Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation.

The influence of busulfan (BU) plasma concentration on outcome of transplantation from HLA identical family members for the treatment of chronic myelogenous leukemia (CML) was examined in 45 patients transplanted in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). All patients received the same regimen of BU, 16 mg/kg orally and cyclophosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (C(SS)BU) during the dosing interval were measured for each patient. The mean C(SS)BU was 917 ng/mL (range, 642 to 1,749; median, 917; standard deviation, 213). Of patients with C(SS)BU below the median, seven (five of 18 in CP and two of four in AP) developed persistent cytogenetic relapse and three of these patients died. There were no relapses in patients with C(SS)BU above the median. The difference in the cumulative incidence of relapse between the two groups was statistically significant (P = .0003). C(SS)BU was the only statistically significant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with C(SS)BU above and below the median (P = .33). There was no statistically significant association of C(SS)BU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 and 0.64 was only 0.24, similarly C(SS)BU above the median was not associated with an increased risk of severe regimen-related toxicity. We conclude that low BU plasma levels are associated with an increased risk of relapse.

Acute dietary tryptophan depletion: effects on schizophrenic positive and negative symptoms.

Because brain serotonin levels depend directly on the amounts of exogenous tryptophan (TRP) available for its synthesis, amounts of TRP in the diet may be manipulated to alter the corresponding levels of serotonin. This technique has been used for probing the role of serotonin in mediating various forms of pyschopathology. In this study, 16 patients meeting DSM III-R criteria for schizophrenia (n = 14) or schizoaffective disorder (n = 2) were assessed for the effects of acute dietary TRP depletion under controlled conditions. The hypothesis was that lowering of serotonin would result in a diminution of 'positive' and/or 'negative' symptoms of psychotic disorders. No clinically or statistically significant improvement compared to baseline occurred when TRP depletion was imposed. Indeed, there was a statistically significant deterioration on measures of negative symptoms. The results are discussed in the context of the methodological issues.

High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells.

Consecutive patients with non-Hodgkin's lymphoma (NHL, n = 133) or Hodgkin's disease (HD, n = 20) were treated with 12.0 Gy of fractionated total body irradiation, etoposide 60 mg/kg, and CY 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Seventy-nine patients received purged (n = 62) or unpurged BM (n = 17), and 74 received unpurged PBSCs alone (n = 56) or with BM (n = 18). The median day for achieving a sustained granulocyte count of 0.5 x 10(9)/I was 14 range (7-66) for BM recipients and 10 (7-30) for PBSC +/- BM recipients (P = 0.03). A platelet count of 20 x 10(9)/I was achieved at a median of day 24 (6-145) in BM recipients and day 11 (range, 7-56) in PBSC +/- BM recipients (P = 0.007). The median number of platelet units transfused was 86 (0-1432) for BM recipients and 30 (6-786) for PBSC +/- BM recipients (P = 0.001). The median number of hospital days was 36 (10-88) for BM recipients and 27 (14-76) for PBSC +/- BM recipients (P = 0.0001). The unadjusted Kaplan-Meier (KM) estimates of survival, event-free survival (EFS) and relapse at 2 years were 0.57, 0.45 and 0.43 for patients receiving BM and 0.55, 0.36 and 0.59 for patients receiving PBSC +/- BM. After adjusting for confounding variables, the estimated relative risk (RR) of death from any cause was 0.92 (P = 0.75), of relapse was 1.25 (P = 0.39), of non-relapse mortality was 0.71 (P = 0.42) and of mortality and/or relapse was 1.17 (P = 0.48) for patients receiving PBSC +/- BM as compared to BM. For 46 patients with NHL receiving unpurged PBSC alone, the unadjusted KM estimate of relapse was 0.61 compared with 0.48 for 52 comparable patients receiving purged BM, while the RR for relapse for patients receiving unpurged PBSCs was 1.37 (P = 0.33) after adjusting for other significant covariates. These data confirm previous observations that patients who receive PBSC +/- BM have faster engraftment, fewer transfusions and shorter hospital stays than patients who receive only BM. There were no statistically significant differences between the two groups in survival, relapse, death from causes other than relapse and event-free survival.

Relevance of marrow fibrosis in bone marrow transplantation: a retrospective analysis of engraftment.

A retrospective study compared posttransplant engraftment parameters in 203 patients with myelofibrosis (MF) with those in a population of 203 matched controls without MF. There were no significant differences between these groups in the proportions of patients who died without achieving engraftment and in the disease-free survival distributions. Furthermore, comparisons between the two groups of patients reaching the respective endpoints showed no differences in the time distributions for reaching 0.5 or 1.0 x 10(9)/L granulocytes, but the time to platelet transfusion independence was 3 days longer in patients with MF. In further analysis, results for 33 patients with severe MF were compared with those of their respective controls. The proportions of patients with severe MF who died without reaching these engraftment endpoints and the disease-free survival distributions in the two groups were similar. Among patients who reached the respective engraftment endpoints, there was no statistically significant difference in the pace of granulocyte recovery. In patients with severe MF, there was a 7-day delay in the time to reach platelet transfusion independence and a 2-day delay in the time to reach red blood cell independence, but the differences were not statistically significant. The present results do not substantiate concerns raised by earlier studies. MF may delay the time to reach platelet independence by approximately 3 days and may increase platelet transfusion requirements, but no other perturbation of hematopoietic reconstitution was apparent.

Bulimia nervosa in overweight individuals.

Patients who have bulimia nervosa and are overweight have received little attention in the medical literature. The authors identified 25 patients who weighed greater than or equal to 130% of their ideal body weight out of a series of 591 patients with bulimia nervosa. This subgroup was contrasted with a sample of 25 patients with bulimia nervosa who were 90% to 110% of their ideal body weight. Members of the overweight bulimia nervosa group were binge-eating and vomiting less frequently than the comparison group but were more likely to be abusing laxatives, and to report a history of self-injurious behavior and suicide attempt(s). Both groups reported frequent binge-eating.

Bulimia nervosa with and without a history of anorexia nervosa.

This study compared two subgroups of women of normal weight with bulimia nervosa: those with a history of anorexia nervosa and those without such a history. Those with a history of anorexia nervosa indicated a desired body weight significantly lower than those without the history. Those with a history of anorexia nervosa were more likely to abuse laxatives and less likely to self-induce vomiting. Both groups reported feeling fat and worrying a great deal about weight and shape issues.

Bulimia nervosa with and without a history of overweight.

In a review of the records of 454 patients with bulimia nervosa, 87 (19.2%) reported having a history of weight greater than 130% ideal body weight, although they were normal weight at evaluation. As contrasted to patients who had no history of having been overweight, this group of patients had a later onset of bulimia symptoms, weighed more and were more likely to be very dissatisfied with their current weight and to fear becoming overweight. The eating problems were similar in both groups.