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Biomedical subjects

M E Trigg

Publications and source records attributed to M E Trigg.

At least 55 records · Page 3Linked to original sources

Bronchoscopy with bronchoalveolar lavage in the evaluation of pulmonary complications of bone marrow transplantation in children.

Pulmonary complications are a frequent cause of morbidity and mortality following bone marrow transplantation. We examined the results of flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) in 27 pediatric bone marrow transplant (BMT) recipients with 29 episodes of pulmonary complications. Bone marrow transplant was performed for a variety of malignancies and hematologic disorders. Median age of BMT was 10.3 years (range, 1.7-17.6 years). Median time of FB following BMT was 60 days (range, 11-1,026 days). Routine cytologic and culture techniques were utilized to detect malignant cells, viruses, fungi, bacteria, and protozoa. Positive results were found in 15 (52%) with cytomegalovirus (CMV), the most common positive finding. In 14 (48%) episodes the results were negative. Fourteen patients had follow-up autopsy or open lung biopsy (OLB). Based on autopsy/OLB results, there were two false negatives and no false positives, giving a diagnostic sensitivity of 75% and specificity of 100%. There was one possible complication of FB and BAL. Survival of both positive and negative patients was poor, only seven patients being alive 90 days post-FB with BAL. We conclude that FB with BAL is a safe and accurate procedure for the diagnosis of pulmonary complications of BMT.

Adolescent↗

Pulmonary resection for fungal infection in children undergoing bone marrow transplantation.

Recipients of bone marrow transplants for hematologic malignancies are at risk for a variety of infectious complications. We have reviewed our experience with six patients 2 to 15 years of age who developed significant fungal infections of the lungs before or after bone marrow transplant. No patient was known to have active fungal or bacterial infection at the time bone marrow transplant was performed. In two patients fungal infections were diagnosed before bone marrow transplant, and operations were performed to permit bone marrow transplant under optimal conditions. Four patients had pulmonary mycoses discovered after bone marrow transplant, and underwent operation 12 to 24 days following transplant. Operations consisted of lobectomy (three), multiple unilateral wedge resections (one), staged segmentectomy and contralateral wedge resection (one), and staged bilateral wedge resection (one). Survival following bone marrow transplant was achieved for 6 months and 11 months in patients undergoing lung resection before transplant, and for 24, 30, 39, and 60 days in patients undergoing lung resections after transplant. Bone marrow transplant recipients are at high risk of pulmonary mycoses, and a vigorous search for occult fungal infections should be carried out before transplant. Aggressive operative treatment of fungal infections of the lungs combined with antifungal chemotherapy before transplant may offer the best hope of extended survival.

Adolescent↗

Monoclonal antibody T-cell-depleted HLA-haploidentical bone marrow transplantation for Wiskott-Aldrich syndrome.

Four patients with Wiskott-Aldrich syndrome received bone marrow transplants (BMT) using monoclonal antibody T cell-depleted HLA-haploidentical marrow from a family member donor. The patients did not receive a significantly larger inoculum of mature T cells than other recipients of T cell-depleted marrow transplants. All four patients achieved quick engraftment, and three of the four patients are alive and well today. The three living patients have all had a complete return of normal T-cell and B-cell function. Infectious complications in the surviving patients were minimal; however, all three experienced some degree of graft-versus-host disease (GVHD). Two of these three patients received GVHD prophylaxis. The patient not receiving GVHD prophylaxis experienced severe GVHD and had a difficult posttransplant course. The patient who did not survive was chronically ill before BMT, whereas the other patients were in relatively good health at the time of BMT. Since the majority of individuals with this disease lack a matched bone marrow donor, our results using partially matched donors suggest that a greater number of patients can be successfully treated for Wiskott-Aldrich syndrome and that outcome is related to control of GVHD and state of health before BMT. Marrow transplantation should be offered earlier in the disease course before the onset of major infectious problems.

Antibodies, Monoclonal↗

Operative treatment of Fusarium fungal infection of the lung.

Systemic fungal infections with Fusarium occur predominantly in immunocompromised patients and are usually fatal. We report a patient with acute lymphocytic leukemia and fusariosis involving the skin and lungs. This patient underwent antifungal chemotherapy and bilateral pulmonary resections. She subsequently had successful bone marrow transplantation. The results of this treatment suggest that this aggressive management of pulmonary fusariosis offers the best chance of survival.

Adolescent↗

Prostaglandin E1 bladder instillations to control severe hemorrhagic cystitis.

