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J E Frödin

Publications and source records attributed to J E Frödin.

At least 19 recordsLinked to original sources
PubMed2002

Irinotecan combined with bolus 5-fluorouracil and folinic acid Nordic schedule as first-line therapy in advanced colorectal cancer.

BACKGROUND: This multicentre phase II study evaluated the efficacy and safety of irinotecan combined with the Nordic schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line therapy in patients with advanced colorectal cancer. PATIENTS AND METHODS: Seventy-four patients with measurable disease and a WHO performance status of 2 or less were treated with irinotecan 210 mg/m(2) as a 30-90 min intravenous infusion on day 1, followed by 5-FU 500 mg/m(2) and FA 60 mg/m(2) bolus on days 1 and 2, every 2 weeks, until disease progression or unacceptable toxicity. The primary end point was the objective response rate. RESULTS: Twenty-nine out of 68 evaluable patients achieved a complete (n = 7) or partial (n = 22) response, leading to an overall response rate of 43% [95% confidence interval (CI) 31% to 55%]. The median duration of response was 10 months. The estimated median time to progression and survival were 6.4 months (95% CI 5.4-9.0) and 15.6 months (95% CI 13.3-19.0), respectively, in the intention-to-treat population. A total of 860 cycles were administered to 74 patients. Neutropenia was the main adverse event with grade 3-4 toxicity in 66% of patients and 17.5% of cycles. Grade 3-4 non-haematological toxicities were infrequent and included diarrhoea in 16% of patients and 2% of cycles and nausea/vomiting in 10% of patients and 1% of cycles. CONCLUSIONS: Irinotecan combined with the bolus Nordic schedule of 5-FU/FA is active in advanced colorectal cancer with an easily managed safety profile which ensures good schedule compliance. The low incidence of grade 3-4 non-haematological toxicity justifies the further evaluation of this combination in the context of randomised clinical trials.

Adenocarcinoma↗
PubMed2001

Incidence of GM-CSF antibodies in cancer patients receiving GM-CSF for immunostimulation.

We have assessed the immunogenicity profile of GM-CSF in patients with either colorectal carcinoma (CRC) at different stages of disease or with multiple myeloma who were given recombinant human GM-CSF (Escherichia coli-derived) combination therapy. Metastatic CRC patients received a colon carcinoma-reactive antibody and high doses of GM-CSF (425--500 microg/day for 10 days), while other CRC patients and those with myeloma received low doses of GM-CSF (75--80 microg/day for 4 days) as an adjuvant along with appropriate tumor antigens. We found that 55% of the patients (11/20) given high doses of GM-CSF developed GM-CSF-reactive antibodies in comparison with an incidence of only 16% (4/25) in patients given low doses of GM-CSF. None of the patients developed neutralizing antibodies and so the biological effects of GM-CSF were not compromised. A majority of patients (80%) (36/45) also developed antibodies to E. coli proteins that were present as trace contaminants in the GM-CSF product. Treatment with recombinant GM-CSF products, therefore, may induce antibodies against this cytokine depending on the regimen and the amounts used. In this study, multiple immunizations with low doses of GM-CSF was associated with a low incidence of GM-CSF antibodies, which did not neutralize the effect of the cytokine. This therapeutic strategy was effective in inducing adjuvant-type effects and needs to be explored in further clinical trials with this cytokine.

Antibodies↗
PubMed2000

Ga733/EpCAM as a target for passive and active specific immunotherapy in patients with colorectal carcinoma.

GA733/EpCAM is an oncofetal antigen abundantly expressed in colorectal carcinoma. This antigen can spontaneously induce a humoral and cellular antitumor immunity and may therefore be a suitable target structure for immunotherapy. Patients with advanced colorectal carcinoma have been treated with monoclonal antibodies (MAb17-1A) against this structure. The data indicate that the chimeric variant was not superior to the original mouse MAb. Addition of cytokines and chemotherapeutics may improve the therapeutic effect of the MAb. A particularly interesting regimen is a combination of MAb17-1A/GM-CSF/alpha-IFN/5-Fu. The GA733 protein antigen can also be used as a vaccine. Patients with colorectal carcinoma stages B and C were vaccinated with this protein antigen in combination with GM-CSF as an adjuvant cytokine. A strong type I T cell response was induced that seemed to be MHC class I as well as class II restricted. No systemic side effects were noted.

