PubMed Health⌕ Search

Biomedical subjects

M Trigg

Publications and source records attributed to M Trigg.

At least 19 recordsLinked to original sources
PubMed2001

Tools for predicting risk of mortality in the ICU setting: do we need a crystal ball or rose colored glasses?

Hematopoietic stem cell transplantation (HSCT) applied to children is associated with high risk for organ failure, ICU admission, morbidity and mortality. "Respiratory failure" after HSCT carries a historically grave prognosis. Factors associated with high risk for critical care complications in HSCT patients have been identified, but are dependent on timing and intensity of interventions. Several ICU severity of illness scoring systems predict prognosis on the basis of physiologic stability, organ system involvement, and intensity of supportive measures; but these tend to underestimate post-transplantation mortality risk. Adjustment of scoring systems and logistic regression factor analysis are promising adjuncts, but have not been adequately validated. Specific endpoints such as death, length of ICU or hospital stay, and neurologic function are relatively easy to quantify; but, quality of life is difficult to assess and report. What constitutes "heroic therapy" in one institution may qualify as "routine" care in another. Therefore, tools to predict mortality in the pediatric HSCT recipient requiring intensive care are difficult to apply to the individual patient, and remain more an art than science. This manuscript attempts to briefly define and review the pertinent types of PICU severity of illness and mortality prognosis scoring systems, and their application to pediatric HSCT patients. Pitfalls in application of physiology, organ system failure, therapeutic intensity, disease specific, and history-based scoring systems are discussed. Prospective validation studies for severity of illness systems and the evolution to concurrent registry-style data collection and analysis are necessary for the HSCT patient requiring ICU care.

Child↗
PubMed2000

Poor outcome in children with refractory/relapsed leukemia undergoing bone marrow transplantation with mismatched family member donors.

The utility of bone marrow transplantation for childhood leukemia in patients unable to achieve a remission prior to transplant is controversial. To address this issue, we analyzed a subset of patients with advanced leukemia entered on prospective transplant trials at our hospital. Fifty-eight patients with ALL or AML (age 1-19) were identified. They had failed standard chemotherapy and were in relapse (22 in 1st, 27 in 2nd, three in 3rd, and three in 4th) or had never achieved an initial remission (three) at the time of transplant. Fifty-two patients received marrow from mismatched family members (haplo or DR-identical), while six received marrow from matched siblings. Most patients received myeloablative therapy consisting of total body irradiation, etoposide, cyclophosphamide, and cytosine arabinoside. Marrow from mismatched donors was T cell depleted. Only one of 52 patients transplanted with a mismatched donor survived long-term while three of six patients transplanted in relapse with a fully matched sibling donor are alive 6-10 years post BMT. The major causes of death were infection (39%) and relapse (28%). Acute GVHD grade III-IV was noted in 7% of patients. A comparable group of patients with leukemia transplanted at our center in remission using similarly mismatched family member donors (haplo or DR-identical) had an event-free survival of 28%. In conclusion, our data suggest that BMT utilizing mismatched family member donors is a poor option for patients in relapse at the time of transplant. New treatment strategies need to be developed to effectively manage these patients.

Adolescent↗
PubMed1997

Clinical features and treatment outcome of children with biphenotypic CD2+ CD19+ acute lymphoblastic leukemia: a Children's Cancer Group study.

Leukemic cells from a subset of children with acute lymphoblastic leukemia (ALL) express lymphoid antigens of both T lineage and B lineage, but the clinical significance of this immunophenotype is unknown. We now report the first comprehensive comparison of treatment outcomes among a large cohort of children with CD2+ CD19+ biphenotypic ALL (N = 77), B-lineage ALL (BL) (N = 1,631), or T-lineage ALL (TL) (N = 347) ALL who were treated on risk-adjusted Children's Cancer Group (CCG) protocols. CD2+ CD19+ patients were more similar to BL than TL patients with respect to presenting features and antigen expression. The percentages of patients achieving successful induction therapy outcome were 98.7%, 97.8%, and 97.3% for CD2+ CD19+, BL, and TL patients, respectively. Univariate comparisons of 4-year event-free survival (83.7%, 72.8%, 75.2% for CD2+ CD19+, BL, and TL patients, respectively) achieved borderline significance (CD2+ CD19+ B, P = .08; CD2+ CD19+ v T, P = .07). Relative hazard rate (RHR) estimates for BL and TL compared with CD2+ CD19+ were 1.79 and 1.90, respectively, implying a better outcome for biphenotypic patients. However, multivariate adjusted RHRs for BL and TL compared with CD2+ CD19+ were 1.43 (P = .29) and 1.16 (P = .76), respectively, suggesting a significant reduction in risk for BL or TL patients once adjustment was made for the more favorable characteristics of the CD2+ CD19+ group. Thus, pediatric ALL patients treated on contemporary CCG protocols who present with CD2+ CD19+ biphenotypic leukemia generally have good treatment outcomes, due in part to their favorable presenting features.

