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Biomedical subjects

C Koller

Publications and source records attributed to C Koller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Interferon maintenance therapy for patients with chronic lymphocytic leukemia in remission after fludarabine therapy.

Many patients with chronic lymphocytic leukemia (CLL) achieve remission after treatment with fludarabine chemotherapy. Most of these patients, however, later experience relapse. In addition, immunologic deficits may persist even in patients in complete remission; lymphopenia, predominantly involving the CD4 population, is universal after fludarabine therapy. We used recombinant alpha interferon (IFN-alpha) maintenance therapy in patients with CLL who achieved remission in response to fludarabine therapy to determine its effect on residual disease, assessed by either bone marrow biopsy or flow cytometry, and on immune restoration. Thirty-one patients were treated with IFN-alpha (3 x 10(6) U by subcutaneous injection three times weekly). Twenty-two patients (71%) were in complete remission (CR) and nine (29%) were in partial remission (PR). Of the 22 patients in CR, 21 (95%) had evidence of residual disease at the start of IFN-alpha therapy. Low CD4 levels were noted in 93% of patients, low IgG levels in 45%, and anergy or hypoergy in 52%. Only one patient in PR achieved a CR on IFN-alpha therapy: the only patient who had had no prior fludarabine but had been treated with chlorambucil and prednisone. All patients in CR with minimal residual disease had persistent disease after IFN-alpha treatment. There were no increases in CD4 counts or IgG levels; three patients with borderline responses to skin testing had an increase in the number of positive tests while on IFN-alpha. The time to progression was no different in patients treated with IFN-alpha than in a historical control group of patients who had received no further therapy after fludarabine. In summary, the use of IFN-alpha maintenance did not eradicate residual disease, restore immune function, or prolong remissions in patients with CLL responsive to fludarabine.

Adult↗
PubMed1995

[Nitrous oxide exposure to personnel in a recovery room with modern climate control].

Epidemiologic studies have shown that trace concentrations of inhalation anaesthetics polluting the air of operating theatres could have deleterious effects on the personnel's health. Nitrous oxide (N2O) oxidises vitamin B12 and thus decreases DNA production by inactivation of methionine synthase. Therefore, the United States and most European health authorities recommend threshold values to protect against potential health risks. These values range from 25 to 100 ppm, expressed as time-weighted averages (TWA). There is a lack of data concerning measurements of trace concentrations under defined conditions. The aim of this study was to quantify levels of N2O in a recovery room (RR) with an air conditioning system. METHODS. Trace concentrations of N2O were determined in the main RR of the University Hospital of Regensburg (Germany). Measurements were taken for 5 days from 8:00 a.m. to 8:00 p.m. Trace concentrations of N2O were measured directly by means of a highly sensitive photoacoustic infrared spectrometry analyser. The lower detection limit was 0.03 ppm. Samples of room air were taken continuously from six different places in the recovery room, five of which had a distance of 50 cm to the patients' heads. One point represented the nurses' desk 5 m away from the patients. TWAs were calculated for each day and location. RESULTS. All values were below 5 ppm TWA at each location. Typical TWA (range) values recorded at day 2 were for point 1:3.5 ppm (0.4-8.9), point 2:3.2 (0.5-7.3), point 3:3.0 (0.5-5.4), point 4:3.7 (0.5-21.2), point 5:3.2 (0.6-6.6), and at the nurses' desk 3.3 (0.5-6.3). Peak concentrations of nearly 25 ppm were reached for at least 10 min. Significant differences between the days and locations could not be found (P < 0.05, Wilcoxon test). CONCLUSION. Exposure to N2O in a climatised RR is determined by several factors: (1) efficacy of air conditioning, with 10.7 changes per hour without recirculation; (2) recovery room size; (3) transport of the patients takes about 15 min, during which some quantities of N2O leave the patient; and (4) high numbers of patients staying 2 and more hours in the recovery room and exhaling smaller concentrations of N2O into the room air. Because of these factors, all measured values are significantly below the standard international threshold values. Under other conditions of room design, such as ventilation and size, measured values may be higher.

