Biomedical subjects

L G Lum

Publications and source records attributed to L G Lum.

At least 55 records · Page 3Linked to original sources

PubMed1988

Pityrosporum folliculitis after bone marrow transplantation. Clinical observations in five patients.

A skin rash in marrow graft recipients often poses difficult diagnostic problems because multiple causes may be implicated, and clinical and histopathologic findings may be nonspecific. Five recipients of allogeneic bone marrow transplants had pityrosporum folliculitis diagnosed by skin biopsy in the early weeks (less than 18 days) after transplantation. In all cases, patients were febrile and leukopenic (granulocyte count, less than 500 cells/mm3), and were receiving broad-spectrum antibiotics at onset of the skin rash. Erythematous macules and papules were distributed primarily over the chest, shoulders, and upper back, and pustules and crusts developed in some cases. Granulocyte counts of more than 500 cells/mm3 were associated with resolution of the rash. Pityrosporum infection should be considered in the differential diagnosis of skin rashes in marrow graft recipients.

Adult↗

PubMed1988

Transfer of specific immunity in marrow recipients given HLA-mismatched, T cell-depleted, or HLA-identical marrow grafts.

The transfer of tetanus toxoid (TT) and diphtheria toxoid (DT) specific immunity was evaluated in 209 short-term (less than 120 days postgrafting) and 257 long-term (greater than 198 days postgrafting) non-boosted recipients after HLA-identical, HLA non-identical, and HLA-identical T cell-depleted marrow transplantation. TT or DT immunizations were not given to donors in the 6 months prior to transplant and the recipients received no immunizations post-transplantation. In 209 short-term recipients, 94% and 74% of recipients had detectable anti-TT and anti-DT titers respectively. In long-term recipients, 110 of 210 (52%) who received HLA-identical grafts, 17 of 38 (45%) who received HLA-non-identical grafts, and seven of seven (100%) who received HLA-identical T cell-depleted grafts had anti-TT titers; and 86 of 212 (40%) who received HLA-identical grafts, 11 of 38 (29%) who received HLA-non-identical grafts, and four of seven (57%) who received HLA-identical T cell-depleted grafts had anti-DT titers. When compared to non-boosted normal donor and control subjects, the magnitudes of anti-TT and anti-DT titers from the recipients were comparable to controls. These data show that transferred specific immunity is detectable in long-term recipients of T cell-depleted or HLA-non-identical grafts without immunizations of donors or recipients before or after transplantation.

Antibodies↗

PubMed1988

Use of thymic grafts or thymic factors to augment immunologic recovery after bone marrow transplantation: brief report with 2 to 12 years' follow-up.

Thymus tissue implants, thymic epithelial cells obtained from third party donors sharing one HLA-A and -B locus with the recipient, or the thymic hormones thymosin fraction 5 and thymopentin were given to recipients of HLA-identical sibling bone marrow to prevent chronic graft-versus-host disease (GVHD) and accelerate immunologic reconstitution. The clinical courses of 17 patients receiving thymus tissue and 18 patients receiving thymic hormones were reported initially 5 years ago and showed no difference in the incidence of chronic GVHD or immunologic recovery from those of concurrent or historical controls. We report here for the first time nine new patients who received thymus tissue implants with modifications of the culture method to lower the number of lymphocytes in the transplanted tissue with the intent of reducing rejection of the thymus tissue grafts. The clinical outcomes and immunologic functions of these nine patients were similar to those of the recipients of the earlier thymus tissue implants. With follow-up now ranging from 2.2 to 12.3 years (median 6.7) for the total group, 16 patients are alive. Seven never developed chronic GVHD. Nine were treated for chronic GVHD, seven of whom recovered and are leading normal lives, one has chronic pulmonary insufficiency, and one is disabled from chronic GVHD. We conclude that thymus tissue grafts or thymic epithelial cells partially HLA-matched to the recipient, thymosin fraction 5, or thymopentin used as described were not effective in reducing the incidence of chronic GVHD, improving immunologic recovery, or altering long-term survival.

