Meta-analysis of cardiovascular toxicity risks in cancer patients on selected targeted agents.

PURPOSE: The purpose was to estimate the risk and severity of cardiovascular toxicities associated with selected targeted agents. METHODS: We searched English-language literature for randomized clinical trials published between January 1, 2000 and November 30, 2013 of targeted cancer therapy drugs approved by the FDA by November 2010. One hundred ten studies were eligible. Using meta-analytic methods, we calculated the relative risks of several cardiovascular toxicities [congestive heart failure (CHF), decreased left ventricular ejection fraction (DLVEF), myocardial infarction (MI), arrhythmia, and hypertension (HTN)], adjusting for sample size using the inverse-variance technique. For each targeted agent and side effect, we calculated the number needed to harm. RESULTS: Regarding CHF, trastuzumab showed significantly greater risk of all-grade and high-grade CHF. There was significant increased risk of all-grade DLVEF with sorafenib, sunitinib, and trastuzumab and high-grade DLVEF with bevacizumab and trastuzumab. Sorafenib was associated with significant increased all-grade risk of MI based on one study. None was associated with high-grade risk of MI or increased risk of arrhythmia. Bevacizumab, sorafenib, and sunitinib had significant increased risk of all-grade and high-grade HTN. CONCLUSIONS: Several of the targeted agents were significantly associated with increased risk of specific cardiovascular toxicities, CHF, DLVEF, and HTN. Several had significant increased risk for high-grade cardiovascular toxicities (CHF, DLVEF, and HTN). Patients receiving such therapy should be closely monitored for these toxicities and early and aggressive treatment should occur. However, clinical experience has demonstrated that some of these toxicities may be reversible and due to secondary effects.

Dental Caries Postradiotherapy in Head and Neck Cancer.

BACKGROUND: Treatment for head and neck cancer (HNC) such as radiotherapy (RT) can lead to numerous acute and chronic head and neck sequelae, including dental caries. The goal of the present study was to measure 2-y changes in dental caries after radiotherapy in patients with HNC and test risk factors for caries increment. METHODS: Cancer and dental disease characteristics, demographics, and oral health practices were documented before and 6, 12, 18, and 24 mo after the start of RT for 572 adult patients with HNC. Patients were eligible if they were age 18 y or older, diagnosed with HNC, and planned to receive RT for treatment of HNC. Caries prevalence was measured as decayed, missing, and filled surfaces (DMFS). The association between change in DMFS and risk factors was evaluated using linear mixed models. RESULTS: On average, DMFS increased from baseline to each follow-up visit: 6 mo, +1.11; 12 mo, +2.47; 18 mo, +3.43; and 24 mo, +4.29 (P < 0.0001). The increase in DMFS during follow-up was significantly smaller for the following patient characteristics: compliant with daily fluoride use (P = 0.0004) and daily oral hygiene (brushing twice daily and flossing daily; P = 0.015), dental insurance (P = 0.004), and greater than high school education (P = 0.001). DMFS change was not significantly associated with average or maximum RT dose to the parotids (P > 0.6) or salivary flow (P > 0.1). In the subset of patients who had salivary hypofunction at baseline (n = 164), lower salivary flow at follow-up visits was associated with increased DMFS. CONCLUSION: Increased caries is a complication soon after RT in HNC. Fluoride, oral hygiene, dental insurance, and education level had the strongest association with caries increment after radiotherapy to the head and neck region. Thus, intensive oral hygiene measures, including fluoride and greater accessibility of dental care, may contribute to reducing the caries burden after RT in HNC. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by clinicians when deciding how to minimize oral complications related to cancer therapy for patients with head and neck cancer. Identification of modifiable factors (e.g., oral hygiene and prescription fluoride compliance) associated with increased caries risk can minimize radiation caries burden.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life.