Adolescent↗
PubMed1997

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: functional analyses of lymphocytes and correlation with immunophenotypic recovery following transplantation.

Reconstitution of the immune system following T-cell-depleted bone marrow transplantation (BMT) in children has yet to be fully elucidated. Thus, we prospectively studied the recovery of immune function in 64 children who underwent T-lymphocyte-depleted marrow transplants using either matched family member donors or matched unrelated donors. We measured in vitro posttransplantation proliferative responses to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen, and Candida albicans antigen and assessed unidirectional allogeneic mixed-lymphocyte culture (MLC) responses at various times. A total of 129 healthy individuals served as normal controls for these assays. Responses to T-cell mitogens normalized within 12 months posttransplantation, while MLC responses normalized by 9 months. The presence of graft-versus-host disease (grade II or greater) and cytomegalovirus infection was associated with delays in immune function recovery. Importantly, immune function recovery correlated temporally with a rise in peripheral lymphocyte count. In contrast, the CD4/CD8 ratio was not predictive of immune recovery. Knowledge of immune function recovery may guide clinicians in devising strategies to minimize the risk of infection post-BMT.

Adolescent↗
PubMed1997

Prognostic significance of the CD10+CD19+CD34+ B-progenitor immunophenotype in children with acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Leukemic cells from most patients with B-lineage acute lymphoblastic leukemia (ALL) appear to originate from normal B-lymphocyte precursors. The earliest B-cell progenitors coexpress the antigens CD10, CD19, or CD34 on their cell surfaces. In a large cohort of 2028 children with ALL, we compared treatment outcomes of a subset of B-lineage ALL patients with CD10+CD19+CD34+ immature B-progenitor leukemia (BPL) to the treatment outcomes of the remaining CD19+ B-lineage ALL patients. Pediatric B-lineage ALL cases enrolled on risk-adjusted ALL treatment protocols of the Children's Cancer Group were immunophenotypically classified as BPL or non-BPL. Patients were stratified further into age groups of > or = 1 year and <12 months. Event-free survival (EFS) outcomes were calculated by standard life table methods. BPL patients in both age groups generally had more favorable presenting characteristics than non-BPL controls. Within the age group of > or = 1 year, BPL patients had a slightly better EFS outcome than non-BPL patients, with 3-year estimates of 83.9% (SD = 1.1%) vs. 78.8% (SD = 1.8%), respectively (P = 0.10). Infants with BPL, representing one-fifth of the total infant patient population, had a significantly better EFS outcome than infants with non-BPL (three-year EFS: 82.4%, SD = 9.2% vs. 34.4%, SD = 5.9%, P = 0.006). In univariate analyses, the relative hazard rate (RHR) was 3.73 for non-BPL vs BPL and this marked difference in EFS outcome was maintained at 5 years of follow-up. The favorable prognostic influence of the BPL immunophenotype for infants remained significant in multivariate analyses with an RHR of 2.72 for non-BPL vs BPL (P = 0.05). CD10+CD19+CD34+ immature B-progenitor immunophenotype is associated with favorable characteristics for children with ALL and identifies a subset of infants who achieve favorable EFS outcomes.

Adult↗
PubMed1996

CD2 antigen expression on leukemic cells as a predictor of event-free survival after chemotherapy for T-lineage acute lymphoblastic leukemia: a Children's Cancer Group study.

