Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinicopathologic records and neuropathologic tissues of 109 patients who underwent necropsy after treatment with bone marrow transplantation (BMT) were examined. Underlying disorders included leukemia (70), aplastic anemia (25), solid tumors (7), lymphoma (5), Hodgkin's disease (1) and Wiskott-Aldrich syndrome (1). There were 34 females and 75 males, ranging in age from 2 to 56 years. Survival after transplantation averaged 3.6 months. The most common findings were cerebrovascular lesions (29), including hematomas, hemorrhagic necrosis, and infarcts. Central nervous system infections comprised the next most common finding, including 10 fungal and four bacterial infections. A recurrence of underlying malignancy for which transplant had been performed occurred in five patients. Leukoencephalopathy of varying severity was found in eight patients, half of whom had received intrathecal chemotherapy and/or cranial radiation. Patients with systemic graft-versus-host disease had a variety of nonspecific neuropathologic findings in the nervous system; however, nearly half (44%) showed no detectable changes. Other nonspecific alterations included hypoxic/ischemic changes, vascular siderocalcinosis, and neuroaxonal spheroids (associated with hemorrhage or necrosis). These findings provide a guide as to likely causes of a neurologic syndrome in a patient who has undergone BMT, and can be compared with neuropathologic findings in other forms of immunosuppression.
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PMID:Neuropathologic findings after bone marrow transplantation: an autopsy study. 219 Sep 10

Neurologic complications are extremely common after bone marrow transplantation and occur in well over half of all patients. Approximately 6 per cent of BMT recipients die as a direct result of neurologic problems. Metabolic encephalopathy, the most common clinical syndrome, is usually due to multiple organ failure. The second most common complication is CNS infection with fungi and viruses. Cerebrovascular disorders are the third most common neurologic problem, and most are related to underlying endocarditis (either infectious or nonbacterial thrombotic endocarditis). Less common neurologic complications include side effects of drugs, recurrence of malignancy, and treatment-induced leukoencephalopathy. Neurologic involvement due to GVHD appears to be limited to rare neuromuscular syndromes. No evidence of CNS involvement from GVHD has been detected.
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PMID:Neurologic complications of bone marrow transplantation. 304 47

Patients with acute lymphoblastic leukemia who have poor prognostic features at diagnosis usually have a short disease-free survival in spite of successful remission induction. Those poor risk features are: age over 30 years, a white blood cell count over 25,000/microliter, certain translocations of chromosomes, and requirement for more than six weeks of induction chemotherapy to attain a complete remission. We have used high-dose radiochemotherapy to prepare 39 patients with acute lymphoblastic leukemia in first complete remission (1 infant and 38 adults; median age 23 years) for bone marrow transplantation from histocompatible sibling donors. Thirty-one of the 39 patients in this study had one (n = 23) or more (n = 8) poor risk features: age (n = 7); high white blood cell count (n = 19); translocations (n = 4), or resistance to initial induction therapy (n = 11). Currently, 26 patients are surviving for 4-72 months (median 18 months) following marrow grafting and are in complete remission. One of the surviving patients had two marrow transplant procedures because of recurrent leukemia. Actuarial survival in complete remission is 63% for the entire group of 39 patients and is 60% if the eight patients who had no poor risk features are excluded from analysis. The following causes for failure were observed: leukemic relapse was encountered in four patients between 3 and 17 months after BMT for an actuarial relapse rate of 16%; bacterial sepsis was the cause of death in two patients; graft-versus-host disease and/or interstitial pneumonia led to the demise of seven patients, and one patient died with leukoencephalopathy. It appears that high-dose radiochemotherapy followed by bone marrow transplantation from a histocompatible sibling donor during first complete remission can result in a high disease-free survival rate for younger adults with poor-risk acute lymphoblastic leukemia. This concept needs to be tested in prospective trials comparing bone marrow transplantation with chemotherapy.
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PMID:Allogeneic bone marrow transplantation for acute lymphoblastic leukemia during first complete remission. 354 96

