alpha should be monitored for signs and symptoms of autoimmunity.

Adolescent↗
PubMed1995

Survival of young patients with chronic lymphocytic leukemia failing fludarabine therapy: a basis for the use of myeloablative therapies.

We examined the survival of 91 young patients (< or = 55 years) with chronic lymphocytic leukemia from the time of failure of fludarabine therapy, in an attempt to identify those with a poor outcome who may benefit from investigative dose-intensive therapies. The median survival of patients unresponsive to fludarabine (n = 42) was 48 weeks, and only 11% responded to subsequent therapies. The median survival of patients relapsing following a fludarabine-induced remission (n = 49) was 87 weeks, and 83% of those who had received fludarabine as their first therapy (n = 14) responded to further fludarabine-containing therapies, with 60% alive at four years. Only 7% of those relapsing patients who had received fludarabine as salvage therapy (n = 35) responded to subsequent therapies (median survival 72 weeks). The poor outlook for these patients justifies the consideration of innovative dose-intensive therapies, such as bone marrow transplantation, with their attendant risk of toxicity.

Adult↗
PubMed1995

Fludarabine plus doxorubicin in previously treated chronic lymphocytic leukemia.

Based on the activity of fludarabine and doxorubicin in chronic lymphocytic leukemia (CLL), 30 patients received this combination. The median age of these patients was 61 years; median Zubrod performance status was one; median number of prior therapies was three; and median time to treatment was 53 months. Rai stage was 0 for two patients, I/II for 19 patients, and III/IV for nine patients. Prior treatment included fludarabine in 25 patients. In this regimen, fludarabine was administered as 30 mg/m2/d IV x 3 to 10 patients, 25 mg/m2/d IV x 4 to three patients, and to 17 patients as 30 mg/m2/d IV x 4. A 50 mg/m2 IV dose of doxorubicin was given to all patients. The first 17 patients received prednisone 30 mg/m2 x 5 days; however, this was discontinued due to other data demonstrating no therapeutic advantage and increased opportunistic infections when corticosteroids were added to fludarabine. Toxicity consisted primarily of infectious episodes: pneumonia nine, bacteremia one, FUO seven, and minor infection five. Two deaths from pneumonia occurred. Standard guidelines for response were used with the addition of a nodular CR group. Despite prior treatment with fludarabine in the majority of patients, the response rate in the 29 evaluable patients was CR 3%, nodular CR 17%, PR 35%, fail 38% and early death 7%. This combination of fludarabine and doxorubicin is active against CLL and warrants further study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Cytogenetic and clinical correlates in AML patients with abnormalities of chromosome 16.

Abnormalities of chromosome 16 in AML include del(16q), inv(16) and t(16;16). These three groups have been categorized together and have been associated with high complete remission (CR) and survival rates following Ara-C-based chemotherapy. We have reviewed the 63 AML or MDS patients with an abnormality of chromosome 16 treated at MD Anderson Cancer Center (MDACC) over the past 18 years. Marked differences in survival and remission duration (RD) were noted between the inv(16) or t(16;16) patients and those with del(16q), whose outcome was no better than other M4 AML or MDS patients treated during the same period. Other differences characterizing del(16q) included a lack of CNS relapses, lower incidences of eosinophilia and M4 FAB subtype. Half the inv(16) patients had additional karyotypic abnormalities. The overall survival and remission duration for those patients were no different from those for patients with inv(16) alone, although the probability of remaining in first CR at 2 years was higher in the inv(16) alone group. There was no difference in overall survival for the 45 patients who received HDAC vs those who did not. The incidence of CNS relapse was, however, markedly reduced for the HDAC patients. Eosinophilia did not correlate with improved survival. We conclude that del(16q) confers a different prognosis from inv(16) and t(16;16) and for the purposes of prognostication or treatment recommendations should no longer be categorized with them. Additional karyotypic changes however, which accompany inv(16) in 50% of cases do not influence the overall outcome compared to patients with inv(16) alone.

Acute Disease↗
PubMed1995

A 3-day schedule of fludarabine in previously treated chronic lymphocytic leukemia.