Air Conditioning↗
PubMed1995

[Exposure of intensive care personnel to isoflurane in long-term sedation].

OBJECTIVE: Isoflurane is a suitable agent to produce sedation in the intensive care unit (ICU). However, data concerning occupational exposure to isoflurane during long-term sedation are not yet available. The purpose of this study was to evaluate occupational exposure to isoflurane in the ICU. DESIGN: Trace concentrations of isoflurane were measured directly by means of photoacustic infrared spectrometry during isoflurane sedation in ten cases over a period of 24 hours. Values were obtained at four personnel-related and two leakage-related locations in an ICU chamber. RESULTS: All measured values were low, the majority under 3 ppm isoflurane at the personnel-related points. Peak concentrations up to 40 ppm were recorded for several minutes during nursing interventions. At measurement point "nearby patient's mouth" values up to 5 ppm were recorded, at location "anaesthesia machine" values ranged from 2 to 69 ppm isoflurane. CONCLUSION: We conclude that an effective high flow scavenging system, a low-leakage anaesthesia machine and an airconditioning equipment without recirculation could keep occupational exposure low. The majority of the measured values was below the NIOSH recommendation (2 ppm). All values was lower than a national state recommendation (10 ppm). Under other circumstances (e.g. without scavenging system) air pollution will be higher and therefore measurements at the working place are needed.

Air Pollutants, Occupational↗
PubMed1995

Fludarabine plus doxorubicin in previously treated chronic lymphocytic leukemia.

Based on the activity of fludarabine and doxorubicin in chronic lymphocytic leukemia (CLL), 30 patients received this combination. The median age of these patients was 61 years; median Zubrod performance status was one; median number of prior therapies was three; and median time to treatment was 53 months. Rai stage was 0 for two patients, I/II for 19 patients, and III/IV for nine patients. Prior treatment included fludarabine in 25 patients. In this regimen, fludarabine was administered as 30 mg/m2/d IV x 3 to 10 patients, 25 mg/m2/d IV x 4 to three patients, and to 17 patients as 30 mg/m2/d IV x 4. A 50 mg/m2 IV dose of doxorubicin was given to all patients. The first 17 patients received prednisone 30 mg/m2 x 5 days; however, this was discontinued due to other data demonstrating no therapeutic advantage and increased opportunistic infections when corticosteroids were added to fludarabine. Toxicity consisted primarily of infectious episodes: pneumonia nine, bacteremia one, FUO seven, and minor infection five. Two deaths from pneumonia occurred. Standard guidelines for response were used with the addition of a nodular CR group. Despite prior treatment with fludarabine in the majority of patients, the response rate in the 29 evaluable patients was CR 3%, nodular CR 17%, PR 35%, fail 38% and early death 7%. This combination of fludarabine and doxorubicin is active against CLL and warrants further study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

A 3-day schedule of fludarabine in previously treated chronic lymphocytic leukemia.

This study was undertaken to determine the efficacy and toxicity of a shorter schedule of fludarabine administration (30 mg/m2 i.v. daily for 3 days every 4 weeks) in patients with previously treated chronic lymphocytic leukemia (CLL). Eighty patients with previously treated advanced (Rai III-IV) (54%) or progressive Rai stage 0-II (46%) were treated. The results of this trial were retrospectively compared with those of previous fludarabine trials using different schedules of administration. The complete response (CR), nodular CR and partial response rates were 10, 15 and 21%. The overall response rate (46%) was slightly lower than prior regimens using a 5-day schedule of fludarabine; however, this difference was not significant. Further evaluation by dual-parameter flow cytometry and immunoglobulin gene rearrangement analysis revealed that minimal residual disease was more common in a 3-day schedule. The overall incidence of infections per treatment course (14%) was significantly lower than that observed on the 5-day or weekly regimens (P < 0.001). The incidence of minor, atypical and viral infections were similar. There was no difference in survival in the various trials. In conclusion, a 3-day schedule of fludarabine in previously treated CLL patients was associated with a lower infection rate and similar survival to a 5-day schedule. These data support the use of a 3-day schedule of fludarabine as a single agent and in combination with other active agents.

