Evaluation of the 3D BacT/ALERT automated culture system for the detection of microbial contamination of platelet concentrates.

Bacterial transmission remains the major component of morbidity and mortality associated with transfusion-transmitted infections. Platelet concentrates are the most common cause of bacterial transmission. The BacT/ALERT 3D automated blood culture system has the potential to screen platelet concentrates for the presence of bacteria. Evaluation of this system was performed by spiking day 2 apheresis platelet units with individual bacterial isolates at final concentrations of 10 and 100 colony-forming units (cfu) mL-1. Fifteen organisms were used which had been cited in platelet transmission and monitoring studies. BacT/ALERT times to detection were compared with thioglycollate broth cultures, and the performance of five types of BacT/ALERT culture bottles was evaluated. Sampling was performed immediately after the inoculation of the units, and 10 replicates were performed per organism concentration for each of the five types of BacT/ALERT bottles. The mean times for the detection of these 15 organisms by BacT/ALERT, with the exception of Propionibacterium acnes, ranged from 9.1 to 48.1 h (all 10 replicates were positive). In comparison, the time range found using thioglycollate was 12.0-32.3 h (all 10 replicates were positive). P. acnes' BacT/ALERT mean detection times ranged from 89.0 to 177.6 h compared with 75.6-86.4 h for the thioglycollate broth. BacT/ALERT, with the exception of P. acnes, which has dubious clinical significance, gave equivalent or shorter detection times when compared with the thioglycollate broth system. The BacT/ALERT system detected a range of organisms at levels of 10 and 100 cfu mL-1. This study validates the BacT/ALERT microbial detection system for screening platelets. Currently, the system is the only practically viable option available for routinely screening platelet concentrates to prevent bacterial transmission.

Evaluation of a new generation of culture bottle using an automated bacterial culture system for detecting nine common contaminating organisms found in platelet components.

BACKGROUND: An automated bacterial culture system (BacT/ALERT 3D, bioMérieux) has been previously validated with a variety of bacteria in platelets. The recovery of bacteria in platelets using a new generation of culture bottles that do not require venting and that use a liquid emulsion sensor was studied. STUDY DESIGN AND METHODS: Bacillus cereus, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus viridans, and Propionibacterium acnes isolates were inoculated into Day 2 platelets to concentrations of 10 and 100 CFU per mL. Samples were then studied with current and new aerobic, anaerobic, and pediatric bottles. RESULTS: All organisms, except P. acnes, were detected in a mean time of 9.2 to 20.4 (10 CFU/mL) or 8.7 to 18.6 (100 CFU/mL) hours. P. acnes was detected in a mean time of 69.2 (10 CFU/mL) or 66.0 (100 CFU/mL) hours. The 10-fold increase in inoculum was associated with a mean 9.2 percent difference in detection time. The aerobic, anaerobic, and pediatric bottles had a mean difference in detection time (hours) between the current and new bottles of 0.10 (p=0.61), 0.4 (p=0.38), and 1.0 (p < 0.001), respectively. CONCLUSION: No difference in detection time between the current and new aerobic and anaerobic bottles was demonstrated. The new pediatric bottles had a small but significant delay in detection.

Evaluation of an automated culture system for detecting bacterial contamination of platelets: an analysis with 15 contaminating organisms.

BACKGROUND: Approximately 1 in 2000 platelet components are bacterially contaminated. The time to detection of 15 seeded organisms in platelets recovered from an automated culture system was studied. STUDY DESIGN AND METHODS: Isolates of Bacillus cereus, Bacillus subtilis, Candida albicans, Clostridium perfringens, Corynebacterium species, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Propionibacterium acnes, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, Streptococcus pyogenes, and Streptococcus viridans were inoculated into Day 2 apheresis platelet components to obtain a final concentration of approximately 10 and 100 CFU per mL (2 units/organism). Each bag was sampled 10 times (20 mL/sample). Four mL of each sample was inoculated into standard aerobic and anaerobic bottles and into aerobic and anaerobic bottles containing charcoal; 2 mL was inoculated into pediatric aerobic bottles (so as to maintain a 1:10 ratio of sample to media) and 1 mL into thioglycollate broth. RESULTS: With the exception of P. acnes, all organisms were detected in a mean of 9.2 to 25.6 hours. A range of 10 serial dilutions in inoculating concentrations was associated with an overall 10.1-percent difference in detection time. A mean of 74.4 and 86.2 hours (100 and 10 CFU/mL inocula, respectively) was required for the detection of P. acnes in anaerobic bottles. CONCLUSION: Bacteria thought to be clinically significant platelet contaminants can be detected in 9.2 to 25.6 hours when the starting concentration is approximately 10 to 100 CFU per mL. P. acnes required considerably longer incubation times for detection (in either aerobic or anaerobic bottles). However, P. acnes is of questionable clinical significance. Such a detection system could be used in either a blood collection center or a transfusion service to screen platelet concentrates for bacterial contamination. Such testing (with sterile sampling performed so as to maintain a closed-bag system) would be expected to save lives and might allow an extension of platelet storage.

