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Biomedical subjects

J L Fahey

Publications and source records attributed to J L Fahey.

At least 109 records · Page 6Linked to original sources
PubMed1987

Allogeneic bone marrow transplantation for acute lymphoblastic leukemia during first complete remission.

Patients with acute lymphoblastic leukemia who have poor prognostic features at diagnosis usually have a short disease-free survival in spite of successful remission induction. Those poor risk features are: age over 30 years, a white blood cell count over 25,000/microliter, certain translocations of chromosomes, and requirement for more than six weeks of induction chemotherapy to attain a complete remission. We have used high-dose radiochemotherapy to prepare 39 patients with acute lymphoblastic leukemia in first complete remission (1 infant and 38 adults; median age 23 years) for bone marrow transplantation from histocompatible sibling donors. Thirty-one of the 39 patients in this study had one (n = 23) or more (n = 8) poor risk features: age (n = 7); high white blood cell count (n = 19); translocations (n = 4), or resistance to initial induction therapy (n = 11). Currently, 26 patients are surviving for 4-72 months (median 18 months) following marrow grafting and are in complete remission. One of the surviving patients had two marrow transplant procedures because of recurrent leukemia. Actuarial survival in complete remission is 63% for the entire group of 39 patients and is 60% if the eight patients who had no poor risk features are excluded from analysis. The following causes for failure were observed: leukemic relapse was encountered in four patients between 3 and 17 months after BMT for an actuarial relapse rate of 16%; bacterial sepsis was the cause of death in two patients; graft-versus-host disease and/or interstitial pneumonia led to the demise of seven patients, and one patient died with leukoencephalopathy. It appears that high-dose radiochemotherapy followed by bone marrow transplantation from a histocompatible sibling donor during first complete remission can result in a high disease-free survival rate for younger adults with poor-risk acute lymphoblastic leukemia. This concept needs to be tested in prospective trials comparing bone marrow transplantation with chemotherapy.

Adolescent↗
PubMed1987

Bone marrow transplantation for acute nonlymphoblastic leukemia during first complete remission. An analysis of prognostic factors.

Sixty-nine patients with acute nonlymphocytic leukemia in first remission received total-body irradiation and chemotherapy followed by allogeneic bone marrow transplantation from histocompatible sibling donors. Patient age was between 1 and 41 years: 20 patients 1-19 years (group 1); 27 patients 20-29 years (group 2); and 22 patients 30-41 years (group 3). Two pretransplant radiochemotherapy regimens were employed: The first 45 patients received total-body irradiation (in a single dose) with cytosine arabinoside and cyclophosphamide; the next 24 patients received total-body irradiation (in a fractionated schedule) with cyclophosphamide alone. For all patients, actuarial disease-free survival is 51% (37 of 69 patients are alive and in continuous remission between 5 months and 9.3 years, median 3.7 years). For group 1 actuarial survival is 56%, group 2 48%, and group 3 48%. When analyzed for pretransplant factors that might predict disease-free survival after bone marrow transplantation neither patient age, white cell count at the time of diagnosis, FAB leukemic subtype, length of time before achieving remission, nor length of time between remission and bone marrow transplantation were established as prognostic.

Acute Disease↗
PubMed1987

Acquired immune deficiency syndrome (AIDS) and neoplasia.

The acquired immune deficiency syndrome (AIDS) is a novel epidemic form of immunodeficiency that has been widely recognized within the last six years. AIDS is characterized by Kaposi's sarcoma, B cell lymphoma, and/or life-threatening opportunistic infections superimposed on an immune deficiency state which consists of lymphopenia with a selective depletion of the CD4 T cells. In addition, lymphocytes from AIDS patients show decreased responses to antigen or mitogen stimulation in vitro. Although the secondary infections and malignancies seen in these patients may be successfully treated, the underlying immune defect persists, leaving the patient susceptible to further complications.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Significance of quantitative enzyme-linked immunosorbent assay (ELISA) results in evaluation of three ELISAs and Western blot tests for detection of antibodies to human immunodeficiency virus in a high-risk population.

