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Biomedical subjects

M E Trigg

Publications and source records attributed to M E Trigg.

At least 37 records · Page 2Linked to original sources
PubMed1998

The sources and uses of hematopoietic stem cells keep increasing.

In summary, stem cell therapies have been used to try and treat a variety of malignant and non-malignant conditions with increasing success. Such therapies, particularly in children, have resulted in a number of long term survivors and an increased number of productive years possible. The first stem cell therapies were used to treat children with immune deficiencies in the late 1960s and some of those children are currently alive. The long term consequences of stem cell therapy, particularly related to the risk for another malignancy developing or for the development of consequences of the high dose therapies given prior to the stem cell infusions, are becoming recognized and will require long term monitoring and intervention as needed.

Adult↗
PubMed1997

Early response to therapy and outcome in childhood acute lymphoblastic leukemia: a review.

BACKGROUND: Early response to therapy is defined as the initial response prior to Day 28 of treatment, the conventional time of marrow evaluation. The number of reports linking early response to therapy with the ultimate outcome of childhood acute lymphoblastic leukemia is substantial and growing. When this study began, these experiences had yet to be comprehensively reviewed. METHODS: A comprehensive search of the published literature yielded contributory reports of 14 trials conducted in the United States and Europe. In addition, unpublished data from one Children's Cancer Group trial were made available. Outcome measures were standardized by conversion to ratios of the incidence of adverse events among poorer and better responders. RESULTS: Early response to therapy was an independent prognostic factor in each of the 15 trials, which together included more than 10,000 patients. The incidence of slower early response ranged from 2-33%, with various measures and criteria used in different trials. Patients with a slower early response were 1.5-6.1 times (median, 2.7) more likely to have an adverse event than patients with a more rapid early response, however defined. Early response maintained prognostic significance after the exclusion of induction failure and within risk strata defined by age, white blood cell count, and/or immunophenotype. Its significance was also maintained in multivariate analyses where performed. CONCLUSIONS: Early response to therapy, whether determined by evaluation of bone marrow or peripheral blood, is a consistent, independent prognostic factor in childhood acute lymphoblastic leukemia. Slower early response may serve as a useful surrogate for outcome, a more complex end point, in investigations of the cellular and molecular determinants of resistance to therapy. It may also allow early identification of a patient subpopulation for whom current therapy is less effective and alternative strategies may be justified.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Clinical features and treatment outcome of children with myeloid antigen positive acute lymphoblastic leukemia: a report from the Children's Cancer Group.

Leukemic cells from a significant number of children with acute lymphoblastic leukemia (ALL) express protein antigens characteristic of both lymphoid and myeloid cells, yet the clinical significance of this immunophenotype has remained controversial. In the current study, we have determined relationships between myeloid antigen expression and treatment outcome in a large cohort of children with newly diagnosed ALL. A total of 1,557 children enrolled on risk-adjusted Children's Cancer Group studies were classified as myeloid antigen positive (My+) or myeloid antigen negative (My-) B-lineage ALL (BL) or T-lineage ALL (TL), according to expression of CD7, CD19, CD13, and CD33 antigens on the surface of their leukemic cells. My+ patients in both BL and TL groups were more likely than My- patients to have favorable presenting features. Induction therapy outcome was similar for My+ and My- patients in both the BL and TL categories. Importantly, 4-year event-free survival (EFS) was similar for My+ BL (77.0%, standard deviation [SD] = 4.0%) versus My- BL (75.9%, SD = 1.8%) and for My+ TL (72.7%, SD = 7.1%) versus My- TL (70.1%, SD = 5.7%). An overall relative hazard rate (RHR) of 0.89 (P = .49) was determined by a cross strata analysis for My+ versus My- patients. Moreover, similar EFS and RHR also were found when My+ and My- BL patients were compared according to National Cancer Institute risk classification. Thus, patients with My+ ALL have similar treatment outcomes as My- ALL patients. In contrast to previous studies, this result was independent of treatment risk category, demonstrating that myeloid antigen expression was not an adverse prognostic factor for childhood ALL.

Adolescent↗
PubMed1997

Successful program to prevent aspergillus infections in children undergoing marrow transplantation: use of nasal amphotericin.