Animals↗
PubMed1999

Augmentation of the immune response with granulocyte-macrophage colony-stimulating factor and other hematopoietic growth factors.

Granulocyte-macrophage colony-stimulating factor is by far the most widely used hematopoietic growth factor to augment immune responses. At present, the best secured effect is as an adjuvant cytokine for vaccination. Granulocyte-macrophage colony-stimulating factor can be delivered as gene-transduced tumor cells, as plasmid DNA, or as the soluble free granulocyte-macrophage colony-stimulating factor protein. Granulocyte-macrophage colony-stimulating factor must be present at the same site as the vaccine component. Granulocyte-macrophage colony-stimulating factor may also augment the effect of therapeutic monoclonal antibodies by enhancing various effector functions such as antibody-dependent cellular cytotoxicity and amplifying an idiotypic network response (i.e., antitumor immunity). It may also be advantageous to combine granulocyte colony-stimulating factor with monoclonal antibodies (neutrophil and monocyte antibody-dependent cellular cytotoxicity) for tumor therapy. However, these growth factors might also induce immune suppression, which may hamper the contemplated effect of the growth factor. It is urgently warranted to better understand these dual effects on the immune system so that we can find optimal uses for the growth factors in various clinical settings.

Antibody Formation↗
PubMed1998

Immunopathology of metastases in patients of colorectal carcinoma treated with monoclonal antibody 17-1A and granulocyte macrophage colony-stimulating factor.

Twenty patients with metastatic colorectal carcinoma were treated with a single infusion (400 mg) of a mouse monoclonal antibody (IgG2a) against the tumor-associated antigen CO 17-1A and with a daily injection of granulocyte macrophage colony-stimulating factor (GM-CSF) for 10 days. The cycle was repeated every month. Metastases from 5 of the 20 patients biopsied on days 1 and 10 of the first two treatment cycles were studied by immunohistochemistry. During treatment, neutrophils, monocytes, and T lymphocytes increased concordantly in the tumor as in the blood of the individual patient. Macrophages (CD68) and CD8+ T cells infiltrated the tumor glands and displayed TIA-1-reactive cytotoxic granules. Neutrophils were seen mainly in areas of necrosis. Activated (HLA-DR+) CD4+ T cells were usually abundant in the stroma. During treatment, few natural killer cells were found in the tumor, contrary to the marked increase seen in blood. Our observations indicate that GM-CSF markedly recruited activated, tumor-infiltrating leukocytes, possibly representing antibody-dependent cellular cytotoxicity and cytotoxic T effector cells. The notion that combined antibody and GM-CSF therapy may also promote a T-cell antitumor response is further supported and advocated by our findings. The study lends further support to combining GM-CSF with monoclonal antibody-based therapy.

Aged↗
PubMed1997

Multiple primary malignant tumors in a national cancer registry--reliability of reporting.

During the years 1958-1988, 808,522 individuals were registered in the Swedish national population-based cancer register with a total of 933,900 primary malignant tumors. Roughly 11% of the tumors reported to the Swedish Cancer Registry in 1988 were found in persons earlier registered for another primary malignancy. One hundred of the individuals registered with multiple primary malignant tumors were randomly selected for a study of the reliability of reporting of multiple malignancies. Medical records and when necessary histopathological slides and other relevant diagnostic material for each malignancy were collected and the diagnoses reevaluated. Three persons had to be excluded; thus 97 cases with 209 reported malignancies were analysed. Of these, 94% of the first, 98% of the second and 79% of the third malignancy were accepted. Twelve of the reported tumors were not accepted as malignant, five were benign or cancer in situ, five were incorrectly reported as new primaries and two were a second incorrect registration of a previously registered malignancy. All 97 persons had at least one malignant tumor, in 90% of the persons all reported diagnoses were accepted and 93% had multiple primary malignancies. The results of this quality control study indicate that suitable data are available in the Swedish Cancer Registry for investigations related to the occurrence of multiple primary malignancies in a large unselected population. The Swedish Cancer Registry, to which all newly diagnosed malignancies by law have to be reported, comprise today close to one million individuals with registered malignancies.

Breast Neoplasms↗
PubMed1996

Humoral anti-idiotypic and anti-anti-idiotypic immune response in cancer patients treated with monoclonal antibody 17-1A.