PURPOSE: This systematic review aimed to assess the literature for prevalence, severity, and impact on quality of life of salivary gland hypofunction and xerostomia induced by cancer therapies. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. Two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results and conclusions for each article. RESULTS: The inclusion criteria were met by 184 articles covering salivary gland hypofunction and xerostomia induced by conventional, 3D conformal radiotherapy or intensity-modulated radiotherapy in head and neck cancer patients, cancer chemotherapy, total body irradiation/hematopoietic stem cell transplantation, radioactive iodine treatment, and immunotherapy. CONCLUSIONS: Salivary gland hypofunction and xerostomia are induced by radiotherapy in the head and neck region depending on the cumulative radiation dose to the gland tissue. Treatment focus should be on optimized/new approaches to further reduce the dose to the parotids, and particularly submandibular and minor salivary glands, as these glands are major contributors to moistening of oral tissues. Other cancer treatments also induce salivary gland hypofunction, although to a lesser severity, and in the case of chemotherapy and immunotherapy, the adverse effect is temporary. Fields of sparse literature included pediatric cancer populations, cancer chemotherapy, radioactive iodine treatment, total body irradiation/hematopoietic stem cell transplantation, and immunotherapy.

A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact.

PURPOSE: This systematic review aimed to assess the literature for management strategies and economic impact of salivary gland hypofunction and xerostomia induced by cancer therapies and to determine the quality of evidence-based management recommendations. METHODS: The electronic databases of MEDLINE/PubMed and EMBASE were searched for articles published in English since the 1989 NIH Development Consensus Conference on the Oral Complications of Cancer Therapies until 2008 inclusive. For each article, two independent reviewers extracted information regarding study design, study population, interventions, outcome measures, results, and conclusions. RESULTS: Seventy-two interventional studies met the inclusion criteria. In addition, 49 intensity-modulated radiation therapy (IMRT) studies were included as a management strategy aiming for less salivary gland damage. Management guideline recommendations were drawn up for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. CONCLUSIONS: There is evidence that salivary gland hypofunction and xerostomia induced by cancer therapies can be prevented or symptoms be minimized to some degree, depending on the type of cancer treatment. Management guideline recommendations are provided for IMRT, amifostine, muscarinic agonist stimulation, oral mucosal lubricants, acupuncture, and submandibular gland transfer. Fields of sparse literature identified included effects of gustatory and masticatory stimulation, specific oral mucosal lubricant formulas, submandibular gland transfer, acupuncture, hyperbaric oxygen treatment, management strategies in pediatric cancer populations, and the economic consequences of salivary gland hypofunction and xerostomia.

Time to clinical response: an outcome of antibiotic therapy of febrile neutropenia with implications for quality and cost of care.

PURPOSE: To determine whether antibiotic regimens with similar rates of response differ significantly in the speed of response and to estimate the impact of this difference on the cost of febrile neutropenia. METHODS: The time point of clinical response was defined by comparing the sensitivity, specificity, and predictive values of alternative objective and subjective definitions. Data from 488 episodes of febrile neutropenia, treated with either of two commonly used antibiotics (coded A or B) during six clinical trials, were pooled to compare the median time to clinical response, days of antibiotic therapy and hospitalization, and estimated costs. RESULTS: Response rates were similar; however, the median time to clinical response was significantly shorter with A-based regimens (5 days) compared with B-based regimens (7 days; P =.003). After 72 hours of therapy, 33% of patients who received A but only 18% of those who received B had responded (P =.01). These differences resulted in fewer days of antibiotic therapy and hospitalization with A-based regimens (7 and 9 days) compared with B-based regimens (9 and 12 days, respectively; P <.04) and in significantly lower estimated median costs ($8,491 v $11,133 per episode; P =.03). Early discharge at the time of clinical response should reduce the median cost from $10,752 to $8,162 (P <.001). CONCLUSION: Despite virtually identical rates of response, time to clinical response and estimated cost of care varied significantly among regimens. An early discharge strategy based on our definition of the time point of clinical response may further reduce the cost of treating non-low-risk patients with febrile neutropenia.