The characteristics of primary (first) tests with three enzyme-linked immunosorbent assay (ELISA) kits for human immunodeficiency virus (HIV) antibody were determined. The three ELISAs were performed on 3,229, 3,130, and 685 specimens from high-risk individuals using the Litton (LT; Litton Bionetics Laboratory Products, Charleston, S.C.), Dupont (DP; E. I. du Pont de Nemours & Co., Inc., Wilmington, Del.), and Genetic Systems (GS; Genetic Systems, Seattle, Wash.) kits, respectively. Evaluation was based on the distribution of quantitative test results (such as optical densities), a comparison with Western blot (WB) results, reproducibility of the tests, and identification of seroconverters. The performances of the GS and the DP kits were good by all four criteria and exceeded that of the LT kit. Primary ELISA-negative results were not always confirmed with repeat ELISA and by WB testing. The largest percentage of these unconfirmed negative test results came from samples with quantitative results in the fifth percentile nearest the cutoff. Thus, supplementary testing was indicated for samples with test results in this borderline negative range. Similarly, borderline positive primary ELISA results that were quantitatively nearest (fifth percentile) the cutoff value were more likely to be antibody negative on supplementary testing than samples with high antibody values. In this study, results of repeated tests by GS ELISA showed the least change from first test results. DP ELISA showed more unconfirmed primary positive test results, and LT ELISA showed more unconfirmed primary negative test results. Designation of a specimen with a single ELISA quantitative level near the cutoff value as positive or negative should be viewed with skepticism. A higher than normal proportion of specimens with high negative optical densities by GS ELISA (fifth percentile nearest the cutoff) and also negative by WB were found to be from individuals in the process of seroconversion.

Antibodies, Viral↗
PubMed1987

Detection of early antibodies in human immunodeficiency virus infection by enzyme-linked immunosorbent assay, Western blot, and radioimmunoprecipitation.

A current concept of the serological response to human immunodeficiency virus (HIV) infection in humans is that antibodies to core antigens (p55, p24, and p15) are detectable earlier during initial stages of antibody production than antibodies against envelope antigens (gp160, gp120, and gp41). Comparative studies of Western blot (immunoblot), radioimmunoprecipitation assay (RIPA), and enzyme-linked immunosorbent assay (ELISA) during initial antibody production are limited to case reports and have not resolved the issue. Thirty of the 37 participants who are part of a prospective study had at least one specimen that was negative for anti-gp41 but had one or more other bands on Western blot. Twenty-seven of these 30 specimens were reactive for anti-gp120/160 in the RIPA. Of the same 30 specimens, kits from Bionetics identified 2 (7%), ElectroNucleonics 4 (13%), Abbott 13 (43%), Du Pont 25 (83%), and Genetic Systems 25 (83%). All participants had evidence of serological progression by Western blot, including a gp41 band, on subsequent visits; the ELISA kits of all manufacturers identified these later specimens with greater accuracy. These data show that the RIPA detects anti-envelope antibodies that may be not detectable by Western blot and that the production of anti-envelope antibodies approximately parallels the production of anti-core antibodies. The false-negative results by ELISA would permit transmission of HIV by blood transfusion from donors in early stages of infection. The sensitivity of licensed ELISA kits should be improved to identify antibody as soon as possible after infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes.

Twenty patients (age range, 4 to 48 years; median age, 36 years) with de novo or drug-induced myelodysplastic syndromes or myeloproliferative disorders were treated with myeloablative immunosuppressive therapy followed by bone marrow transplantation (BMT). Four preparative regimens were used; three regimens consisted of combined total body irradiation (TBI) and chemotherapy and one of combination chemotherapy only. One patient received marrow from his identical twin brother, whereas the other 19 patients were grafted with marrow from histocompatible siblings. In 19 patients the abnormal clone was at least temporarily ablated, while in one patient the congenital myelodysplasia persisted. Eight patients are alive and well for +108 to +3,359 days post-transplantation. Nine patients died of transplant-related complications (six of interstitial pneumonia, two of gastrointestinal bleeding, and one of fungal sepsis) and three patients died with persisting or recurring disease. One patient with a late recurrence has undergone a second successful bone marrow transplant procedure. Outcome of BMT was not related to French-American-British (FAB) type, marrow fibrosis, cytogenetic abnormalities, or preparation regimen. Marrow transplantation as a means of providing long-term disease-free survival and possible cure should be considered in patients if a suitable donor is available.

Adolescent↗
PubMed1987

Immune interventions in disease.

Three therapeutic areas of clinical immunology that have seen active development recently are immunopharmacology of immunosuppressive drugs; clinical use of the alpha-, beta-, and gamma-interferons and interleukin-2; and monoclonal antibody applications in marrow transplantation and antitumor therapy. Understanding of the immune regulatory systems and of the soluble factors that convey information between immune and related cells (for example, lymphokines and cytokines and their receptors) has improved substantially. New information about established immunosuppressive drugs and the introduction of new drugs are providing new opportunities for effective treatment of autoimmune diseases and improved effectiveness of organ transplantation. Clinical trials are evaluating the use of interleukin-2 in immunodeficiency disorders and neoplastic disease. Monoclonal antibodies, which have been successfully applied to diagnostic procedures, have been shown to be useful for therapeutic applications in marrow transplantation and antitumor treatment.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunology of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. An update.