A group of 96 patients with advanced colorectal carcinoma were treated with the mouse (m) or chimeric (c) (mouse variable regions x human IgG1 constant regions) monoclonal antibody (mAb) 17-1A recognizing the tumour-associated antigen GA733-2. Eighty-two of the 83 patients treated with mmAb 17-1A and 69% of the patients given cmAb17-1A (n = 13) developed anti-idiotypic antibodies (ab2). Auto-antibodies binding to tumour cells expressing GA733-2 were found in 7% of the patients. In a further 38 patients (40%) antitumour-cell antibodies, i.e. anti-anti-idiotypic antibodies (ab3), were induced by the mAb17-1A therapy. Patients with detectable ab3 after treatment had significantly higher ab2 levels than those not developing ab3. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of ab2 as well as induction of anti-anti-idiotypic antibodies (ab3) compared to mmAb17-1A alone. Patients with a high increase in antitumour-cell antibodies (ab3) induced by the therapy lived significantly longer than patients with no or a low level of induction of ab3 (P = 0.016). The results indicate that induction of an idiotypic network response might be an important effector mechanism in mAb therapy.

Adolescent↗
PubMed1996

Radiotherapy in Sweden--a study of present use in relation to the literature and an estimate of future trends.

This report addresses the role of radiotherapy for treating solid tumors. It is based on a systematic and critical review of the scientific literature, covering close to 1700 published studies, involving more than 700000 patients. The report also compares current practice in radiotherapy with scientific evidence and estimates the cost of radiotherapy. The review of the literature shows there is a fairly solid basis for conclusions about appropriate practices in radiotherapy. There are about 650 studies available which are judged to be of high scientific quality, covering more than half a million patients. This article is a summary of the complete report, which appears as Supplement 6 and 7 of this issue. A third volume, 'Critical Issues in Radiotherapy' is available at SBU.

Evaluation Studies as Topic↗
PubMed1996

Lung cancer.

This synthesis of the literature on radiotherapy for lung cancer is based on 80 scientific articles, including 2 meta-analyses, 29 randomized studies, 19 prospective studies, and 21 retrospective studies. These studies involve 28172 patients. Basic treatment for limited-stage small cell lung cancer (SCLC), is chemotherapy. Addition of radiotherapy to the primary tumor and mediastinum reduces local recurrence, prolongs long-term survival, and is often indicated. Current, and future, studies can be expected to show successive improvements in results for SCLC by optimizing the combination of radiotherapy and chemotherapy. Should these treatments be given simultaneously or sequentially, and in which order? Which fractionation is best? Probably, no change in resource requirements for radiotherapy will be necessary, with the possible exception of changes in fractionation. Surgery constitutes primary treatment for nonsmall cell lung cancer (NSCLC) stages I and II. Radiotherapy may provide an alternative for patients who are inoperable for medical reasons. The value of radiotherapy following radical surgery for NSCLC remains to be shown. It is not indicated based on current knowledge. For NSCLC stage III, radiotherapy shrinks tumors and prolongs survival at 2 and 3 years. Whether it influences long-term survival after 5 years has not been shown. Considering the side effects of treatment, one must question whether limited improvements in survival motivate routine radiotherapy in these patients. Earlier attempts to add chemotherapy to radiotherapy to improve treatment results of NSCLC have not yielded convincing results. Several studies are currently on-going. Prophylactic cranial irradiation (PCI) greatly reduces the risk for brain metastases from SCLC. However, it has little influence on survival. Many treatment centers give PCI to SCLC patients who have achieved complete remission. This practice may be questioned since PCI is associated with serious complications. PCI is not indicated in patients with NSCLC. In SCLC, where the disease is extensive, only palliative radiotherapy is appropriate. Radiotherapy is an important treatment alternative in special palliative situations involving severe cough, severe bleeding, pain, pulmonary obstructions, and vena cava superior syndrome. In these situations, good results may be achieved with few fractions.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Prostate cancer.

