Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

The single centre experience with allogeneic bone marrow transplantation over 25 years is reviewed. 473 allogeneic stem cell transplants have been performed since 1973. Sixty-eight (14%) were done between 1973-80, 216 (46%) between 1981 and 1990 and 189 (40%) between 1991 and 1998. 437 were first trans plants, 36 were second or subsequent transplants. Bone marrow stem cells were given in 421 cases (89%), and peripheral blood stem cells have been used since 1994 in 52 (11%) transplants. Of 437 patients, 101 (23%) had acute lymphoblastic leukaemia, 131 (30%) acute myeloid leukaemia, 101 (23%) chronic myeloid leukaemia, 24 (5%) a myelodysplastic or myeloproliferative disorder, 23 (5%) lymphoproliferative disease and 53 (12%) severe aplastic anaemia. Of patients with leukaemia, 187 (52%) were transplanted at an early disease stage, i.e. first complete remission or first chronic phase, and 48% with advanced disease. Median age was 27 years (range: 1 to 58), 55% were male. Pretransplant conditioning was with cyclophosphamide (Cy) and total body irradiation (TBI) in 192 patients (41%), Cy + TBI + VP-16 in 182 (39%), Cy alone in 53 (11%), busulfan + Cy in 24 (5%) and other regimens in 22 (5%). Graft-versus-host disease prophylaxis was with methotrexate (MTX) in 41 cases (9%) in the seventies, in the eighties and nineties cyclosporine (CSA) was used in 202 patients (43%) or CSA + MTX in 161 (34%). 51 (11%) received T-cell depleted transplants and 18 were transplanted without GVHD prophylaxis. Donors were HLA-identical siblings for 405 transplants (86%), identical twins for 18 (4%), volunteer unrelated donors for 32 (7%) and HLA-mismatched relatives for 18 (4%). Changes over time have affected not only transplantation practices but also patient selection. 31% of leukaemia patients in the seventies but 58% in the eighties and 55% in the nineties were transplanted in an early disease stage (p <0.01). The 15-year survival probability for all patients is 38 +/- 6%. The 5-year survival probability increased from 35 +/- 12% in the seventies to 46 +/- 7% in the eighties and 59 +/- 8% in the nineties (p <0.006). In the last 25 years, allogeneic stem cell transplantation has become accepted treatment for a number of malignant and non-malignant haematological diseases. Over a third of transplant patients become long-term survivors. Transplant outcome is improving probably due to patient selection and improved transplant technology.

Background: In a single-center phase II setting the efficacy and toxicity of the combination of 5-fluorouracil, vincristine and mitomycin C were tested in patients with advanced non-small-cell lung cancer (NSCLC) in order to limit side effects and costs.Materials and Methods: Fifty-four patients with inoperable or metastatic NSCLC were treated with 5-fluorouracil 450 mg/m2 i.v. on days 1-3 and days 22-24, vincristine 1.2 mg/m2 i.v. on day 22, and mitomycin C 12.5 mg/m2 i.v. on day 1. 'FOM' treatment was repeated every 6 weeks.Results: Three out of 47 evaluable patients demonstrated a complete response of 10+, 15 and 21 months duration. Ten patients experienced partial responses of 3 to 14 months duration. The overall response rate in all 54 patients was 24% (95% confidence interval 13-38%). No change in tumor size was seen in 17 patients after 3-10 months duration (median 4.7 months). Fifty patients with a total of 190 cycles are evaluable for toxicity. Forty-one patients (82%) had worst toxicity grade 0 or 1 only. The regimen was very well tolerated on an outpatient basis.Conclusions. The acceptable activity of 'FOM' treatment combined with its very low toxicity makes this regimen attractive to be tested in a randomized trial versus current cisplatin- or anthracycline based combinations for advanced NSCLC, evaluating primarily quality of life and including a control arm with best supportive care.

A 12-year-old girl with acute promyelocytic leukemia has been treated with conventional chemotherapy. The patient remained in complete remission for a year when the first bone marrow relapse occurred. Since reinduction chemotherapy was rejected by the parents, an alternative treatment with oral all-trans retinoic acid was administered. A second complete remission was achieved within 100 days. After 14 months a second bone marrow relapse occurred. All-trans retinoic acid and the combination with interferon-alpha failed.

We present 2 patients with carotenemia who also suffered from iron deficiency anemia. A causal relationship between the ingestion of excessive quantities of carrots and iron deficiency is postulated, since iron deficiency is known to be responsible for change of appetite (pica). A knowledge of this condition, which follows an indolent, reversible course, is necessary for the clinician mainly in view of the differential diagnostic aspects.