Adult↗
PubMed1995

[Nitrous oxide exposure of operating room personnel in intubation anesthesia].

INTRODUCTION: Epidemiological studies have shown that trace concentrations of inhalation anaesthetics polluting the air of operation theatre could have adverse effects on the personnel's health. Nitrous oxide (N2O) oxidizes vitamin B12 and thus decreases DNA production by inactivation of methionine synthase. Therefore, US and most European health authorities recommend threshold values to protect against potential health risks. These values range from 25 ppm to 100 ppm, expressed as time-weighted averages (TWA). There is a lack of data concerning measurements of trace concentrations under defined conditions. The aim of this study was to quantify levels of N2O in an operating theatre (OT) under modern working environment conditions. METHODS: Trace concentrations of N2O were determined in the OT at three personnel-related and three potential leakage related points and TWA's were calculated. Trace concentrations of N2O were measured directly by means of a highly sensitive photoacoustic infrared spectrometry analyser. The lower detection limit was 0.03 ppm. RESULTS: Values were below 100 ppm TWA at personnel-related locations. NIOSH 25 ppm threshold limit value was exceeded several times. Significant differences between location surgeon and anaesthetist and auxiliary nurse were detected (p < 0.05, Wilcoxon test). CONCLUSION: Exposure to N2O in a climatised OT is determined by several factors: 1. Efficacy of the air-conditioning with 20 changes per hour without recirculation, 2. OT size, 3. low leakage anaesthesia machine, and 4. avoidance of intermittent nitrous oxide supply during induction. Due to these factors, most measured values are below threshold values. In case of other concepts of room design such as ventilation and size, measured values may be higher.

Adult↗
PubMed1994

All-trans retinoic acid followed by chemotherapy for salvage of refractory or relapsed acute promyelocytic leukemia.

BACKGROUND: All-trans retinoic acid (ATRA) is effective in the treatment of relapsed or refractory acute promyelocytic leukemia (APL), but relapse is the rule if response is unmaintained. METHODS: Seventeen patients with APL were salvaged with ATRA at a dosage of 50 mg/m2/day for 3 months or until complete remission (CR) was achieved; idarubicin (12 mg/m2/day for 4 days) was added if blast plus promyelocyte count either was or reached > or = 10 x 10(3)/microliters. After CR was achieved, patients received three courses of idarubicin (12 mg/m2 daily for 3 days) followed by three courses of mitoxantrone (5 mg/m2 daily for 3 days) and etoposide (250 mg/m2 daily for 3 days). Maintenance was with 6-mercaptopurine and methotrexate. RESULTS: A CR was achieved in 14 patients (82%), the disease was refractory in 2 patients, and one patient died during induction. Three patients underwent allogeneic bone marrow transplant during CR. After a median follow-up of 26 weeks, six patients remain in CR. Median CR duration is 40 weeks (range 8-56+). Patients treated with ATRA plus chemotherapy in first salvage, when compared to a historic control group treated with chemotherapy alone, had a significantly better CR rate (87% vs. 57%; P = 0.04) and a lower induction death rate (7% vs. 29%; P = 0.08), resulting in longer median survival (26 vs. 17 weeks; P = 0.13). Four patients developed the "retinoic acid syndrome", which was fatal in one case. Three patients developed thrombotic events. CONCLUSIONS: ATRA followed by chemotherapy is effective treatment for patients with APL who relapse after conventional therapy, and it may be superior to chemotherapy alone.

Adolescent↗
PubMed1994

Lack of effect of 2-chlorodeoxyadenosine therapy in patients with chronic lymphocytic leukemia refractory to fludarabine therapy.

