Beryl Jameson

CYCLOSPORIN A TO PREVENT GRAFT-VERSUS-HOST DISEASE IN MAN AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION

Cyclosporin A has been used in conjunction with allogeneic bone-marrow transplantation in the treatment of 23 patients--21 with acute leukaemia, 1 with chronic granulocytic leukaemia, and 1 with aplastic anaemia. The drug was given twice daily from the day before transplant. At the start of the study cyclosporin prophylaxis was stopped in 3 patients within 44 days of transplantation because of non-specific rashes and/or deteriorating renal function. All 3 patients had acute graft-versus-host disease (GVHD) and died. Thereafter the drug was not stopped because of possible toxic manifestations, and 20 patients have been studied (median follow-up 7 months; maximum 13 months). 2 patients have acquired GVHD; 1 patient died of acute GVHD and 1 has chronic mild disease. 3 other patients have died, 2 of recurrent leukaemia and a third of staphylococcal pneumonia with renal failure. Of the remaining patients, 1 has recurrent leukaemia and 1 has moderately severe renal failure. Several toxic effects of cyclosporin A have been observed but they are mostly reversible and no second malignant neoplasm has developed.

MISMATCHED FAMILY DONORS FOR BONE-MARROW TRANSPLANTATION AS TREATMENT FOR ACUTE LEUKAEMIA

35 patients were treated for acute myeloid leukaemia or acute lymphoblastic leukaemia with allogeneic bone-marrow grafts from a parent, child, or sibling who was mismatched at the major histocompatibility complex (MHC). 11 of these patients are alive at least 6 months after grafting, 5 of them after more than 2 years. Of the 15 patients aged under 20 at the time of the graft, 8 are alive and well 6 months to 3 years later. Cyclosporin A was given to all patients after grafting. 1 patient died of acute graft-versus-host disease and in 2 other cases this was a major factor in their death. Graft failure caused the death of 2 patients. 4 patients died of recurrent leukaemia. A fatal complication in 12 patients was pulmonary oedema, often associated with convulsions, intravascular haemolysis, and renal failure. Some of these patients had viral or bacterial infections, but in the majority the syndrome was not associated with demonstrable infection. This syndrome, in which the essential lesion appears to be vascular, was much more common in recipients of mismatched than matched grafts. 3 others died from lung disease in which infection was a factor.

THE PLACE OF BONE-MARROW TRANSPLANTATION IN ACUTE MYELOGENOUS LEUKÆMIA

28 patients with acute myeloid leukaemia (AML) in first remission were maintained on chemotherapy, consisting of courses of cytosine arabinoside and daunorubicin, and immunotherapy with irradiated AML cells and BCG. The relapse rate and survival rate of these patients were compared with those of a simultaneously treated group of 22 patients in first remission who received sibling bone-marrow transplants after cyclophosphamide (60 mg/kg) given for 2 days and followed by a single dose of 1000 rads total body irradiation. Substantially fewer transplanted patients (4 out of 22) than chemo-immunotherapy patients (19 out of 28) relapsed (p less than 0.005) and 14 (64%) transplanted patients remain alive, well, and disease-free. Survival curves of the two groups of patients show that the transplanted patients never fared worse than the chemo-immunotherapy patients. We suggest that when possible young AML patients in remission should be offered transplantation as an alternative form of treatment.

Parenteral acyclovir therapy for herpesvirus infections in man.

Acyclovir is a new antiviral agent which is highly active against herpesviruses in vitro and in laboratory animals. Twenty-three cancer patients with cutaneous and/or systemic herpes zoster or herpes simplex infections were treated with parenteral acyclovir. All had received previous specific treatment for their malignant disease and ten had undergone bone-marrow transplantation. The drug seemed to arrest the progress of the infections and was most effective when given early. Although two patients showed transient increases in blood-urea, possibly the result of acyclovir, the drug was remarkably non-toxic in the doses used.

ORAL NON-ABSORBED ANTIBIOTICS PREVENT INFECTION IN ACUTE NON-LYMPHOBLASTIC LEUKÆMIA

113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.