Aspergillus infections in the pediatric bone marrow transplant (BMT) patients are usually fatal. We began the use of a prophylactic nasal spray of amphotericin in 1990. This nasal spray was provided in addition to low-dose intravenous amphotericin. During the time of this study, the number of fatal cases of aspergillus in the pediatric BMT population was reduced significantly from 13.8% to 1.8% (P < 0.0025) thereby suggesting that the use of nasal amphotericin in this population helps to prevent fatal aspergillus infections. The lack of significant side-effects and the ease of administration make this a very helpful preventive measure in the supportive care of pediatric bone marrow transplant patients.

Administration, Intranasal↗
PubMed1997

Clinical features and treatment outcome of childhood T-lineage acute lymphoblastic leukemia according to the apparent maturational stage of T-lineage leukemic blasts: a Children's Cancer Group study.

PURPOSE: Leukemic cells from T-lineage acute lymphoblastic leukemia (ALL) patients are thought to originate from T-lymphocyte precursors corresponding to discrete stages of T-cell ontogeny. Here we sought to determine the influence of leukemic cell apparent maturational stage on treatment outcomes in pediatric T-lineage ALL. PATIENTS AND METHODS: From 1983 through 1993, 407 pediatric T-lineage ALL patients were enrolled onto two sequential series of risk-adjusted treatment protocols of the Children's Cancer Group. In the current analysis, T-lineage ALL patients were immunophenotypically classified as follows: CD7+ CD2- CD5- pro-thymocyte leukemia (pro-TL), CD7+ (CD2 or CD5)+ CD3- immature TL, and CD7+ CD2+ CD5+ CD3+ mature TL. RESULTS: Similar induction outcomes of 91.4%, 97.1%, and 98.3% were obtained by the pro-, immature, and mature TL groups, respectively. Four-year event-free survival (EFS) was lower for pro-TL patients (57.1%; SD = 8.4%,) compared with immature and mature TL patients (68.5%; SD = 3.5%; and 77.1%; SD = 4.0%, respectively) with an overall significance of .05 (log-rank test) or .04 (log-rank trend test). Relative hazards rates (RHR) were 2.11 and 1.22 for pro-TL and immature TL versus mature TL, respectively. Highly significant differences were found for overall survival (P = .005, log-rank test; P = .009, log-rank trend test). Multivariate analysis confirmed that the prognostic influence of ontogeny grouping was independent of that of other prognostic factors. CONCLUSION: Leukemic cells of the pro-TL maturation stage identify a small subgroup of T-lineage ALL patients who have a significantly worse EFS outcome than patients whose cells are of a more mature stage of development.

Analysis of Variance↗
PubMed1997

Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: a report from the Children's Cancer Group.

PURPOSE: Compared with previous Children's Cancer Group (CCG) acute lymphoblastic leukemia (ALL) trials, therapy based on the Berlin-Frankfurt-Munster (BFM) 76 trial has effected an improvement in event-free survival (EFS). In an attempt to improve EFS further, CCG investigators formulated an augmented BFM (A-BFM) regimen that provides prolonged, intensified postinduction chemotherapy relative to the CCG-modified BFM regimen. PATIENTS AND METHODS: We tested A-BFM in 101 patients with ALL and unfavorable presenting features that showed slow early response (SER) to induction therapy who attained remission on day 28. Their outcome was compared with that of 251 concurrent patients with unfavorable presenting features, a rapid early response to therapy (RER), and remission by day 28, treated with CCG-BFM with or without cranial radiation (CRT). RESULTS: The 4-year EFS rate from the end of induction for SER patients treated with A-BFM was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission beyond 5 years. Vincristine (VCR) neurotoxicity developed in 50% of patients, but was rarely debilitating. Allergies to Escherichia coli L-asparaginase (L-ASP) occurred in 35% of patients. Avascular necrosis of bone (AVN) developed in 9% of patients. In comparison, a concurrent RER group treated with standard BFM +/- CRT had a 4-year EFS rate of 73.1% +/- 4.6%. CONCLUSION: The toxicity of A-BFM is significant, but acceptable. Compared with historical control SER patients treated with CCG-modified BFM, A-BFM therapy appears to produce a significant improvement in EFS. This is the first study to show that intensive chemotherapy, as given in the A-BFM regimen, can abrogate the adverse prognostic significance of SER.

Adolescent↗
PubMed1996

Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome.