This study was undertaken to determine the efficacy and toxicity of a shorter schedule of fludarabine administration (30 mg/m2 i.v. daily for 3 days every 4 weeks) in patients with previously treated chronic lymphocytic leukemia (CLL). Eighty patients with previously treated advanced (Rai III-IV) (54%) or progressive Rai stage 0-II (46%) were treated. The results of this trial were retrospectively compared with those of previous fludarabine trials using different schedules of administration. The complete response (CR), nodular CR and partial response rates were 10, 15 and 21%. The overall response rate (46%) was slightly lower than prior regimens using a 5-day schedule of fludarabine; however, this difference was not significant. Further evaluation by dual-parameter flow cytometry and immunoglobulin gene rearrangement analysis revealed that minimal residual disease was more common in a 3-day schedule. The overall incidence of infections per treatment course (14%) was significantly lower than that observed on the 5-day or weekly regimens (P < 0.001). The incidence of minor, atypical and viral infections were similar. There was no difference in survival in the various trials. In conclusion, a 3-day schedule of fludarabine in previously treated CLL patients was associated with a lower infection rate and similar survival to a 5-day schedule. These data support the use of a 3-day schedule of fludarabine as a single agent and in combination with other active agents.

Adult↗
PubMed1995

Press coverage of the Cleveland child sexual abuse enquiry: a source of public enlightenment?

BACKGROUND: The objective of this study was to assess national and local newspaper reporting of events considered by a Public Enquiry which investigated a major crisis involving child protection services. The Judicial Enquiry, held in Cleveland, North East England, examined the actions of statutory bodies and the professionals working within them following the diagnosis of suspected sexual abuse in 121 children. METHODS: This is a descriptive study using analysis of legal transcripts and newspaper reports. The data involved a total of 216,360 lines of transcript evidence given by 111 witnesses and lawyers representing them at the Judicial Enquiry which lasted 74 days; together with 344,899 words in reports covering 17 newspapers (seven local and ten national). The main outcome measures were based on the volume and type of newspaper coverage including that for each witness' and lawyer's evidence. A coverage index related the amount of newspaper reporting to the extent of evidence given. RESULTS: The highest coverage of any single day of the Enquiry in both local and national newspapers occurred when Dr Marietta Higgs (one of the two principal paediatricians involved) made her first appearance. However, the highest interest (coverage index) was shown in evidence given by lawyers for the parents and the least in evidence given by public bodies. The evidence of witnesses was used very selectively by the press in emotive headlines to imply blame or support for the main protagonists or their actions. This sustained several lines of reporting: criticism of the doctors and social workers, inter-professional conflicts, damage and wrong-doing to the families and the search for someone to blame. CONCLUSIONS: The Cleveland crisis occupied newspaper headlines in the United Kingdom for more than a year. Much of the newspaper coverage took an adversarial approach which sought to apportion blame and take sides. The press appeared to report negative issues which were newsworthy and did not give a balanced view. Broader policy issues, which formed an important part of the Enquiry report's influence on subsequent child protection legislation, were largely ignored.

Child↗
PubMed1995

Clinical and prognostic significance of trisomy 21 in adult patients with acute myelogenous leukemia and myelodysplastic syndromes.

Trisomy 21 is the second most common trisomy in patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). However, its clinical and prognostic significance is not known. We analyzed the records of 1187 consecutive patients with untreated AML or MDS. Thirty-seven (3.3%) had trisomy 21: four (0.3%) as the only cytogenetic abnormality and 33 (2.7%) with other cytogenetic abnormalities (-5 and/or -7 in 15, +8 in nine, t(15;17) in three, inv(16) in three, t(8;21) in one, and hyperdiploid with several other additional chromosomes in two). Twenty-eight patients had AML and nine MDS. No patients had megakaryocytic phenotype (M7), common in patients with constitutional trisomy 21 (Down's syndrome) and AML. Overall, 57% achieved complete remission (CR), with median CR duration of 39 weeks, and median survival of 31 weeks. When patients with additional cytogenetic abnormalities were compared to patients with similar abnormalities but no trisomy 21, their clinical features as well as their CR rate, CR duration and survival were similar, with or without trisomy 21. We conclude that trisomy 21 in AML typically presents in conjunction with other cytogenetic abnormalities, especially -5/-7 and +8 whose presence rather than the presence of +21 dictates the clinical outcome.

