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Biomedical subjects

N Flournoy

Publications and source records attributed to N Flournoy.

51 records · Page 3Linked to original sources
PubMed1980

Cell-mediated immunity to varicella-zoster virus after allogeneic marrow transplant.

The cellular immune response of normal persons and marrow transplant recipients to varicella-zoster virus (VZV) antigen was measured with use of the lymphocyte transformation response. Ninety-nine of 100 normal persons with previous VZV infection had a stimulation index of greater than or equal to 4.8, while 10 susceptible persons had responses of less than or equal to 3.0. Before transplant, responses were lower than normal in patients with leukemia in relapse (P = 0.001), but not in patients with leukemia in remission or with aplastic anemia. Throughout the first 100 days after transplant, lymphocyte response was depressed (P less than 0.0005), especially among recipients of antithymocyte globulin during days 41-80 (P less than 0.05). Patients with aplastic anemia had higher responses than those with leukemia during days 20-60 (P less than 0.02). By one year, most responses were normal. Long-term survivors who had recurrent VZV infection had positive responses more often than those without recurrent infection (P = 0.01). The lymphocyte response to VZV antigen parelleled, and thus may predict, periods of increased susceptibility to VZV infection.

Adolescent↗
PubMed1980

Infection with herpes simplex virus and cell-mediated immunity after marrow transplant.

The relationship between herpes simplex virus (HSV) infection and specific cell-mediated immunity was investigated in 141 patients before and for the first four months after marrow transplant. Sixty-two (82%) of 76 seropositive patients but only one of 65 seronegative patients developed HSV infection. Lymphocyte responses to HSV antigen were suppressed immediately after transplant and subsequently became reactive in those patients with HSV infection. The presence or absence of antibody to HSV in the donor before transplant did not influence the response. Seventy long-term survivors of marrow transplant were also studied. Among 60 patients who had pretransplant serum available for study, 26 (68%) of 38 who had been seropositive before transplant had positive responses compared with none of 22 who had been seronegative. Recovery of responsiveness to HSV antigen after marrow transplant is primarily related to recurrent virus infection and not to the pretransplant immune status of the donor.

Antigens, Viral↗
PubMed1980

Cytomegalovirus infection and specific cell-mediated immunity after marrow transplant.

Patients were studied prospectively after marrow transplant to correlate cytomegalovirus (CMV) infection with the in vitro lymphocyte transformation response to CMV antigen. Ninety-two (58%) of 158 patients developed CMV infection. The lymphocyte response to CMV antigen of patients who were seropositive before transplant was significantly suppressed immediately after transplant. Isolation of CMV was associated with further suppression of responses; seroconversion to CMV was associated with a significant increase. The lymphocyte response of 73 long-term survivors was similar to that of normal persons. The presence of antibody to CMV in the donor before transplant had little effect on the lymphocyte response of patients after transplant even though the patients' lymphocyte s were of donor origin. As in previously reported studies of immunity to other herpesviruses after marrow transplant, it was concluded that recovery of the response to CMV antigen is related primarily to active virus infection and not to patient or donor pretransplant immunity.

Anemia, Aplastic↗
PubMed1979

Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts.

To determine whether allogeneic bone-marrow transplantation is associated with a graft-versus-leukemia effect, we examined the relation between relapse of leukemia and graft-versus-host disease in 46 recipients of identical-twin (syngeneic) marrow, 117 recipients of HLA-identical-sibling (allogeneic) marrow with no or minimal graft-versus-host disease, and 79 recipients of allogeneic marrow with moderate to severe or chronic disease. The relative relapse rate was 2.5 times less in allogeneic-marrow recipients with graft-versus-host disease than in recipients without it (P less than 0.01). This apparent antileukemic effect was more marked in patients with lymphoblastic than nonlymphoblastic leukemia, and in those who received transplants during relapse rather than during remission, and was most evident during the first 130 days after transplantation. Survival of all patients was comparable since the lesser probability of recurrent leukemia in patients with graft-versus-host disease was offset by a greater probability of other causes of death.

Acute Disease↗
PubMed1978

The analysis of failure times in the presence of competing risks.

