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PubMed2006

Tumor cell detection in peripheral blood and bone marrow.

PURPOSE OF REVIEW: Whether the occurrence of tumor cells in peripheral blood or bone marrow from patients with solid tumors is predictive for disease recurrence or of any other prognostic relevance remains unknown. This article reviews recently published results focusing on the various methods used, their correlations with clinical or biological parameters and their potential prognostic value. RECENT FINDINGS: An increasing number of marker genes and different techniques, alone or in combinations, have been used for the detection of tumor cells in peripheral blood and bone marrow. Various results obtained are hardly comparable, most often due to the different methods in use. The frequency of circulating tumor cells in peripheral blood varied within a broad range and their clinical relevance appeared to be contradictory, at least in part. Disseminated tumor cells in bone marrow reached an independent prognostic value in breast cancer patients, but several investigations led to inconsistent correlations with clinical or prognostic criteria. SUMMARY: Still many questions remain unanswered; hence, the detection of tumor cells in peripheral blood or bone marrow cannot yet be taken into account for therapeutic decisions.

Biomarkers, Tumor↗

PubMed1985

[Extended radical nephrectomy in renal carcinoma involving the inferior vena cava: a case report].

A case of successful removal of right renal cell carcinoma extending into inferior vena cava in a 62-year-old man was reported. The tumor thrombus reached the level of the liver and almost completely obliterated both caval and contralateral renal veins. With cooperation of cardiovascular and hepatic surgeons, the operation was performed under thoracoabdominal exposure. Extensive mobilization of the liver enabled us to regulate vena caval and hepatic blood circulation. The tumor thrombus, though partly adhesive to the caval vein, could be completely removed safely through a long cavotomy incision. To cope with the recent advance in more aggressive cancer surgery, it seems mandatory for urologists to acquire a broad knowledge of thoracic, cardiovascular and hepatic surgery as well.

Carcinoma, Renal Cell↗

PubMedDate not supplied

[Current biological markers of cutaneous melanoma progression].

Melanoma is the most agressive skin cancer in humans. The most important prognostic factors are the histological features of the tumor, while the clinical ones play a secondary role. Melanoma progression is characterized by the metastatic process which directly threatens the patients life. Unfortunately, routine imaging methods cannot estimate early enough this metastatic risk. Are biologic markers of cancer progression more efficient than those applied in everyday practice? Are they able to evaluate the metastatic risk and thus help the therapeutic strategy? In this review, we analysed the analytical and the clinical aspects of biologic markers of cutaneous melanoma currently available or in development. At the present time it is very difficult to distinguish one single marker of melanoma progression in the blood which correlates with the stage and the prognosis of melanoma. The most specific and sensitive enough are the melanoma associated antigens protein S-100, MIA (melanoma inhibiting activity) and the melanin precursors 5-S-cysteinyldopa and the ratio L-dopa/L-tyrosine. Tyrosinase mRNA remains the best target for the detection of circulating metastatic melanoma cells by RT-PCR. Simultaneous detection of several markers might be useful if they are carefully selected. Despite the progress in the field, more clinical studies should be performed for the development of new techniques or improvements of the existing ones for the follow-up of cutaneous melanoma.

Antigens, Neoplasm↗

PubMed2006

Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance.

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.

Adult↗

PubMed1976

[Lymph node pathology during dermatoses with circulating Sézary cells].

The authors reported 12 cases of patients with cutaneous involvment associated with the presence of Sezary cells in the peripheral blood and specific lymph node involvment. They classify these cases as partial, early segmentary types, advanced types and diffuse types. either leukemic or sarcomatous. This study, once again, suggests the possibility that the Sezary syndrome and mycosis fu ngoïdes are different expressions, either predominantly leukemic, or predominantly sarcomatous, of the same chronic malignant hemopathy of "T" lymphocytes.

Aged↗

PubMed2006

Thyroid-stimulating hormone receptor messenger ribonucleic acid measurement in blood as a marker for circulating thyroid cancer cells and its role in the preoperative diagnosis of thyroid cancer.

