Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study

The SCHOLAR-5 study examines treatment patterns and outcomes of real-world follicular lymphoma (FL) patients on 3^rd line of treatment (LoT) or higher, for whom existing data are limited. SCHOLAR-5 is a retrospective cohort study using data from adults (≥ 18 years) with grade 1-3a FL, initiating ≥3^rd LoT after June 2014 at major lymphoma centers in the US and Europe. Objective response rate (ORR), complete response (CR), progression-free survival (PFS) and overall survival (OS) were analyzed by LoT. Time-to-event outcomes were assessed using Kaplan-Meier methods. Of 128 patients, 87 initiated 3^rd LoT, 63 initiated 4^th LoT, and 47 initiated 5^th LoT. At 1^st eligible LoT, 31% progressed within 24-months of 1^st LoT anti-CD20 combination therapy, 28% had prior autologous stem cell transplantation, and 31% were refractory to the previous LoT. The most common regimen in each LoT was chemoimmunotherapy; however, experimental drugs were increasingly used at later LoT. In the US, anti-CD20 monotherapy was more common at ≥3^rd LoT compared to Europe, where stem cell transplants were more common. ORR at 3^rd LoT was 68% (CR 44%), but decreased after each LoT to 37% (CR 22%) in ≥5 LoT. Median OS and PFS at 3^rd LoT were 68 and 11 months, respectively, and reduced to 43 and 4 months at ≥5 LoT. Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved CR in later LoT, and duration of response and survival diminished with each subsequent line.     

Minipress in the treatment of arterial hypertension in light of results from a multicenter study. II. Results of long-term monotherapy

Of 218 patients with arterial hypertension, who responded to monotherapy with prazosin (Minipress) during the first 3 months, 178 persons completed the 12-month treatment according to the study protocol. In 9 patients (4.1%) treatment was discontinued because of increase of blood pressure and/or side effects. In the remaining cases patients did not apply for the control examination or the obtained records were incomplete. During all periods of treatment the mean values of systolic and diastolic blood pressure were significantly lower than the corresponding initial values. No significant symptoms of drug tolerance were observed. Mean daily dose of Minipress after 12 months was 5.9 in comparison with 5.6 mg after 3-month therapy. Normal systolic and diastolic pressures at the end of treatment were found in 114 (64%) and 153 (86%) patients, respectively. Full normalization of blood pressure (less than or equal to 140/90) was achieved in 105 (59%) patients. It was found that an important factor determining the antihypertensive effectiveness of Minipress is the initial blood pressure. The inverse correlation between the decrease of systolic pressure and age was found, whereas the age did not affect requiring the drug withdrawal occurred in 27 (14.4%) patients; they were usually the efficacy of Minipress in relation to diastolic blood pressure. Side effects not of moderate intensity and transient character.     

Characteristics of liver cirrhosis in Italy: results from a multicenter national study

BACKGROUND: In 1992, the characteristics of liver cirrhosis in Italy were assessed in a cross-sectional study among 1829 cirrhosis patients attending 21 tertiary centres. AIM: To evaluate the characteristics of cirrhosis patients 9 years later. PATIENTS: A total of 2185 consecutive cirrhosis patients were enrolled over a 6-month period in 79 hospitals located throughout Italy, randomly selected by means of systematic cluster sampling. RESULTS: The main agent associated with cirrhosis was hepatitis C virus, which was found in 69.9% of the patients and was the only etiologic factor in 51.1% of the patients. Hepatitis B surface antigen was present in the serum of 13.0% of the cases (in 7.3%, it was the only etiologic factor). A history of alcohol abuse was found in 31.9% of the cases (12.4% without viral infection). Patients with hepatitis C virus-related cirrhosis were older (mean age of 64.4 years) and more likely to be female (male:female ratio of 0.7), compared to patients with other pathogenic factors. Virus-related cirrhosis was more likely to be observed in southern Italy, whereas alcohol-related cirrhosis was prevalent in the North. CONCLUSIONS: As found in the 1992 study, the results of the present study show that in Italy, liver cirrhosis is mainly associated with hepatitis C virus infection, reflecting the high prevalence of this infection in the general population.     