Long-term survival and improved neuropsychological function have occurred in selected children with Hurler syndrome (MPS I H) after successful engraftment with genotypically matched sibling bone marrow transplantation (BMT). However, because few children have HLA-identical siblings, the feasibility of unrelated donor (URD) BMT as a vehicle for adoptive enzyme therapy was evaluated in this retrospective study. Forty consecutive children (median, 1.7 years; range, 0.9 to 3.2 years) with MPS I H received high-dose chemotherapy with or without radiation followed by BMT between January 27, 1989 and May 13, 1994. Twenty-five of the 40 patients initially engrafted. An estimated 49% of patients are alive at 2 years, 63% alloengrafted and 37% autoengrafted. The probability of grade II to IV acute graft-versus-host disease (GVHD) was 30%, and the probability of extensive chronic GVHD was 18%. Eleven patients received a second URD BMT because of graft rejection or failure. Of the 20 survivors, 13 children have complete donor engraftment, two children have mixed chimeric grafts, and five children have autologous marrow recovery. The BM cell dose was correlated with both donor engraftment and survival. Thirteen of 27 evaluable patients were engrafted at 1 year following URD BMT. Neither T-lymphocyte depletion (TLD) of the bone marrow nor irradiation appeared to influence the likelihood of engraftment. Ten of 16 patients alive at 1 year who received a BM cell dose greater than or equal to 3.5 x 10(8) cells/kg engrafted, and 62% are estimated to be alive at 3 years. In contrast, only 3 of 11 patients receiving less than 3.5 x 10(8) cells/kg engrafted, and 24% are estimated to be alive at 3 years (P = .05). The mental developmental index (MDI) was assessed before BMT. Both baseline and post-BMT neuropsychological data were available for 11 engrafted survivors. Eight children with a baseline MDI greater than 70 have undergone URD BMT (median age, 1.5 years; range, 1.0 to 2.4 years). Of these, two children have had BMT too recently for developmental follow-up. Of the remaining six, none has shown any decline in age equivalent scores. Four children are acquiring skills at a pace equal to or slightly below their same age peers; two children have shown a plateau in learning or extreme slowing in their learning process. For children with a baseline MDI less than 70 (median age, 2.5 years; range, 0.9 to 2.9 years), post-BMT follow-up indicated that two children have shown deterioration in their developmental skills. The remaining three children are maintaining their skills and are adding to them at a highly variable rate. We conclude that MPS I H patients with a baseline MDI greater than 70 who are engrafted survivors following URD BMT can achieve a favorable long-term outcome and improved cognitive function. Future protocols must address the high risk of graft rejection or failure and the impact of GVHD in this patient population.

Bone Marrow Transplantation↗
PubMed1996

Cutaneous mucor infection treated with wide excision in two children who underwent marrow transplantation.

Cutaneous mucor infection developed in two children who had undergone bone marrow transplantation for treatment of leukemia. One infection occurred before transplantation, and the other occurred during the period of profound neutropenia after transplantation. Both children were treated with an extensive wide excision of the infected area, and there was no evidence of mucor along the resected edges of tissue. Both patients received extensive treatment with either amphotericin (case 1) or amphotericin and itraconazole (case 2). These two cases represent aggressive management of cutaneous mucor infections, which is believed to be required for the successful completion of a marrow transplantation procedure.

Adolescent↗
PubMed1996

Bacterial contamination rates following processing of bone marrow and peripheral blood progenitor cell preparations.

BACKGROUND: The performance of cultures to assess possible bacterial contamination of bone marrow and peripheral blood progenitor cell preparations is required by the standards of the American Association of Blood Banks. STUDY DESIGN AND METHODS: Consecutive (n = 893) bone marrow and peripheral blood progenitor cell preparations were cultured for assessment of possible contamination by microorganisms. RESULTS: Consecutive bone marrow and peripheral blood progenitor cell preparations (n = 893) were cultured; the overall positive rate detected was 2.5 percent (22/893). The isolates predominantly were skin contaminants (gram-positive cocci) and so-called water-borne organisms (gram-negative rods). The 6.0-percent rate of positivity in 317 bone marrow preparations was higher than the 0.5-percent rate in 576 peripheral blood progenitor cell preparations (p < 10(-6)). Culture-positive preparations were transfused to 16 patients at this institution; however, none of these transfusions led to documented sepsis with the contaminating organism. CONCLUSION: The culture method described here complies with the standards of the American Association of Blood Banks. Contamination can be detected in both bone marrow and peripheral blood progenitor cell preparations. When contaminated preparations are transfused, there are few complications that can be attributed to the contamination.

