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Biomedical subjects

K M Sullivan

Publications and source records attributed to K M Sullivan.

At least 289 records · Page 16Linked to original sources
PubMed1983

Ocular manifestations of graft-v-host disease.

Graft-v-host disease is the major complication of bone marrow transplantation for the leukemias and aplastic anemia. In the clinical evaluation of eye problems of patients with acute graft-v-host disease, findings reveal a disease process of keratoconjunctivitis that appears to represent a specific pathologic eye syndrome in which the conjunctivae and occasionally the cornea represent an immunologic target of graft-v-host disease. Additional studies of eye problems of chronic graft-v-host disease reveal the persistent nature of keratitis sicca and the morbid sequelae of the immunoincompetent patient.

Acute Disease↗
PubMed1983

The predictive value of elevated labial saliva sodium concentration: its relation to labial gland pathology in bone marrow transplant recipients.

Labial minor gland salivary flow rate and sodium concentration were analyzed in relation to 1) histologic findings in labial biopsy specimens and 2) the occurrence of chronic graft-versus-host disease (GVHD) in patients who received bone marrow transplants. Biopsy specimens and samples were obtained from 61 recipients of marrow transplants (including three twins) 51 to 1,260 days post transplantation. Labial saliva sodium concentrations were elevated in some patients, and these increases were associated with inflammation and destruction of minor salivary gland acini and ducts by chronic GVHD or other factors. The predictive value of the salivary sodium changes in evaluating labial salivary gland pathologic changes was 91 per cent, and the sensitivity was 74 per cent. Thus, if a transplant recipient is found to have an elevated labial saliva sodium level, then the probability that he has pathologic labial gland changes is 91 per cent. When analyses were restricted to include only patients who received no irradiation during transplantation, then elevated labial saliva sodium concentration was significantly associated with the occurrence of chronic GVHD. The sensitivity of this relationship was 42 per cent, but the predictive value was 100 per cent. Thus, if a nonirradiated transplant recipient is found to have an elevated labial saliva sodium concentration, then it is virtually certain that he has chronic GVHD. We found no significant changes in labial saliva flow rates in these bone marrow transplant recipients.

Adolescent↗
PubMed1983

The pathophysiology and treatment of graft-versus-host disease.

Acute and chronic GVHD remain major impediments to the wider application of allogeneic marrow transplantation. It is presumed that human acute GVHD is analogous to the murine model which is initiated by donor T lymphocytes reacting with recipient 'minor' histocompatibility antigens. Chronic GVHD may result from immunoaggression of donor lymphoid cells that have developed and differentiated within the host. Lack of GVHD (i.e., the development of tolerance) may be due either to generation within the host of specific suppressor lymphocytes or to clonal deletion of alloreactive donor cells. Over the last five years progress has been made in the recognition, early diagnosis and successful therapy of chronic GVHD. Methods of prevention and therapy of acute GVHD are still largely unsuccessful. With improved understanding of immune regulation, it is hoped that GVHD can be eliminated in patients transplanted for non-malignant conditions and adroitly modified (without loss of anti-leukaemic potential) in patients with malignant disorders. The challenge of the coming decade is to reach these goals while speeding the return of full immunological competence in the marrow transplant recipient.

Acute Disease↗
PubMed1983

Recombinant leukocyte A interferon for the treatment of serious viral infections after marrow transplant: a phase I study.

Six marrow-transplant patients with serious virus infections (four with cytomegalovirus and two with adenovirus) were treated with recombinant leukocyte alpha interferon at daily doses of 6,000,000-50,000,000 units to determine safety and tolerance. Fever and gastrointestinal side effects attributable to interferon occurred in two patients each. Hepatic function abnormalities were observed in all six patients, although five had such abnormalities before treatment. Treatment of one patient was stopped because of apparent suppression of marrow activity. Natural cytotoxic activity increased in the four patients treated for cytomegalovirus infection. All six patients died of pneumonia, with four proven to have cytomegalovirus-related pneumonia at autopsy. Except for the presence of abnormal hepatic function, recombinant leukocyte alpha interferon was well tolerated after marrow transplantation. Efficacy remains to be established in treatment or prophylactic trials.

Adenoviridae Infections↗
PubMed1983

Disordered salivary immunoglobulin secretion and sodium transport in human chronic graft-versus-host disease.

Whole saliva samples and lip biopsies were collected from 12 allogeneic bone marrow transplant recipients who developed extensive chronic graft-versus-host disease (GVHD) and from 10 healthy allogeneic and syngeneic recipients without GVHD. Six of ten biopsies from patients with chronic GVHD had lichenoid stomatitis or sialadenitis, or both, with sialodochitis. Seven of nine biopsies from patients free of chronic GVHD were entirely normal, and two had either mild glandular or mucosal changes. Salivary gland involvement in chronic GVHD was associated with decreased or absent levels of salivary IgA and inorganic phosphate, decreased salivary flow rates, and increased concentrations of salivary sodium, albumin, and IgG. The most striking abnormalities were found in patients with histologic evidence of sialadenitis. In contrast, marrow transplant recipients without chronic GVHD had normal salivary immunoglobulin and electrolyte levels. Secretory IgA deficiency may contribute to the frequent sinobronchial infections observed in patients with chronic GVHD.

