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Biomedical subjects

D M Sutton

Publications and source records attributed to D M Sutton.

31 records · Page 2Linked to original sources

Sezary syndrome in a patient with hairy cell leukemia in remission.

A 65-year-old man was evaluated for pancytopenia in March 1979, and found to have hairy cell leukemia (HCL). Treatment with splenectomy and subsequently interferon produced temporary remissions. In July 1985, the patient began intravenous deoxycoformycin (DCF) therapy, and after 1 year complete peripheral blood and bone marrow remission was achieved. Fourteen months after cessation of therapy, the patient developed a skin rash and was found to have cutaneous T-cell lymphoma and Sezary syndrome. Morphologic study of the hairy cells (HC) in the peripheral blood at presentation and the Sezary cells was distinct by light and electron microscopic study. Immunophenotyping of peripheral blood mononuclear cells showed clearly that the HC were of B-cell origin (CD20+, sIg+), whereas the lymphoid population at second presentation was T-cell (CD3+, CD4+, HLA-DR-). Clonal rearrangement of T-cell antigen receptor beta-chain gene was detected by Southern analysis of the Sezary cell population, whereas immunoglobulin heavy and light chain genes remained in germ line configuration. This is the first case of Sezary syndrome developing in a patient previously treated for HCL where studies have confirmed distinct B-cell and T-cell origin of the two neoplasms. The authors suggest that treatment and disease-related immunosuppression are possible etiologic factors in the development of this second lymphoid neoplasm.

Aged↗

GM-CSF therapy for delayed engraftment after autologous bone marrow transplantation.

Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after high-dose therapy and autologous bone marrow transplantation (ABMT). Three patients responded to a 14-day course of GM-CSF (10 micrograms/kg body weight/day) with at least a sevenfold rise in circulating granulocytes and a corresponding increase in granulopoietic activity in the bone marrow. A fourth patient died of infection on the 8th day of GM-CSF therapy with no evidence of response, and the remaining two, one of whom received a lower dose of GM-CSF (5 micrograms/kg/day), did not respond. There was no change in platelet or red cell transfusion requirements in any patient during the treatment. In two of the three responders, the granulocyte counts returned to pretreatment levels by 4 and 7 weeks after stopping the drug, respectively. We observed a marked increase in marrow-derived as well as in circulating granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day course of GM-CSF in the three responders. There was no change in the frequency of circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis, but the effect is transient in some patients.

Acute Disease↗

Complications of plasma exchange.

For the past few years, the Canadian Apheresis Study Group has collected data on most apheresis procedures carried out throughout the country. The information accumulated during calendar year 1985 has been reviewed, and the complications that occurred as a result of therapeutic plasma exchange (PE) have been assessed. There were side effects during 612 (12%) of the 5235 procedures done, involving 252 (40%) of the 627 patients treated. The most common reactions were fever, chills, urticaria, muscle cramps, or paresthesias; these reactions were encountered more frequently when plasma was used in the replacement fluid. Most reactions had little or no clinical significance. However, there were 28 severe complications, including one cardiac arrest and two respiratory arrests. Five late deaths occurred, but these were not related directly to PE. Although PE is relatively safe, life-threatening reactions do occur, and patients require careful observation during the procedure.

Adolescent↗

Immunotherapy for chronic myelogenous leukemia: survival not affected by treatment in the stable phase.

Thirty-one consecutive patients with chronic myelogenous leukemia were treated in the chronic phase with immunotherapy in addition to chemotherapy. Immunotherapy consisted of Bacillus Calmette-Guérin and allogeneic myeloblasts given by vaccination, and chemotherapy comprised busulfan p.o. in most patients. No randomly allocated control group was designated, but patient characteristics appear to be typical of those of other published groups. Twenty-eight of 31 patients were followed from diagnosis to death, and the three remaining patients were followed for over 5 years. The median survival of the patients in our group was 37 months. There was a constant rate of decline in survival with time, with a mean annual death rate of 30% per year. Twenty-five of the 31 patients terminated in blast crisis. One of 21 patients achieved complete remission in blast crisis of myeloid or indeterminate type, and three of four patients achieved complete remission for blast crisis of lymphoid type. The median survival, the rate of decline in survival, and the remission rate in blast crisis do not appear to differ from those of comparable groups of patients treated with chemotherapy alone.