Alternating cycles of combination chemotherapy for patients with recurrent Hodgkin's disease following radiotherapy. A prospectively randomized study by the Cancer and Leukemia Group B.

A randomized clinical trial of combination chemotherapy for patients who relapsed following primary radiation therapy for Hodgkin's disease was conducted from 1975 to 1981 by the Cancer and Leukemia Group B (CALGB). One hundred thirteen patients were prospectively randomized to receive 12 cycles of either CVPP (CCNU, vinblastine, procarbazine, and prednisone), ABOS (bleomycin, vincristine [Oncovin; Lilly, Indianapolis], doxorubicin [Adriamycin, Adria Laboratories, Columbus, Ohio], and streptozotocin), or alternating cycles of CVPP and ABOS. The median length of observation for patients in this report is 4 years. Toxicities of the three treatment programs were primarily hematologic. Frequencies of complete response were 72% for CVPP, 70% for ABOS, and 82% for CVPP/ABOS (P = .37). Females and patients who had nodular sclerosing disease at initial diagnosis had significantly higher complete response rates. The 5-year disease-free survival for the complete responders was 55%; the 5-year overall survival was 60%. There were no significant differences among the treatments on disease-free survival (P = .78) or overall survival (P = .18). Age under 40 years was the only significant positive prognostic factor for disease-free survival (P = .095) and overall survival (P = .003). This study demonstrates no statistically significant advantage for alternating cycles of combination chemotherapy in affecting complete response frequency, disease-free survival, or overall survival as compared with therapy with CVPP or ABOS alone. However, the power to detect differences in these outcome parameters is somewhat limited by the sample sizes.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous low-dose radiation and low-dose chemotherapy in the treatment of advanced Hodgkin's disease.

Simultaneous combination chemotherapy (CT) (BCNU 40 mg/m2, procarbazine 50 mg/m2, prednisone 40 mg/m2, and vincristine 1.4 mg/m2) with low-dose radiation therapy [(RT) 2000 rad] delivered to all areas of tumor involvement aside from the bone marrow was given to 28 patients with advanced Hodgkin's disease. Upon completion of RT and CT, the BCNU and procarbazine was increased by 100% until a total of six cycles of CT (with and without RT) were given. Eleven patients had received prior CT and had not achieved complete remission (CR) or had relapse from CT-induced CR within 1 year. Seventeen others had not had prior CT (7 had prior RT). Among the previously treated patients, one patient died in autopsy-proven CR during treatment. The other 10 patients achieved CR. Eight had relapsed at 4-36 months (median time to relapse, 6 months). Five patients died of Hodgkin's disease, three others died of status asthmaticus and pneumonia, radiation pneumonitis, and acute nonlymphocytic leukemia, respectively. Three patients are still alive (2 in continuous CR) at 28, 89, and 90 months. Among the previously untreated patients, four died during treatment, one of acute myocardial infarction, two of liver failure, and one of radiation pneumonitis. Twelve of the other 13 patients achieved CR. One of the CR died of pneumonia and sepsis 3 months after completion of treatment; two other patients relapsed at 10 and 15 months. Nine remain in continuous CR at 42-89 months of follow-up, (median follow-up, 81 months). Of 107 tumor areas treated with RT, in-field relapse occurred in two areas (1.9%). Hematologic tolerance to this treatment was good in both groups of patients. Radiation pneumonitis occurred in 50% of the patients whose lungs were irradiated, and it was fatal in two. By design or for other reasons, the median and mean doses of BCNU and procarbazine given to previously treated patients were 62% and 65.2%, respectively. In untreated patients, the median and mean doses of these two agents were 66.6% and 61.4%, respectively. There were no differences in dosage of these two agents between patients who remain alive in CR and those who relapsed and died. The potential of similar programs of radiation and chemotherapy is discussed.