Minipress in the treatment of arterial hypertension in light of results from a multicenter study. I. 3-month treatment: monotherapy versus combination treatment

Multicenter study of the effectiveness and safety of prazosin (Minipress) in patients with arterial hypertension was carried out in 15 medical centers. Of 366 patients who entered the study, 328 persons satisfying all the protocol conditions were included into the final analysis. The treatment lasted 3 months. Highly significant decrease of systolic and diastolic blood pressure was obtained in all periods of observation. In about two-thirds of patients Minipress was effective as a single drug and in the remaining persons the decrease of blood pressure was achieved using prazosin in combination with other antihypertensive drugs. Patients requiring combination therapy were almost 2 years older (however, the difference was not significant), had higher initial blood pressure and greater body mass. Mean daily doses of Minipress in the monotherapy and combination treatment were 5.6 and 10 mg, respectively. Side effects were observed in 27% of patients, but only in 5% they were the cause of drug withdrawal.     

Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH

BACKGROUND & AIMS: Increasing evidence points toward a role of hepatitis C virus (HCV) infection in the etiology of malignant lymphomas. However, previous epidemiologic studies were limited in size to establish an association between HCV infection and specific lymphoma subtypes. We performed a large, multicenter, case-control study to address this question. METHODS: The study comprised 5 European countries and included newly diagnosed cases of any lymphoid malignancy recruited between 1998 and 2004. Controls were matched to cases by 5-year age group, sex, and study center. In-person interviews were conducted to collect data on demographic, medical, and family history as well as environmental exposures. Serum samples of 1807 cases and 1788 controls (excluding human immunodeficiency virus-positive and organ-transplantation subjects) were screened for HCV infection using an enzyme immunoassay. Positive as well as randomly selected negative samples were subjected to HCV RNA detection and HCV genotyping. RESULTS: HCV infection was detected in 53 (2.9%) lymphoma cases and in 41 (2.3%) control subjects (odds ratio [OR], 1.42; 95% confidence interval [CI]: 0.93-2.15). Restricted to individuals who tested positive for HCV-RNA (indicating persistent infection and active viral replication), the OR was 1.82 (95% CI: 1.13-2.91). In subtype-specific analyses, HCV prevalence was associated with diffuse large B-cell lymphoma (OR, 2.19; 95% CI: 1.23-3.91) but not with chronic lymphocytic leukemia or follicular, Hodgkin's, or T-cell lymphoma. The sample size was not sufficient to derive any conclusions for rare lymphoma entities such as splenic marginal zone lymphoma. CONCLUSIONS: These results support a model that chronic HCV replication contributes to lymphomagenesis and establish a specific role of HCV infection in the pathogenesis of diffuse large B-cell lymphoma.     

Chitra heart valve: results of a multicenter clinical study

BACKGROUND AND AIM OF THE STUDY: The Chitra tilting disc valve was developed in India to meet the need for a low-cost cardiac valve. The valve has an integrally machined cobalt-based alloy cage, an ultra-high molecular-weight polyethylene disc, and a polyester suture ring. An important feature of this valve is its soft closing sound, by virtue of a plastic occluder. METHODS: Between December 1990 and January 1995, 306 patients underwent isolated aortic (AVR, n = 101) or mitral valve replacement (MVR, n = 205) at six institutions in India. The early mortality rate was 6.9% (seven after AVR; 14 after MVR). A total of 285 survivors was followed up until September 1998; total follow up was 1212 patient-years (pt-yr) (AVR, 445 pt-yr; MVR, 767 pt-yr). RESULTS: There were 52 late deaths (4.3%/pt-yr; AVR 2.2%/pt-yr; MVR 5.5%/pt-yr). Thirty-five deaths were valve-related (23 were due to unknown causes). One AVR patient (0.2%/pt-yr) and 12 MVR patients (1.6%/pt-yr) developed valve thrombosis, and embolic episodes occurred in 25 patients (seven after AVR, 1.6%/pt-yr; 18 after MVR, 2.4%/pt-yr). Bleeding events and infectious endocarditis occurred infrequently (AVR 0.9 and 0.7%/pt-yr; MVR 0.4 and 0.5%/pt-yr, respectively). There was no incidence of paravalvular leak or structural dysfunction of the valve. Actuarial survival rates at seven years were 82.4+/-4.0% for AVR and 65.2+/-5.0% for MVR. During the same interval, thrombus-free and embolism-free survival after AVR and MVR occurred in 98.9+/-1.1% and 94.1+/-1.9%, and 92.3+/-2.8% and 82.1+/-5.7% of patients, respectively. Freedom from all valve-related mortality and morbidity at seven years was 81.5+/-4.1% after AVR, and 64.2+/-5.1% after MVR. CONCLUSION: The Chitra valve appears to be safe and to have performance comparable with that of other currently used tilting disc valves. This valve costs substantially less than other valves, and is therefore within reach of a larger subset of Indian patients.     