Adolescent↗
PubMed1995

High remission rate, short remission duration in patients with refractory anemia with excess blasts (RAEB) in transformation (RAEB-t) given acute myelogenous leukemia (AML)-type chemotherapy in combination with granulocyte-CSF (G-CSF).

A study was made to determine CR rate, response duration and survival in patients with RAEB or RAEB-t given AML-type chemotherapy, in particular the newer agents idarubicin and fludarabine. Eighty-five adults (58 RAEB-t, 27 RAEB) received either IA (idarubicin 12 mg/m2 daily on days 1-3, ara-C 1.5 g/m2 daily on days 1-4 CI), FA (fludarabine 30 mg/m2 daily on days 1-5, ara-C 2 g/m2 daily on days 1-5) or FLAG (FA + G-CSF 400 micrograms/m2 daily from day-1 until CR). IA was given exclusively to patients with better prognosis (as assessed by pretreatment karyotype), while FA and FLAG were given first to patients with worse and then to those with better prognosis. In remission, patients received lower doses of the same regimens for 6-12 months. The 85 patients comprise the largest reported series of RAEB or RAEB-t patients given AML-type chemotherapy. Their median age was 61 years, 33% had chromosome 5 or 7 abnormalities (-5/-7), and 55% were treated in laminar air flow rooms. The CR rate was 66%. While rates were highest in younger patients with a normal karyotype, CR rates in excess of 50% were also obtained in patients over age 60 (27/47; 57%) and in patients with -5/-7 (17/29; 59%). In 11 of the 14 cytogenetically abnormal patients in whom cytogenetic analysis was repeated at the time of CR, only normal metaphases were found. In the remaining 3 the number of abnormal metaphases was substantially reduced. However, the probability of continued CR was low (e.g. 452 +/- 0.08 at 12 months), and the only patients alive in CR beyond two years were patients under age 60 without -5/-7 and with RAEB-t. Survival probability was 0.35 +/- 0.05 at one year. Eight of 56 patients died in CR. While current AML-type chemotherapy can produce higher CR rates than is perhaps usually appreciated, in some patients with RAEB or RAEB-t (e.g. older patients with -5/-7) the brevity of the remissions and the risk entailed suggest that new post-remission therapies are needed to make this approach generally worthwhile.

Adult↗
PubMed1995

Interferon-alpha and interleukin-2 as treatment for leukemia relapse after allogeneic bone marrow transplantation.

We treated 12 patients with leukemia relapse after allogenic bone marrow transplantation with a combination of interferon-alpha (IFN-alpha) ((2.5-5.0) x 10(6) u/m2 subcutaneously three times a week) and interleukin-2 (IL-2) ((1.8-3.6) x 10(6) IU/m2 subcutaneously five times a week) to determine the toxicity and efficacy of combination cytokine therapy in this setting. The median age of the patients was 39 years (range: 16-50). There were nine females and three males. The median time to relapse from BMT was 98 days (range: 0-963). At the time of relapse, six patients had AML, four patients had CML (two in blast crisis and two in chronic phase with clonal evolution), and one patient had lymphoblastic lymphoma. Combination cytokine therapy was started a median of 108 days post BMT (range: 37-2404). Nine patients treated at the higher dose level required a 50% dose reduction because of toxicity or GVHD (three CNS, two GVHD, one high fever, one diarrhoea with hypotension, and one pericarditis). At a lower dose level, 2 of 10 patients had their treatment discontinued because of toxicity or GVHD. Six patients developed clinical findings consistent with acute GVHD while on combination cytokine therapy. Two patients responded to combination cytokine therapy: one with CML and one with AML. Combination cytokine therapy is feasible in the setting of relapse post allogeneic BMT. The combination of IL-2 1.8 x 10(6) IU/m2 five times a week with IFN-2 2.5 x 10(6) U/m2 three times a week seems to be tolerable, and merits further study in this setting.