Staging laparotomy and splenectomy in early Hodgkin's disease. No therapeutic benefit.

In a prospective randomized study of treatment for early-stage Hodgkin's disease presenting above the diaphragm, 76 patients had staging by laparotomy (Group I) and 28 had staging by closed techniques (Group II). Treatment consisted of involved-field radiotherapy alone (44 patients), involved-field radiotherapy followed by chemotherapy (38 patients), total nodal radiotherapy alone (15 patients), or total nodal radiotherapy followed by chemotherapy (seven patients). On presentation, both groups had similar clinical features and similar treatment distribution. With similar follow-up (87 months), no significant differences in remission or survival were observed between Groups I and II: remission 59 versus 68 percent; survival 74 versus 92 percent; p value 0.27 and 0.09, respectively. Multiple areas of relapse were more frequently observed in Group I (11 of 32 had relapse) as compared with Group II (none of nine had relapse, p less than 0.082). In Group I, relapse in the abdomen was observed as an isolated event or as part of disseminated relapse in 12 percent of patients compared with 3 percent (one patient) in Group II with abdominal relapse alone. Seven patients in Group I and two patients in Group II died with Hodgkin's disease. Six other patients in Group I died with complete remission of non-Hodgkin's lymphoma (one patient), leukoencephalopathy (one patient), sepsis during chemotherapy (two patients), myocardial infarction (one patient), and cerebrovascular accident (one patient). Three other patients in this group had other secondary malignancies successfully controlled (histiocytic lymphoma, squamous cell carcinoma of the cervix, and malignant schwannoma). No second primary lesions or death with complete remission were observed in Group II. Staging laparotomy with splenectomy in early-stage Hodgkin's disease did not improve the duration of remission or survival or decrease the number of abdominal relapses compared with closed staging.

Large mediastinal mass in Hodgkin's disease. Results of two treatment modalities.

Sixty-eight untreated patients with Hodgkin's disease (HD), stages I-III, presenting with a large mediastinal mass were treated as follows: patients with "good-risk HD" (lymphocyte predominant or nodular sclerosis and no "B" symptoms) stages I and II were treated by randomization with involved field radiotherapy (IF RT) or IF RT plus six cycles of combination chemotherapy (CT). Those with "poor-risk HD" (presence of B symptoms or with other histologic types) stages I and II and all patients with stage III were treated by randomization with total nodal radiation (TNR) or TNR + CT. Complete remission (CR) was achieved in 66/68 patients (97%) with the initial RT. A significantly longer duration of remission (p = 0.001), but not of survival (p = 0.08) was observed in patients treated with RT + CT compared to RT alone. Significantly longer duration of remission (p = 0.01), but not of survival, was observed in patients with good-risk stages I-II treated with RT + CT. In this category, remission and survival was better with RT + CT than with RT alone in stage III, but these differences were not statistically significant. In poor-risk patients stages I-II, a trend for longer remission and survival (not significant) was observed in patients treated with RT + CT; in stage III, both treatment modalities gave similar poor results. Both treatment modalities were well tolerated by most patients. One patients died with radiation pneumonitis shortly after completion of TNR. One patient developed a malignant schwannoma after treatment with IF RT, and another one developed acute nonlymphocytic leukemia after TNR + CT. Decrease in the transverse diameter of the heart without overt manifestations of cardiac disease was observed in 59% of the patients evaluated for this parameter.

Effect of methanol extraction residue of Bacillus Calmette-Guerin in advanced Hodgkin's disease.

One-hundred-ninety-six patients with Stage III and IV Hodgkin's disease were prospectively randomized to receive either treatment with the methanol extraction residue of Bacillus Calmette-Guerin (MER/BCG) or no immunotherapy. Prior to the MER/BCG randomization, patients received six courses of induction and two years of maintenance chemotherapy so that a group with a presumptively low tumor burden could be established. Only patients achieving a complete remission were evaluated. During the first two years of immunotherapy, the MER/BCG group had a relapse frequency twice that of controls. The overall crude relapse frequency and disease-free survival were similar between the two treatment groups. The MER/BCG dose schedule used in this study was associated with a high frequency of unacceptable toxicity. Ulcerations of greater than 1 cm occurred in one-third of the patients with associated pain, fever, and occasional lymphadenopathy. A high degree of patient noncompliance (36%) was observed. Age (P = 0.002), prior radiotherapy (P = 0.032), and chemotherapy (P = 0.044) were prognostic factors found to significantly influence remission duration. These factors were balanced between patients treated with immunotherapy and those who were not. MER/BCG therapy did not significantly delay or prevent relapse.