BACKGROUND: Fludarabine and 2-chlorodeoxyadenosine are nucleoside analogues that have proved effective in patients with chronic lymphocytic leukemia (CLL). Although their mechanism of action is thought to be similar, a small number of patients who do not respond to fludarabine do respond to 2-chlorodeoxyadenosine. The extent to which 2-chlorodeoxyadenosine is effective in patients who do not respond to fludarabine is not known, however. METHODS: We treated 28 patients with CLL refractory to fludarabine therapy with a continuous infusion of 2-chlorodeoxyadenosine at a daily dose of 4 mg per square meter of body-surface area for seven days. The treatment could be repeated monthly. The number of treatments ranged from one to five; patients who responded continued to receive treatment until the maximal response was achieved. RESULTS: Two patients (7 percent) had partial remissions, but no patients had complete remissions. One other patient had a substantial response but had residual thrombocytopenia. The rate of response in most affected organs was 20 percent, but anemia or thrombocytopenia rarely improved. Myelosuppression was frequent, and 65 percent of the courses of 2-chlorodeoxyadenosine therapy were accompanied by febrile episodes or infections. Ten patients died within 60 days of starting therapy with 2-chlorodeoxyadenosine; eight deaths were related to infection. The median platelet count at the start of 2-chlorodeoxyadenosine therapy in these 10 patients was 24,000 per cubic millimeter, as compared with 109,000 per cubic millimeter in the other 18 patients. Five patients were alive after a median follow-up of 24 months. CONCLUSIONS: Patients with advanced CLL refractory to fludarabine therapy are unlikely to benefit from treatment with 2-chlorodeoxyadenosine. Although 20 percent of the patients have some response, thrombocytopenia and anemia are rarely corrected and may be made worse by 2-chlorodeoxyadenosine therapy.

Adult↗
PubMed1994

Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor.

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF) administered before, during, and after fludarabine plus cytarabine (ara-C; FA) chemotherapy affected complete response (CR) rate, infection rate, blood count recovery, or survival in patients with newly diagnosed acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS). PATIENTS AND METHODS: A total of 112 patients with newly diagnosed AML (n = 69) or MDS (n = 43) received G-CSF 400 micrograms/m2/d 1 day before (presenting WBC count < 50,000/microL) and/or during (all patients) fludarabine 30 mg/m2/d and ara-C 2 g/m2/d for 5 days (FLAG). G-CSF continued until a CR was achieved. Results were compared with those in 85 newly diagnosed patients (54 AML, 31 MDS) previously treated with FA without G-CSF. RESULTS: Patients in both groups were relatively old (median age of all patients, 63 years), and were likely to have prognostically unfavorable cytogenetic abnormalities (36% had abnormalities of chromosomes 5 and 7 [-5/-7]). G-CSF accelerated recovery to > or = 1,000 neutrophils (P < .0001; median, 34 days for FA, 21 days for FLAG), but logistic regression provided no evidence that the CR rate was higher with FLAG than with FA (P = .50), with unadjusted CR rates of 63% and 53%, respectively. This may reflect relatively high rates of death before neutrophil recovery in both groups. Rates of infection were similar in both groups. The follow-up duration in remission is short, and much of these data remain censored. To date, survival is similar with FA and FLAG. CONCLUSION: On average, G-CSF before, during, and after FA had no effect on CR or infection rates in this population, in which elderly patients and poor prognostic factors were prevalent. The use of FA and laminar airflow rooms rather than more usual therapy needs to be considered when analyzing the results.

Aged↗
PubMed1994

Therapy-related leukemia and myelodysplastic syndrome in chronic lymphocytic leukemia.

