HnRNP CBP35.CBP67 interaction during stress response and ageing.

Previous studies have demonstrated the existence of nuclear carbohydrate binding proteins in a variety of mammalian cells with molecular masses of 35,000, 67,000, and 70,000 (CBP35, CBP67, and CBP70), which are associated with nuclear ribonucleoprotein (RNP) complexes. CBP35 consists of two domains, an amino-terminal portion that is homologous to certain regions of proteins of the heterogeneous nuclear RNP complex, and a carboxyl-terminal portion homologous to beta-galactoside-specific lectins. CBP35 it has been proposed, like the glucose-specific lectin, CBP67, to guide RNP complexes through the nuclear pore. Here we show that the exposure of mature rats to stress induces an increase in nuclear CBP35 bound to CBP67 and retained on immobilized glucose. Nuclear extracts from the livers of old rats displayed no detectable stress response. This CBP35.CBP67 association detected in rat liver is considered with respect to the CBP35.CBP70 association recently observed in HL60 cell nuclear extracts.

Prostaglandin E2 for prophylaxis of oral mucositis following BMT.

Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT. The incidence of severe oral mucositis was similar for both groups, 55% in patients receiving PGE and 52% in patients receiving placebo. The duration of severe mucositis did not differ between PGE and placebo groups (chi-square 0.95, p = NS). The incidence of HSV infection was significantly higher in patients receiving PGE. Patients with HSV infection receiving PGE also had a higher incidence of severe oral mucositis. The results presented indicate that PGE is not effective for prophylaxis of oral mucositis in BMT recipients.

Allogeneic bone marrow transplantation for acute leukaemia--IGCI experience. International Group for Chemo-Immunotherapy.

From October 1984 to December 1994, 142 patients from six IGCI-BMT centers (78 acute myelogenous leukemia and 64 acute lymphoblastic leukemia) received allogeneic bone marrow from their HLA-identical sibling. The probability of LFS at 60 months is 41% for AML patients and 39% for ALL patients. A better LFS was documented in patients allografted in first CR compared to the patients treated in advanced stage of the disease. The overall relapse rate is 27% for AML patients and 45% for ALL patients. The relapse rate is higher for patients allografted in advanced stage of the disease (47 vs 26% at 60 months for AML and 55 vs 38% at 60 months for ALL). The incidence of moderate to severe acute GVHD is between 45-50% for both AML and ALL patients. Chronic GVHD was documented in 30% of AML patients and 38% of ALL patients. Transplant-related mortality for both AML and ALL is about 25%. Relapse and GVHD with or without infection are the main causes of death. These results confirmed that allogeneic BMT is very effective therapy for patients with acute leukemia, especially for patients transplanted in first CR.

Anxiety as a possible predictor of acute GVHD.

In order to determine the influence of anxiety on the development of BMT complications and survival, we analysed data on 35 consecutive patients undergoing BMT in our Centre between June 1992 and December 1994. All patients received bone marrow from HLA-identical MLC non-responsive siblings. For GVHD prophylaxis, all patients received cyclosporin (CsA) and short methotrexate (MTX). The diagnosis and severity of acute GVHD were defined according to the Seattle Transplant Team criteria. The patients were tested with the Spielberger STAI test as a measure of anxiety as a state (STAI-S) and as a trait (STAI-T). The STAI-S/1 and STAI-T/1 were performed during the first week of isolation (day -5 to day -3 prior BMT) and STAI-S/2 and STAI-T/2 at the end of the discharge from laminar air flow units (day +35 to day +40 post-transplant). During isolation all patients had daily psychiatric support. Out of 35 patients, 31 (89%) fulfilled the STAI-S and STAI-T during the first week and at discharge from laminar air flow isolation. The level of anxiety at the beginning of isolation as measured by STAI-S/1 and STAI-T/1 tests had been significantly higher in patients who subsequently developed acute grade II-IV GVHD as compared to patients with GVHD grade 0-I (P < 0.001), irrespective of age, sex or stage of the disease prior to BMT. In those patients who died, the STAI-S/1, STAI-T/1 and STAI-T/2 tests had been almost identical to those of surviving patients, while STAI-S/2 had been significantly higher (P = 0.034). These data clearly indicate an association between the level of anxiety and the risk for BMT complications, but this should be confirmed in further controlled clinical trials.