Chemotherapy and combined modality therapy for Hodgkin's disease: a progress report on Cancer and Leukemia Group B studies.

Between 1974 and 1977, the Cancer and Leukemia Group B (CALGB) initiated four studies which address current major questions in the therapy for Hodgkin's disease. The efficacy of chemotherapy alone as compared with combined modality therapy in patients with poor-prognostic stages I and II is evaluated in CALGB 7751. Currently, both therapies produce very high complete remission rates in asymptomatic patients; the remission rate is better with combined modality therapy in symptomatic patients. Single and combined modality therapies are compared for stage III patients in CALGB 7451. Complete remission rates have been similar, but relapse-free survival is superior for patients treated with local nodal radiotherapy followed by chemotherapy (P = 0.04). In particular, stage IIIA patients with nodular sclerosis seem to benefit from the inclusion of radiotherapy in their initial treatment. In CALGB 7551, the efficacy of chemotherapy alone versus chemotherapy plus radiotherapy to areas of bulky disease is under study in patients with stages IIIB and IV. Currently, a relapse rate of less than 10% has been seen among sites irradiated, and survival is best for patients treated with radiotherapy bracketed by chemotherapy. Finally, the role of two alternating non-cross-resistant combination chemotherapy programs is being studied in CALGB 7552. Relapse-free and overall survival is better with the doxorubicin-containing regimen than with either the alternating or alternate chemotherapy program. At present, the median followup for each of these studies is less than 5 years. Further observation is required to answer the critical questions relating to prolonged disease-free survival and cure.

The influence of histologic type on the incidence and duration of response in non-Hodgkin's lymphoma.

A group of 227 cases of non-Hodgkin's lymphoma included seven favorable and four unfavorable histologic classes with collective median survival times of 83 and 16 months, respectively. The favorable group included three follicular subgroups (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt's noncleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse subgroups (plasmacytoid lymphocytic, mixed, and small and large noncleaved). There were significant differences in collective median survivals between patients in Stage I--II and those in Stage III--IV in both the favorable group (not reached, NR versus 62 months, P less than 0.001) and the unfavorable group (57 months versus 12 months, P less than 0.01). The incidence of complete response to primary treatment was higher in the favorable than in the unfavorable group (75% versus 56%, P = 0.002) and in those with limited as compared with advanced disease. Complete responders in both prognostic groups had longer survival times than did partial or minimal responders. A significant difference in median complete remission duration was found between responders in Stage I--II versus Stages III-IV in the favorable group (not reached versus 40 months, P = 0.001) but not in the unfavorable one (56 months versus 22 months, P greater than 0.05). The absence of relapses after 41 months among complete responders in the favorable but not in the unfavorable group suggests a potential for cure in a proportion of cases from the former group. The incidence of complete response was lower and median remission duration was shorter after secondary as compared with primary treatment. The results of this study confirm the prognostic value of the Lukes and Collins classification system and the importance of initial staging and of achieving a complete response to primary treatment in both the favorable and unfavorable lymphomas.

Combinations of methotrexate (COP or CHOP) in the treatment of previously untreated and treated lymphomas.

A regimen consisting of two courses of methotrexate (MTX) with leucovorin rescue followed 1 week later by cyclophosphamide, vincristine, and prednisone (MTX-COP) was studied in ten patients with disseminated diffuse non-Hodgkin's lymphoma who had had no prior chemotherapy. A similar regimen with the addition of doxorubicin (MTX-CHOP) was used for patients who had had previous chemotherapy: 11 with diffuse non-Hodgkin's lymphoma and two with Hodgkin's disease. The response rate to initial MTX administration was 55%, and the clinical onset of effect was usually observed within 48 hours. Responses were observed in previously treated and untreated patients. The remission rate was 100% with both regimens. There were seven complete remissions with MTX-COP and six with MTX-CHOP. The median durations of remission were 23 and 13 months, respectively; median survival was not reached in either group. MTX was well-tolerated by both groups of patients without serious toxic effects. Overall, significantly more hematologic toxicity was observed in previously treated patients; however, no life-threatening toxic effects were observed in either group. The incorporation of MTX and other antimetabolites into schedules of chemotherapy for previously treated and untreated patients with non-Hodgkin's lymphoma is well tolerated and deserved further exploration.