Adolescent↗

PubMed1987

In vitro immunoglobulin production, proliferation, and cell markers before and after antithymocyte globulin therapy in patients with aplastic anemia.

Peripheral blood lymphocytes from 16 aplastic anemia patients were studied for in vitro biosynthesis of immunoglobulins (Ig), proliferative responses, and cell markers before and after antithymocyte globulin (ATG) treatment in an attempt to identify immune functions that would be useful in predicting responses to ATG therapy. Six of the 16 aplastic anemia patients were complete responders to ATG therapy, two were partial responders, and eight failed to respond to ATG therapy. The proportion of E+, CD4, CD8, and surface Ig-positive cells did not correlate with in vitro lymphocyte functions nor clinical responses before or after ATG therapy. Lymphocyte proliferative responses to phytohemagglutinin, tetanus toxoid, alloantigens, or pokeweed mitogen were generally present before and after ATG therapy. When pokeweed mitogen, herpes simplex type I virus, and tetanus toxoid were used as probes to elicit in vitro Ig production using a hemolytic plaque assay, some patients had 1) B cells that failed to produce Ig, 2) T cells that failed to provide helper activity, and 3) T cells that exhibited excessive suppressor activity in the various antibody production systems. These measures of immune function, however, did not correlate with clinical responses to ATG therapy.

Anemia, Aplastic↗

PubMed1987

Phenotypical and functional studies on a subtype of suppressor cells (CD8+/CD11+) in patients after bone marrow transplantation.

Dual labeling with the monoclonal antibodies anti-Leu 2 (fluorescein-conjugated) and anti-Leu 15 (phycoerythrin-conjugated) was used to phenotype and sort the lymphocytes from 12 short-term (100 days postgrafting) recipients, 8 long-term (6 months postgrafting) stable, and 11 long-term patients with chronic graft-versus-host disease (GVHD). The proportion of Leu 2+ 15+ cells was increased in 11 of 12 short-term patients (mean + SEM: 31% +/- 3.6)-and in 6 of 11 patients with chronic GVHD (18% +/- 2.4) compared with normal controls (n = 8; 7.5% +/- 1.9). However, there was no correlation between proportions of Leu 2+ 15+ or Leu 2+ 15- cells and the presence of acute GVHD. Long-term patients with chronic GVHD tended to have a higher proportion of Leu 2+ 15- cells. To functionally characterize these two T cell subsets, Leu 2+ 15- and Leu 2+ 15+ subsets were sorted from purified T cells obtained from two recipients and one normal subject. Both Leu 2+ 15+ and Leu 2+ 15- cells from a short-term patient suppressed pokeweed mitogen--stimulated immunoglobulin production of normal B cells. Leu 2+ 15- cells from a long-term survivor with chronic GVHD and the normal control provided help, whereas the Leu 2+ 15+ cells also strongly suppressed immunoglobulin synthesis. The suppressor activity of the Leu 2+ 15+ subset in all three individuals was radiosensitive (12 Gy). These results illustrate the need for careful correlative phenotyping and functional studies. Furthermore, these studies clearly demonstrate that different functions may exist within a particular T cell phenotype after bone marrow transplantation.

Adolescent↗

PubMed1987

Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation.