Early transformation from follicular lymphoma to Burkitt lymphoma

We report a rare case of follicular lymphoma which rapidly showed transformation to the Burkitt type of lymphoma after a treatment consisting of chemotherapy and irradiation. A 51-year-old male visited our hospital in August 2000 because of bilateral neck lymphadenopathy. He was diagnosed as having follicular lymphoma (grade 2) (clinical stage IIIA) with complex karyotypic abnormalities involving t(14 ; 18)(q32 ; q21) and CD20 expression. Initially he was followed as an outpatient without chemotherapy. Six months later, he was admitted because of hydronephrosis due to an intrapelvic tumor. He underwent chemotherapy with 4 courses of CHOP regimen following irradiation therapy and a partial response was obtained. Four months after initiation of the treatment, his disease recurred with numb chin syndrome. Bone marrow aspiration revealed bone marrow involvement by lymphoma cells which had a Burkitt-like appearance. A cytogenetic study using bone marrow blood showed complex abnormalities involving t(8 ; 22)(q24 ; q11) in addition to t(14 ; 18). In spite of salvage chemotherapy, the patient died in September 2001.     

Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: Results of a Swiss multicenter study. Part II: Bacteriological results

Summary Thein vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study. The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin. Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin againstStreptococcus agalactiae. The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid. The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination againstNeisseria meningitidis andStreptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations againstHaemophilus influenzae type b.

---

Einmal tägliche Ceftriaxon-Kurzzeittherapie der akuten bakteriellen Meningitis bei Kindern: Resultate einer Schweizerischen Multizenterstudie. Teil II: Bakteriologische Resultate

Zusammenfassung DieIn vitro-Aktivität von Ceftriaxon, Ampicillin und Chloramphenicol wurde im Rahmen einer pädiatrischen Schweizerischen Multizenter-Meningitis-Studie gegen die Erreger der ersten 33 Patienten mit akuter bakterieller Meningitis geprüft. Bei 31 Stämmen wurden die MHK-Werte — in mit 2 g/l Albumin-angereichertem Medium — zusätzlich durch je zwei Sätze Abtötungskurven ergänzt. Ceftriaxon zeigte gemessen am geometrischen Mittel die niedrigsten Hemmkonzentrationen für alle Bakterienspezies ausgenommen der von Ampicillin gegenStreptococcus agalactiae. Die bakterizide Aktivität von Ceftriaxon und Ampicilin — alleine und in Kombination mit Chloramphenicol — wurden bei je sechsfacher MHK der Isolate sowie bei im Liquorraum gut erreichbaren antibakteriellen Konzentrationen getestet. Die bakterizide Aktivität von Ceftriaxon entsprach derjenigen, von Ampicillin alleine oder in Kombination gegenNeisseria meningitidis undStreptococcus pneumoniae, oder übertraf sie, obschon die Konzentration von Ceftriaxon bei sechsfacher MHK sehr viel kleiner als die der Vergleichspräparate war. Selbst gegen die auf die Ampicillin-Chloramphenicol-Kombination äußerst empfindlichenHaemophilus influenzae Typ b erwies sich Ceftriaxon als nur geringfügig weniger aktiv als höhere Konzentrationen von besagter Kombination.

