D. K. Hossfeld

18FDG-PET following treatment as valid predictor for disease-free survival in Hodgkin's lymphoma

PURPOSE The value of 18FDG-PET to predict the outcome after therapy in Hodgkins lymphoma was compared to morphologic staging and ESR. PATIENTS AND METHODS A total of 50 concurrent 18FDG-PET and CT studies were performed in 37 patients with Hodgkins lymphoma. ESR was evaluated 32 times after treatment was completed. RESULTS Out of 39 residual masses found by CT 8 relapses could be proven. Out of 11 CT exams with CR 3 relapses occurred. CT turned out to show a sensitivity, specificity, PPV, NPV, and accuracy of 72%, 21%, 21%, 73%, and 32%, with respect to predict disease-free survival (DFS). 18FDG-PET was positive in 22 examinations with 10 recurrences in this group. Out of 28 negative 18FDG-PET 1 relapse developed 3 years later. 18FDG-PET turned out to show promising sensitivity, specificity, PPV, NPV, and accuracy of 91%, 69%, 46%, 96%, 74%, with respect to predict DFS. ESR was elevated in 12 studies of which 5 relapses could be proven, while out of 20 normal ESR-studies 3 relapses occurred. Thus, ESR turned out to show sensitivity, specificity, PPV, NPV, and accuracy of 63%, 71%, 42%, 85%, and 75%, with respect to predict DFS. In summary, only 18FDG-PET was able to predict DFS statistically significant. CONCLUSION 18FDG-PET can be very useful in patients with residual masses after treatment.

A Randomized Phase III Study Comparing Weekly Folinic Acid(FA) and High-Dose 5-Fluorouracil (5-FU) with Monthly 5-FU/FA (days 1-5) in Untreated Patients with Metastatic Colorectal Carcinoma

Background: The combination of 5-fluorouracil (5-FU) and folinic acid (FA) given over 5 days every 4 weeks is one of the most frequently used regimens in metastatic colorectal carcinoma (CRC). It results in remission rates ranging from 20 to 30% and a median survival of about 12 months. Phase II studies suggest a distinctly higher remission rate and possibly longer survival times for a combination of weekly FA and high-dose 5-FU 24-hour infusion. The aim of our study was to test whether weekly FA/high-dose 5-FU is superior to 5-FU/FA day 1–5 in terms of remission rate and survival time. Patients and Methods: Between January 1993 and December 1996 149 patients entered the study. 76 patients were randomized to receive treatment A (monthly standard: 5-FU 425 mg/m2 iv bolus days 1–5, FA 20 mg/m2 iv bolus days 1–5, repeated every 28 days) and 73 patients were randomized to receive treatment B (weekly high dose: weekly 5-FU 2,600 mg/m2 as 24-hour infusion and FA 500 mg/m2 as 1-hour infusion prior to 5-FU; one course consisting of 4 infusions and repeated after a therapy-free interval of 2 weeks). In cases of progressive disease (PD) therapy was stopped, whereas in cases of partial remission (PR) or stable disease (SD) with improvement of the patient’s clinical condition treatment was continued for a total of 6 courses of treatment A and a total of 3 courses of treatment B. Results: 67 treatment A and 64 treatment B pa-tients were evaluable for response. Treatment A led to 17.9% PR, 34.3% SD and 47.7% PD, and treatment B to 23.4% PR, 57.8% SD and 18.8% PD. PD occurred with statistically higher frequency under treatment A compared with treatment B (p <0.01). Treatment B resulted in statistically significant longer survival times compared with treatment A (p =0.047): Median survival time with treatment B 463 days (95% confidence interval 355–540 days) vs. 370 days (95percnt; confidence interval 276–412 days) with treatment A. The differences in both effects, however, were also found statistically significant in an analysis including other prognostic factors. Toxicity was moderate and roughly comparable between both treatment arms with the exception of a higher occurrence of hand-foot syndrome under treatment B. Conclusion: This is the first phase III study demonstrating a small, but statistically significant superiority of weekly FA/high-dose 5-FU over a conventional 5 day 5-FU/FA regimen in terms of survival time.

Lactic acidosis and hypoglycemia in a patient with high-grade non-Hodgkin's lymphoma and elevated circulating TNF-α

A 71-year-old patient with high-grade non-Hodgkins lymphoma stage IVB, severe lactic acidosis and tumor-associated hypoglycemia is described. Endocrine causes of hypoglycemic episodes were excluded because of low serum concentrations of insulin and “insulin-like growth factor 1”, and normal concentrations of growth hormone and thyroid hormone. Clinical conditions associated with lactic acidosis such as diabetes mellitus, biguanide intoxication, septicemia, acute hypoxemia, or circulatory insufficiency were ruled out. Enhanced glucose metabolism within the tumor was visualized by positron emission tomography employing 2-fluoro-2-deoxy-d-glucose (FDG) as a tracer. A markedly elevated tumor necrosis factor-alpha (TNF-α) level was found which decreased after cytoreductive therapy paralleling the normalization of serum lactate. In contrast to the majority of cases of lymphoma-associated lactic acidoses reviewed to date, in our case lactate elimination was not reduced.

Philadelphia chromosome-positive secondary acute myeloid leukemia following high-dose chemotherapy with peripheral blood progenitor cell support for relapsed low-grade non-Hodgkin's lymphoma

Abstract We report the case of a 47-year-old patient who developed acute myelogenous leukemia (AML) 18 months after receiving high-dose chemotherapy with peripheral blood progenitor cell support (PBPCT) for relapsed low-grade follicular non-Hodgkins lymphoma (NHL). Cytogenetic analysis of the leukemic cells showed the translocation (9;22)(q34;q11). In three mitoses, an addiditional Philadelphia chromosome (Ph1) was present. In the literature, Philadelphia chromosome-positive secondary AML has been described only once before in a patient with multiple myeloma.

