Chemotherapy has been traditionally reserved as a last-time treatment for cervical cancer patients and in this setting long-term remissions are unusual. Platinum-based combination chemotherapy has been associated with high tumor response rates in patients with advanced and metastatic cervical tumors and past experience encouraged evaluation of chemotherapy as a first-line treatment in patients with locally advanced tumors where there is a high likelihood of relapse with local treatment. Thirty patients were treated initially with three courses of cis-platinum, vinblastine, and bleomycin with an overall response rate of 67%, and then had either radiotherapy or surgical resection. The initial results have been encouraging and the integration of chemotherapy into the management of locally advanced cervical cancer warrants further investigation.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1984

Recovery of in vivo cellular immunity after human marrow grafting. Influence of time postgrafting and acute graft-versus-host disease.

Three hundred thirty-two marrow graft recipients and 241 healthy marrow donors were studied by skin testing with recall and neoantigens. Two hundred thirty patients with leukemia and seventy-eight patients with aplastic anemia received allogeneic HLA-identical sibling marrow. Twenty-four patients with leukemia received syngeneic marrow. The conditioning regimen prior to marrow infusion consisted of 120 mg/kg cyclophosphamide and 9.2-15.75 Gy total-body irradiation (leukemia) or 200 mg/kg cyclophosphamide (aplastic anemia). The patients were skin-tested with the neoantigens dinitrochlorobenzene (DNCB), keyhole limpet hemocyanin, and a battery of five recall antigens around 100, 150, 365, 730, 1095, 1460, and 1825 days after grafting. A binary logistic regression analysis was used to investigate the factors thought to influence immunocompetence. At 3 months postgrafting, the proportion of patients positive to DNCB was equal to that of normal marrow donors, but thereafter it was lower until 2 years. The proportion of patients positive to keyhole limpet hemocyanin was lower than normal regardless of the time after grafting. The proportion of patients positive to recall antigens was lower than that of normal marrow donors until 4 years after grafting. Patients with a history of acute graft-versus-host disease had the lowest probability of a positive reaction to recall antigens. None of the other factors was significantly associated with an increased or reduced level of response.

Acute Disease↗

PubMed1984

Cyclosporin-associated central nervous system toxicity after allogeneic bone marrow transplantation.

Five of 64 recipients of HLA-identical sibling marrow allografts who were given cyclosporin (CSP) to minimize graft-versus-host disease posttransplant had a serious neurological illness thought to be due to CSP. Characteristic clinical features included a motor spinal cord syndrome, a cerebellar-like syndrome, and mental confusion. All five recovered when the CSP dose was reduced or the drug was stopped.

Acute Kidney Injury↗

PubMed1984

Late onset pyridoxine-responsive sideroblastic anaemia after allogeneic bone marrow transplantation.

We report the late development of transfusion-dependent sideroblastic anaemia in two patients who received a bone marrow transplant for chronic granulocytic leukaemia in blast crisis and T-cell acute lymphoblastic leukaemia respectively. Treatment with pyridoxine has either stopped or reduced these transfusion requirements. Red cell transfusion dependence later after marrow transplantation is rare and sideroblastic anaemia must be excluded.

Adult↗

PubMed1984

Oral administration of cyclosporin A for recipients of allogeneic marrow transplants: implications of clinical gut dysfunction.

Cyclosporin A (CyA) was used to minimize graft-versus-host disease (GVHD) in 28 recipients of allogeneic marrow transplants. When given orally, the absorption of CyA was markedly dependent on normal gut function. Patients without gut dysfunction showed normal serum concentration-time curves while those with diarrhoea from any cause (chemo-radiation enteritis, acute GVHD of the gut, infectious enteritis) showed minimal absorption of the drug. These data indicate the desirability of the intravenous administration of CyA during periods of gut dysfunction in marrow transplant recipients.

Administration, Oral↗

PubMed1984

Current management of aplastic anemia.

Explore the source record for details and available documents.

Anemia, Aplastic↗

PubMed1984

Distribution and concentration of cyclosporin in human blood.

In patients receiving cyclosporin to minimise graft versus host disease after allogeneic bone marrow transplantation, whole blood cyclosporin concentration was roughly twice the serum concentration when blood was separated at 37 degrees C. In turn, blood separation at 37 degrees C resulted in a doubling of serum cyclosporin concentration compared with separation at room temperature. In vitro studies showed that the latter phenomenon was due to a temperature dependent partitioning of cyclosporin between plasma and red cells, such that increased cyclosporin was taken up from the serum into red cells at room temperature. Increasing delay in separation of patient blood (at either temperature) resulted in a gradually increasing cyclosporin serum concentration. Further in vitro studies showed that a distribution equilibrium between blood components was reached within 30 min incubation. Red cell uptake of cyclosporin was saturable at an incubation concentration of greater than 4 microgram/ml, while plasma and mononuclear cells showed a linear uptake to 7 micrograms/ml. The cellular cyclosporin content of a mononuclear cell was roughly 1000 times greater than that of an erythrocyte. For clinical monitoring we recommend the measurement of cyclosporin concentration either in whole blood or in serum separated at 37 degrees C without delay after venepuncture.

Bone Marrow Transplantation↗

PubMed1984

Tissue distribution and toxicity of cyclosporin A in the mouse.

Groups of mice were given cyclosporin A (CyA) subcutaneously for 6 wk at a dose of 12.5, 50 or 200 mg/kg/d. After 7, 21 and 42 days of CyA administration the CyA content of serum, thymus, mesenteric lymph nodes, spleen, kidney, liver, lung, small and large intestine and brain was measured, each organ was examined histologically, and the total viable nucleated cell content of thymus, mesenteric lymph nodes, spleen and femoral marrow was analysed. CyA was detected in every organ assayed at each concentration of CyA administered. The mean concentration of CyA per organ was consistently highest in organs of mice given CyA 200 mg/kg/d and lowest in those given 12.5 mg/kg/d at each time point, but there was pronounced variability in the concentration of CyA between individual mice. Repeated administration of CyA after the first week did not further elevate CyA tissue concentrations. At doses of 50 or 200 mg/kg/d CyA caused weight loss, diarrhea, intussusception and fatal neurotoxicity. In addition, the spleen, thymus and mesenteric lymph nodes of mice given CyA 50 or 200 mg/kg/d were hypocellular and disorganized, and all lymphoid organs contained numerous pyknotic lymphocytes. The liver showed fatty change and the kidney degeneration of proximal tubules. Femoral marrow showed enlarged and congested sinuses. No abnormalities were noted in mice given CyA 12.5 mg/kg/d.

Animals↗