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This phase I study was conducted to determine the maximal safe concentration of 4-hydroperoxycyclophosphamide (4HC) that could be used for in vitro treatment of bone marrow from patients with acute leukemia undergoing autologous bone marrow transplantation. Concentrations of 40 to 120 micrograms/mL of 4HC were used in 30 patients with relapsed or high-risk acute leukemia and in six patients with nonleukemic malignancies. All patients received marrow-lethal cytoreductive therapy followed by infusion of the 4HC-treated marrow. Complete inhibition of granulocyte and macrophage colony-forming cells was obtained at 80 micrograms/mL. Nevertheless, only one transplant-related death and otherwise full hematologic recovery was observed at concentrations of 4HC up to 100 micrograms/mL. At 120 micrograms/mL, there were three transplant-related deaths, including two of the three patients who required the infusion of reserve marrow. Among the acute leukemia patients, three remain in complete remission at 1,337, 1,017, and 967 days after transplant. Among the nonleukemic patients, two remain in complete remission at 1,081 and 1,017 days after transplant. At the maximum safe concentration of 4HC (100 micrograms/mL), satisfactory hematologic recovery can be obtained, despite elimination of detectable hematopoietic progenitors.

Although standard supportive care for bone marrow transplant (BMT) recipients includes total parenteral nutrition (TPN), it has not been shown that this is the most appropriate method of nutritional support. To determine whether current BMT recipients require TPN during the early recovery period, we conducted a prospective, randomized clinical trial comparing TPN and an individualized enteral feeding program (counseling, high protein snacks and/or tube feeding). Nutritional assessment included measurement of serum proteins, anthropometry, and body composition analysis. For the latter, total body water and extracellular fluid were measured by standard radioisotope dilution techniques and used to quantitate body cell mass and body fat plus extracellular solids (FAT + ECS). In 27 TPN patients, body composition 28 days after BMT, expressed as a percentage of baseline, was body cell mass, 100%, extracellular fluid, 108%, FAT + ECS, 108%, and in 30 enteral feeding program patients, was body cell mass, 93%, extracellular fluid, 104%, and FAT + ECS, 94%. Only the difference in FAT + ECS was statistically significant (p less than 0.01). Compared to the enteral feeding program, TPN was associated with more days of diuretic use, more frequent hyperglycemia, and more frequent catheter removal (prompted by catheter-related complications), but less frequent hypomagnesemia. There were no significant differences in the rate of hematopoietic recovery, length of hospitalization, or survival, but nutrition-related costs were 2.3 times greater in the TPN group. We conclude that TPN is not clearly superior to individualized enteral feeding and recommend that TPN be reserved for BMT patients who demonstrate intolerance to enteral feeding.

The results of therapy with carbenicillin plus trimethoprim-sulfamethoxazole (C-T/S) were compared to those obtained with carbenicillin plus gentamicin (C-G) in a prospective double-blind study of empiric antibiotic therapy in granulocytopenic patients. Patients were stratified into two groups: favorable-prognosis, group 1 (carcinoma, lymphoma, multiple myeloma), or unfavorable-prognosis, group 2 (acute leukemia, bone marrow transplantation), based on anticipated duration of granulocytopenia. Over-all, empiric antibiotic trials were more often successful (P = 0.004) in group 1 (55 of 62 patients or 89 per cent) than in group 2 (42 of 64 patients, 66 per cent)mwithin group 1, there was a favorable outcome in 30 of 32 (94 per cent) C-T/S trials and in 25 of 30 (83 per cent) C-G trials (P = 0.25); within group 2, there was a favorable outcome in 23 of 30 (77 per cent) C-T/S trials and in 19 of 34 (56 per cent) C-G trials (P = 0.14), Combined results in both groups indicated a higher proportion of favorable outcome in C-T/S trials (53 of 62, 85 per cent) than in C-G trials (44 of 64, 69 per cent). Further analysis (Manetl-Naenszel test) showed the over-all difference in outcome to be significant (P = 0.049), but the general applicability of this result may be limited by the rather low incidence of gram-negative bacterial infections in this study. There was no difference between the treatment regimens in antibiotic toxicity, and serious superinfection occurred only in group 2 patients (21 per cent of trials), equally divided between treatment arms. Initial protocol dosing achieved target plasma levels of trimethoprim (3 to 8 micrograms/ml) or gentamicin (4 to 10 micrograms/ml) in 57 of 68 (84 per cent) C-T/S trials compared to 21 of 60 (35 per cent) C-G trials.

In a group of cancer patients selected to exclude common causes of abnormal lipid absorption, we have examined this function using a breath test. Abnormal breath tests of fatty acid absorption (FABT) are found in most cancer patients, as has been previously claimed. These tests are abnormal in both quality (delayed peak in nine of ten patients, and quantity (reduced maximum peak in five of ten patients) of fatty acid absorption. In many patients abnormal FABT is not due to chemotherapy. Our preliminary results indicate no definite malabsorption mechanism but more stringent tests of absorption need to be applied. Malnutrition is common in cancer patients, even in those with little or no weight loss, and some of the malnutrition may be related to abnormal lipid absorption or to other disturbed aspects of lipid metabolism.