Recent advances in the understanding of the pathogenesis of infection with human immunodeficiency virus (HIV) stems from the demonstration that the membrane glycoprotein, CD4, is the cellular receptor for HIV. This glycoprotein is found mainly on the surface of a major subpopulation of T lymphocytes and also on macrophages, natural killer cells, some B lymphocytes, and neuronal cells. Cells infected with HIV may be destroyed or have their normal function impaired. Host immune responses to HIV are poor and are not sustained. Neutralizing antibody often is not produced, or HIV may escape from normal immunosuppressive mechanisms through the process of rapid antigenic variation. Factors and markers that may be important in the outcome or that may predict progression of HIV infection are genetic (Gc type), environmental (nutritional status or intercurrent sexually transmitted diseases sustained by the host), and immunologic (rate of decline in number and impairment of function of CD4 lymphocytes and of decline in antibody titers to HIV core protein, p24). A recombinant vaccine will probably be developed for testing in future clinical trials.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Bone marrow transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We report the treatment outcome of allogeneic bone marrow transplantation in ten patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Six patients are alive and well for 6 to 30 months (median 19 months) after transplantation. Four patients died with transplant related complications. In view of the poor prognosis associated with this disease, marrow ablation followed by allogeneic or syngeneic marrow grafting may be the preferred treatment modality if a suitable marrow donor is available.

Acute Disease↗
PubMed1987

Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies.

In a phase I/II study, 47 patients (median age, 24 years) with hematologic malignancies (33 patients with acute leukemia not in first remission and 14 patients with other advanced malignant hematologic disorders) were treated with total body irradiation and high doses of etoposide (VP16-213) followed by bone marrow transplantation. At the time of analysis, 21 patients were alive, and 19 of them were in continued complete remission for 101 days to greater than 40 months (median, 12 months). The actuarial disease-free survival rate of the 33 acute leukemia patients is 43% (2 SEM, 18%) and the actuarial relapse rate is 32% (2 SEM, 20%). Five of the 14 patients with the other hematologic malignancies are alive, and four of them continue to be free of disease for 8 to 27 months. Pharmacokinetic studies established a strong correlation between the administered drug doses and their plasma levels and also demonstrated complete drug clearance prior to marrow grafting. An etoposide dose of 60 mg/kg body weight was found to be the maximum tolerated dose. This new preparatory regimen was well tolerated and was not associated with specific acute or long-term regimen-related toxicities. Our data suggest that total body irradiation with high-dose etoposide presents a viable alternative to other preparatory regimens. The role of this novel combination remains to be defined by future prospective randomized trials.

Acute Disease↗
PubMed1987

Cytarabine, cisplatin, and etoposide chemotherapy for refractory non-Hodgkin's lymphoma.

A phase II trial of cytarabine, cisplatin, and etoposide was conducted in 38 patients with refractory stage III and IV non-Hodgkin's lymphoma. There were two complete and nine partial responses (32%) among 35 evaluable patients. Response rate in patients with large cell lymphoma was 45%. The dose-limiting toxic effect was myelosuppression in 66% of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Heterogeneity of epidemic Kaposi's sarcoma. Implications for therapy.

Kaposi's sarcoma (KS) in acquired immune deficiency syndrome (AIDS) is a new manifestation of a previously rare disease, and generally has a fatal course. Variations in the clinical course and in response to treatment by patients with this disease suggest that specific immunologic or clinical parameters may be important in the prognosis. Retrospective analyses of clinical parameters with respect to survival in 96 patients with epidemic Kaposi's sarcoma indicated that earlier tumor stage, the lack of prior opportunistic infections, and the absence of systemic symptoms correlated most closely with survival. Sixteen immune parameters were also assessed for their prognostic value. Total T4 (CD-4) cell number levels and the T4: T8 ratio correlated most closely with survival. Response to treatment with recombinant alpha interferons, while not well correlated with tumor stage, was more frequent in patients without systemic symptoms or a history or prior opportunistic infections. Treatment response was associated with a greater degree of intact T-cell function. These findings emphasize the importance of cellular immunity in the pathogenesis and subsequent course of patients with epidemic Kaposi's sarcoma, suggesting that different therapeutic strategies may be necessary to address specific prognostic subgroups.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis.

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.

Anemia↗
PubMed1986

A statistical method for assessing change in immunologic parameters in a patient.