Vascular access by physician assistants: evaluation of an implantable peripheral port system in cancer patients.

PURPOSE: To determine the ability of a physician assistant (PA) to insert, in an ambulatory setting, a peripheral subcutaneous implanted vascular-access device (VAD) and to evaluate the ability to transfer this training to a second PA. We also evaluated the performance and complications associated with this new device. PATIENTS AND METHODS: The Peripheral Access System (PAS) Port catheter system (Sims-Deltec Inc, St Paul, MN) was inserted in patients who required long-term (> 3 months) vascular access for infusion therapy. RESULTS: The first PA (PA-1) successfully inserted 57 of 62 devices (92%) after gaining experience with the technique in 10 patients (success rate, five of 10 [50%]; P = .003). The second PA (PA-2) was successful in eight of 10 initial attempts (80%) and 25 of 30 overall (83%). Complications were few and limited to phlebitis, thrombosis, and a low infection rate (0.2 per 1,000 catheter days). CONCLUSION: PAs can be taught to insert a peripheral subcutaneous implanted VAD. This technique is transferable from one PA to another, and the device studied is appropriate for outpatient VAD programs.

Incidence, cost, and outcomes of bleeding and chemotherapy dose modification among solid tumor patients with chemotherapy-induced thrombocytopenia.

PURPOSE: To describe the incidence and outcomes of bleeding and chemotherapy dose modifications associated with chemotherapy-induced thrombocytopenia (platelets < 50,000/microL). PATIENTS AND METHODS: Six hundred nine patients with solid tumors or lymphoma were followed-up during 1,262 chemotherapy cycles complicated by thrombocytopenia for development of bleeding, delay or dose reduction of the subsequent cycle, survival, and resource utilization. The association between survival and bleeding or dose modification was examined using the Cox proportional hazards model. Predisposing factors were identified by logistic regression. RESULTS: Bleeding occurred during 9% of cycles among patients with previous bleeding episodes (P <.0001), baseline platelets less than 75,000/microL (P <.0001), bone marrow metastases (P =.001), poor performance status (P =.03), and cisplatin, carboplatin, carmustine or lomustine administration (P =.0002). Major bleeding episodes resulted in shorter survival and higher resource utilization (P <.0001). Chemotherapy delays occurred during 6% of cycles among patients with more than five previous cycles (P =.003), radiotherapy (P =.03), and disseminated disease (P =.04). They experienced similar clinical outcomes but used significantly more resources. Dose reductions occurred during 15% of cycles but were not associated with poor clinical outcomes or excess resource utilization. Significantly shorter survival and higher resource utilization were observed among the 20% of patients who failed to achieve an adequate response to platelet transfusion. CONCLUSION: The incidence of bleeding is low among solid tumor patients overall but exceeds 20% in some subgroups. These subgroups are easily identifiable using routinely available clinical information. A clinical prediction rule is being developed. Poor response to platelet transfusion is a clinically and financially significant downstream effect of thrombocytopenia and warrants further investigation.

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Platelet transfusion for patients with cancer: clinical practice guidelines of the American Society of Clinical Oncology.

OBJECTIVE: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. OUTCOMES: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost-effectiveness. EVIDENCE: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. VALUES: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. BENEFITS/HARMS/COST: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. RECOMMENDATIONS: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. VALIDATION: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. SPONSOR: American Society of Clinical Oncology

Pseudomonas bacteremia. Retrospective analysis of 410 episodes.

We reviewed 410 episodes of Pseudomonas bacteremia occurring in patients with cancer during a ten-year period. Pseudomonas bacteremia was most common among patients with acute leukemia. The majority of patients acquired their infections in the hospital, and 51% had received antibiotic therapy for other presumed or proved infection during the preceding week. Shock occurred in 33%, and 32% had concomitant pneumonia. The overall cure rate was 62%; it was 67% for patients receiving appropriate antibiotics but only 14% for those receiving inappropriate antibiotics. A one- to two-day delay in the administration of appropriate antibiotic therapy reduced the cure rate from 74% to 46%. Patients who received an antipseudomonal beta-lactam antibiotic with or without an aminoglycoside had a significantly higher cure rate than patients who received only an aminoglycoside (72% and 71% vs 29%). Patients with shock, pneumonia, or persistent neutropenia had a substantially poorer prognosis.

