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Acute renal failure (ARF) with fluid overload (FO) occurs often in stem cell transplant (SCT) recipients. We have previously demonstrated that an increased percentage of FO prior to the initiation of continuous renal replacement therapy (CRRT) is associated with mortality in children with ARF. Based on these data, we devised a protocol for the prevention of FO in SCT patients with ARF. SCT patients with ARF and 5% FO were started on furosemide and low-dose dopamine. To allow for nutrition, medication, and blood product administration, RRT was initiated for patients with > or =10% FO. There were 272 patients who received allogeneic SCT from 1999 to 2002. Of these, medical records of 26 SCT patients with a first episode of oliguric ARF were reviewed. The mean patient age was 13+/-5 years (range 2-23.5 years). Mean days to ARF after SCT were 28+/-29 days (range 2-90 days). Of the 26 patients, 11 (42%) survived an initial ARF episode. All 11 survivors either maintained <10% FO during their course or re-attained <10% FO with RRT treatment. Of the 15 non-survivors, 6 had <10% FO at the time of death. Of 14 patients who received RRT, 4 (29%) survived. Mechanical ventilation and pediatric risk of mortality score > or =10 at the time of admission to the intensive care unit were associated with lower survival ( P<0.05). The use of one or more pressors, the presence of graft-versus-host disease, and septic shock were not correlated with survival. Our data demonstrate that maintenance of euvolemia ( <10% FO) is critical but not sufficient for survival in SCT patients with ARF, as all non-euvolemic patients died. We suggest that aggressive use of diuretics and early initiation of RRT to prevent worsening of FO may improve the survival of SCT patients.

Broadening the applicability of stem cell therapies requires safer preparative regimens for patients. The CD45 antigen is present on all cells of the hematopoietic lineage, and using a murine model, we determined whether a lytic CD45 monoclonal antibody could produce persistent aplasia and whether it could facilitate syngeneic or allogeneic stem cell engraftment. After its systemic administration, we found that all leukocyte subsets in peripheral blood were markedly diminished, but only the effect on the lymphoid compartment was sustained and marrow progenitor cells were spared from destruction. Given the transient effects of the monoclonal antibody on myelopoiesis and the more persistent effects on lymphopoiesis, we asked whether this agent could contribute to donor hemopoietic engraftment after subablative transplantation. Treatment with anti-CD45 alone did not enhance syngeneic engraftment, consistent with its inability to destroy progenitor cells and permit competitive repopulation with syngeneic donor stem cells. By contrast, the combination of anti-CD45 and an otherwise inactive dose of total-body irradiation allowed engraftment of H2 fully allogeneic donor stem cells. We attribute this result to the recipient immunosuppression produced by depletion of CD45-positive lymphocytes. We next assessed a pair of unconjugated rat anti-human CD45 monoclonal antibodies (MAbs), YTH54.12 and YTH25.4, in a clinical trial in patients who were to receive stem cell transplantation for acute leukemia. The maximum tolerated dose of these MAbs, 400 microg/kg/day, produced a pattern of response identical to that seen in the mice, with marked reductions in circulating lymphoid and myeloid cells and sparing of early marrow progenitors. In two of three patients with active leukemia, the MAbs also produced a decrease in the percentage of leukemic blast cells in bone marrow. These pre-clinical and clinical results warrant further evaluation of anti-CD45 MAbs in subablative preparative regimens for stem cell transplantation.

Summary:Infectious complications due to adenovirus are of increasing concern after allogeneic stem cell transplantation. Over the past 4 years, we have modified our conditioning regimens to use alemtuzumab in preference to anti-thymocyte globulin (ATG) for pediatric patients receiving stem cell transplants from alternate donors. Recent reports in adult studies implicate alemtuzumab as a risk factor for adenovirus infection. We therefore evaluated the incidence of adenovirus infection in pediatric patients receiving either ATG or alemtuzumab in their conditioning regimens. Of the 111 patients evaluated, a total of 54 patients received ATG and 57 patients received alemtuzumab. In total, 35/111 (32%) patients were infected by adenovirus, and 9/111 (8%) had adenovirus disease (AD). Adenovirus infection was greater in the alemtuzumab group than the ATG group (23/57 vs 12/54) (P=0.039) and disseminated AD was more frequent in the alemtuzumab group vs the ATG group (8/57 and 1/54 respectively) (P=0.032). The presence of Grade 3–4 graft-versus-host disease was a risk factor for adenovirus infection. Our findings highlight the fact that adenovirus infection is a frequent complication after stem cell transplantation from alternate donors in the pediatric population and that alemtuzumab increases the risk of infection compared to ATG. This work will help in identifying at-risk populations for our upcoming immunotherapy trial using adoptively transferred donor-derived adenovirus-specific cytotoxic T lymphocytes.Bone Marrow Transplantation (2005) 36, 1001–1008. doi:10.1038/sj.bmt.1705164; published online 26 September 2005 [ABSTRACT FROM AUTHOR]

Presents several case studies of acquired peripheral ascending polyneuropathy, consistent with the diagnosis of Guillain-Barré syndrome, that developed after allogeneic hematopoietic stem cell transplantation. Background on the cases; Characteristics of GBS; Factors attributed to the observed neurotoxicity in patients.