The progress of 24 children with acute lymphoblastic leukemia treated with cyclophosphamide, total-body irradiation, and marrow transplantation during a second or subsequent remission was compared with that of 21 children treated with conventional chemotherapy after they had entered a second remission. Eleven of the transplantation group are alive, including nine in continuing complete remission for 17 to 55 months; only two of the chemotherapy group are alive, one in complete remission after 20 months. Relapse was the major cause of failure in both groups. Acute and chronic graft-versus-host disease in the transplantation group and leukoencephalopathy in both groups were the other major causes of morbidity and mortality. This study demonstrates that marrow transplantation currently offers the best chance of long-term remission and potential cure after a child with acute lymphoblastic leukemia has had a relapse in the marrow.
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PMID:A comparison of marrow transplantation with chemotherapy for children with acute lymphoblastic leukemia in second or subsequent remission. 702 4

Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy is reported. The conditioning regimen consisted of thiotepa (150 mg/m2 x 4), melphalan (70 mg/m2 x 2) and 12 Gy total body irradiation. She received peripheral blood CD34 positive cells (4.17 x 10(6)/kg) from her HLA-mismatched father and tacrolimus hydrate was used for GVHD prophylaxis. Engraftment was rapid and grade 1 acute GVHD of the skin responded well to pulse therapy. From day 27 she became irritable and sleepless, and right facial convulsions developed on day 37. No abnormality was found in the cerebrospinal fluid. Cranial CT findings showed no abnormalities except for low density lesions around the bilateral ventricle. Leukoencephalopathy was suspected and tacrolimus hydrate was discontinued. Thereafter psychosomatic symptoms improved, temporarily however, similar symptoms again developed following cyclosporine administration. Therefore we had to halt the administration of both tacrolimus and cyclosporine. She died on day 104 because of GVHD and fungal infection without recovering from leukoencephalopathy.
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PMID:[Leukoencephalopathy probably caused by tacrolimus hydrate after stem cell transplantation in a girl with MDS 7 monosomy]. 926 67

A 32-year-old Japanese male in his second remission of acute lymphoblastic leukemia (ALL) received a matched unrelated donor bone marrow transplant (BMT) from the Japan Marrow Donor Program. On day +83, a bone marrow examination revealed 5.2% leukemic cells. Despite the cessation of cyclosporine, leukemic cells in the bone marrow increased to 18.4% on day +91. Treatment was started with interferon (IFN)-alpha-2b 3 x 10(6) U/body s.c. daily on day +92 and leukemic cells in the bone marrow disappeared completely. The toxicity of IFN-alpha treatment included leukoencephalopathy consisting of somnolence, disorientation, short-term memory loss, lack of coordination and ataxia, myelotoxicity requiring multiple platelet transfusions and exacerbation of graft-versus-host disease (GVHD) of oral cavity, skin and lung. Because of progressive GVHD, IFN-alpha was discontinued on day +124. On day +132, a bone marrow aspirate showed 6.4% leukemic cells. The patient died of progressive ALL on day +178. IFN-alpha may be useful for the treatment of leukemic relapse following BMT, although its toxicity is marked.
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PMID:Interferon-alpha treatment of acute lymphoblastic leukemia relapse after unrelated bone marrow transplantation. 959 46