The influence of histologic type on survival in non-Hodgkin's lymphoma.

Histologic groups in 231 cases of malignant lymphoma were correlated with survival data at 100 months from the time of initiation of the study. Patients in the first two decades of life fared comparably with adults, but those over 60 years of age showed a poorer survival trend. Seven favorable and four unfavorable histopathologic groups were found with collective median survivals of 83 and 16 months, respectively (P less than 0.001). The favorable group included three follicular classes (cleaved, mixed, and large noncleaved) and four diffuse classes (small lymphocytic, cleaved, Burkitt non-cleaved, and convoluted lymphocytic). The unfavorable group consisted of four diffuse classes (plasmacytoid lymphocytic, mixed, and small and large non-cleaved). The group of 88 patients with follicular lymphoma had significantly longer overall survival than the group of 143 patients with diffuse lymphomas. No significant differences in survival were noted within three grades of follicular involvement. The favorable and unfavorable diffuse lymphomas had collective median survivals of 82 and 16 months, respectively (P = 0.01). Significant survival differences due to pattern of nodal involvement (P = 0.01) were found in patients with mixed and large non-cleaved cell lymphomas, but not in those with cleaved cell lymphomas. The group with large cleaved cells had significantly longer survival than those with large non-cleaved cells. Patients with mixed and large non-cleaved cell lymphomas of the same nodal pattern had similar survival data.

MER immunotherapy and combination chemotherapy for advanced, recurrent Hodgkin's disease. Cancer and Leukemia Group B study.

The effects of chemotherapy and chemoimmunotherapy in previously treated advanced Hodgkin's disease were evaluated in a randomized study of 167 patients by CALGB. Combination chemotherapy consisted of treatment with one of three regimens with further randomization of MER (methanol extraction residue BCG) immunotherapy or no MER during chemotherapy. CVPP (CCNU, vinblastine, procarbazine, prednisone) was compared to a new combination, BAVS (bleomycin, Adriamycin, vincristine, streptozotocin), and to a third regimen consisting of alternating cycles of CVPP and BAVS. At the current analysis there is no significant difference in complete responses among the chemotherapy regimens. MER did not improve complete response frequency and was associated with significantly poorer survival for patients previously treated with chemotherapy. There was also no benefit with MER for patients with at least one pretreatment positive skin test. Because of the documented lack of therapeutic benefit and the morbidity of painful ulcers, MER treatment has been discontinued.

A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease.

Five hundred and sixty-six patients with either Stage III or IV Hodgkin's disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbazine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.

Gastrointestinal involvement in non-Hodgkin's lymphoma.

A total of 813 patients admitted to Roswell Park Memorial Institute from 1963--1972 with non Hodgkin's lymphoma (NHL) were reviewed for gastrointestinal (GI) involvement. Primary involvement was found in 71 and secondary involvement in 31 patients. Occult GI involvement was detected in 46% of the autopsy cases. The median survival time after the diagnosis of secondary GI involvement was nine months. The occurrence of primary GI-NHL was: 33 in the stomach, 18 in the small intestine, 14 in the ileocecal area including appendix, and 6 in the large intestine. Retrospective staging according to the Ann Arbor staging classification showed 24 to have presented as Stage I, 30 as Stage II, 4 as Stage III, and 13 as Stage IV. The primary diagnostic and therapeutic approach was operative, except in 2 patients with rectal lymphoma. Resection of the principally involved site was carried out in 42 patients. The remainder had palliative procedures or biopsy examinations only. Postoperative radiation therapy was given to 38 patients. Prognostically important features for primary GI-NHL were: stage; histologic type; site of the primary disease; and whether or not radiotherapy was administered. The age of the patient, size or degree of local extension, and type of operative procedure were prognostically of no importance. The results of this study would indicate that in Stage I and II primary GI-NHL, elective resection is not necessary prior to radiation therapy and that resection alone cannot be considered adequate treatment. A modified staging classification is proposed.