STUDY OBJECTIVE: To determine the efficacy of prophylactic interferon for prevention of cytomegalovirus infection and relapse of leukemia after allogeneic marrow transplantation. DESIGN: Randomized trial with intermittent interferon administration to day 80 after transplantation. SETTING: Marrow transplantation units of a cancer research center. PATIENTS: Consecutive patients with acute lymphocytic leukemia in remission at the time of transplantation. Thirty-nine patients received interferon, and 40 were control patients. INTERVENTIONS: Partially purified human leukocyte interferon given every 3 days beginning after marrow engraftment and continuing to day 80 after transplantation. After initial safety testing, the starting and minimum dose was 6 X 10(4) units/kg of body weight, with dose escalations determined by the circulating neutrophil count. Transplant conditioning and post-transplantation prophylaxis of graft-versus-host disease with methotrexate followed standard procedures. MEASUREMENTS AND MAIN RESULTS: No difference was observed in the probability or severity of cytomegalovirus infection or in the probability or severity of graft-versus-host disease. Relapse of leukemia occurred in 9 interferon recipients and 21 control patients, with a minimum follow-up of 4 years among surviving patients. The probability of relapse among all interferon recipients was 0.36 (95% confidence interval [Cl], 0.56 to 0.17) and among all control patients was 0.74 (95% Cl, 0.91 to 0.58) (p = 0.04 by log-rank test). Among patients who received transplants in first or second remission, the probability of relapse among interferon recipients was 0.19 (95% Cl, 0.37 to 0.02) compared with 0.71 (95% Cl, 0.97 to 0.51) among control patients (p = 0.008 by log-rank test). Survival rates did not differ between interferon recipients and control patients. Transient decreases in leukocyte count and anorexia and nausea occurred among interferon recipients. Six interferon recipients, all of whom had received chemoradiotherapy of the central nervous system before transplantation, developed leukoencephalopathy after transplantation. CONCLUSIONS: These data suggest that interferon given after transplantation reduces the risk for subsequent relapse of leukemia. The effect of longer administration and of administration in patients with other underlying diseases will require additional trials. No effect was observed on cytomegalovirus infection, either because interferon was not initiated until a median of 18 days after transplantation or because of a lesser effect among marrow allograft recipients.

Adolescent↗

PubMed1987

Adoptively transferred immunity persists in human marrow graft recipients.

This study was designed to determine if antibodies (Abs) to recall antigens (Ags) were produced after bone marrow transplantation (BMT). Sera from marrow recipients (recipients) were tested for Abs to recall Ags post-grafting, and T and B cells from recipients were tested for their ability to produce anti-tetanus toxoid antibody (anti-TT) using in vitro biosynthesis assays. Neither the donors nor recipients received booster immunizations with recall Ags before or after BMT. Serum Ab titers to tetanus toxoid (TT), diphtheria toxoid (DT), and measles virus (MV) were in the normal range for the majority of 235 short-term recipients (less than 100 days postgrafting) and for the majority of 149 long-term (greater than 6 months postgrafting) recipients. Anti-TT was produced in vitro by peripheral blood lymphocytes (PBL) from 6 of 14 long-term recipients after TT stimulation. In another system, purified B cells from 9 of 21 long-term recipients also produced anti-TT after Epstein-Barr virus (EBV) stimulation. The presence of Ab titers to TT, DT, and MV in the serum of recipients and the production of in vitro anti-TT by T and B cells from recipients show that Ag-specific memory was transferred via the marrow inoculum. These data show that adoptively transferred immunity persists in recipients for years postgrafting.

Antibody-Producing Cells↗

PubMed1987

Treatment of marrow graft recipients with thymopentin.

Four adult patients with acute non-lymphocytic leukemia were given marrow grafts from HLA-identical siblings following 120 mg/kg cyclophosphamide and 10-12 Gy total body irradiation. All received intermittent intravenous methotrexate as prophylaxis against graft-versus-disease (GVHD). In an attempt to accelerate immune recovery and prevent GVHD, each patient received thymopentin (TP5) for 100 days after grafting. No adverse effects were seen with TP5 administration. All four patients developed acute GVHD (one grade I, one grade II, and two grade III). Two patients died of late infections: one at 6 months from Pneumocystis carinii pneumonia and one at 11 months from disseminate Pseudomonas, Candida and cytomegalovirus infection. Two patients survive more than 3.9 years after transplantation with Karnofsky scores of 100%. One required treatment for chronic GVHD and recovered. Delayed-type hypersensitivity, antibody production to specific antigen in vivo, and results of in vitro immunologic studies were not altered by TP5 treatment. We conclude that while the administration of TP5 in these patients as described was not harmful, it did not prevent opportunistic infection, improve immunologic reconstitution or lower the incidences of acute or chronic GVHD from that of our previous experiences without thymopentin.