As advances in cancer therapy improve the prognosis of patients with childhood malignancies, awareness of the consequences of treatment methods assumes increasing importance. All cancer treatment modalities are associated with toxic effects, and the spectrum of therapy-induced complications involves all organ systems. Radiologists have a pivotal role in detecting these sequelae, which can be categorized by the affected organ system and by whether they occur (a) at diagnosis or during initial therapy or (b) after the completion of treatment. The first group consists of oncologic emergencies, infectious complications, and irritant effects. Oncologic emergencies can be further categorized as space-occupying lesions (e.g., superior vena cava syndrome or spinal cord compression), vascular abnormalities (e.g., hyperleukocytosis, anemia, coagulopathy), and metabolic emergencies (e.g., tumor lysis syndrome). Common complications developing after completion of treatment include leukoencephalopathy and neurocognitive defects; cataract formation; cardiomyopathy and congestive heart failure; hepatic dysfunction, fibrosis, and cirrhosis; radiation enteritis; renal dysfunction or failure; scoliosis and short stature; hypothyroidism; gonadal dysfunction; graft-versus-host disease; and development of secondary malignancies. Physician awareness of these complications will permit more effective patient surveillance, which may afford patients the opportunity for earlier intervention in these situations and improved quality of life.
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PMID:Complications of cancer therapy in children: a radiologist's guide. 1019 80

We analyzed the incidence of neurological complications in 77 patients receiving stem cell transplantation (SCT), and 12 patients (15.8%) had the following symptoms: convulsions, intracranial hemorrhage, and leukoencephalopathy. Although statistically not significant, neurological complications were seen more frequently in patients after allogeneic transplantation, and in those with acute graft-versus-host disease (GVHD) exceeding grade II. The most significant risk factor for neurological complications was identified as unrelated donor allogenic transplantation (P = 0.016). Complications were categorized into three groups, based on time of onset and symptoms: (1) convulsions during the conditioning period, (2) intracranial hemorrhage during the period of granulocyte recovery, and (3) leukoencephalopathy at around 2 months after SCT. We propose awareness of the risks of neurological complications in each period after SCT so that immediate and effective treatment of patients can be instigated.
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PMID:Neurological complications after stem cell transplantation in childhood. 1049 Jul 31

Tacrolimus has been shown to be more effective than cyclosporine for prevention of acute graft-versus-host disease (GVHD). A number of transplant centers have therefore adopted tacrolimus as standard prophylaxis, but with additional experience, current management of tacrolimus differs from that in the clinical studies. Therefore, a consensus conference was convened to assess the current practices. For prevention of GVHD, conference participants recommended administering tacrolimus at 0.03 mg/kg/day (by lean body weight) i.v. by continuous infusion from day -1 or -2 pretransplant, with day -2 used especially for pediatric patients. Therapeutic drug monitoring was considered essential in the management of patients on tacrolimus. The consensus target range for the whole blood concentration was 10-20 ng/ml. Doses were modified for blood levels outside the target range or for nephrotoxicity, and tacrolimus was discontinued for intolerable tremor, hemolytic uremic syndrome, leukoencephalopathy or other serious toxicity. Tacrolimus was employed most frequently in combination with minimethotrexate (5 mg/m2 i.v. days 1, 3, 6 and 11). Tapering was individualized according to center practice. No patient category was excluded from use of tacrolimus based on age, extent of disease, patient-donor histocompatibility or stem cell source. Tacrolimus was also used successfully for treatment of chronic GVHD. The responsiveness of steroid-refractory acute GVHD was marginal, so it was deemed more prudent to use tacrolimus for prophylaxis instead.
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PMID:Practical considerations in the use of tacrolimus for allogeneic marrow transplantation. 1057 54

We reported a 15-year-old boy with an acute myelomonocytic leukemia and FK 506-induced leukoencephalopathy. He was received FK 506 for graft versus host disease occurred after peripheral blood stem cell transplantation. He, four weeks later, had generalized seizures and consciousness disturbance. The serum level of FK 506 was high (27.5 ng/ml). His brain MRI showed abnormal high intensity areas in the frontal and parietal white matter lesions on T2-weighted images. Neuropathological studies revealed the destruction of myelin sheeths and axons in the cerebral white matter corresponded with abnormal lesions on MRI. There were calcification and mineralization in the small vessel walls of the cortex and white matter. Osteopontin immunoreactivity was detected in the endothelial cells of small vessels. These findings suggest that the vascular damage was involved in the FK 506-induced leukoencephalopathy.
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PMID:[A case of FK 506-induced leukoencephalopathy]. 1186 53


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