Adult↗

Central nervous system toxicity of high-dose cytosine arabinoside.

Ten patients with refractory acute leukemia were treated with high-dose cytosine arabinoside (Ara-C) infusions. Nine patients had previously achieved at least one complete remission using standard chemotherapy protocols that include cytosine arabinoside. Eight of the ten had been on maintenance therapy. Twelve courses of treatment were given, with the cytosine arabinoside infused over 1-2 hours in a dose of 3 gm/m2. Each course consisted of 12 to 16 doses given at 12-hour intervals. The drug was generally well tolerated but five patients developed central nervous system symptoms characterized by ataxia, dysphasia, nystagmus, dysdiadochokinesis, and a decreased level of consciousness. These changes began 3 to 34 days after the initiation of therapy and were severe at the time of death in two of the patients. One complete and one partial remission, lasting 2.5 months and 1 month, respectively, were documented. This experience suggests that high-dose Ara-C is of limited usefulness in refractory acute leukemia and may be frequently associated with significant neurotoxicity.

Acute Disease↗

A controlled trial evaluating intensive plasma exchange in renal transplant recipients.

Sixty patients have been entered into a controlled trial evaluating the use of intensive plasma exchange (IPE) in renal transplant recipients. During the first three months post-transplant, patients receive either conventional anti-rejection therapy alone (control group) or conventional anti-rejection therapy and IPE (IPE group) for all rejection episodes. Twenty percent of the grafts in the control group versus 10% in the IPE group have been lost to rejection (p = NS). The actual three month patient and graft survival in the control group (97% and 70%), respectively, is similar to the IPE group (94% and 80%), as is the one year actuarial graft and patient survival in the two groups. No statistically significant benefit of IPE has yet been demonstrated but the trend is encouraging and the complication rate sufficiently low so as to justify continuing the study.

Clinical Trials as Topic↗

Cerebral and retinal vascular complications of inflammatory bowel disease.

Recurrent retinal branch artery occlusions, carotid thromboembolism, cerebral venous thrombosis, transient brainstem ischemia, and massive brainstem and cerebral infarction complicated the course of inflammatory bowel disease in 5 patients. Three patients had ulcerative colitis and 2 had regional enteritis. The usual risk factors for stroke were absent. Neuropathological examination in 1 patient showed in situ thrombosis of small cerebral and brainstem arteries and veins. Coagulation studies showed thrombocytosis, short partial thromboplastin times, and elevation of fibrinogen and Factor VIII levels. Platelet counts and coagulation factors returned toward normal after control of intestinal inflammation in each of the 4 surviving patients. Inflammatory bowel disease can be accompanied by a hypercoagulable state that predisposes to stroke.

Adult↗

Intensive plasma exchange, complement dependent microcytotoxicity and renal transplant rejection.

Intensive plasma exchange (IPE) was used to treat 13 rejection episodes in eight renal transplant recipients with biopsy evidence of humoral rejection. Prior to IPE, each patients had several rejection episodes treated with high dose steroids. The IPE-treated rejections had not responded to conventional anti-rejection therapy and all patients appeared likely to lose their grafts. IPE reversed 7 of the 13 rejections (5 of 8 patients responded). Two of the 8 grafts continue to have adequate function 6 and 8 months after IPE. IPE temporarily reverses rejection but not increase long term graft survival.

Blood Transfusion↗

A rapid tube technique for fetal cell typing.

A modification of Greendyke technique for fetal cell typing is described in which incubation time and quantities of antisera are reduced without affecting the sensitivity of the test.

Blood Group Antigens↗