Adult↗

PubMed1987

Proliferative and differentiative responses of B cells from human marrow graft recipients to T cell-derived factors.

Upon activation, B cells express growth and differentiation receptors that permit them to proliferate and differentiate. The aim of this study is to define the nature of the intrinsic B cell defects found in marrow recipients using assays for B cell activation, proliferation, and differentiation. B cells from five short-term (less than three months postgrafting) and 15 long-term (greater than one year postgrafting) marrow recipients (ten with and five without chronic graft-v -host disease [GVHD]) were studied. T cell supernatants (T-sup) were prepared by stimulating normal T cells with 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and phytohemagglutinin. Highly purified B cells were used to assess B cell proliferation responses to T-sup after Staphylococcus aureus Cowan I (SAC) activation and for B cell immunoglobulin production responses to T-sup stimulation after SAC activation. B cells from all five short-term patients and one long-term patient with chronic GVHD did not respond to any stimulation. B cells from two patients with chronic GVHD responded to SAC but had decreased proliferative and differentiative responses to T-sup. B cells from three of seven patients with chronic GVHD and two of five long-term healthy patients could proliferate but could not secrete immunoglobulin in response to SAC plus T-sup stimulation. Furthermore, there was a significant correlation between serum IgG and/or IgM in marrow recipients and the differentiative responses of their B cells to T-sup (P = 0.0075, Fisher's Exact). B cell defects occur at various stages of maturation postgrafting. These defects include the failure to respond to the SAC activation signal, the failure to proliferate in response to T-sup, and the failure to differentiate in response to T-sup. These findings are probably due to the inability of B cells from certain marrow recipients to undergo a second round of ontogeny.

Antibody Formation↗

PubMed1987

The kinetics of immune reconstitution after human marrow transplantation.

Human marrow transplantation for the treatment of malignant and nonmalignant disorders is becoming an established modality of therapy. As in any aggressive therapeutic modality, the benefits must be balanced with the risks of the therapy. The aggressive chemoradiotherapy used to prepare patients for marrow transplantation creates a transient immunodeficiency disorder postgrafting until the transferred donor marrow reestablishes a competent immune system. Immune reconstitution posttransplant follows a general pattern developing from immature to mature immune functions. Immune reactivity during the first month postgrafting is extremely low. Cytotoxic and phagocytic functions recover by day 100, while more specialized and cooperative functions of T and B cells remain impaired up to one year or more postgrafting. After the first year postgrafting, the various components of the immune systems of most healthy marrow recipients begin to work synchronously, whereas the immune systems of recipients with chronic graft-v-host disease (GVHD) remain crippled. Recent evidence shows that transfer of specific immunity from marrow donors to marrow recipients plays a role in reestablishing immunocompetence. Transferred antigen-specific immunity may explain why more recipients do not die from overwhelming infections.

Bone Marrow Transplantation↗

PubMed1986

The transfer of antigen-specific humoral immunity from marrow donors to marrow recipients.