---

---

Members of the Swiss Multicenter Meningitis Study Group: Dr.E. Martin, Zürich; Dr.S. Rampini, Zürich; Dr.P. Sigg, Zürich; Dr.A. Fanconi, Winterthur; Dr.K. Baerlocher, St. Gallen; Dr.R. Haller, Münsterlingen; Dr.D. Vischer, Chur; Dr.O. Toenz, Luzern; Dr.H. Frei, Baden; Dr.E. Gugler, Aarau; Dr.G. Stalder, Basel; Dr.M. Vest, Bruderholz; Dr.H. Suter, Biel;Dr. M. Gianinazzi, Lugano; Dr.V. D'Appuazzo, Mendrisio; Dr.C. Godard, Monthey.     

Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: Results of a Swiss multicenter study. Part I: Clinical results

Summary In a prospective Swiss multicenter study, 119 children (aged three weeks to 15.5 years) with acute bacterial meningitis were treated with single daily doses of ceftriaxone (100 mg/kg on days one and two and 60 mg/kg thereafter). All patients were randomly assigned to either short course (four, six, seven days) or full course (eight, 12, 14 days) therapy depending on whether they had contracted meningococcal,Haemophilus influenzae type b or pneumococcal meningitis. Bacteriological cure was obtained in 92 children who fully completed the study and in all the 20 culture-positive of the 27 children secondarily excluded from the study for failure to meet all bacteriological and initial safety criteria for continuation in protocol (secondary exclusions). Complete clinical recovery was noted in 105 of 119 patients (88%) and was as frequent in the short course (91%) as in the full course (89%), and as in the secondary exclusion (81%) group. All patients survived. At follow-up examination three to six months after hospital discharge only seven infants and seven children (11.8%), mostly those with poor presentation on admission (p=0.0012), showed residual neurological sequelae. Side effects of antibiotic therapy were minor but more frequent, albeit not statistically significant (p=0.065), in children receiving the full course therapy. The results of this study suggest that short course treatment of acute bacterial meningitis in children with single daily ceftriaxone monotherapy is as efficacious as full course therapy and at least as well tolerated.

---

Einmal tägliche Ceftriaxon-Kurzzeittherapie der akuten bakteriellen Meningitis bei Kindern: Resultate einer Schweizerischen Multizenterstudie. Teil I: Klinische Resultate

Zusammenfassung 119 Kinder (im Alter zwischen drei Wochen und 15,5 Jahren) mit einer akuten bakteriellen Meningitis wurden in einer prospektiven Schweizerischen Multizenterstudie einmal täglich mit einer parenteralen Dosis Ceftriaxon (100 mg/kg am 1. und 2. Tag, gefolgt von 60 mg/kg pro Tag) behandelt. Alle Patienten wurden randomisiert, wobei sich die Dauer der Behandlung in beiden Gruppen nach der Art des Meningitiserregers richtete. Sie betrug in Reihenfolge der Keime(Neisseria meningitidis, Haemophilus influenzae Typ b oderStreptococcus pneumoniae) vier, sechs, resp. sieben Tage bei der Kurzzeittherapie und acht, 12, resp. 14 Tage bei der Therapie von üblicher Dauer. Sowohl bei den 92 Kindern, die die randomisierte Studie protokollgemäß abschlossen, als auch bei den 20 (von insgesamt 27) kulturpositiven sekundär von der Studie ausgeschlossenen aber gleichwohl mit der Ceftriaxon-Monotherapie weiterbehandelten Kindern wurde eine bakteriologische Heilung erzielt. Alle 119 Kinder überlebten; in 105 Fällen (88%) wurde eine vollständige klinische Heilung beobachtet. Die klinische Heilungsrate war bei beiden randomisierten Gruppen identisch (91% vs. 89%) und lag nur wenig höher als bei der Gruppe der sekundär ausgeschlossenen Kinder (81%). Bei Nachuntersuchungen zwischen drei und sechs Monaten nach Spitalentlassung waren bei sieben Säuglingen und sieben Kindern (11,8%) neurologische Spätfolgen erkennbar: Bei allen handelte es sich um Kinder, die schon bei Eintritt durch einen sehr schlechten Allgemeinzustand aufgefallen waren (p=0,0012). Die Nebenerscheinungen unter Ceftriaxontherapie waren klinisch unbedeutend; sie wurden unter Kurzzeittherapie weniger häufig beobachtet als unter Therapie üblicher Dauer, wenn auch nicht in statistisch signifikantem Maß (p=0,065). Die Resultate der vorliegenden Studie zeigen, daß eine Kurzzeitbehandlung der akuten bakteriellen Meningitis bei Säuglingen und Kleinkindern mit einer einmal täglichen Dosis von Ceftriaxon mindestens gleich effizient und sicher wirkt wie eine Therapie von üblicher (meist doppelter) Dauer mit dem gleichen Präparat.