We examined the prognostic impact of CD2 antigen expression for 651 patients with T-lineage acute lymphoblastic leukemia (ALL), who were enrolled in front-line Childrens Cancer Group treatment studies between 1983 and 1994. There was a statistically significant correlation between the CD2 antigen positive leukemic cell content of bone marrow and probability of remaining in bone marrow remission, as well as overall event-free survival (EFS) (P = .0003 and P = .002, log-rank tests for linear trend). When compared with patients with the highest CD2 expression level (> 75% positivity), the life table relative event rate (RER) was 1.22 for patients with intermediate range CD2 expression level (30% to 75% positivity) and 1.81 for "CD2-negative" patients (< 30% positivity). At 6 years postdiagnosis, the EFS estimates for the three CD2 expression groups (low positivity to high positivity) were 52.8%, 65.5%, and 71.9%, respectively. CD2 expression remained a significant predictor of EFS after adjustment for the effects of other covariates by multivariate regression, with a RER of 1.47 for CD2-negative patients (P = .04). Analysis of T-lineage ALL patients shows a significant separation in EFS after adjustment for the National Cancer Institute (NCI) age and white blood cell (WBC) criteria for standard and high-risk ALL (P = .002, RER = 1.67). The determination of CD2 expression on leukemic cells helped identify patients with the better and poorer prognoses in both of these risk group subsets. For standard risk T-lineage ALL, CD2-negative patients had a worse outcome (P = .0007, RER = 2.92) with an estimated 5-year EFS of 55.9% as compared with 78.3% for the CD2-positive patients. Thus, CD2 negativity in standard risk T-lineage ALL identified a group of patients who had a worse outcome than high-risk T-lineage ALL patients who were CD2 positive. The percentage of CD2 antigen positive leukemic cells from T-lineage ALL patients is a powerful predictor of EFS after chemotherapy. This prognostic relationship is the first instance in which a biological marker in T-lineage ALL has been unequivocally linked to treatment outcome.

Adolescent↗
PubMed1996

Craniospinal irradiation for acute lymphoblastic leukemia with central nervous system disease at diagnosis: a report from the Children's Cancer Group.

PURPOSE: This study attempted to determine if central nervous system (CNS) disease at diagnosis is a poor prognostic factor in children with acute lymphoblastic leukemia (ALL) and whether 6 Gy of spinal irradiation is an adequate dose for these patients. METHODS AND MATERIALS: Previously the Children's Cancer Group (CCG) treated patients with ALL and CNS disease at diagnosis with cranio (24 Gy)-spinal (12 Gy) irradiation, as well as systemic and intrathecal chemotherapy. In a series of CCG trials completed in 1989 the spinal dose was empirically reduced to 6 Gy for patients receiving systemic chemotherapy with an intensive consolidation phase to limit hematopoietic toxicity. The spinal dose was left at 12 Gy for patients treated with a less intensive consolidation phase. RESULTS: With a median follow-up for surviving patients of 74 months, the 5-year event-free survival for 53 patients with CNS disease at diagnosis was 69 +/- 13% (+/- 2 standard deviations), similar to the value obtained for 3364 patients without CNS disease, 67 +/- 2%. Corresponding values for 5-year survival were 77 +/- 12% and 80 +/- 1%, and for freedom from isolated first CNS relapse, were 90 +/- 9% and 94 +/- 1%. Event-free survival, survival, and freedom from isolated first CNS relapse in the 6-Gy group were as good as in the 12-Gy group. CONCLUSION: CNS disease at diagnosis is not a poor prognostic factor for children with ALL who are treated with intensive systemic chemotherapy, craniospinal irradiation, and intrathecal chemotherapy. Six Gy is an adequate dose of spinal irradiation for these patients.

Central Nervous System Neoplasms↗
PubMed1996

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

Adolescent↗
PubMed1996

Comparison of idarubicin to daunomycin in a randomized multidrug treatment of childhood acute lymphoblastic leukemia at first bone marrow relapse: a report from the Children's Cancer Group.