Severe hemorrhagic cystitis developed in 6 children after marrow transplantation, 3 of whom had a viral etiology. All 6 patients received instillations of prostaglandin E1 directly into the bladder and 5 of the 6 had complete resolution of hematuria. This finding contrasts with our previous experience with severe hemorrhagic cystitis, particularly the type due to a viral infection, persisting in the face of numerous bladder manipulations. We encourage the use of this nontoxic treatment to gain further information regarding its effect on the bladder epithelium. The mechanism of action remains completely unknown.

Administration, Intravesical↗

Bone marrow transplantation improves survival for acute lymphoblastic leukemia in relapse: a preliminary report.

Acute lymphoblastic leukemia of childhood is the most common malignant disease in children greater than 1 year of age. Chemotherapy has improved the survival of children with this disorder. More than 95% of children will achieve a remission with chemotherapy. However, 30% of children with acute lymphoblastic leukemia who achieved a remission will have a relapse sometime after successful remission-inducing chemotherapy. Although a second remission can be induced in most of these children, in 10-40% a remission cannot be induced or they relapse shortly thereafter and develop refractory leukemia. We present in this preliminary report the early results of therapy for refractory leukemia with an intensive preparative regimen for bone marrow transplantation including etoposide, cytosine arabinoside, cyclophosphamide, and fractionated total body irradiation. Transplantation was done in twenty-three patients with refractory leukemia. Projected survival at 917 days after transplantation in these patients is 43.4% +/- 11%. The survival of these patients so far is similar to the survival of children with acute lymphoblastic leukemia transplanted in second remission. All patients treated with this regimen who had transplantation in relapse were free of leukemia 27 days after transplantation. The results of this preliminary report suggest that an intensive preparative regimen can improve the outlook of refractory leukemia and may rescue some patients who otherwise would have died of their disease.

Adolescent↗

PA utilization on a pediatric bone marrow transplant unit.

Operating without residents or fellows in continuous attendance, The University of Iowa Hospitals and Clinics Pediatric Bone Marrow Transplant Unit utilizes PAs to assume primary responsibility for patients and to assure continuity of care. Major tasks assigned to the PAs include evaluation and assessment, writing notes and orders, and clinic follow-up. Basic PA training in pharmacology, physiology, and pathology has proved to be a sufficient background, supplemented by extensive on-the-job training; a knowledge of hematology is helpful. Severity of illnesses being treated contributes to burnout, which is addressed by staff support groups. This PA utilization model is strongly recommended for other such wards.

Adult↗

Poor-risk non-lymphoblastic lymphoma of childhood: results of an intensive pilot study.

Children with "poor-risk" nonlymphoblastic lymphoma, especially those with marrow or nervous system (CNS) involvement at presentation, have fared poorly even on aggressive chemotherapy regimens. We report here the results of a pilot study of 30 children treated with a highly intensive chemotherapy regimen. This regimen includes an intensive Induction Phase consisting of three cycles of CHOP therapy (cyclophosphamide, doxorubicin, vincristine, and corticosteroids) as well as intensive intrathecal therapy with each cycle. This is followed by a CNS Consolidation Phase consisting of a single cycle of CHOP therapy with five intrathecal doses of "triple" chemotherapy (methotrexate, cytosine arabinoside, and hydrocortisone). Thereafter, a Maintenance Phase consists of alternating cycles of 1) cytosine arabinoside and 6-thioguanine, 2) oral methotrexate and VP-16, and 3) CHOP, for a duration that varied from 36 to 72 wk. Neither debulking surgery nor radiation therapy were recommended. There were 20 patients with Stage III disease (St. Jude's Staging System) and an additional ten patients with bone marrow and/or CNS involvement. The latter group included six patients with B-cell leukemia, three of whom also had CNS disease at presentation. Two additional patients had CNS disease without marrow involvement. Twenty-nine of 30 patients achieved a complete response. Six patients died with recurrent or progressive disease. Twenty-three patients are alive without any adverse events between 21 and 65 mo after diagnosis, with the median time of survival not yet reached (at least 32 mo). All seven adverse events occurred within 7 mo of diagnosis. Event-free survival for all patients is 77%, for Stage III patients is 80%, and for patients with marrow and/or CNS involvement is 70%. This pilot study offers encouragement for improvement in the prognosis of children with "poor-risk" nonlymphoblastic lymphoma and merits evaluation in a Phase III randomized trial in the multicenter cooperative group setting.