---

---

Members of the Swiss Multicenter Meningitis Study Group: Dr.E. Martin, Zürich; Dr.S. Rampini, Zürich; Dr.P. Sigg, Zürich; Dr.A. Fanconi, Winterthur; Dr.K. Baerlocher, St. Gallen; Dr.R. Haller, Münsterlingen; Dr.D. Vischer, Chur; Dr.O. Toenz, Luzern; Dr.H. Frei, Baden; Dr.E. Gugler, Aarau; Dr.G. Stalder, Basel; Dr.M. Vest, Bruderholz; Dr.H. Suter, Biel;Dr. M. Gianinazzi, Lugano; Dr.V. D'Appuazzo, Mendrisio; Dr.C. Godard, Monthey.These results were presented in part at the 24th ICAAC, Washington, D.C., USA, 1984, at the International Congress for Infectious Diseases, Cairo, Egypt, 1985, and at the 14th International Congress of Chemotherapy, Kyoto, Japan, 1985.     

Ofatumumab is active in patients with fludarabine-refractory CLL irrespective of prior rituximab: results from the phase 2 international study

Ofatumumab, the human CD20 monoclonal antibody that binds a distinct epitope from rituximab, has demonstrated clinical benefit as monotherapy for patients with chronic lymphocytic leukemia refractory to fludarabine and alemtuzumab (FA-ref) and patients refractory to fludarabine with bulky (> 5 cm) lymph nodes (BF-ref). To potentially gain insight into outcomes in patients previously treated with or refractory to rituximab, we performed an ad hoc retrospective analysis in the final 96 FA-ref and 111 BF-ref patients. There were 117 patients previously treated with rituximab (98 rituximab-refractory); 89 patients were rituximab-naive. For rituximab-treated, rituximab-refractory, and rituximab-naive patients, overall response rate was 43%, 44%, and 53%; median progression-free survival was 5.3, 5.5, and 5.6 months; and median overall survival was 15.5, 15.5, and 20.2 months. There were no significant differences in ofatumumab-related infusion reactions, or hematologic or infectious adverse events between subgroups. In summary, ofatumumab monotherapy was effective and well tolerated in patients with fludarabine-refractory chronic lymphocytic leukemia, including in patients with previous rituximab exposure. This trial was registered at www.clinicaltrials.gov as #NCT00349349.     

ABVD vs BEACOPP escalated in advanced-stage Hodgkin’s lymphoma: Results from a multicenter European study

The optimal first-line treatment for advanced-stage Hodgkin's lymphoma (HL) is still a matter of debate. While ABVD is less toxic and as effective as other, more intensive chemotherapy regimens, escalated BEACOPP (BEACOPPesc) is superior to ABVD for initial disease control and prolonged time-to-relapse. However, this advantage is associated with higher rate of early and late toxicities. As most of these data have been accumulated from clinical trials, a retrospective analysis was conducted in a large database of patients treated outside clinical trials to investigate the advantages and disadvantages of these regimes in a real-world setting. From October 2009 to October 2018, 397 advanced-stage HL patients treated with either ABVD or BEACOPPesc were retrospectively assessed in 7 European cancer centers (2 Austrian and 5 Italian centers). Complete metabolic remission (CMR) by PET was achieved in 76% and 85% of patients in the ABVD and BEACOPPesc groups, respectively (p = .01). Severe adverse events occurred more frequently with BEACOPPesc than ABVD. At a median follow-up of 8 years, 9% of the patients who achieved CMR after BEACOPPesc relapsed compared to 16.6% in the ABVD group (p = .043). No statistical difference in progression free survival (PFS) was observed between the two cohorts overall (p = .11), but there was a trend towards a superior PFS in high-risk patients treated with BEACOPPesc (p = .074). Nevertheless, overall survival was similar between the two groups (p = .94). In conclusion, we confirm that ABVD is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control, the long-term outcome remains similar between the two regimens.     

Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study

The FL2000 study was undertaken to evaluate the combination of the anti-CD20 monoclonal antibody rituximab with chemotherapy plus interferon in the first-line treatment of follicular lymphoma patients with a high tumor burden. Patients were randomly assigned to receive either 12 courses of the chemotherapy regimen CHVP (cyclophosphamide, adriamycin, etoposide, and prednisolone) plus interferon-alpha2a (CHVP+I arm) over 18 months or 6 courses of the same chemotherapy regimen combined with 6 infusions of 375 mg/m(2) rituximab and interferon for the same time period (R-CHVP+I arm). After a median follow-up of 5 years, event-free survival estimates were, respectively, 37% (95% confidence interval [CI], 29%-44%) and 53% (95% CI, 45%-60%) in the CHVP+I and R-CHVP+I arm (P = .001). Five-year overall survival estimates were not statistically different in the CHVP+I (79%; 95% CI, 72%-84%) and R-CHVP+I (84%; 95% CI, 78%-84%) arms. In a multivariate regression analysis, event-free survival was significantly influenced by both the Follicular Lymphoma International Prognostic Index score (hazard ratio = 2.08; 95% CI, 1.6%-2.8%) and the treatment arm (hazard ratio = 0.59; 95% CI, 0.44%-0.78%). With a 5-year follow-up, the combination of rituximab with CHVP+I provides superior disease control in follicular lymphoma patients despite a shorter duration of chemotherapy. This study's clinical trial was registered at the National Institutes of Health website as no. NCT00136552.     

High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS

Doxorubicin-based immunochemotherapy, with interferon, has been shown to improve survival in patients with advanced follicular lymphoma. High-dose chemotherapy with stem-cell support is effective in follicular lymphoma in relapse but remains controversial as a first-line therapy. In a randomized study using a purged autologous stem-cell support, we compared these 2 approaches in patients with advanced follicular lymphoma. Newly diagnosed advanced follicular lymphoma patients (172 patients) were randomly assigned either to an immunochemotherapy regimen (cyclophosphamide, doxorubicin, teniposide, prednisone, and interferon) or to a high-dose therapy followed by purged autologous stem-cell transplantation. Compared with the patients who received chemotherapy and interferon, patients treated with high-dose therapy had a higher response rate (69% vs 81%, P = .045) and a longer median event-free survival (not reached vs 45 months). This did not translate into a better survival rate due to an excess of secondary malignancies after transplantation. The Follicular Lymphoma Prognostic Index identified a subgroup of patients with a significantly higher event-free survival rate after high-dose therapy. Autologous stem-cell transplantation cannot be considered as the standard first-line treatment of follicular lymphoma for patients younger than 60 years old with a high tumor burden.     

Intolerance to tartrazine in aspirin-induced asthma: results of a multicenter study

One hundred and fifty-six German, Italian and Polish patients with confirmed aspirin-induced asthma underwent open oral challenges with increasing doses of tartrazine up to 25 mg. All positive challenges were repeated under double-blind conditions. Only 4 of 156 patients (all Polish) had positive reactions in a double-blind test, as evidenced by a fall in FEV1 greater than 25% from baseline and corresponding clinical symptoms. Sixty-five patients who tolerated 25 mg tartrazine well received 50-3,000 mg tartrazine and none showed adverse reactions. Thus, intolerance to tartrazine appears to be rare among Central-European and South-European patients with aspirin-induced asthma, its frequency amounting to about 2.6%.