The outcome of children with acute lymphoblastic leukemia (ALL) and bone marrow relapse has been unsatisfactory largely because of failure to prevent subsequent leukemia relapses. Ninety-six patients were enrolled and received vincristine, prednisone, L-asparaginase, and an anthracycline as reinduction therapy. Ninety-two patients were randomized to receive either daunomycin (DNR) or idarubicin (IDR). After achievement of second complete remission (CR2), maintenance chemotherapy included the same anthracycline, IDR or DNR, high-dose cytarabine, and escalating-dose methotrexate. Compared to DNR (45 mg/m2/week x 3), IDR (12.5 mg/m2/week x 3) was associated with prolonged myelosuppression and more frequent serious infections. Halfway through the study, the dose of IDR was reduced to 10 mg/m2. Overall, second remission was achieved in 71% of patients. Reinduction rate was similar for IDR and DNR. Reasons for induction failure differed; none of 15, 1 of 5, and 5 of 7 reinduction failures were due to infection for DNR, IDR (10 mg/m2), and IDR (12.5 mg/m2), respectively. Two-year event-free survival (EFS) was better among patients who received IDR (12.5 mg/m2) (27 +/- 18%) compared to DNR (10 +/- 8%, P = 0.05) and IDR (10 mg/m2) (6 +/- 12%, P = 0.02). However, after 3 years of follow-up, late events in the high-dose IDR group result in a similar EFS to the lower-dose IDR and DNR groups. In conclusion, IDR is an effective agent in childhood ALL. When used weekly at 12.5 mg/m2 during induction, the EFS outcome during the first 2 years of treatment appears better than lower-dose IDR or DNR (45 mg/m2), although this difference was not sustained at longer periods of follow-up. Increased hematopoietic toxicity seen at this dose might be reduced through the use of supportive measures, such as hematopoietins and intestinal decontamination.

Antibiotics, Antineoplastic↗
PubMed1996

Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

PURPOSE: To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. METHODS: Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. RESULTS: For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. CONCLUSIONS: The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.

Adolescent↗
PubMed1996

Improved clinical outcome for children with T-lineage acute lymphoblastic leukemia after contemporary chemotherapy: a Children's Cancer Group Study.

The prognostic importance of T-lineage acute lymphoblastic leukemia (ALL) in contemporary programs of intensive chemotherapy has been controversial. We therefore assessed the impact of this biological feature in risk-adjusted frontline chemotherapy studies of the Children's Cancer Group (CCG), conducted from 1983 to 1994. A substantially greater proportion of T-lineage patients (N = 730) presented with poor-risk features as compared to B-lineage patients (N = 3668) treated in the same studies (71.1% vs. 39.7%, P < 0.0001). Consequently, in the CCG-100 series of clinical trials (1983-1989), which tested regimens that were largely of moderate intensity, T-lineage ALL patients had an excess of adverse early events compared to patients in the B-lineage group: 3-year event-free survival (EFS) estimate, 65.8% vs 78.2% (P < 0.0001). With the introduction of more intensive chemotherapy in studies from 1989 to 1994 (CCG-1800 series). We observed a progressive and significant improvement in the clinical outcome of patients with T-lineage immunophenotype. Three- and 5-year EFS probabilities increased from 65.8% to 78.1% and from 61.0% to 75.2%, respectively, becoming comparable to or slightly better than results for B-lineage ALL patients. When adjusted for the competing effects of leukocyte count, age, organomegaly and other poor-risk features, T-lineage immunophenotype showed no important impact on the overall EFS pattern. These findings demonstrate the loss of adverse prognostic by T-lineage ALL in a large program of intensive chemotherapy developed over the past decade.

Adolescent↗
PubMed1995

Leukemic cell growth in SCID mice as a predictor of relapse in high-risk B-lineage acute lymphoblastic leukemia.

Mice with severe combined immunodeficiency (SCID) provide a model system to examine the in vivo homing, engraftment, and growth patterns of normal and malignant human hematopoietic cells. The relation between leukemic cell growth in this model and the treatment outcome in patients from whom cells were derived has not been established. Leukemic cells from 42 children with newly diagnosed high-risk B-lineage acute lymphoblastic leukemia were inoculated intravenously into CB.17 SCID mice. Mice were killed at 12 weeks or when they became moribund as a result of disseminated leukemia. All mice were necropsied and subjected to a series of laboratory studies to assess their burden of human leukemic cells. Twenty-three patients whose leukemic cells caused histopathologically detectable leukemia in SCID mice had a significantly higher relapse rate than the 19 patients whose leukemic cells did not (estimated 5-year event-free survival: 29.5% v 94.7%; 95% confidence intervals, 11.2% to 50.7% v 68.1% to 99.2%; P < .0001 by log-rank test). The occurrence of overt leukemia in SCID mice was was a highly significant predictor of patient relapse. The estimated instantaneous risk of relapse for patients whose leukemic cells caused overt leukemia in SCID mice was 21.5-fold greater than that for the remaining patients. Thus, growth of human leukemic cells in SCID mice is a strong and independent predictor of relapse in patients with newly diagnosed high-risk B-lineage acute lymphoblastic leukemia.