Distinct problems in the analysis of failure times with competing causes of failure include the estimation of treatment or exposure effects on specific failure types, the study of interrelations among failure types, and the estimation of failure rates for some causes given the removal of certain other failure types. The usual formation of these problems is in terms of conceptual or latent failure times for each failure type. This approach is criticized on the basis of unwarranted assumptions, lack of physical interpretation and identifiability problems. An alternative approach utilizing cause-specific hazard functions for observable quantities, including time-dependent covariates, is proposed. Cause-specific hazard functions are shown to be the basic estimable quantities in the competing risks framework. A method, involving the estimation of parameters that relate time-dependent risk indicators for some causes to cause-specific hazard functions for other causes, is proposed for the study of interrelations among failure types. Further, it is argued that the problem of estimation of failure rates under the removal of certain causes is not well posed until a mechanism for cause removal is specified. Following such a specification, one will sometimes be in a position to make sensible extrapolations from available data to situations involving cause removal. A clinical program in bone marrow transplantation for leukemia provides a setting for discussion and illustration of each of these ideas. Failure due to censoring in a survivorship study leads to further discussion.

Bone Marrow Transplantation↗
PubMed1977

A prospective analysis interstitial pneumonia and opportunistic viral infection among recipients of allogeneic bone marrow grafts.

A prospective study of 80 bone marrow transplant recipients with acute leukemia and aplastic anemia employed serial viral cultures, determination of complement-fixing antibody to cytomegalovirus (CMV), and study of material obtained from open lung biopsy and autopsy. There were 43 episodes of interstitial pneumonia, 28 of which were fatal. About 40% of the cases were idiopathic. CMV was the most common candidate pathogen, present in 47% of affected lungs. By a median of 53 days following transplantation, 46% of the recipients were shedding CMV from some site. This event was three times more frequent among recipients who had positive titers of antibody to CMV before transplantation than among seronegative recipients. Failure to respond werologically to CMV infection markedly increased the hazard of dying of interstitial pneumonia. Graft-vs-host disease significantly increased the incidence and lethality of interstitial pneumonia. The presence of leukemia (rather than aplastic anemia) and/or certain factors in the technique of preparation for engraftment may have been significant.

Acute Disease↗
PubMed1977

One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation.

One hundred patients, 54 with acute myelogenous leukemia (AML) and 46 with acute lymphoblastic leukemia (ALL), considered to be in the end stages of their disease, after combination chemotherapy were treated by marrow transplantation. All patients were given a marrow graft from an HLA-identical sibling after receiving 1000-rad total body irradiation (TBI). One group of 43 patients was given cyclophosphamide (CY), 60 mg/kg on each of 2 days, 5 and 4 days before TBI. In a second group of 31 patients, additional chemotherapy was given before CY and TBI. In a third group of 19 patients, BCNU was given before CY and TBI. A fourth group of 7 patients received other chemotherapy regimens before TBI. Six patients died 3-17 days after marrow infusion without evidence of engraftment. Ninety-four patients were engrafted and only one patient rejected the graft. Thirteen patients are alive with a marrow graft, on no maintenance antileukemic therapy, and without recurrent leukemia 1-4 1/2 yr after transplantation. Three have chronic graft-versus-host disease (GVHD). Four patients are alive 1 1/2 - 3 1/2 yr after grafting but have had a relapse of their leukemia. Of 93 evaluable patients, 19 did not develop GVHD and 24 developed very mild GVHD. Fifty patients developed moderate to severe GVHD, and 40 of these were treated with antithymocyte globulin. Interstitial pneumonia occurred in 54 patients and was the primary cause of death in 34. Interstitial pneumonia often occurred in association with GVHD and the most common etiologic agent was cytomegalovirus. A total of 31 patients have had a relapse of leukemia. There was no definite correlation between relapse of leukemia and the presence or absence of GVHD. The relapse rate appeared to be relatively constant over the first 2 yr and was extremely low after that time. Neither survival nor leukemic relapse appeared to be influenced by the type of leukemia nor by the preparative chemotherapy regimen given before TBI. Patients in fair clinical condition at the time of transplantation showed significantly longer survival times than patients in poor condition (p = 0.001). This observation, coupled with the observation that some patients may be cured of their disease, indicates that marrow transplantation should now be undertaken earlier in the management of patients with acute leukemia who have an HLA-matched sibling marrow donor.