Antilymphocyte globulin for treatment of pure red cell aplasia after major ABO incompatible marrow transplant.

A patient developed pure red cell aplasia after ABO incompatible BMT for leukemia. He did not respond to plasma exchange. Antilymphocyte globulin therapy was followed by complete and permanent erythroid recovery with disappearance of recipient-derived isoagglutinins.

Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation for leukemia.

From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups. The incidence of moderate to severe acute GVHD was significantly higher in the CSP group compared with the CSP + MTX group (20 (51%) versus 9 (25%), chi 2 = 4.76, p less than 0.02). There was no significant difference in the incidence of chronic GVHD. Survival was significantly better for the CSP + MTX group (63 +/- 16%) compared to CSP alone (42 +/- 18%). Leukemia-free survival tended to be better for the CSP + MTX group (55 +/- 17% versus 32 +/- 16%).

Total body irradiation with or without lung shielding for allogeneic bone marrow transplantation.

From June 1986 to June 1990, 64 patients with leukaemia (25 acute myelogenous leukaemia, 21 acute lymphoblastic leukaemia and 18 chronic myeloid leukaemia) undergoing marrow transplantation were randomized to receive cyclophosphamide (CY) and fractionated total body irradiation (TBI) without lung shielding (n = 33) or CY and fractionated TBI with lung shielding (n = 31, control group) as conditioning. Patients conditioned with TBI without lung shielding received a significantly higher total lung dose compared with the control group (p less than 0.0001). The 3-year leukaemia-free survival for patients receiving TBI without lung shielding is 54 +/- 18% versus 51 +/- 18% for patients receiving TBI with lung shielding (p = ns). There was no significant difference in the probability of leukaemia relapse (22 +/- 18% for TBI without lung shielding versus 24 +/- 18% for control group; p = ns). The probability of interstitial pneumonitis is 15 +/- 14% for TBI without lung shielding and 5 +/- 5% for TBI with lung shielding (p = ns). A higher incidence of lung fungal infection (15 versus 3%) and interstitial pneumonitis (12 versus 3%) has been documented in patients receiving TBI without lung shielding compared with the control group. The results indicate that higher radiation dose to the lung did not increase antileukaemic efficacy of TBI but seemed to be associated with the increased pulmonary toxicity.

Second HLA-identical sibling transplants for leukemia recurrence.

We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno-occlusive disease were higher after the second than the first transplant. Two-year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14-30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status.

[Treatment of neoplastic hematologic diseases with intensive radio-chemotherapy and transplantation of cryopreserved autologous bone marrow]. / Lijecenje neoplastickih hematoloskih bolesti intenzivnom radiokemoterapijom i transplantacijom krioprezervirane autologne kostane srzi.

Autologous bone marrow transplantation (ABMT) allows application of intensive myeloablative therapy aimed at eradication of neoplastic disease by facilitating haematopoietic reconstitution. Between March and June 1988, four patients (two with acute myelogenous leukaemia in first remission, one with acute lymphoblastic leukaemia in second remission, and one with Burkitt lymphoma, stage IV with CNS involvement in second remission) received this treatment. Methods of collecting, processing and freezing bone marrow as well as thawing and reinfusion of the marrow into patients after intensive chemoradiotherapy are described. Viability of bone marrow cells tested by the dye exclusion method after freezing and thawing process was 89, 88, 91 and 78%, respectively. CFU-GM recovery in culture, as a test of marrow stem cells clonogenicity was between 63,3 and 156,5%. Patients received between 1,7 and 3,0 x 10(8)/kg nucleated cells and 4,0 to 7,6 x 10(4)/kg CFU-GM, respectively. In all four patients stable haematopoietic reconstitution was achieved. The bone marrow function was evident mainly at 11th day after marrow reinfusion. Leukocyte count reached 1,0 x 10(0)/L in 11 to 15 days, and granulocyte count raised more than 0,5 x 10(9)/L in 19 to 37 days after transplantation. Platelet recovery was prolonged with the minimum of 29 days and maximum of more than 60 days to reach 20 x 10(9)/L. Side effects caused by the intensive radiochemotherapy were moderate. Bacterial, fungal and viral infections in early posttransplant period were successfully treated. All patients have survived and left the hospital 63, 54, 36 and 65 days after ABMT, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)