Adolescent↗

Alpha-interferon therapy for lymphoproliferative disorders developing in two children following bone marrow transplants.

Two children developed lymphoproliferative processes following marrow transplantation. One of the two lymphoproliferative processes was documented to be Epstein-Barr virus (EBV)-associated. Both children received an extended course of alpha-interferon and gammaglobulin and responded with the disappearance of the lymphoproliferative process. Side effects from the alpha-interferon were minimal. Previous experience with EBV-associated lymphoproliferative processes following marrow transplantation have been usually fatal. This report further substantiates that alpha-interferon has a role in the treatment of EBV-associated lymphoproliferative processes following marrow transplantation.

Anemia, Aplastic↗

Epstein-Barr virus-related lymphoproliferative disorders following bone marrow transplantation: an immunologic and genotypic analysis.

Four patients from 1.5 to 18 yr of age who had received partially matched T-cell-depleted bone marrow transplants for acute leukemia succumbed to a widespread lymphoproliferative disorder (LPD) at 56 to 147 days after transplant. Premortem diagnosis of LPD was suggested in two because plasmacytoid cells were observed in the blood and bone marrow, and in the cerebrospinal fluid of one of these patients. Serum clonal immunoglobulins (Igs) were also demonstrated in these two patients premortem, while the other two had clonal Igs in serum obtained at autopsy. Autopsies revealed a plasmacytoid infiltrate or immunoblastic lymphoma involving lymph nodes, spleen, liver, lungs, gastrointestinal tract, and kidneys. Immunoglobulin gene rearrangement studies performed in three revealed B-cell clonality. Both immunohistochemical and DNA gene rearrangement studies were useful in differentiating the LPD from the pretransplant leukemia. Epstein-Barr virus (EBV) genome was found in the tissues of the three patients studied. The diagnosis of EBV-induced LPD must be considered in bone marrow transplant patients who deteriorate and who exhibit serum clonal Igs or prominent plasmacytoid cells in laboratory specimens.

Adolescent↗

Low rejection rate when using unrelated or haploidentical donors for children with leukemia undergoing marrow transplantation.

Thirty-nine children with leukemia were entered into a bone marrow transplantation study comparing the use of unrelated donors who were HLA-Dr identical and matched at least with three of the four HLA-A or B loci, with haploidentical related donors. Although marrows were prepared by T lymphocyte depletion in vitro, the rejection rate of marrow in these patients was only 13% (5/39). Four patients had early rejections, and three of these four had autologous recovery immediately without evidence of leukemic recurrence. The fifth had a delayed rejection occurring approximately 2 1/2 months after transplant. These results were achievable by an ablative regimen incorporating increased immunosuppression. Although the small sample size does not yet permit evaluation of outcome comparing one donor type versus another, the early findings document a high rate of successful engraftment.

Adolescent↗

Bone marrow transplantation for treatment of leukemia in children.

BMT is a well-established treatment for children with ALL in second remission, ANLL in first and second remission and children with JCML and CML. Improvements in transplantation technology and supportive care have resulted in significant increases in the percentage of long-term survivors of allogeneic marrow transplantation. Newer strategies, such as partially matched donor, unrelated matched donor, and autologous transplants, are bineg pursued to overcome the histocompatability barrier. The development of more effective antileukemic cytoreductive chemotherapy and radiation therapy regimens and better methods of preventing GVHD are areas in which further improvements are necessary. Newer methods of marrow purging, such as the use of monoclonal antibodies linked to immunotoxins, already are being tested. In addition, the recent development of molecularly cloned hematopoietic growth factors, such as CSFGM, may make it possible to improve marrow recovery and hasten return of normal immunologic function, thereby increasing the overall safety of the transplant procedure. It is hoped that these innovations eventually will increase the overall applicability of BMT and its role in the treatment of leukemia.

Acute Disease↗

Fatal cardiac toxicity in bone marrow transplant patients receiving cytosine arabinoside, cyclophosphamide, and total body irradiation.

Three patients developed fatal cardiac toxicity from the combination of cytosine arabinoside, cyclophosphamide, and total body irradiation while undergoing preparation for a bone marrow transplant. The pattern of the toxicity was unique for this combination of ablative chemotherapy. All three patients had autopsies demonstrating characteristic myocardial and pericardial toxicity. The cardiotoxic effects of this combination may be averted by lowering the dose of the cyclophosphamide.

Adolescent↗