Animals↗
PubMed1988

Aspergillus coronary embolization causing acute myocardial infarction.

An increased frequency of disseminated aspergillosis has been observed in the last decade, mostly occurring in immunocompromised patients including the bone marrow transplant population. Cardiac involvement by Aspergillus remains rare. We report the clinical and postmortem findings of an unusual case of Aspergillus pancarditis in a 7-year-old bone marrow transplant patient with Aspergillus embolization to the coronary arteries leading to a massive acute myocardial infarction. This case suggests that myocardial injury secondary to disseminated aspergillosis should be included in the differential diagnosis of chest pain in the immunocompromised pediatric patient.

Aspergillosis↗
PubMed1987

Reconstitution of T- and B-cell function after T-lymphocyte-depleted haploidentical bone marrow transplantation in severe combined immunodeficiency due to adenosine deaminase deficiency.

A 4-month-old male received a T-lymphocyte-depleted haploidentical bone marrow transplant (BMT) for correction of severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency. Although previous haploidentical bone marrow transplants have been attempted in ADA-deficient SCID, complete reconstitution of both B-lymphocyte and T-lymphocyte function has not been obtained after a single transplant. In this patient, however, rapid, complete, and persistent engraftment occurred. Potential reasons for this successful reconstitution include the use of ablation by chemotherapy (busulfan, cyclophosphamide, and cytosine arabinoside), the in vitro technique of using monoclonal antibody (CT-2) and complement to deplete the donor cells of T lymphocytes, and the relative good health of the patient prior to the transplant. Further trials using this method of haploidentical BMT may prove it to be a successful method of immunologic reconstitution in ADA-deficient SCID patients for whom an HLA-identical marrow is not available.

Adenosine Deaminase↗
PubMed1987

Thymus and B cell reconstitution in severe combined immunodeficiency after transplantation of monoclonal antibody depleted parental mismatched bone marrow.

Two brothers were transplanted with bone marrow which was depleted of mature T cells with monoclonal antibody CT-2 plus complement. One child died of sepsis due to candida present prior to transplant. The other is alive and well with full T and B cell reconstitution over 36 months after transplant. Thymus biopsy taken after transplant demonstrated normal morphology and cellularity. Portions of the marrow that were radiolabeled permitted an assessment of traffic patterns of aliquots that were injected intravenously and directly into the marrow space. The studies reported here document that a one haplotype mismatch is not a sufficient disparity to preclude both B and T cell reconstitution, and that monoclonal antibody plus complement is an effective method for T cell depletion.

Antibodies, Monoclonal↗
PubMed1985

Angiosarcoma of the liver and spleen in an infant.

A 14-month-old white male was diagnosed as having angiosarcoma of both the liver and spleen. At 17 months he developed pulmonary metastases and died. There was no apparent environmental or hormonal exposure either prenatally or during infancy. The malignant tumor probably arose from its benign counterpart (hemangioendothelioma), which was found in the spleen. This is the fifth case reported of splenic angiosarcoma in the pediatric age group (18 years or younger).

Adolescent↗
PubMed1984

Adverse histopathologic effects of chemotherapeutic agents in childhood leukemia and lymphoma.

Pathologic material from 84 children with leukemia or lymphoma who died and were autopsied at the University of Wisconsin Hospital between 1967 and 1980 was reviewed to assess the adverse tissue changes due to the chemotherapy administered. In each case the histopathologic findings were correlated with the chemotherapy given. Individual drug dosage is administered (per m2) correlated with the adverse tissue findings at autopsy. Data presented suggest that the drug dose administered should be correlated not only with tumor response but also with tissue effects (some of which produce no noticeable, immediate, clinically apparent changes) to decrease the likelihood of producing irreversible tissue changes.

Adolescent↗