BACKGROUNDThe benefits of aminoglycoside antibiotics, such as tobramycin, administered as a once-daily dose to manage febrile neutropenia, have been demonstrated in many patient populations. However, toxicity and safety data are lacking for pediatric stem cell transplant recipients, who are at especially high risk for aminoglycoside-related toxicity and infectious morbidity. In particular, the relative nephrotoxicity and efficacy of tobramycin administered as a single daily dose or as three daily doses among this patient population is not known.METHODSWe conducted a randomized, double-blind controlled study of tobramycin dosing among children 18 years or younger who had fever and neutropenia while undergoing stem cell transplantation. From October 2000 through November 2002, 60 children were randomly assigned to receive intravenous tobramycin, as either a single daily dose (n = 29) or every 8 hours (n = 31), in combination with either piperacillin or ceftazidime (intravenous). Tobramycin doses were adjusted to achieve pharmacokinetic targets. The primary outcome was nephrotoxicity, as represented by the maximal percent increase in serum creatinine concentration throughout the episode of febrile neutropenia relative to the baseline serum creatinine concentration. Efficacy was a secondary outcome and was defined as survival of the episode without modification of the antibacterial regimen. All statistical tests were two-sided.RESULTSIn a modified intent-to-treat analysis, the mean maximal percent increase in serum creatinine concentration was 32% (N = 26) in the once daily dose group and 51% (N = 28) in the every 8 hours dose group (difference = 19%, 95% confidence interval [CI] = 0% to 38%; P =.054). Among patients evaluable for efficacy, 12 (46%) of 26 patients in the once daily dose group and five (19%) of 27 patients in the every 8 hours dose group survived the episode of febrile neutropenia without requiring antibacterial treatment modification (difference = 27%, 95% CI = 4% to 52%; P =.03). There was one death in each group.CONCLUSIONSIn febrile neutropenic children undergoing stem cell transplantation, tobramycin may be less nephrotoxic and more efficacious when administered as a once daily dose than when administered every 8 hours.

Summary. Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)‐matched related donor (MRD). For these children, BMT from a matched unrelated donor (MUD) represents a therapeutic option. We reviewed the course of 62 children with ALL who received fully matched marrow allografts at our institution between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics were similar in the two groups. The interval from attainment of pre‐BMT complete remission to transplant was significantly longer in the MUD group. Conditioning (etoposide/total body irradiation) and graft‐versus‐host disease (GVHD) prophylaxis regimens were the same for all patients, and all received T cell‐replete bone marrow. There was no significant difference in probability of engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a significantly greater incidence of grade II–IV acute GVHD (58% versus 24% in the MRD group; P= 0·02), and demonstrated a trend towards more chronic GVHD (39% versus 15%; P= 0·06). Three years post BMT, the probabilities of transplant‐related mortality were 33 ± 11% and 20 ± 8% in MUD and MRD groups respectively (P = 0·38); the probabilities of relapse were 28 ± 12% and 41 ± 9% respectively (P = 0·19). Lansky or Karnofsky performance scores in event‐free survivors were 90–100 in 87% of the MUD group and 83% of the MRD group. With a median follow up of 38 months (range, 3–97), 3‐year event‐free survival was 49 ± 11% and 47 ± 9% in the MUD and MRD BMT groups respectively (P = 0·71). These results suggest that MUD BMT is a valuable therapy for children with ALL in whom BMT is indicated, and underscore the importance of efforts aimed at expediting unrelated donor searches for patients lacking a MRD.

The purpose of this study was to evaluate the efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) therapy in patients with neutropenia and/or neutrophil dysfunction secondary to glycogen storage disease (GSD) type 1b. Thirteen patients with neutropenia and/or neutrophil dysfunction secondary to GSD type 1b were treated with rhG-CSF. The effects of therapy on neutrophil numbers and in vitro neutrophil function and on bone marrow cellularity and morphology were studied. The clinical status of the patients and the occurrence of adverse events associated with rhG-CSF use were monitored. Use of rhG-CSF therapy was associated with a significant increase in circulating neutrophil numbers (P <. 01) and an improvement in neutrophil function as assessed in vitro. In addition, rhG-CSF therapy produced a significant increase in marrow cellularity and an increase in myeloid:erythroid (M:E) ratio, indicating stimulation of granulopoeisis. No adverse effects on marrow function were noted; in particular, no myelodysplasia or marrow exhaustion was seen. Use of rhG-CSF therapy was associated with objective and subjective improvements in infection-related morbidity. The therapy was well tolerated, although all patients developed splenomegaly, and 5 patients developed mild hypersplenism that did not require any specific treatment. rhG-CSF therapy is efficacious in the management of neutropenia and neutrophil dysfunction associated with GSD type 1b. Patients on this therapy need to be monitored for hypersplenism. Continued follow-up will be necessary to confirm long-term safety; however, no significant short-term toxicity was noted.

Calderwood, S.; Kilpatrick, L.*; Rolland, M.*; Freedman, M. H.; Kurtzberg, J. Author Information