Reduced dose intravenous immunoglobulin does not decrease transplant-related complications in adults given related donor marrow allografts.

Graft-vs.-host disease (GVHD) and infection are major complications of allogeneic bone marrow transplantation. Intravenous immunoglobulin (IVIg) given at a dose of 500 mg/kg/wk has been shown to decrease the risk of acute GVHD, interstitial pneumonia, and infection in adults early after allogeneic transplantation. The current study is a controlled trial to determine whether a lower total dose of IVIg given with pretransplant loading reduces the incidence of transplant-related complications. In a randomized trial of 241 patients > or =20 years of age who were given related donor marrow allografts, 121 individuals receiving Ig prophylaxis (500 mg/kg/d loading from day -6 to -1 and then 100 mg/kg every 3 days from day 3 to 90) were compared with 120 control patients who did not receive IVIg. Randomization was stratified by human leucocyte antigen-matching, remission status of malignancy, GVHD prophylaxis, and cytomegalovirus (CMV) serology. The study was powered to detect a reduction in acute GVHD by 18% and a decrease in transplant-related mortality by 17%. Pretransplant IVIg loading and posttransplant maintenance achieved median serum IgG levels >1350 mg/dL, which were approximately twofold greater than the untreated controls (p<0.01). White blood cell and platelet recoveries were similar for the two groups, although control patients required fewer units of platelets per day (2.5 vs. 3.3, p = 0.008). No significant differences in the incidence of CMV infection, interstitial pneumonia, or bacteremia were observed. The incidence of acute GVHD did not differ between the two groups; however, acute GVHD was less frequent among IVIg recipients achieving maximum serum IgG levels >3000 mg/dL (60 vs. 79%). Neither transplant-related mortality nor disease-free survival was significantly altered by Ig prophylaxis. However, the cumulative incidence of relapse of malignancy was higher in IVIg recipients than in controls (31 vs. 18%, p = 0.03). Multivariable regression analysis demonstrated a 1.89 increased relative risk of relapse for individuals given IVIg (p = 0.021). We conclude that pretransplant loading and a shorter course and lower total dose of IVIg prophylaxis did not appear to decrease the risk of acute GVHD or mortality among adults receiving related donor marrow transplants. Note, IVIg administration may be associated with an increased risk of recurrent malignancy, a finding that warrants further investigation.

Prevalence of clinically relevant bacteremia after upper gastrointestinal endoscopy in bone marrow transplant recipients.

PURPOSE: To determine the prevalence of clinically relevant bacteremia after upper endoscopy in patients undergoing bone marrow transplantation. PATIENTS AND METHODS: We retrospectively reviewed the records of 151 patients who received an HLA-identical allogeneic bone marrow transplant (BMT) at the Seattle Veterans Affairs Medical Center between September 1983 and December 1988. Forty-seven patients who required esophago-gastroduodenoscopy (EGD) during their first 100 days after transplant were selected for evaluation. Clinically relevant bacteremia was defined as the development of hypotension, temperature greater than 38.5 degrees C, and a positive blood culture occurring within 24 hours after endoscopy. The presence of acute graft-versus-host disease (GVHD) at the time of endoscopy and the use of prednisone prior to endoscopy were considered possible risk factors for the development of bacteremia. The proportion of subjects who became bacteremic were compared using Fisher's exact test. RESULTS: Within 24 hours following endoscopy, nine patients (19%) developed clinically evident bacteremia (hypotension, temperature greater than 38.5 degrees C, and a positive blood culture). Eight of 14 patients receiving prednisone at the time of endoscopy developed bacteremia, compared to one of 33 not receiving prednisone (p less than 0.01). Nineteen patients had acute GVHD of at least grade 2 at the time of EGD, six of whom developed bacteremia. Although acute GVHD alone did not increase the risk of post-EGD bacteremia in patients not receiving prednisone (one of 21 versus zero of 12, p greater than 0.9), the risk of bacteremia was particularly high in patients with acute GVHD treated with prednisone at the time of EGD (six of seven). CONCLUSION: Allogeneic BMT recipients receiving prednisone for immunoprophylaxis after grafting or for treatment of acute GVHD are at high risk for clinically relevant bacteremia following EGD. Such patients are candidates for antibiotic prophylaxis prior to endoscopy.

Bone marrow toxicity of total-body irradiation combined with radiosensitizers.

The effect of the addition of radiosensitizers to low-dose total-body irradiation was studied. SR2508 (1 g/kg) or misonidazole (0.35 g/kg) was given 30 min prior to single-dose total-body irradiation, delivered at 0.1 Gy/min. Six dogs received either SR2508 or misonidazole and 2 Gy irradiation, and 14 dogs served as controls, receiving no drug and either 2 or 3 Gy of total-body irradiation. All dogs had a decline in their white blood cell and platelet counts and were supported with prophylactic antibiotics and platelet transfusions. High plasma levels of both radiosensitizers were achieved. The degree of cytopenia with 2 Gy total-body irradiation when combined with either radiosensitizer was not significantly greater than that seen with 2 Gy alone, and the neutropenia was significantly less than that seen with 3 Gy alone. The only observed toxicity of the drugs was vomiting, which started shortly after the infusion of SR2508 and before the radiation treatment. A single high-dose infusion of a radiosensitizer combined with total-body irradiation appears to cause a mild increase in bone marrow toxicity but is otherwise well tolerated.

Successful long-term use of a plasmapheresis reactor system in dogs with lymphoma.

The successful long-term use of asparaginase-glutaminase reactor in dogs with lymphoma is described. The limitations of the system consisting of an activation of enzymes leading to rapid neosynthesis of asparagine and glutamine are outlined. The possible beneficial effect of future combination therapy with amino acid analogues is discussed.

Nonbacterial nonfungal pneumonia following marrow transplantation in 100 identical twins.

Pneumonia attributable to causes other than bacterial or fungal infection is a major complication of allogeneic marrow transplantation. In this study, the incidence, mortality, and possible risk factors for the development of nonbacterial, nonfungal pneumonia after 100 syngeneic marrow transplants for hematological malignancy are reviewed and compared with the results found in 351 allogeneic marrow transplants performed during the same time period. Both the incidence and mortality of pneumonia were far lower among syngeneic patients, especially for pneumonia associated with cytomegalovirus. Idiopathic pneumonia, however, occurred with about equal frequency in the two populations. Among twins, an increased incidence of pneumonia was seen in older patients and in those who received chemotherapy in addition to cyclophosphamide and total body irradiation as part of the preparative regimen for transplantation.