Appraisal of aspiration cytology in management of Hodgkin's disease.

The value of aspiration cytology in the management of Hodgkin's disease is shown in this study of 228 patients and 403 aspirations; 385 from lymph nodes and 18 from extranodal masses. In all patients the initial diagnosis was established on surgical biopsy. Aspirates were helpful in staging, defining extension of unusual radiation fields, and in recognizing residual disease and relapses after therapy. Adequate material was obtained in 80% of aspirations. The diagnosis of Hodgkin's disease could not be established in the adequate cytologic sample in 9.9% of cases. In 5.5%, the diagnosis was that of benign reactive hyperplasia and in 4.4%, non-Hodgkin's lymphoma. Unsatisfactory material was usually obtained from nodes less than 1 cm in diameter or from residual lesions following radiation or chemotherapy. Only 14 of 93 such lesions proved to have active disease during follow up. There were no significant complications. Characteristics of the varied aspects of aspirated tumor cells found in Hodgkin's disease are described.

Polymorphonuclear neutrophil function in malignant lymphomas and effects of splenectomy.

Granulocyte (PMN) directional locomotion (migration) in vitro and in vivo, resting nitroblue tetrazolium (NBT)-reduction and adherence to nylon wool of polymorphonuclear neutrophils (PMN) were assayed in 7 patients with Hodgkin's disease (HD) and in 11 patients with non-Hodgkin's lymphoma (NHL) prior to therapy. In most patients with HD, NBT-reduction was increased and in all directional locomotion was markedly decreased both in vitro and in vivo. In addition to being depressed, accumulation of PMN into skin chambers in patients with HD correlated with the peripheral blood count (r = 0.95). In vitro directional migration of PMN in NHL was depressed in half the patients, but increased in the in vivo assay. After splenectomy, PMN-adherence tended to increase and NBT-reduction to decrease. These findings are compatible with a constant cellular defect of PMN in HD, whereas in NHL abnormal PMN function is more likely mediated by extracellular factors. Abnormal PMN function may correlate with clinical susceptibility to infection in malignant lymphomas.

Oral amphotericin for candidiasis in patients with hematologic neoplasms. An autopsy study.

Autopsy examinations were conducted in 72 patients with hematologic malignant neoplasms who received antibacterial therapy before their deaths. These patients were participants in a large double-blind study designed to assess the efficacy of oral amphotericin B in decreasing the incidence of candidal infection. The patients received either 50 mg of amphotericin B orally four times a day, or they received a matching placebo. Eight of 33 patients (24%) who had received placebo and two of 39 (5%) who had received amphotericin had histopathologic evidence of disseminated candidiasis. We conclude that in these patients with hematologic malignant neoplasms who received antibiotics within two weeks of death, the concomitant oral administration of amphotericin was effective in decreasing the incidence of systemic candidal infections, indicating that the gastrointestinal tract serves as a portal of entry for Candida albicans.

Long term follow-up of combination chemotherapy-radiotherapy of stage III Hodgkin's disease: a Cancer and Acute Leukemia Group B study.

The Cancer and Acute Leukemia Group B studied the effect of combination chemotherapy-radiotherapy on Stage III Hodgkin's disease. Chemotherapy consisting of 4 weekly doses of vinblastine and one dose of mechlorethamine hydrochloride was followed by no therapy (CT), radiation to involved fields (CTIF) or total nodal radiation (CTTN). Two other treatment arms included total nodal radiation alone (TN) or total nodal radiation followed by chemotherapy (TNCT). Maximum follow-up is ten years. Complete remission percentages were 36 (8/22) for CT, 71 (17/24) for CTIF, 100 (21/21) for CTTN, 86 (19/22) for TNCT and 89 (16/18) for TN. Disease-free survival in patients receiving radiation +/- chemotherapy is 23% (19/73) at 5 years, but even after 9 years relapses were observed in two patients. Forty-one percent of all patients are alive and 32% have survived for five years. Ability to administer adequate therapy was the main determined for response duration and survival. Factors influencing the outcome of the disease include histology, age, splenectomy, initial white blood cell count and performance status, whereas symptomatology, initial absolute lymphocyte count and sex played no role on survival.