This study shows that specific humoral immunity could be transferred from marrow donors to marrow recipients. Peripheral blood lymphocytes from long-term human marrow recipients produced IgG anti-tetanus toxoid antibody after in vitro tetanus toxoid stimulation. Antitetanus toxoid antibody biosynthesis was induced using a new tetanus toxoid-specific system employing high lymphocyte numbers, many replicate microcultures, and antigen washout. Anti-tetanus toxoid antibody in 12-day culture supernatants was detected using an enzyme-linked immunosorbent assay. Of 14 marrow recipients, 6 (5 with and 1 without chronic graft-vs-host disease) had lymphocytes that produced anti-tetanus toxoid antibody. Culturing additional numbers of marrow recipient lymphocytes increased in vitro biosynthesis of anti-tetanus toxoid antibody. The presence of circulating serum antibodies to tetanus toxoid and the production of specific anti-tetanus toxoid antibody by peripheral blood lymphocytes from marrow recipients show that engrafted donor lymphocytes can produce in vitro specific antibodies to recall antigens without postgrafting reimmunization.

Adolescent↗

PubMed1986

IgG anti-tetanus toxoid antibody production induced by Epstein-Barr virus from B cells of human marrow transplant recipients.

This investigation shows that Epstein-Barr virus (EBV)-activated human B cells from marrow transplant recipients can produce in vitro IgG anti-tetanus toxoid antibody (anti-TT) without booster immunizations with tetanus toxoid (TT). Purified B cells (E-rosette negative) from 8 normal subjects, 6 healthy long-term marrow graft recipients, and 15 long-term marrow graft recipients with chronic graft-vs-host disease (GVHD), were stimulated for 12 days with EBV to induce anti-TT production in culture supernatants. The amount of anti-TT in culture supernatants was quantitated using a enzyme-linked immunosorbent assay. B cells from all 8 normal controls produced in vitro IgG anti-TT after EBV stimulation. Five of 6 healthy recipients had B cells that produced anti-TT after EBV stimulation. Four of 15 recipients with chronic GVHD had B cells capable of producing anti-TT after EBV stimulation. The number of cultures making anti-TT responses was less in those with chronic GVHD than in those without chronic GVHD or normal individuals (P less than 0.001). B cells from patients with chronic GVHD had fewer responses exceeding the overall median of 0.7 ng/ml when compared with the other two groups (P less than 0.03). These data show that B cells of donor origin can produce in vitro IgG anti-TT antibody to tetanus toxoid antigen in a T-independent fashion.

Adolescent↗

PubMed1986

Severe aplastic anemia associated with chronic mucocutaneous candidiasis. Immunologic and hematologic reconstitution after allogeneic bone marrow transplantation.

Chronic mucocutaneous candidiasis (CMC) is typically associated with the inability of T lymphocytes to proliferate and produce lymphokines in response to Candida antigen. A 7-year-old girl with CMC developed severe aplastic anemia and, after conditioning with cyclophosphamide, 200 mg/kg, underwent bone marrow transplantation from her HLA-identical sister. Engraftment was prompt and complete. The patient is surviving more than 3 years after transplantation with normal donor-derived hemopoiesis and immune function. Manifestations of CMC have resolved completely and she has not received antifungal therapy for more than 2 years.

Anemia, Aplastic↗

PubMed1986

Antigen-specific antibody responses of lymphocytes to tetanus toxoid after human marrow transplantation.

In vitro IgG anti-tetanus toxoid (IgG anti-TT) antibody produced by peripheral blood lymphocytes (PBL) from 16 normal subjects (9 marrow donors and 7 random healthy subjects) and 17 marrow graft recipients from 45-1058 days postgrafting was measured with an enzyme-linked immunosorbent assay (ELISA). PBL from 11 of 13 seropositive (anti-TT greater than or equal to 1:1024) normal subjects produced IgG anti-TT in vitro, whereas the PBL from the 3 seronegative (IgG anti-TT less than 1:1024) normal subjects did not. In our normal subjects, there was a high correlation between seropositivity and in vitro IgG anti-TT production (P = .0048, chi 2, two-tailed). PBL from only one of 13 seropositive marrow graft recipients produced in vitro IgG anti-TT antibody. B and T cell functions of 8 marrow graft recipients were assessed by coculturing their T and B cells with those from their HLA-identical marrow donors. One short-term patient and 7 long-term patients (4 with and 3 without chronic graft-versus-host disease) were studied. Recipient B cells failed to produce antibody in the presence of donor T cells in 7 of these 8 cases. However, T cells from long-term survivors provided helper activity to immune donor B cells in 7 of 9 evaluable cases. TT-specific helper T cell activity was present in most seropositive long-term recipients, and B cells from marrow recipients failed to produce specific antibody in the presence of normal donor TT-specific helper T cells. These results, TT-specific T cell helper activity, and normal circulating serum IgG anti-TT antibody levels in marrow graft recipients without postgrafting TT boosters suggest that specific immunity had been transferred from the marrow donor to the marrow recipient.

