Allogeneic stem cell transplantation (allo-SCT) has been extensively investigated as a potentially curative treatment strategy for myeloma. Early studies using myeloablative conditioning showed an unacceptable transplant-related mortality (TRM) of 53%, despite long-term remission rates (39%). 1 Recent improvements in transplant conditioning, graft-versus-host disease (GvHD) prophylaxis and treatment, and supportive care have seen allo-SCT for myeloma re-emerge as a viable option, in particular for young patients with high-risk disease, in whom the prognosis remains poor. 2 Despite this, newer therapeutic strategies have raised the bar for what allo-SCT would need to achieve to be seen as a useful option. 3 At our institution, we use a low-intensity fludarabine/cyclophosphamide conditioning regimen without pre-emptive T-cell depletion. This has been shown to be safe and effective in acute myeloid leukemia, 4 acute lymphoblastic leukaemia 5 and lymphoid malignancies 6 for patients over a wide age range (the latter report included 11 of the current cohort).For this study, we retrospectively collected data from myeloma patients who underwent allo-SCT. Patients received reduced intensity conditioning with fludarabine 25 mg/ m 2 /day for 5 days and cyclophosphamide 1 g/m 2 /day for 2 days, followed by infusion of stem cells from human leukocyte antigen (HLA)-matched donors. GvHD prophylaxis consisted of short-course methotrexate (5 mg/m 2 on days +3, +6 and +11), and cyclosporin (5 mg/kg on day À2 and 3 mg/kg per day thereafter, adjusted according to blood levels). Standard supportive therapy and antimicrobial prophylaxis were employed. Full details of the protocol are as previously described. 4 Myeloma was monitored with serum and urine protein electrophoresis, and latterly serum-free light chain assay. From 2007 onwards, patients received their conditioning in an ambulatory setting, with admission to the hospital ward only if medical complications arose. Details of the statistical methods are given in Supplementary Materials.All 37 patients with myeloma undergoing allo-SCT between 2000 and 2018 were included in the analysis. The majority were male (76%) with a median age at transplant of 52 years (range 31-63). International Staging System (ISS) values were recorded for 32 patients as follows: I 21Á9%, II 40Á6% and III 38Á0%. At least one high-risk cytogenetic feature (t(4:14), t(14:16),17pÀ or 1q+) was present for 57% of the cohort who had available cytogenetic analysis, consistent with a high-risk population.
Thirty-four patients with haematological malignancies were studied to investigate the effect of empirical broad-spectrum antibiotic therapy (ceftazidime and gentamicin) on the gastro-intestinal flora. Twenty-five patients with acute myeloid leukaemia or post-autologous bone-marrow transplantation were given framycetin, nystatin and colistin (Fracon), and two patients with non-Hodgkin's Lymphoma were on co-trimoxazole, as long-term gut prophylaxis. Semi-quantitative microbiology was carried out on oropharyngeal swabs and quantitative microbiology on faecal specimens. The oropharyngeal flora consisted mainly of streptococci, coagulase-negative staphylococci and coryneforms, and was little affected by ceftazidime/gentamicin. A strain of Enterobacter cloacae resistant to ceftazidime and gentamicin colonized one patient, who later developed septicaemia. The faecal flora of patients on Fracon was dominated by enterococci; the few enterobacteria present were eliminated by ceftazidime/gentamicin. The anaerobic flora was absent in 15% of patients; in the remainder, it consisted mainly of Bacteroides spp., and was little affected by ceftazidime/gentamicin. The faecal flora of patients not on Fracon always contained anaerobes, and some strains of enterobacteria persisted throughout antibiotic treatment. None of the patients was colonized by Clostridium difficile or Pseudomonas aeruginosa. Broad-spectrum therapy with ceftazidime and gentamicin appeared to have little effect on the gastro-intestinal flora, except to encourage the overgrowth of enterococci and reduce the numbers of enterobacteria.
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