A retrospective analysis was performed to determine the incidence and clinical features of acute myelogenous leukemia/myelodysplastic syndrome (AML/MDS) developing in chronic lymphocytic leukemia (CLL) patients. AML/MDS occurred in 3/1374 CLL patients seen at a single institution between 1972 and 1992. The median follow-up exceeded 7 years and 72% of these patients had received prior alkylating agent therapy. The expected number of AML/MDS developing in a general population of the same size was 1.2 as calculated from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program data (observed-to-expected ratio = 2.49; 95% confidence interval = 0.9-7.3; p = 0.12). Although, not included in the incidence calculation, four patients with CLL were referred at the time of development of AML/MDS. CLL and AML/MDS were diagnosed concurrently in two patients. Three of the patients had received no prior alkylating agents. The median survival was 17 months in patients who had received no prior treatment, and 5 months in those who had received prior chemotherapy. Our results suggest that patients with CLL in whom AML/MDS develops have similar prognoses to other patients with AML/MDS. Furthermore, this analysis does not provide evidence for a heightened risk of AML/MDS in CLL patients, despite treatment with known leukemogenic agents.

Aged↗
PubMed1993

Results of fludarabine and prednisone therapy in 264 patients with chronic lymphocytic leukemia with multivariate analysis-derived prognostic model for response to treatment.

Two hundred sixty-four patients with chronic lymphocytic leukemia were treated with fludarabine 30 mg/m2 intravenously for 30 minutes each day for 5 days and with prednisone 30 mg/m2 orally each day for 5 days. Courses were repeated monthly. Of the 264 patients. 125 patients (47%) had Rai stage III-IV disease; 169 patients (64%) were previously treated with a median of 3 prior regimens; and 138 of them (82%) were refractory to therapy with alkylating agents. The overall response (OR) and complete response (CR) rates in the 169 previously-treated patients were 52% and 37%; these were 74% and 63%, respectively, in Rai stage O-II patients and declined to 64% and 46%, respectively, in Rai III-IV disease. Among the previously untreated patients, the OR and CR rates were 79% and 63%, these being 85% and 70%, respectively, in Rai O-II patients, and declining to 64% and 46%, respectively, in Rai III-IV disease. The incidence of minor infections or fever of unknown origin was similar in all patient groups and occurred in 22% of courses. The incidence of sepsis and/or pneumonia was significantly correlated with the extent of prior therapy and with Rai stage, and ranged from 3% of courses in the previously untreated Rai O-II patients, to 13% of courses in the previously treated Rai III-IV patients. Listeria sepsis or Pneumocystis carinii pneumonia was noted in 14 patients. With therapy, CD4 levels were uniformly depressed from a median 1,015/microL pretreatment to a median 159/microL after 3 months of fludarabine therapy. Median time to progression in previously treated patients was 22 months. In previously untreated patients, median time to progression was 30 months for patients who achieved a partial remission and has not been reached in patients who achieved a CR with a median follow-up of 2 years. The median survival was 18 months for previously treated patients and has not been reached for previously untreated patients. Response rates in previously treated and untreated patients, as well as infection rates, were identical to those seen in 110 patients treated with the same dose schedule of fludarabine alone. Logistic regression analysis selected 4 factors to be significantly associated with worse response: Rai III-IV stage disease, prior therapy, older age, and low albumin levels. The regression equation was used to derive a probability of response based on the 4 characteristics. When the model was applied to the same population, patients could be divided into 4 prognostic groups with different outcomes.

Antigens, CD↗
PubMed1993

Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent.

The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown.

Adult↗
PubMed1993

Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia.

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to-moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.

Acute Disease↗
PubMed1993

Platelet crossmatches of single-donor platelet concentrates using a latex agglutination assay.