Adolescent↗
PubMed1983

Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation.

One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.

Acute Disease↗
PubMed1983

Mycobacterial infections in marrow transplant patients.

Bone marrow transplant recipients undergo ablation of host immune defenses with total-body irradiation or high dose chemotherapy, or both. Over a 5.6-year period, mycobacterial infections were observed in 7 of 682 patients with leukemia who received marrow grafts. Four patients had pulmonary and three extrapulmonary infection. Granulomas were observed in the lungs of three patients, in the liver of one patient, and in the skin of one patient. Cultures revealed Mycobacterium tuberculosis in two patients, Mycobacterium fortuitum in two patients, and Mycobacterium kansasii in one patient. In the six patients treated with antimycobacterial therapy in either the pretransplant or posttransplant period, complete resolution of the infection was achieved. Pretransplant chest radiograph abnormalities suggesting mycobacterial infections should be aggressively evaluated in these immunocompromised hosts. Prophylaxis should be considered in marrow graft recipients with a well-established history of inadequately treated tuberculosis, previous Bacille Calmette-Guerin immunotherapy, known family contacts, recent skin test conversion, or past skin test positivity.

Adolescent↗
PubMed1983

Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings.

One hundred ten of 175 patients with aplastic anemia conditioned by cyclophosphamide had sustained engraftment of marrow from human leukocyte antigen (HLA)-identical siblings and lived for more than 6 months. Forty-nine of the 110 patients developed chronic graft-versus-host disease between 85 and 464 days. Ninety-seven patients are alive from 1.4 to 11 years after engraftment; 13 died between 208 and 726 days. Twenty of the 36 surviving patients with chronic graft-versus-host disease have Karnofsky performance scores of 100%, 7 of 90%, 5 of 80%, 1 of 70%, 2 of 60%, and 1 of 40%. Our analysis, using a binary logistic regression model, identified three factors predicting chronic graft-versus-host disease: moderate to severe acute graft-versus-host disease with an estimated relative risk of 11.65; increasing patient age; and the use of viable donor buffy coat cells in addition to the marrow to prevent graft rejection. The last two factors were significant only in patients without acute graft-versus-host disease.

Adolescent↗
PubMed1983

Marrow transplantation from HLA-identical siblings for treatment of aplastic anemia: is exposure to marrow donor blood products 24 hours before high-dose cyclophosphamide needed for successful engraftment?

The present study in patients with aplastic anemia was undertaken to determine whether exposure of recipients to donor blood products 24 hr before preparation with cyclophosphamide (1) enhanced the rate of sustained engraftment of marrow from HLA-identical siblings as suggested by animal experiments, (2) increased the rejection rate, in particular in transfused patients who may already have been exposed to donor antigens by blood products, or (3) was of no relevance to the outcome of transplantation of marrow from HLA-identical siblings. One-hundred fifty-five patients were studied, of whom 78 received blood products from the marrow donor 24 hr before cyclophosphamide and 77 did not. A binary logistic regression analysis was applied to the data, simultaneously considering five previously known risk factors for rejection. Results showed that preceding transfusion of donor blood products had neither a significant beneficial nor detrimental effect on the incidence of sustained engraftment.

Anemia, Aplastic↗
PubMed1983

Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse.

Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2-6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.

Acute Disease↗
PubMed1983

Fanconi's anemia treated by allogeneic marrow transplantation.

Eight patients with Fanconi's anemia were given cyclophosphamide alone (seven patients) or combined with procarbazine and antithymocyte globulin (one patient) followed by marrow grafts from HLA-identical siblings. All patients had engraftment. Seven developed acute and three chronic graft-versus-host disease (GVHD). Three patients died with GVHD and infectious complications (days 19, 56, and 82) and one with an intracerebral hemorrhage (day 540). Four patients are surviving 647-3435 days after grafting, two are well, and two have chronic GVHD that is improving. These results show that Fanconi's anemia can be treated successfully by allogeneic marrow transplantation.

Anemia, Aplastic↗
PubMed1983

Combined modality therapy of advanced non-Hodgkin's lymphoma: an analysis of remission duration and survival in 95 patients.