Haemophilus species bacteremia in patients with cancer. A 13-year experience.

We reviewed the clinical and laboratory presentation of Haemophilus species bacteremia at our institution, with special attention to predisposing and prognostic factors. Of 36 cases, 18 presented with pneumonia, 1 with cellulitis, and another with sinusitis. No cases of meningitis or endocarditis were detected. Most episodes were caused by Haemophilus influenzae, and the overall response rate to treatment was 72%. Factors including chronic obstructive pulmonary disease, alcoholism, prior splenectomy, and neutropenia did not play an important role in these patients' infections. Most of the isolates serotyped were found to be nontypable. The occurrence of ampicillin resistance was 6% throughout the study. Ampicillin, chloramphenicol, and second-generation cephalosporins were all effective therapeutic regimens. Bacteremia due to Haemophilus species remains an uncommon infection in patients with cancer, despite the predominance of traditional predisposing factors.

Moxalactam plus ticarcillin or tobramycin for treatment of febrile episodes in neutropenic cancer patients.

Moxalactam disodium in combination with ticarcillin disodium or tobramycin sulfate was used to treat 445 episodes of suspected or confirmed infection in patients with cancer. The majority had leukemia and neutropenia. The rate of cures during the 231 confirmed infections was 65% for moxalactam and ticarcillin and 64% for moxalactam and tobramycin. Both regimens were comparable against aerobic gram-negative and polymicrobial infections. In gram-positive infections, the response rate for moxalactam and ticarcillin was 73% and for moxalactam and tobramycin, 53%. Only three of nine enterococcal infections responded to treatment. Thirteen percent of all organisms recovered were resistant to moxalactam. Side effects occurred infrequently; the most important was coagulopathy due to moxalactam. Nephrotoxic effects occurred in six patients receiving moxalactam and tobramycin and in none of those receiving moxalactam and ticarcillin. In 39 patients, a superinfection was confirmed. Fourteen were fungal, three were due to enterococcus, and one due to Klebsiella species. Eleven of the 14 fungal episodes occurred in the moxalactam-ticarcillin group. Moxalactam with ticarcillin and moxalactam with tobramycin are equally active for the initial treatment of presumed infection in patients with neutropenia.

A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenic patients.

BACKGROUND: Neutropenic patients with cancer are traditionally treated with empiric antibiotic combinations when they become febrile. The availability of broad-spectrum antibiotics such as ceftazidime and imipenem has made it possible to initiate therapy with a single agent (monotherapy). The objectives of this trial were to compare ceftazidime and imipenem as single agents for the therapy of febrile episodes in neutropenic patients and to ascertain whether the addition of an aminoglycoside (amikacin) to either of these agents would provide an advantage. METHODS: A prospective clinical trial was conducted in which eligible neutropenic patients with cancer were randomized to one of four treatment arms: ceftazidime alone; imipenem alone; ceftazidime plus amikacin; and imipenem plus amikacin. Efficacy analysis was done for 750 assessable episodes. A multivariate logistic-regression analysis was also performed to examine the unique contribution of various prognostic factors. RESULTS: The overall response rates were 76% with imipenem plus amikacin, 72% with imipenem, 71% with ceftazidime plus amikacin, and 59% with ceftazidime alone. Single-organism gram-positive infections occurred in 101 of 750 episodes. Without a change in antibiotics, the response rates were 50% with imipenem, 40% with imipenem plus amikacin, 39% with ceftazidime plus amikacin, and 38% with ceftazidime. Most responded to vancomycin or other antibiotics, and the mortality associated with gram-positive infections was only 5%. Regardless of the antibiotic regimen, the majority of uncomplicated gram-negative infections responded to therapy and the majority of complicated gram-negative infections failed to respond. Multivariate logistic-regression analysis showed that recovery of the neutrophil count was the most favorable prognostic factor in a patient's response to infection, whereas the presence of gram-positive infection, acute leukemia, pulmonary or enteric infection, and therapy with ceftazidime were unfavorable factors. CONCLUSIONS: Single-agent therapy with imipenem is as effective as more conventional combination antibiotic therapy for the empirical treatment of febrile episodes in neutropenic patients with cancer.