This synthesis of the literature on radiotherapy for prostate cancer is based on 53 scientific articles, including 4 randomized studies, 3 prospective studies, and 44 retrospective studies. These studies involve 52005 patients. The literature provides no apparent evidence to motivate radiotherapy, or any treatment, for highly differentiated T0 tumors. Some findings suggest that radiotherapy or surgery may be indicated for poorly differentiated tumors. The literature however shows no differences in tumor effects between these two methods for treating T0 tumors. Radiotherapy is milder and less mutilating. Conclusions cannot be drawn from the literature concerning whether surgery (radical prostatectomy) or external radiotherapy is preferable for T1 and T2 tumors. Most probably, some patients are more suitable for surgery, others for radiotherapy. More patients are, nevertheless, candidates for radiotherapy. The value of external radiotherapy for T3 tumors is documented. Radiotherapy is valuable as palliative treatment for T4 tumors. Radiotherapy may be valuable as localized, symptom-relieving treatment for generalized prostate cancer. Treatment given via a few high fractions saves patients' time, hospitalization, and resources. Concerning individualized treatment, the differentiation grade is important for the choice of treatment method, mainly in early, but even in late clinical stages. This may involve choosing between radiotherapy and endocrine therapy, or even choosing between radiotherapy and surgery. The value of external radiotherapy increases as the differentiation grade of the tumor decreases. It is essential to treat patients at facilities that have the diagnostic potential to establish the differentiation grade of tumors. The value of postoperative radiotherapy has not yet been demonstrated at any clinical stage of prostate cancer. Treatment results from interstitial brachytherapy alone appear to be clearly inferior to the results from other methods. The value of combining interstitial/external radiotherapy should be studied further.

Brachytherapy↗
PubMed1995

Mutation screening in the hMLH1 gene in Swedish hereditary nonpolyposis colon cancer families.

Hereditary nonpolyposis colorectal cancer is caused by heritable defects in the DNA mismatch repair genes hMLH1, hMSH2, hPMS1, and hPMS2. We have used denaturing gradient gel electrophoresis to analyze the 19 exons and exon-intron borders of hMLH1 in 39 Swedish hereditary nonpolyposis colorectal cancer families. Germline mutations were found in eight of these families: two splice mutations affecting exons 3 and 7, respectively, and six missense mutations, of which, four were in exon 2 and one each were in exons 1 and 16. The relatively high number of missense mutations raises several important clinical and technical issues. Such alterations can be identified only when using methods that target DNA or mRNA sequence alteration because they do not cause protein truncations detected by in vitro translation assays. Furthermore, the relationship between these missense mutations and the predisposition to colon cancer is difficult to determine without additional information; thus, genetic counseling based on mutation data is difficult.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Tumor regression in monoclonal antibody-treated patients correlates with the presence of anti-idiotype-reactive T lymphocytes.

Treatment of cancer patients with unconjugated mAbs directed against tumor-associated antigens is considered passive immunotherapy due to the main suggested effector mechanisms: antibody-dependent cellular cytotoxicity, complement-dependent cytolysis, and apoptosis. The therapeutic antibody (ab1) may, however, also give rise to an idiotypic network response, i.e., an immunizing effect. Induced anti-idiotypic antibodies (ab2) mimicking the epitope that ab1 recognizes might subsequently induce an anti-anti-idiotypic humoral (ab3) and T-cell (T3) response recognizing the nominal tumor-associated antigen. Twenty-four patients with metastatic colorectal carcinoma were treated with MAb17-1A against the tumor associated antigen GA733-2 and were analyzed for the induction of T3 cells. Five of the patients responded to mAb therapy with tumor regression. These five patients all had T cells specifically recognizing human ab2 (DNA synthesis) after treatment, while all nonresponding patients lacked such T cells. Four of the five patients with ab2-reactive T cells also showed induction of T cells recognizing GA733-2. The association between T3 cells and tumor regression was highly significant (P = 0.0005). Thus, induction of T3 cells might be an important secondary antitumor effector function of therapy with unconjugated mAbs. Antibody therapy may therefore also be considered active specific immunotherapy.

Adult↗
PubMed1995

Granulocyte/macrophage-colony-stimulating factor augments the induction of antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal antibodies.

A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n = 76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P < 0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15 micrograms/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P < 0.05). Moreover, patients with a high ab2 concentration (at least 15 micrograms/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P = 0.01).

Adolescent↗
PubMed1994

Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients.

The pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM-CSF (250 micrograms/m2/d; Escherichia coli-derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM-CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/- 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown.

Adolescent↗
PubMed1994

Induction of an immune network cascade in cancer patients treated with monoclonal antibodies (ab1). II. Is induction of anti-idiotype reactive T cells (T3) of importance for tumor response to mAb therapy?