Serial measurement of in vitro immunologic parameters in patients is used to detect change in immune status over time due to disease progression and/or immunodulatory therapy. A statistical method is presented for looking at serial measurements on an individual to detect whether a change in a parameter is outside the bounds of expected within-individual variation. Analysis of variance is used, assuming a normal distribution, to obtain percentiles of the distribution of the absolute difference between consecutive values of immunologic parameters in a healthy population. The assumptions in this analysis are justified from a statistical point of view. We discuss how to use this statistical method to make judgments relevant to clinical immunology, including how to construct a table that can be used to determine quickly if an "interesting" change for some standard immunologic parameters has occurred, whether a linear (additive) or logarithmic (proportional) model for change might be more appropriate for a given parameter, and how to modify the calculations if change is expected in a certain direction or if multiple pre- and/or postevent (clinical change or intervention) measurements are available.

Adult↗
PubMed1986

Characterization of a distinct subgroup of high-risk persons with Kaposi's sarcoma and good prognosis who present with normal T4 cell number and T4:T8 ratio and negative HTLV-III/LAV serologic test results.

Three homosexual male patients with biopsy-proved Kaposi's sarcoma were classified as having the acquired immune deficiency syndrome (AIDS) by Centers for Disease Control criteria when first seen in 1983 and 1984. These patients, however, differed from most patients with AIDS and Kaposi's sarcoma in having normal CD4 cell numbers and normal CD4:CD8 ratio. Furthermore, these immunologic parameters remained normal for eight to 24 months of follow-up, and the disease did not progress. Results of recent testing of serum from these patients were negative for HTLV-III/LAV antibodies. The Kaposi's sarcoma was limited to skin (stage I tumors) and the patients did not have persistent lymphadenopathy, fever, night sweats, or weight loss. In contrast to AIDS, the serum immunoglobulin levels (IgG, IgA, IgM) and number of B cells that were spontaneously forming immunoglobulin were within normal range with no evidence of polyclonal activation. The lymphocyte proliferative responses to phytohemagglutinin and Candida were reduced in two of the three patients, and skin test anergy was observed in the two patients tested. These findings are not frequently encountered in other healthy, homosexually active men or in classic Kaposi's sarcoma. They may be indicative of functional T cell changes (without numerical changes) induced by factors other than HTLV-III/LAV virus, which made these homosexually active men susceptible to development of low-grade Kaposi's sarcoma lesions.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Bone marrow transplantation for hematologic malignancies in patients aged 30 years or older.

During the past 10 years, 86 patients 30 to 54 years of age with hematologic malignancies were prepared with high-dose radiochemotherapy and received histocompatible bone marrow grafts. Thirty-four of these patients are surviving for 4 months to 9 years (median, 26 months) following marrow transplantation and 32 of them are in continuing complete remission (CR). Disease-free survival is 44% for 37 patients who were in first remission of acute leukemia or in the chronic phase of chronic granulocytic leukemia (CGL), 23% for 39 patients whose leukemia had relapsed at least once before transplantation or who had advanced stages of CGL, and 60% for ten patients who had hematologic malignancies other than leukemia. The median age of the surviving 34 patients is 36 years (range, 30 to 43 years). The incidence of moderate to severe acute graft-v-host disease (GVHD) was 48% and of chronic GVHD, 26%. The major causes of failure were interstitial pneumonia in 31 patients (24 of whom had antecedent acute GVHD) and recurrent leukemia in 12 patients (11 of whom had either never entered a CR or had relapsed at least once with acute leukemia or had progressive CGL before transplantation). Our data warrant further prospective studies in patients with hematologic malignancies who are older than 30 years.

Actuarial Analysis↗
PubMed1986

Cytosine arabinoside induced changes in natural killer and antibody dependent cellular cytotoxicity functions in multiple sclerosis patients.

Five multiple sclerosis patients were treated weekly with cytosine arabinoside (araC) on an escalating dose schedule. The dose was initiated at 50 mg/M2 and then increased once each week by 50 mg/M2 (unless toxicity caused delay). Dosage decisions were based on whether or not the antibody-dependent cellular-cytotoxicity (ADCC) or natural killer (NK) cytotoxicity levels had been reduced to a level more than 2 standard deviations below the control range. Cytosine arabinoside treatment was discontinued in 2 of 5 subjects at doses of 500 mg/M2 due to toxicity. The 3 remaining patients demonstrated sustained reductions in the percentage of FcR+ cells in their peripheral blood. The maximum percentage reductions from the baseline values ranged from 50% to 76%. Concomitant reductions in the NK activity at the same doses ranged from 65% to 83%. ADCC activity in all 3 patients, however, was relatively resistant to suppression. The nadirs for the ADCC activity were only 16% to 44% below the baseline minimum. AraC was shown to reduce the proportion of FcR+ cells and NK cytotoxic activity in preference to ADCC activity.

Antibody-Dependent Cell Cytotoxicity↗