We investigated prospectively cytomegalovirus (CMV) IgG antibody kinetics following infusion of a CMV hyperimmune globulin preparation in 19 consecutive patients undergoing allogeneic bone marrow transplantation (BMT). CMV IgG against late antigen was measured by enzyme-linked immunosorbent assay. On a prophylactic hyperimmune globulin regimen (100 mg/kg body weight every 20 days), the mean half-life (t1/2) +/- SD of CMV IgG in seronegative patients with seronegative marrow donors was 19.7 +/- 7.9 days after the first infusion on day -7 before BMT, 24.9 +/- 12.5 days after the second infusion on day +13 after BMT, and 19.4 +/- 6.9 days after the third infusion on day +33. The t1/2 in individual patients showed a wide variation ranging from 10.9 to 47.6 days. A therapeutic high-dose hyperimmune globulin regimen (200-400 mg/kg body weight at 4-day intervals) given to five patients resulted in high serum levels of CMV IgG, which were maintained throughout therapy, even in two patients with severe intestinal graft-versus-host disease. The variation of CMV IgG kinetics between individual BMT recipients may contribute to the lack of protection from active CMV infection observed in some patients.

Therapy of systemic fungal infection with amphotericin B (AmB) must be continued for several months and is usually performed on an inpatient basis because of the risk of drug toxicity. Between 1983 and 1987 we treated 14 outpatients with a total of 164 AmB infusions. Side effects were generally mild and easy to control. Progressive impairment of renal function led to dose reduction and interruption of therapy in only one patient. Ambulatory therapy with AmB is feasible in an outpatient unit with adequate experience, and a significant reduction of treatment costs can result. Outpatient therapy is an acceptable alternative to inpatient treatment. Patients with malignant diseases under palliative therapy will profit most from the reduced duration of hospital stay.

Bone marrow transplantation (BMT) is not possible without the substitution of blood cell components [1]. Cytostatic conditioning and total body irradiation (TBI) as the usual preparative regimen for BMT induces severe bone marrow aplasia lasting at least 2–4 weeks until marrow function takes place, as well as profound humoral and cellular immunosuppression. Under these circumstances transfusion of blood cells can be associated with several hazards. Clinical consequences of HLA-sensitization due to leukocyte contamination in random donor blood products include febrile transfusion reactions, random donor platelet transfusion refractoriness, and poor granulocyte increments after granulocyte transfusions. Because of possible sensitization for non-MHC-antigens, transfusions from close relatives should be strictly avoided prior to transplantation. Use of single random donors for platelet substitution [2] and leukocyte depletion of red blood cell (RBC) and platelet (PLI) concentrates [1] are important in patients when BMT is attempted. For patients with severe aplastic anemia, blood transfusion therapy should be restricted as much as possible since the survival of untransfused patients is significantly better [3]. In the post-transplantation period there is hardly a risk of alloimmunization owing to the profound immunosuppression. Major risks after BMT, however, include transmission of viral disease (Epstein-Barr virus, cytomegalovirus, and recently HIV), since these viruses can be latently present in the circulating leukocytes [4, 5, 6, 7]. Viral reactivation occurs as a consequence of the severe immunodeficiency state. These risks increase greatly when granulocyte transfusions are administered. Selection of seronegative blood donors, use of frozen RBC units, leukocyte depletion of RBC and PLT concentrates, and use of the marrow donor for PLT substitution are effective in reducing some of these hazards.

We analyzed three different methods for removing red blood cell (RBC) antibodies in 28 patients before a major ABO-incompatible bone marrow transplantation (BMT). Six patients were treated with extensive plasma exchange. Antibody titers were lowered from 1:512 to 1:4 (median values). In ten patients antibodies were removed by extracorporeal immunoadsorption using an adsorbent column. Titers decreased from 1:128 to 1:32. In four of these ten patients plasma exchange was added to complete antibody removal. Twelve patients were treated with simple in vivo adsorption with donor-type RBCs before marrow infusion. In eight of them, titers became undetectable. Advantages and disadvantages of the three methods are discussed.

Interstitial pneumonia (IP) is still a life-threatening complication after allogeneic bone marrow transplantation (BMT). It is reported to occur in about 40% of all patients [1]. Almost half the cases of IP are associated with cytomegalovirus (CMV), whereas one-third of IP remains idiopathic. CMV-associated IP has a mortality of up to 90% [1].