The antitumor effector functions of unconjugated monoclonal antibodies (mAb) in cancer therapy are not fully understood. Direct cytotoxic mechanisms such as antibody-dependent cellular cytotoxicity, complement-dependent cytolysis and apoptosis have been suggested. Induction of anti-idiotypic (ab2) and anti-anti-idiotypic (ab3) antibodies as well as the corresponding T cells (T2 and T3) has also been proposed to be of therapeutic significance. In this study induction of an immune network cascade in ten patients with colorectal carcinoma, treated with mAb 17-1A (ab1) was assessed. After treatment, all ten patients had anti-idiotypic antibodies and anti-anti-idiotypic antibodies with ab1-like binding specificity while only five of ten patients had T cells corresponding to ab3 (T3) as assessed by a proliferation assay (DNA synthesis), and an assay of interferon gamma production (ELISPOT) (Enzyme-linked immuno SPOT) in vitro or by a delayed-type hypersensitivity reaction in vivo. Purified T cells from four of the five patients with a positive T3 test responded with DNA synthesis after stimulation using human anti-mAb 17-1A anti-idiotypic monoclonal antibodies. These four patients had a clinical response showing a tumor reduction after therapy, while all six patients lacking a proliferative response failed to show tumor regression. Induction of a cell-mediated immune network cascade might accordingly be an important antitumor effector function of mAb and should be considered in the future design of mAb-based therapy protocols in cancer patients.

Adult↗
PubMed1994

Cytotoxicity of white blood cells activated by granulocyte-colony-stimulating factor, granulocyte/macrophage-colony-stimulating factor and macrophage-colony-stimulating factor against tumor cells in the presence of various monoclonal antibodies.

Unconjugated monoclonal antibodies (mAb) kill tumor cells in vivo by activating immune functions. One of these is ADCC (antibody-dependent cellular cytotoxicity). The efficacy of mAbs might be augmented if the cytotoxic capacity of the effector cells could be increased. In this study the augmenting effect of granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage(GM)-CSF and macrophage(M)-CSF was analyzed. Effector cells [peripheral blood mononuclear cells (PBMC) or granulocytes] were activated for 4-6 h by the respective CSF and assayed in an 18-h Cr51-release assay. Human colorectal, lymphoma, glioma and melanoma cell lines were target cells. Mouse mAbs of different isotypes, as well as chimeric and humanized mAbs, were used. mAbs having the human Fc part of the IgG molecule were the most effective. The killing capacity of PBMC as well as of granulocytes was statistically significantly enhanced when mAbs were added. M-CSF and GM-CSF were the best CSF for augmenting the lytic capacity of PBMC in ADCC. G-CSF had no significant effect on PBMC. Spontaneous cytolysis of PBMC was significantly augmented only by M-CSF. Granulocytes were, in general, significantly less effective than PBMC but may be equally effective killer cells together with mouse or human mAbs of the IgG1 isotype, particularly against melanoma cells. Granulocytes may also be significantly stimulated to increased lytic capacity when activated with G-CSF or GM-CSF. On the basis of the present evaluation, clinical trials in tumor patients are warranted, combining mAbs with GM-CSF or M-CSF. Preference might be given to GM-CSF as this cytokine activates both PBMC and granulocytes.

Adult↗
PubMed1993

Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma--long-lasting, complete remissions can be induced.

Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of unconjugated monoclonal antibodies (MAbs) in tumor therapy. The antitumor activity of MAbs might therefore be augmented if the cytotoxic capability of the effector cells could be increased. In an in vitro system, the killing capacity of MAb was significantly enhanced by pre-treatment of the effector cells with granulocyte-macrophage colony-stimulating factor (GM-CSF). Based on these findings, the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) and GM-CSF was evaluated in 20 patients with metastatic colorectal carcinoma (CRC). The patients received GM-CSF for 10 days and a single i.v. infusion of MAb 17-1A on day 3 of the cycle. Four cycles were given at 1-monthly intervals. There was a continuous increase in blood monocytes and lymphocytes during all 4 GM-CSF cycles. Neutrophils and eosinophils were also significantly augmented but in a biphasic manner and the cell counts on day 10 of cycle IV were significantly lower than in cycles I and II. GM-CSF-related side-effects were of no major clinical importance. During the third cycle, an immediate-type allergic reaction (ITAR) against MAb 17-1A occurred in most patients, necessitating reduction of the MAb dose as well as of the infusion rate. Two patients achieved complete remission. One patient had a minor response, and 3 other patients were considered to have stable disease > 3 months.

Adolescent↗