Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Atopic allergy to chloramine-T and the demonstration of specific IgE antibodies by the radioallergosorbent test

Summary Chloramine-T is a small molecular oxidizing agent that has been widely used as a disinfectant since the beginning of this century. It is generally used in a 5% solution but it is also supplied in powder form. Sporadic case reports of immediate-type sensitization to this agent associated with symptoms of asthma, rhinitis and urticaria have appeared during recent decades. In one of the reports, specific IgE antibodies in sera of four patients who developed asthmatic symptoms after exposure to chloramine-T were demonstrated using a radioimmuno-assay. Three cases of bronchial asthma in workers who had handled chloramine-T powder are described in the present report. Positive skin-prick test reactions to chloramine-T were observed and specific IgE antibodies to human serum albumin treated with chloramine-T were detected using the classic radioallergosorbent (RAST) technique in all three patients.     

Postoperative Energy Intake in Patients after Colorectal Cancer Surgery

In a prospective noninterventional study of 75 consecutive patients (mean age 71 ± 12 years) undergoing surgery for colorectal cancer, standard postoperative energy intake was evaluated. Seventeen patients expended 40%–60% of estimated basal energy during hospitalization, 33 patients 60%–80%, 22 patients 80%–100% and three patients 100%–125%. Weight loss was observed in 67 patients (mean loss 4.7 ± 4.4%) during hospitalization. Men had a significantly higher mean total calorie deficit (p < 0.001), and mean weight loss percentage (p < 0.01), compared to women. Preoperative nutritional status, nutrition-associated complications and length of hospital stay did not change the nutritional support and intake. Correlation analyses resulted in significant associations between gender and total calorie deficit (r_s = 0.41, p < 0.01), postoperative weight loss and total calorie deficit (r_s = ?0.32, p<0.01), and between postoperative weight loss and length of stay (r_s = 0.27, p < 0.05). We concluded that the patients' energy intake was insufficient compared to estimated basal energy expenditure. These results suggest a need for individualized nutritional care, based on each patient's energy needs and on registration of daily calorie intake, all with the aim of increasing energy intake postoperatively in standard hospital care.     

Barrier properties of vernix caseosa

Experiments are described which show that vernix caseosa has a mechanical barrier effect if it is deposited in an unbroken layer. Specific antibacterial properties were not detected in vernix. It is suggested that vernix is best left on a newborn infant because of its mechanical obstruction to bacterial passage.