Acute Disease↗
PubMed1994

Sequential operation of disconnected cerebral hemispheres in split-brain patients.

When two concurrent sensorimotor tasks require separate responses, selection of the first response generally delays selection of the second. Dual-task performance was examined in four patients who had undergone surgical transection of the forebrain commissures including the corpus callosum. One light flash was presented to each visual field in succession, and patients made a choice response to each stimulus with the ipsilateral hand, thereby confining the tasks to separate hemispheres. All four showed dual-task interference very similar to that found with normal individuals. Therefore, still-intact subcortical structures must play a critical role in sequencing response selection processes (the 'dual-task bottleneck'), confirming the distinction between the attentional limitations involved in planning actions and those involved in perceptual analysis.

Brain↗
PubMed1994

Prognostic factors for survival in patients treated in phase I clinical trials.

BACKGROUND: Patients with advanced or metastatic cancer treated in Phase I clinical trials are considered to have a poor prognosis. Survival from first treatment in a Phase I trial was determined for 349 patients. Univariate and multivariate survival analyses were performed to determine whether potential prognostic factors and distinct risk groups could be identified. METHODS: Patients were identified retrospectively from a large data base of patients with advanced or metastatic cancer treated in Phase I clinical trials at the University of Chicago between February 1987 and October 1991. RESULTS: With a median follow-up of 29 months, 10% of patients were alive at the time of analysis. Twenty-nine percent were alive 1 year after the initiation of Phase I chemotherapy, and the median survival from first treatment in a Phase I study was 6.5 months. Multivariate analysis indicated that a better pretreatment performance status, a higher pretreatment serum albumin concentration, a lower pretreatment platelet count, no prior cisplatin chemotherapy, and a genitourinary or gynecologic cancer diagnosis were predictive of better survival. Three risk groups incorporating these five variables were identified, with median survivals of 12.7, 7.4, and 3.5 months for the good, intermediate, and poor risk groups, respectively. CONCLUSION: Patients treated in Phase I clinical trials have a median survival of 6.5 months, even though some patients have been treated at early (subtoxic and potentially subtherapeutic) dose levels. The results of this study may allow the identification of patients who are likely to survive long enough to contribute information on acute and cumulative drug-related toxicities and, possibly, tumor response.

Adult↗
PubMed1994

2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders.

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.

Adult↗
PubMed1994

All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is effective in the treatment of relapsed or refractory acute promyelocytic leukemia (APL), but relapse is the rule if response is unmaintained. METHODS: Seventeen patients with APL were salvaged with ATRA at a dosage of 50 mg/m2/day for 3 months or until complete remission (CR) was achieved; idarubicin (12 mg/m2/day for 4 days) was added if blast plus promyelocyte count either was or reached > or = 10 x 10(3)/microliters. After CR was achieved, patients received three courses of idarubicin (12 mg/m2 daily for 3 days) followed by three courses of mitoxantrone (5 mg/m2 daily for 3 days) and etoposide (250 mg/m2 daily for 3 days). Maintenance was with 6-mercaptopurine and methotrexate. RESULTS: A CR was achieved in 14 patients (82%), the disease was refractory in 2 patients, and one patient died during induction. Three patients underwent allogeneic bone marrow transplant during CR. After a median follow-up of 26 weeks, six patients remain in CR. Median CR duration is 40 weeks (range 8-56+). Patients treated with ATRA plus chemotherapy in first salvage, when compared to a historic control group treated with chemotherapy alone, had a significantly better CR rate (87% vs. 57%; P = 0.04) and a lower induction death rate (7% vs. 29%; P = 0.08), resulting in longer median survival (26 vs. 17 weeks; P = 0.13). Four patients developed the "retinoic acid syndrome", which was fatal in one case. Three patients developed thrombotic events. CONCLUSIONS: ATRA followed by chemotherapy is effective treatment for patients with APL who relapse after conventional therapy, and it may be superior to chemotherapy alone.

Adolescent↗