Re: Severe interaction between methotrexate and a macrolide-like antibiotic.
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Bone Marrow Transplantation↗
Biomedical subjects
S M Devine
Publications and source records attributed to S M Devine.
Early detection of human cytomegalovirus viremia in bone marrow transplant recipients by DNA amplification.
Surveillance blood cultures for human cytomegalovirus (HCMV) are commonly used to identify the bone marrow transplant (BMT) recipients with the highest risk of serious HCMV disease and for whom early interventional ganciclovir therapy would be beneficial. We monitored 36 allogeneic BMT recipients weekly for the presence of HCMV in the blood from 0 to 100 days posttransplantation. Viable HCMV in leukocytes (WBC) was detected by shell vial and tube culture methods. HCMV DNA in WBC and plasma was detected by PCR and DNA hybridization using primers and a probe from the EcoRI fragment D region of HCMV AD169. A uracil-N-glycosylase-dUTP PCR protocol was used to prevent false-positive results due to amplicon carryover. Seventeen patients had multiple consecutive positive samples containing HCMV DNA in plasma or WBC. In 14 of 17 patients, HCMV was also detected by blood culture. HCMV DNA was detected sporadically in six patients, none of whom had positive cultures. One patient had HCMV viremia detected by WBC culture only. The remaining 12 patients had no positive PCR assays or blood cultures. For the patients with positive blood cultures, PCR detection of HCMV DNA in plasma preceded detection of HCMV in culture by a mean of 8 days and detection in WBC preceded detection in culture by 6 days. HCMV disease (interstitial pneumonia) was documented for two patients with viremia (blood culture and PCR positive) and one patient without viremia (blood culture and PCR negative). The earlier recognition of high-risk patients provided by detection of HCMV DNA in plasma or WBC may improve the efficacy of early interventional antiviral therapy.
Bone Marrow Transplantation↗
Light and setting times of visible-light-cured orthodontic adhesives.
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Analysis of Variance↗
FK 506-based immunosuppression for prevention of graft versus host disease after unrelated donor marrow transplantation.
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Acute Disease↗
Thrombotic thrombocytopenic purpura associated with FK506 following bone marrow transplantation.
Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) have been observed after bone marrow transplantation (BMT), typically occurring 1-6 months following BMT. We describe two patients who developed TTP very early after BMT while receiving intravenous FK506. They were treated with platelet support and plasma exchange (PE) using either fresh frozen plasma (FFP) or cryosupernatant fraction of plasma (CFP), resulting in remission of TTP activity.
Adult↗
Viral infections in severely immunocompromised cancer patients.
Immunocompromised cancer patients are susceptible to infection by many viral pathogens. The most serious morbidity results from active infection by members of the herpes virus family. Reactivation of latent virus occurs as a sequela of cytotoxic therapy and deficiency of cell-mediated immunity, especially cytotoxic responses, the major host protective defense. Herpes simplex virus and varicella zoster virus infections are problematic in patients with all types of cancer; cytomegalovirus infections cause life-threatening morbidity in bone marrow transplant patients. Several antiviral agents are highly active against these pathogens and different strategies of using them have resulted in reduced morbidity and mortality. Ultimately, the resolution of these infections is dependent on the control of the malignancy and the ability of the patient to mount an adequate immune response.
Chickenpox↗
New preparative regimens with diaziquone or cytarabine in combination with busulfan and cyclophosphamide.
Preparative regimens used prior to bone marrow transplantation (BMT) in patients with malignancies must mediate engraftment and eradicate malignant cells without producing significant extramedullary toxicities. The first agents to be tested in BMT preparative regimens, total body irradiation (TBI) and cyclophosphamide (Cy), were ineffective as single agents, but resulted in long-term disease-free survival in some leukemic patients when combined. However, Cy/TBI regimens are associated with significant acute and chronic toxicities as well as technical constraints involving the administration of radiation. Accordingly, a nonradiation-based regimen consisting of Cy and busulfan (Bu) was developed. Regimens using either a 4-day course (BuCy4) or a 2-day course (BuCy2) of Cy have been shown to have significant antileukemic effects. In general, however, BuCy regimens do not appear to result in greater antileukemic activity or lower treatment-related toxicity than Cy/TBI regimens. New preparative regimens are currently being developed to lower the incidence of disease recurrence after BMT. One such regimen consists of BuCy plus etoposide. At our institution, we are currently testing the efficacy and toxicity of regimens in which cytarabine or diaziquone are administered in combination with Bu and Cy. It is hoped that these new preparative regimens will enhance the antileukemic effects of BMT without significantly increasing treatment-related toxicity.
Antineoplastic Combined Chemotherapy Protocols↗
A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia.