Antilymphocyte Serum↗
PubMed1976

An estimate of the recombination frequency between the B locus and the D locus within the major histocompatibility complex.

Mixed leukocyte culture studies on 120 families, including 120 HLA haplo-identical siblings and 210 HLA-identical siblings, were analyzed for unusual patterns of reactivity. Three discrepant reactions were noted in which cells from HLA-identical siblings showed strong mutual stimulation. These data provide an estimate of 0.0065 as the recombination frequency between the HLA-B and HLA-D regions of the major histocompatibility chromosome in man. When combined with the data of Keuning et al. (1975), the value is 0.0068 with a 95% confidence interval of 0.0022 to 0.0158.

Crossing Over, Genetic↗
PubMedDate not supplied

Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience.

Pneumonia due to causes other than bacterial or fungal infection has been a frequent complication of allogeneic marrow transplantation. Data on 525 patients who received allogeneic marrow transplants during a 10-year period were reviewed. Of these patients, 41% developed pneumonia; this incidence was significantly higher than that among recipients of syngeneic (twin) transplants. Cytomegaloviral pneumonia (85 cases) and idiopathic pneumonia (63 cases) occurred most commonly. The incidence of pneumonia was higher among older patients, among patients who received transplants because of hematologic malignancy, and among patients with aplastic anemia who received total-body irradiation or procarbazine plus antithymocyte globulin for conditioning before transplantation. The development of cytomegaloviral pneumonia was unrelated to the serologic characteristics of either the patient or the donor before transplantation, and an increase in the titer of antibody to cytomegalovirus did not significantly improve the chances for survival. Mortality from all forms of pneumonia was high. Until effective means for prevention or treatment of cytomegaloviral and idiopathic pneumonia become available, the occurrence of these infections will continue to limit the success of allogeneic marrow transplantation.

Acute Disease↗
PubMedDate not supplied

Plasma fatty acid patterns of bone marrow transplant patients primarily supported by fat-free parenteral nutrition.

Oral food tolerance is compromised by drug and radiation therapy administered to patients undergoing bone marrow transplantation for hematological malignancy or aplastic anemia. Resultant decreases in oral fat intake coincident with fat-free parenteral nutrition may predispose patients to essential fatty acid (EFA) deficiency. Determinations were made of the fatty acid composition of plasma total lipid from 20 bone marrow transplant patients on admission, at the time of bone marrow transplant, and on days 7, 14, 30, and 60 post-bone marrow transplant. Patients ate ad libitum but with little appetite and received fat-free parenteral nutrition interrupted for numerous blood product and drug infusions. Abnormal EFA status was manifest (20:3 omega 9/20:4 ratio greater than 0.2) in 12 of 20 patients during the course of treatment. Plasma EFA status was consistently correlated with oral fat intake but not with sex, age, percentage of ideal body weight, or amount of plasma infused. This suggests that dietary fat was absorbed limiting the severity of EFA deficiency. Interruptions of glucose infusion averaging only about 2 hours/day, also may have helped moderate the deficiency.

Adolescent↗
PubMedDate not supplied

Aggressive doxorubicin-containing regimen (prednisone, methotrexate, 5-FU, doxorubicin, and cyclophosphamide; PM-FAC) in disseminated estrogen receptor-negative breast cancer.

Twenty-seven women with disseminated estrogen receptor-negative breast cancer received an aggressive chemotherapy program of prednisone, methotrexate, 5-FU, doxorubicin, and cyclophosphamide. Responses were achieved in 21 of 26 (81%) evaluable patients, eight (31%) of whom had complete responses. The median survival was 17 months. Despite the favorable overall response and a significant number of complete responses, all patients eventually relapsed. Although most patients relapsed systematically, two relapsed initially in the CNS.

Adult↗