Time benefit in the assessment of recurrences following fractionated radiotherapy in an experimental tumour system using positron‐emission tomography with 18F‐fluorodeoxyglucose

Purpose: To determine the sensitivity and specificity of 18F‐fluorodeoxyglucose‐positron‐emission tomography (FDG‐PET) in the diagnosis of R1H tumours after fractionated radiotherapy, and the dependency of sensitivity and specificity on time after therapy. In addition, the time benefit of FDG‐PET concerning early recognition of recurrences after fractionated radiotherapy was assessed. Material and methods: Subcutaneously growing rat rhabdomyosarcoma R1H tumours were irradiated by applying total doses of 80 or 85 Gy after reaching a start volume of 0.8 cm3. Twenty animals were treated. Tumour volume was determined twice a week. FDG‐PET was performed weekly before, during and for 6 months after therapy using a conventional full‐ring whole‐body PET scanner. In total, 600 PET results were evaluated qualitatively using a six‐scale score. PET results and actual tumour volumes were compared. The sensitivity and specificity of tumour detection by PET was calculated for different times after the onset of therapy. The optimal score for tumour detection and the influence of time after therapy on the quality of PET (time benefit) was evaluated using receiver‐operating characteristics. Results: After irradiation, 8/20 tumours (40%) were locally controlled, while 12/20 recurred. In this tumour model, evidence of relapse is assured when a volume of 0.1 cm3 is reached. Sensitivity of tumour diagnosis by PET increases with time, i.e. with the volume of recurrent tumours after the onset of therapy, mounting to >0.95 after 100 days. Specificities of 0.95–1.0 were determined after therapy, showing no increase with time. Tumour diagnosis by PET is highly accurate when performed 80 days after the start of treatment. On average, tumours were recognized by PET on 31, 62, 74 and 81 days (median) before approaching volumes of 0.2, 0.5, 0.8 or 1.0 cm3, respectively. Conclusion: An experimental system was implemented that allows reproducible detection of recurrent R1H tumours after radiotherapy using FDG‐PET. The usefulness of PET as a diagnostic test for R1H tumours is very good and a reliable resolution for PET is demonstrated for volumes<1 cm3. The results indicate that FDG‐PET enables early recognition of recurrences after fractionated radiotherapy.

Treatment of Adult Metastatic Soft-Tissue Sarcoma with Doxorubicin/ Ifosfamide: Better Hematologic Tolerance by G-CSF?

Background: The combination of doxorubicin/ifosfamide is an effective chemotherapy regimen in metastatic soft-tissue sarcomas (STS), generally resulting in remission rates between 30 and 40%. A seriou

Metastasectomy following Chemotherapy in Patients with Advanced Soft Tissue Sarcomas

Background: The prognosis of patients with metastasized soft tissue sarcomas (STS) is very poor. Cure by chemotherapy alone is a rare exception. Patients and Methods: Between 1982 and 1991 96 adult pa

Tnf-alpha induces gm-csf secretion in leukemic-cell lines u-937 and kg-1a.

GM-CSF is constitutively secreted by myeloblasts of some patients with AML. Recently it has been shown that IL-1 and TNF-alpha can induce GM-CSF production in fresh leukemic cells of patients who do not release GM-CSF spontaneously. To further characterize this phenomenon we investigated GM-CSF induction by TNF-alpha in two leukemic cell lines, U 937 and KG-1a. KG-1a constitutively expresses GM-CSF mRNA as demonstrated by Northern blots and PCR analysis. Unstimulated U 937 cells contained no detectable GM-CSF transcripts. After incubation with TNF-alpha, GM-CSF specific m-RNA was found in U 937 cells. Only slight increases of GM-CSF transcripts were noted in KG-1a cells after TNF-alpha treatment. In unstimulated cultures, GMCSF concentrations were below 1 pg/ml. After 3 days of culture detectable levels of GM-CSF were found after stimulation with 1 ng/ml TNF-alpha and reached a mean of 11.9 pg/ml for U 937 and 59.3 pg/ml for KG-1a after incubation in 50 ng/ml TNF-alpha. Therefore mechanisms of GM-CSF expression are regulated differently in each of these cell lines.

781 Infection during severe neutropenia in 182 patients with acute myeloid leukemia (AML)–morbidity and mortality

Infections still remain the major cause of morbidity and mortality in neu-tropenic patients with leukemia. Especially fungal infections are critical during neutopenia. 487 febrile phases were evaluated retrospectively during 377 neutropenic episodes (leukocytes 9 /l) of 182 AML-patients treated in our institution from 1982–1993. We observed 16 neutropenic phases without fever. In 156 episodes (32%) the origin remained unknown (FUO), but 331 (68%) were clinically or microbio-logically identified infections mostly gram-positive bacterial (37%), followed by fungal (31%) and gram-negative bacterial infections (21%). Sepsis (220) and pneumonia (86) represented the major type of infections. 70% of pneumonia were caused by fungi. Urinary tract infections (27), tonsillitis (17), oesophagitis (16) and abscesses (13) turned out to be the other main infection sites. 48 patients died during neutropenia. The leading cause of death was fungal sepsis or pneumonia in 73% (29). 38% (11) of lethal fungal infections were discovered at autopsy; in 9 of these 11 patients mixed infections were observed—frequently a combination of fungal and gram-negative infection. To conclude all patients with pneumonia in neutropenia should be treated early with high dosage antimycotic therapy; in addition a mixed infection should be considered.