Septicemia due to Xanthomonas species and non-aeruginosa Pseudomonas species: increasing incidence of catheter-related infections.

We reviewed 149 episodes of septicemia caused by X. maltophilia and Pseudomonas spp. occurring over a 15-year period. The incidence of septicemia caused by these organisms increased in recent years and was most frequently associated with central venous catheterization. These infections were occasionally complicated by pneumonia or endocarditis, which was often fatal. Although the survival rate was superior to that seen with septicemia caused by other gram-negative organisms, recurrence of infection was significantly more frequent. Removal of central venous catheters is an essential component of therapy of this infection.

Bacteremia caused by non-sporulating anaerobes in cancer patients. A 12-year experience.

The clinical, epidemiological and laboratory characteristics of bacteremia caused by anaerobic organisms other than Clostridium spp. in cancer patients are described and compared to other previously reported series. Of the 315 episodes, 246 (78%) were caused by a single organism and 69 (22%) were polymicrobial. The most common underlying malignancies were genitourinary and gynecological tumors, acute leukemia, and gastrointestinal malignancies. Most patients (94%) were febrile, and septic shock was documented in 24% of monomicrobial episodes and in 58% of those with polymicrobial infection. Soft-tissue infection was present in 44% of the cases, and it presented as tissue necrosis in 11%. The most common sites identified as the portal of entry were intra-abdominal abscesses, soft tissue, and the oropharynx. The most common organisms were Bacteroides fragilis (57%) and other Bacteroides spp. (22%). Most polymicrobial infections were caused by 2 organisms, the second most commonly another anaerobe or an aerobic gram-negative bacillus. The most active antibiotic in vitro was chloramphenicol. High rates of resistance to penicillin were observed not only among B. fragilis, but also among Bacteroides spp. The frequency of penicillin resistance increased throughout the study years. The overall survival was 70%. The cure rate for monomicrobial bacteremias was 76% vs. 51% for polymicrobial episodes. Infection was the cause of death in 20 and 16 episodes, respectively. The response rate for patients in septic shock was 47% in contrast to an 85% recovery rate for those without it. Ninety-five patients had documented abscesses accompanying the bacteremic episode. The most effective antibiotics were clindamycin and chloramphenicol. Overall response to penicillin was only 13%. Suboptimal responses were also observed for the antipseudomonal penicillins. High response rates (82%) were also obtained with cefoxitin, metronidazole, and moxalactam.

Polymicrobial septicemia in the cancer patient.

The medical records of 507 patients with polymicrobial septicemia were examined to determine prognostic and descriptive factors. Over 50% of the episodes occurred in patients with solid tumors and 80% originated during hospitalization. Invasive procedures and immunosuppressive therapy frequently preceded development of polymicrobial septicemia, and infection was often accompanied by shock and pneumonia. A majority of infections were caused by at least 1 aerobic gram-negative bacillus (76%) and anaerobic infections were not infrequent. Overall response among these patients was 50%, with poorest response seen among patients with persistent neutropenia (25%), pneumonia (19%), and gram-negative bacillary infection (46%). Therapy with an antibiotic regimen to which all causative organisms were sensitive was of greatest prognostic significance. Response to appropriate therapy was 58%, whereas only 10% of those who received inappropriate therapy were cured (p less than .0001).

Aztreonam in the prevention and treatment of infection in neutropenic cancer patients.