Ninety-five patients with advanced non-Hodgkin's lymphoma were treated with four courses of cyclophosphamide, adriamycin, vincristine and prednisone, with or without procarbazine [CHOP(P)] chemotherapy; either 150 rad total body irradiation (for "extensive" disease) or 3,500 rad local radiation therapy (for "limited" disease); and a final four courses of CHOP(P) chemotherapy. Sixty-four patients had stage IV, 22 stage III, and 9 abdominal stage II disease. Histologic material was available in 80 patients for review according to the new Working Formulation: 16 had low grade, 38 intermediate grade (20 large cell, 18 diffuse small cleaved and mixed cell), and 26 high grade (12 lymphoblastic, 8 immunoblastic, 6 small noncleaved) malignancies. Complete remission was achieved in 78% of 92 evaluable patients. The remission duration curve for diffuse large cell lymphoma patients showed a plateau at 72% after 2 yr, but a pattern of continued relapse (median 3 yr) was seen in the other histologies. Multivariate analysis showed that "B" symptoms, bulky abdominal masses, and stage IV disease adversely affected survival. Overall survival by Kaplan-Meier analysis showed that 67% of diffuse small cleaved and mixed cell, 49% of large cell and immunoblastic, and 44% of lymphoblastic lymphoma patients survive 6 yr after diagnosis. When compared to reported remission duration and survival with CHOP chemotherapy alone, these data suggest a possible advantage for combined modality treatment.

Adult↗
PubMed1982

Treatment of chronic granulocytic leukaemia in chronic phase by allogeneic marrow transplantation.

Ten patients with chronic granulocytic leukaemia in the chronic phase have been treated with chemoradiotherapy followed by transplantation of bone marrow from HLA-identical siblings. Engraftment was achieved in all patients, and Philadelphia chromosome disappeared from the nine patients who had it before transplantation. Four patients have died, three with interstitial pneumonitis and one with severe graft-versus-host disease (GvHD). Six patients are alive and well in complete clinical, cytogenetic, and haematological remission, 1-3 years after transplantation, despite complications in three patients (one had interstitial pneumonitis, one had mild veno-occlusive disease of the liver, and one had severe GvHD).

Adult↗
PubMed1982

Allogeneic marrow transplantation for acute leukemia in relapse.

The results of allogeneic marrow transplantation in 75 patients with acute lymphoblastic leukemia and 63 patients with acute non-lymphoblastic leukemia in relapse are reviewed. The effects of various chemotherapeutic regimens added to the basic regimen of cyclophosphamide (Cy) 60 mg/kg given on each of two successive days followed by 1000 rad of total body irradiation (TBI) were evaluated. The regimens tested were dimethylbusulphan (DMB), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and daunorubicin. Seventeen of 138 patients are alive between three and nine and a half years from transplantation. The addition of other chemotherapeutic agents to th basic Cy and TBI regimen did not decrease relapse frequency or prolong survival.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation for acute non-lymphoblastic leukemia in relapse using fractionated total body irradiation.

Twenty-three patients with acute non-lymphoblastic leukemia in relapse were treated with cyclophosphamide, fractionated total body irradiation (200 rad/day for six days) and allogeneic marrow transplantation. Six patients are alive in remission 756-1306 days following transplantation. One patient died of infection on day 17 without evidence of engraftment; all others achieved sustained engraftment. Eight patients died of recurrent leukemia, four of interstitial pneumonitis, two of infection, one of veno-occlusive disease of the liver and one of cardiac failure. The median survival time was 181 days.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation for patients with acute non-lymphoblastic leukemia in second remission.

Twenty-four patients with acute non-lymphoblastic leukemia (ANL) in second remission were transplanted from HLA-matched siblings. Twelve patients died of non-leukemic causes and four of recurrent leukemia. One patient is alive after relapse and seven patients are alive and free of disease 114-1907 days after transplantation. The first seven patients received 1000 rad total body irradiation (TBI) in a single exposure. The last 17 were entered on a randomized study to receive 1000 rad TBI as a single dose (seven patients) or 1200 rad TBI fractionated over six days (10 patients). Only one of the 10 patients receiving the fractionated TBI is alive and free of disease 786 days after transplantation while three of the seven receiving single-dose TBI remain in remission 114-541 days after grafting. Even if larger numbers of patients were accrued to this study, it is unlikely that the use of fractionated TBI would prove superior to single-exposure TBI. The actuarial analysis showed that the relapse rate for all 24 patients transplanted in second remission was 50% which was equivalent to patients with ANL transplanted in relapse. The disease-free survival two years after transplant was 24% for patients transplanted in second remission as compared to 26% for patients transplanted in relapse.

Adolescent↗
PubMed1982

Allogeneic marrow transplantation using fractionated total body irradiation in patients with acute lymphoblastic leukemia in relapse.

Six fractionated total body irradiation (TBI) regimens given over 2-7 days to a total midline dose of between 1200 and 1750 rads were evaluated in 41 patients with acute lymphoblastic leukemia in relapse. Cyclophosphamide 120 mg/kg was given prior to TBI in all cases, and dimethylbusulphan was added to cyclophosphamide and 1500 rad TBI in one regimen. Relapses occurred in all regimens. The overall disease-free survival of three of 41 patients was not different from previous studies with 1000 rad TBI given in a single dose. Graft-vs-host disease occurred in only 12 of 41 patients. Two of three disease-free survivors had significant graft-vs-host disease.

Adolescent↗