Adolescent↗

PubMed1986

The detection of specific antibody formation to recall antigens after human bone marrow transplantation.

The results of this study show that donor-derived immunity can be detected and persists in long-term survivors with and without chronic graft-v-host disease (GVHD) after human marrow grafting. Seventy-one marrow recipients (60 long-term and 11 short-term survivors) were studied for the presence of specific serum IgG antibodies to tetanus toxoid (TT), and 46 marrow recipients (35 long-term and 11 short-term) were tested for antibodies to diphtheria toxoid (DT) and measles virus after marrow grafting using an enzyme-linked immunosorbent assay. Of the 60 long-term survivors, 31 were healthy and 29 had chronic GVHD. None of the recipients were immunized to the test antigens postgrafting. Most long-term healthy recipients exhibited antibody titers to the recall test antigens, whereas only a minority of those with chronic GVHD had antibody titers to recall antigens. In healthy long-term recipients (greater than or equal to one year postgrafting) whose donors were immune to the test antigens, 25 of 31 had titers to TT, 11 of 17 had titers to DT, and 12 of 20 had titers to measles. In recipients with C-GVHD, 13 of 29 had titers to TT, six of 15 had titers to DT, and six of 15 had titers to measles virus. Within 100 days postgrafting, 11 of 11 had anti-TT titers, ten of ten had anti-DT titers, and seven of eight had antimeasles virus titers.

Antibodies↗

PubMed1985

Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease.

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.

Adolescent↗

PubMed1985

Regulatory roles of human OKT4/OKT8 subsets in polyclonal immunoglobulin production induced by herpes simplex type 1 virus.

T cells, OKT4 cells and OKT8 cells from the peripheral blood of normal individuals seropositive for herpes simplex type 1 virus (HSV) were studied for their capacity to regulate in vitro polyclonal immunoglobulin (Ig) production induced by inactivated HSV. Polyclonal Ig production induced by HSV has been demonstrated to be T-cell dependent. T cells, OKT4 cells and OKT8 cells were co-cultured with autologous non-T cells in the presence of HSV or pokeweed mitogen (PWM) and the number of plaque-forming cells (PFC) was measured with an hemolytic plaque assay after 6 days of culture. The results in the HSV system show that the OKT4 cells provided significantly more helper activity than OKT8 cells (p = 0.002); and the OKT8 cells exhibited more suppressor activity than OKT4 cells for Ig production (p = 0.02). The helper activity of OKT4 cells after HSV stimulation was significantly less than that obtained after pokeweed mitogen stimulation (p = 0.01). The in vitro polyclonal immunoglobulin response to HSV antigen is regulated by the balance of helper/suppressor activity exerted by OKT4 and OKT8 cell subsets.

Antibodies, Monoclonal↗

PubMed1985

Is the leukocyte group-5a antigen associated with reduced NK cell function?

The leukocyte group-5a antigen has an increased frequency in lymphoid malignancy. We have investigated the possibility that expression of this antigen is associated with diminished or reduced natural killer function since natural killer cells are believed to represent a vital component of protection against developing malignancy. Natural killer function of a group of 18 subjects who expressed the group-5a antigen on their cells was substantially lower than that of a group of 24 subjects who did not express 5a.

Adolescent↗