The treatment of bacterial infections in neutropenic cancer patients presents a serious challenge to physicians. Although gram-positive infections have become more common in recent years, most infections in this population are caused by gram-negative bacilli. No single regimen has been found to be optimal, and most commonly used regimens are associated with significant disadvantages. Extensive investigation is therefore under way to evaluate the potential of several promising newer antimicrobial agents. Aztreonam, for example, is active against most gram-negative pathogenic bacteria and has been evaluated in several clinical trials in neutropenic patients. As the only agent with gram-negative activity or in combination either with aminoglycosides or with other beta-lactam antibiotics, aztreonam proved useful in the treatment of gram-negative infections in this population. Combination with an aminoglycoside, however, was not found to improve efficacy over aztreonam alone. In fact, since aminoglycosides may potentiate ototoxicity and nephrotoxicity, it may be more appropriate to replace the aminoglycoside component of a combination regimen with aztreonam, as indicated by data from a study of aztreonam plus cefoperazone. Aztreonam selectively inhibits the aerobic gram-negative intestinal flora with only minimal disruption of anaerobic flora, and may be useful for infection prevention, but the importance of anaerobic preservation is not clear. It was concluded that aztreonam appears to be a useful agent for the treatment of febrile neutropenic patients, but further study is recommended.

Survey of antibiotic susceptibility among gram-negative bacilli at a cancer hospital.

A survey was conducted of the susceptibility of gram-negative bacilli to selected broad-spectrum antibiotics. The organisms were isolated from all patient specimens submitted to the routine microbiology laboratory during two three-month periods. Overall, the least resistance was observed against imipenem and ciprofloxacin. Considering all of the gram-negative bacilli, differences in susceptibilities to the other antibiotics (aztreonam, cefoperazone, ceftazidime, piperacillin) were minimal. Significant increases in resistance to some antibiotics occurred during the latter period.

Escherichia coli bacteremia in cancer patients.

During a 10-year period, 621 episodes of Escherichia coli bacteremia occurred in 575 cancer patients. The infection was most common in patients with acute leukemia and genitourinary and gastrointestinal malignancies. Most of the patients acquired their infection while in the hospital, and 38 percent had received antibiotics during the preceding 10 days. Fever occurred in 96 percent of patients, and afebrile patients had an especially poor prognosis. Only 4.5 percent of the patients had disseminated intravascular coagulation, although hemorrhage contributed to the death of 15 percent of the patients. The overall response rate was 66 percent, but it increased from 48 percent in 1972 to 76 percent in 1981. Patients without pulmonary infection had a response rate of 78 percent, whereas patients with pulmonary infection had a response rate of only 41 percent. Patients who had positive blood culture results while receiving appropriate antibiotic therapy had a poor prognosis. There was no correlation between the patients' initial neutrophil counts and response, but patients whose neutrophil count increased during therapy had a response rate of 75 percent, compared with a 47 percent response rate for patients whose neutrophil count decreased. The response rate was 71 percent for patients who received appropriate antibiotics, 38 percent for patients who received inappropriate antibiotics, and 8 percent for patients who received no antibiotics. A single appropriate antibiotic was as effective as a combination.

Prospective randomized trial of antibiotic prophylaxis in acute leukemia.

Patients undergoing initial remission induction chemotherapy for acute leukemia in a protected environment unit were randomly assigned to parenteral antibiotic prophylaxis or oral and parenteral antibiotic prophylaxis. Complete remissions were obtained in 82 percent of the 45 patients receiving oral and parenteral antibiotic prophylaxis and 76 percent of the 41 patients receiving parenteral antibiotic prophylaxis. Approximately 20 percent of the patients in both groups have had a continuous complete remission for more than five years. The episodes of fever of unknown origin and major infection were significantly more common in patients receiving parenteral antibiotic prophylaxis, although the episodes of local infection were similar in both groups. The duration of remission and survival was similar in both groups. Hence, the oral and parenteral antibiotic regimen was more effective for infection prophylaxis, but had no effect on response to antileukemic chemotherapy.