Co-trimoxazole versus non-absorbable antibiotics in acute leukaemia.

Abstract In a single-centre prospective trial patients with acute myeloid leukaemia in protective isolation and undergoing remission induction or allogeneic bone-marrow transplantation were randomised to receive one of two prophylactic antibacterial regimens—absorbable co-trimoxazole or non-absorbable neomycin plus colistin. Co-trimoxazole prevented infection more effectively and was associated with less gastrointestinal disturbance, but it may have caused some bone-marrow suppression.

Phenoxyethanol is effective topical therapy of Gram-negative cellulitis in neutropenic patients

In neutropenic patients cellulitis caused by Gram-negative organisms may prove difficult to control and cause considerable tissue damage. Phenoxyethanol has activity against a range of bacteria, including Pseudomonas aeruginosa, and is absorbed by intact skin. Three severely neutropenic patients are described in whom cellulitis failed to respond to appropriate intravenous antibiotics. However the topical application of phenoxyethanol solution gave prompt local control. This cheap and nontoxic agent may give dramatic improvement in this difficult clinical situation.

ACUTE MYELOID LEUKAEMIA: COMPARISON OF SUPPORT REQUIRED DURING INITIAL INDUCTION OF REMISSION AND MARROW TRANSPLANTATION IN FIRST REMISSION

Two groups of patients with acute myeloid leukaemia (AML), treated concurrently, were compared to assess the support required during bone-marrow hypoplasia. One group of patients received drugs to induce initial remission; patients in the other group (in first remission) each received a bone-marrow transplant from a matched allogeneic sib. The patients who received marrow transplants required less time in hospital, were febrile on fewer days, received less therapeutic antibiotic treatment, and had fewer bacterial infections. They also required half as many units of platelets and blood per 100 days. The mean weight-loss per patient was the same in each group, and no patient required intravenous feeding. Transplantation for AML in first remission requires less supportive care than initial remission induction.

Infection Prevention in Acute Myeloid Leukaemia: Oral Non-Absorbed Antibiotic Prophylaxis

Despite advances in cancer chemotherapy and supportive care, infection remains the major cause of death in patients with malignant blood disease, more than a quarter of these patients dying of infection before antineoplastic therapy has had an opportunity to induce remission (1–3). The effective prevention of infection in these patients should therefore improve the prognosis of the primary disease by permitting more prolonged and more intensive anti-leukaemic therapy and consequently result in better remission rates and survival.

Book Review: Microbial Diseases; Notes, Reports, Summaries, TrendsMicrobial Diseases; notes, reports, summaries, trends. MayC W (ed) pp 322

aspects of presentation and how the fetal allograft avoids maternal cellular recognition are discussed. One of the contributors protests against the use of the term fetal allograft. The critical question is whether there are immunogenic alloantigens on the surface of the trophoblasts or not. This concept is very much related to various immunological ways of diagnosing early pregnancy and whether pre-eclampsia is an immune disorder or not. This is well discussed in the relevant chapters in this volume as well as the immunological factors in male and female infertility in which there is considerable confusion, especially with respect to methods of management. The second half of the book discusses immunological possibilities in infertility control. There is a realistic appraisal of the potential of limiting reproduction by antibodies to luteinizing hormone releasing hormone, zona pellucida antigens, the beta subunit of HCG, discussed with candour by the world experts who have been attempting to develop an immunological method of fertility control. Interesting relationships to animal husbandry are discussed, but the underlying issue is that an immunological method of fertility control is still a long way off. Nevertheless, interesting avenues for further research are identified and discussed, and the reasons why the earlier promise has not been fulfilled are clearly identified. This volume is a most valuable contribution to our knowledge in this interface between immunology and reproduction and it will be of interest to research workers in the immunological and reproductive field. It is an important volume to have in any library catering for the needs of research workers in reproduction and the development of new contraceptive methods. It is warmly recommended for the breadth and excellence of its subject material and the clear way in which it has been presented.