A latex agglutination assay was evaluated for the purpose of identifying compatible platelet donors for alloimmunized recipients. Assay reagents were prepared by adsorbing detergent-solubilized, donor-specific platelets to polystyrene latex beads. Semiquantitative results for up to 30 donors can be completed in less than 1 hour. These reagents retained their immunoreactivity for at least 3.5 months. A retrospective study has established the assay's upper limit of compatibility. The prospective study evaluated transfusions to a group of multiply transfused patients. Part I evaluated 143 crossmatched, single-donor platelet transfusions given to 50 patients. In 96 percent of the cases, a positive crossmatch was associated with an unsuccessful transfusion outcome; in 84 percent of the transfusions, a negative crossmatch predicted a satisfactory platelet increment. The overall predictability, sensitivity, and specificity were 87, 62, and 99 percent, respectively. Part II evaluated 105 transfusions given to the 43 patients (of 50) in whom no incidence of fever, sepsis, or bleeding could be documented. A positive crossmatch was 96-percent efficient in predicting an unsuccessful transfusion, whereas a negative crossmatch was associated with an adequate platelet increment following 89 percent of the transfusions. The overall predictability was 91 percent, the sensitivity was 72 percent, and the specificity was 99 percent. Within-run and between-run variations were 6.3 and 6.2 percent, respectively. These results demonstrate that detergent-solubilized platelet antigens, immobilized on latex particles, can be used in a cost-effective crossmatching procedure.

Adult↗
PubMed1993

An open trial of cefoperazone plus sulbactam for the treatment of fever in cancer patients.

Cancer patients received cefoperazone plus sulbactam for 673 febrile episodes presumed to be caused by infection. Overall, 415 (76%) of the 545 evaluable episodes responded. There were 213 responses (84%) amongst the 254 fevers of unknown origin and 202 responses (69%) amongst the 291 documented infections. Fifty-one (61%) of the 83 episodes pneumonia and 74 (64%) of the 115 episodes of bacteraemia responded. Only 39 (58%) of the 67 infections caused by Gram-positive bacteria responded compared with 55 (86%) of 64 Gram-negative infections which included seven of eight caused by Pseudomonas aeruginosa. Eighteen (67%) of 27 polymicrobial infections responded to the regimen. Response rates were significantly lower amongst the 125 patients whose neutrophil counts decreased during therapy than amongst the 158 patients whose neutrophil counts increased. Adverse events which were possibly or probably related to antibiotic therapy were observed during 73 of the episodes; the most commonly reported side-effects were diarrhoea and skin rash. Six patients developed a coagulopathy without haemorrhage and two experienced anaphylactic reactions. In this open trial cefoperazone plus sulbactam proved to be an effective regimen for initial therapy of fever in cancer patients. It should be combined with a glycopeptide in those institutions where infections caused by methicillin-resistant staphylococci are frequently encountered.

Adolescent↗
PubMed1993

Phase II clinical trial of fludarabine in chronic lymphocytic leukemia on a weekly low-dose schedule.

The major complication during therapy of chronic lymphocytic leukemia (CLL) with the purine nucleotide analogue fludarabine is infection, which is also the main cause of morbidity and mortality in the disease. As the incidence of infectious episodes during therapy correlated with severity of neutropenia, stage of disease, and response to therapy, an effort was made to reduce therapy-related myelosuppression and improve response by altering the conventional therapy regimen. The protocol which yielded a response rate of 57% in previously treated patients with CLL consisted of five consecutive daily doses of 25-30 mg/m2 fludarabine given every three to four weeks. Based on observations from intracellular pharmacology studies it was hypothesized that repetitive single weekly doses of fludarabine would allow normal bone marrow cells to recover while maintaining cytotoxic levels in the leukemic cells. The cumulative four-week dose of the once-weekly regimen was approximately 80% of the original protocol. Eleven out of 46 evaluable patients (24%) responded to the therapy. Seven patients (15%) achieved a complete remission, and four (9%) a partial remission. While myelosuppression was reduced by about 30% compared with the original protocol, the incidence of febrile episodes was increased by 17%. Pretreatment serum IgG levels below the normal range correlated significantly with a high incidence of infectious episodes and with a short median survival time. These observations suggest that in addition to myelosuppressive therapy, disease related depressed immune function causes morbidity and mortality due to infections. The results further show that changes in the scheduling of the therapy regimen, associated with a slightly lower dose, resulted in reduced efficacy as measured by the response rate.

Adult↗