Invasive aspergillosis continues to be a significant cause of morbidity and mortality in patients with prolonged neutropenia. We performed a phase I trial of escalating doses of aerosolized amphotericin B given by a face mask nebulizer system with a disposable bacterial exhale filter. Five, 10, 15, and 20 mg of drug were dissolved in sterile water and inhaled over 10 to 15 minutes twice daily. Tolerance was studied in 26 patients (18 transplant recipients, and 8 leukemia patients). No side effects were observed at any dose level. Prophylactic treatment ended for 14 patients (54%) when intravenous (IV) amphotericin B was begun empirically for antifungal coverage following fevers. Eleven patients (43%) continued inhaled amphotericin B until blood counts recovered. One patient was taken off study when she developed cardiogenic pulmonary edema. No patient developed clinically suspicious or pathologically documented infection with invasive aspergillosis. Prophylactic aerosolized amphotericin B is well tolerated at 5, 10, 15, and 20 mg twice daily dosing. In addition, prophylactic aerosolized amphotericin B does not appear to sensitize patients to the subsequent use of IV amphotericin B. Although this study suggests that prophylactic inhaled amphotericin B is well tolerated and effective, a large scale controlled trial is needed.
Adult↗
Bronchiolitis obliterans organizing pneumonia as a complication of allogeneic bone marrow transplantation.
We report a patient who underwent two allogeneic bone marrow transplants for chronic myelogenous leukemia, initially in 1984 and again after relapse in 1990, who developed an identical pulmonary syndrome at a similar interval following each transplant. The patient presented with a non-productive cough, bilateral inspiratory crackles, and multiple patchy infiltrates on chest X-ray. Pulmonary function testing revealed a restrictive abnormality but no obstructive defects. The appearance of this pulmonary disorder after each transplant coincided with the development of chronic graft-versus-host disease. In both instances, this pulmonary syndrome completely reversed with corticosteroid therapy. The patient's chest computed tomographic scan and lung biopsy specimens were consistent with the diagnosis of bronchiolitis obliterans with organizing pneumonia (BOOP). While bronchiolitis obliterans has been reported following allogeneic transplant, BOOP has not previously been reported in this setting.
Adult↗
Chemotherapeutic and biologic radiation enhancement.
The main objectives of concomitant chemoradiotherapy are to increase local tumor control, decrease the incidence of distant metastases, and improve survival. In addition, concomitant therapy may reduce long-term cancer therapy morbidity either by reducing the need for radical surgery or by permitting the use of lower radiation doses. This article briefly summarizes the rationale for concomitant chemoradiotherapy and summarizes the most recent clinical experience for selected solid tumors. In addition, recent data that suggest additive or synergistic interaction between radiation and certain biologic response modifiers such as tumor necrosis factor and interferon are reviewed.
Combined Modality Therapy↗
Acute leukemia in adults: recent developments in diagnosis and treatment.
Major advances in the diagnosis, classification, and treatment of adult acute leukemias have resulted in significant increases in the number of complete remissions and long-term disease-free survivors. Despite these improvements, most adult patients with acute leukemias still eventually die from their disease or complications of its treatment. New experimental and clinical approaches used to diagnose, monitor, and treat these diseases hold promise for further increased cure rates in the future. This article reviews the classification, immunobiology, cytogenetics, diagnosis, and treatment of adult acute leukemias and describes new directions being taken toward their cure.
Acute Disease↗
Mesenchymal stem cells: stealth and suppression.
Human post-natal bone marrow contains mesenchymal stem cells (MSCs), which are capable of giving rise to multiple mesenchymal cell lineages. Large quantities of human MSCs can be readily obtained following a simple bone marrow aspiration procedure and subsequent expansion over a million-fold in culture. This extensive capacity for clinical scale expansion in vitro has facilitated the development of preclinical models as well as clinical studies designed to assess the safety, feasibility, and efficacy of transplanting allogeneic MSCs for a variety of indications. This review focuses on the rationale for performing clinical studies of MSC transplantation and will discuss the potential role that MSCs may have in the field of hematopoietic stem cell transplantation as well as for the repair or regeneration of bone, cartilage, and cardiac tissues.
Animals↗
The paranasal sinuses of patients with acute graft-versus-host disease.
PURPOSE: To determine whether patients who have acute graft-versus-host disease (AGVHD), are more likely to have radiographically abnormal paranasal sinuses after bone marrow transplantation than patients without AGVHD. METHODS: This retrospective case-control study population comprised 45 adult allogeneic or matched unrelated donor patients who underwent bone marrow transplantation. Twenty-eight patients had AGVHD, and 17 patients did not. All patients had paranasal sinus imaging with either CT or plain films for evaluation of possible sinusitis after bone marrow transplantation. The severity of radiographic changes was measured with an objective scoring system based on mucosal findings. RESULTS: An odds ratio revealed no association between AGVHD and the presence of radiographically abnormal sinuses. CONCLUSION: The diagnosis of AGVHD should not complicate the radiographic evaluation of acute sinusitis after bone marrow transplantation.
Acute Disease↗