Blood↗
PubMed1996

Cytoreduction and prognosis in acute lymphoblastic leukemia--the importance of early marrow response: report from the Childrens Cancer Group.

PURPOSE: To quantify the residual marrow lymphoblast fraction that best defines patients at high risk for relapse, and the optimal time for assessment during remission induction. PATIENTS AND METHODS: The residual lymphoblast percentage was evaluated on day 7 (n = 220) and day 14 (n = 205) during a four- or five-drug induction in patients with poor prognostic factors. The rate of cytoreduction was related to event-free survival (EFS) and other factors. RESULTS: On the New York (NY) regimen, 68%, 14%, and 18%, and on the Berlin-Frankfurt-Munster (BFM) regimen, 56%, 15%, and 29% of patients had M1 (< 5% blasts), M2 (5-25%), or M3 (> 25%) responses on day 7 (P = .075). On day 14, the corresponding values were 87%, 6%, 7% on NY and 84%, 8%, 8% on BFM. For patients who achieved remission by day 28 and a day-7 marrow rating of M1, M2, or M3, the 6-year EFS rate was 78%, 61%, and 49% (P < .001). The day-14 ratings predicted for a 72%, 32%, or 40% EFS (P < .001). Patients with 5% to 10% blasts day 7 had three times as many events as those with less than 5% and had no better EFS than those with 11% to 25% blasts. Patients with a WBC count more than 200,000/microL at diagnosis and an M1 day 7 marrow had an EFS rate of 69%, while for those with M2 or M3, the EFS rate was 41%. Day-7 marrow had greater prognostic significance than the day-14 evaluation. For slow responders on day 7, the day-14 marrow provided additional information. EFS for patients who achieved M1 by day 14 was 65%. EFS decreased to 20% for those still M2 or M3 on day 14. Day-7 and -14 evaluations had significance for patients of all ages and WBC levels. CONCLUSION: Marrow aspiration on day 7 of therapy provided more useful information than that on day 14. However, day-14 marrow provided additional information for patients with a poor day-7 response. The rate of cytoreduction is a powerful, independent prognostic factor that can identify patients with a slow early response who are at risk for a short remission duration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

What is the merit of an alternative bone marrow transplant?

Bone marrow transplantation has been applied for the treatment of a variety of diseases. There are definite indications for using alternative donors for transplant purposes. Methods to reduce graft-versus-host disease and limit morbidity should be coupled with ways to accelerate immune recovery and decrease infection rates. There is a continued need for workshops to compare data and results so clues will be gained and shared by all as to the indications for transplant, the best approach, and how to limit the short- and long-term morbidity.

Bone Marrow Transplantation↗
PubMed1995

Rapid epidemiologic characterization of cytomegalovirus strains from pediatric bone marrow transplant patients.

BACKGROUND: DNA amplification by the polymerase chain reaction (PCR) of human cytomegalovirus (CMV) nucleotide sequences recently has been reported for differentiation of CMV strains. DESIGN: Retrospective study. OBJECTIVE AND PATIENTS: Evaluate the strain patterns of 15 CMV-positive buffy coat specimens from five pediatric bone marrow transplant patients. SETTING: Pediatric bone marrow transplant unit. METHODS: We perform PCR using primers corresponding to two distinct regions of the CMV genome, the major immediate-early (MIE) region and the a-sequence region, with subsequent restriction enzyme analysis of the amplified products. RESULTS: Restriction enzyme analysis with Hae III and Hinf I of products amplified with nested PCR for the MIE region revealed distinguishable digestion patterns between patients but similar patterns for samples from each patient. All were distinct from the CMV Towne laboratory control strain. In contrast to these results, amplification of specimens with a-sequence primers, followed by restriction enzyme analysis, did not allow differentiation between all patients. CONCLUSION: Our results indicate that nested amplification directly from buffy coat specimens using primers for the CMV MIE gene allows rapid CMV strain characterization that is useful for laboratory quality control and epidemiological studies. Distinct CMV strains were found in each patient, suggesting horizontal transmission was not responsible for acquisition of CMV infection in these patients.

Adolescent↗
PubMed1994

Brain parenchymal infection in bone marrow transplantation patients: CT and MR findings.

OBJECTIVE: The purpose of this study was to assess the MR and CT appearance of brain infection after bone marrow transplantation and to correlate the appearances with laboratory and pathologic findings. MATERIALS AND METHODS: We retrospectively reviewed the records of seven bone marrow transplant recipients with radiologic evidence of brain infection. RESULTS: Forty-one lesions were detected in seven patients with proved infectious foci outside the brain before brain infection was suspected clinically. Six patients had low total WBC or lymphocyte counts and one patient had normal total WBC and lymphocyte counts. Most lesions in patients with low total WBC or lymphocyte counts showed no appreciable edema or contrast enhancement. However, all lesions detected in the patient with normal total WBC and lymphocyte counts showed marked vasogenic edema and ring enhancement. CONCLUSION: Brain infection in bone marrow transplant recipients during immunosuppression exhibited MR characteristics different from those typically seen in immunocompetent patients. This appearance may be related to a diminished immunologic/inflammatory response.

Adult↗
PubMed1993

The role of radiation therapy in the treatment of acute lymphoblastic leukemia with lymphomatous presentation: a report from the Childrens Cancer Group.

PURPOSE: Childrens Cancer Group 123 was a trial of intensive multidrug chemotherapy as well as cranial irradiation and bulk disease irradiation in children with acute lymphoblastic leukemia with lymphomatous presentation (bulk disease and either T-cell phenotype, high white blood count, or absence of anemia), a poor prognostic group with an increased risk of central nervous system (CNS) and other extramedullary recurrence. METHODS AND MATERIALS: Three hundred eight patients without CNS disease were randomized among three regimens: A--BFM chemotherapy (designed for high risk ALL patients) with 1800 cGy cranial irradiation; B--LSA2L2 chemotherapy (designed for non-Hodgkins lymphoma patients) with 1800 cGy cranial irradiation and 1500 cGy to nonabdominal bulk disease; C--Reg B without cranial irradiation. All patients received intrathecal methotrexate throughout therapy. Radiation treatment records were reviewed. RESULTS: With a minimum 52-month follow-up, Regimen B and C patients had 5-year actuarial CNS relapses of 7% and 17% (p = 0.01) and event-free survivals of 53% and 39% (p = 0.04). Patients with white blood count < 50,000/mm3 did not benefit from cranial irradiation. Regimen A patients had the same CNS relapse rate as Regimen B patients but an improved event-free survival. Regimen B and C patients with large mediastinal masses who received their assigned chest radiation had a lower event rate than those who did not (p = 0.06). Patients whose cranial fields did or did not encompass the entire meningeal surface had equivalent CNS relapse rates. CONCLUSION: Patients treated with LSA2L2 chemotherapy, a less than optimal regimen, benefited from cranial and mediastinal irradiation. Compliance with radiation volume guidelines was not essential for patients to receive the benefit of cranial irradiation.

Actuarial Analysis↗
PubMed1993

Disseminated adenoviral infection presenting as acute pancreatitis.

Adenoviruses are gradually being recognized as a significant source of morbidity and mortality in the immunocompromised patient population. We report a bone marrow transplant patient who developed severe abdominal pain accompanied by marked elevations in serum pancreatic and hepatic enzyme levels. She died shortly thereafter. Autopsy revealed hemorrhagic pancreatitis and fulminant hepatic necrosis. Both the pancreas and liver contained intranuclear inclusions consistent with adenovirus; electron microscopy confirmed that there were, indeed, adenoviral particles. This report of adenoviral pancreatitis emphasizes the diversity of manifestations seen with adenoviral infection.

Acute Disease↗
PubMed1993

Bone marrow transplantation using alternative donors. Mismatched related donors or closely matched unrelated donors.

PURPOSE: Bone marrow transplantation has been used with increasing frequency for the treatment of children with leukemia that is resistant to conventional therapy or in cases that have initial features indicating a poor prognosis. PATIENTS AND METHODS: For those children who are in need of a transplant but who do not have a matched sibling as bone marrow donor, transplantation can be performed with marrow from either a closely matched unrelated donor or from a partially matched family member. RESULTS: Comparable results have been reported for transplants using either one of these alternative types of donor marrow, but these results are not as good as those using HLA-matched siblings as donors. CONCLUSIONS: Delays in engraftment, increased infection rates, and complications related to graft-versus-host disease makes transplants using marrow from alternative donors more difficult and less successful. Improved methods to control graft-versus-host disease and greater ability to prevent infections, particularly opportunistic viral infections, will increase the success rate for marrow transplants using alternative donors. In addition, expansion of the National Marrow Donor Registry increases the likelihood of finding unrelated donors for children requiring such transplants.

Bone Marrow Transplantation↗