CONTEXT: Thyroid cancer cells express TSH receptor (TSHR) mRNA, and its measurement in the circulation may be useful in the diagnosis/management of differentiated thyroid cancer (DTC). OBJECTIVE: Our objective was to assess the diagnostic value of circulating TSHR mRNA for preoperative detection of DTC in patients with thyroid nodules. PATIENTS: We measured TSHR mRNA levels by RT-PCR in 258 subjects: 51 healthy subjects and 207 patients (thyroid nodules, n = 180; recurrent thyroid cancer, n = 27) with fine-needle aspirations (FNA) and/or thyroid/neck surgery. Eighty-nine patients also had d-1 postoperative levels assessed. OUTCOME MEASURES: TSHR mRNA levels were compared with FNA cytology for cancer detection preoperatively and serum thyroglobulin and/or whole-body 131I scans postoperatively. RESULTS: Based on cytology/pathology, 88 patients had DTC and 119 had benign thyroid disease. The TSHR mRNA levels in cancer patients were significantly higher than in benign disease (P < 0.0001). At a cutoff value of 1.02 ng/microg total RNA, the TSHR mRNA correctly classified 78.7% of patients preoperatively (sensitivity = 72.0%; specificity = 82.5%). Of 131 patients with FNA and surgery, 51 were FNA positive (all cancer), 17 were FNA negative (15 benign, two cancer), and 63 were indeterminate. TSHR mRNA correctly diagnosed DTC in 16 of 24 (67%) and benign disease in 29 of 39 (74%) patients with indeterminate FNA (combined sensitivity = 90%; specificity = 80%). Combining TSHR mRNA and ultrasound features for follicular lesions correctly classified all follicular cancers and could have spared surgery in 31% of these patients with benign disease. TSHR mRNA has a short life in circulation, and normalized levels on postoperative d 1 correlated with disease-free status, whereas elevated levels predicted residual/metastatic disease. CONCLUSIONS: TSHR mRNA measured with FNA enhances the preoperative detection of cancer in patients with thyroid nodules, reducing unnecessary surgeries, and immediate postoperative levels can predict residual/metastatic disease.

Adenocarcinoma, Follicular↗

PubMed2000

Circulating tumorous cells in patients with hepatocellular carcinoma. Clinical impact and future directions.

The circulation of liver-derived cells in patients with hepatocellular carcinoma (HCC) has been demonstrated by reverse transcriptase-polymerase chain reaction (RT-PCR) analyses. Contrasting results have been reported until now about the clinical impact of these assays, mainly due to technical differences. The use of RT-PCR approaches is now clearly, not suitable for recognition of circulating tumorous cells (CTC) when the test is performed after invasive medical or surgical procedures. Furthermore, the RT-PCR approach is incapable of analyzing the expression of invasion-related genes in CTC. Recently, new assays have been proposed to isolate CTC. They allow immunomorphological and molecular characterization of individual tumor cells. Based on these new results, new therapeutic approaches of metastases should be developed in the near future.

Albumins↗

PubMed2003

Feasibility of fludarabine added to VAD during induction therapy in multiple myeloma: a randomised phase II-study.

Multiple myeloma (MM) is considered to be an essentially incurable haematological malignant disease, probably because of the existence of resistant clonal precursor cell with self-renewal capacity. Recent data have indicated that the myeloma cell hierarchy includes circulating clonal memory B cells, which differ considerably from the classical end-stage plasma cells, infiltrating the bone marrow. The pathophysiological significance of these cells is unknown, but hypothetically they may serve as 'sleeping' myeloma stem cells responsible for and 'feeding' post-treatment relapse and progression. The present study evaluates the toxicity and feasibility of fludarabine, added to the VAD-induction regimen in MM, and investigates the effect on the myeloma cell hierarchy. Nineteen patients were randomised to receive either four cycles of VAD (n = 9) or two cycles of VAD, followed by two cycles of VAD combined with 5 days fludarabine 25 mg/m2/day i.v. (n = 10). Toxicity evaluation showed more profound neutropenia in the fludarabine-treated patients and two infectious episodes in each study arm: three were fever of unknown origin while one, in the fludarabine-arm, was a local skin infection at the insertion site of the central venous line. Nine of the fludarabine-treated patients responded to treatment (two complete remission, seven partial remission), compared with five responders (all PR) in the control-arm. The effects on the blood circulating myeloma compartments identified an increased reduction of CD19+ B cells and myeloma plasma cells in the fludarabine-arm. In conclusion, adding fludarabine to VAD induction in multiple myeloma is feasible and may be clinically effective by reducing the myeloma clone.

Aged↗

PubMed2002

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA.

KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribonucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P<0.002). None of the latter developed a pancreatic cancer within the 36 months of median follow-up. The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.

Adenocarcinoma↗

PubMed1997

Detection of disseminated tumor cells in peripheral blood of colorectal cancer patients.

All cancer staging systems seek to identify clinical and pathological features that can predict outcome or guide therapy. In particular, a non-invasive method for the early detection of disseminating disease would be of great interest. We investigated the use of cytokeratin genes expression to detect blood metastases from colorectal tumors. Epithelial tumor cells were isolated from whole blood using the monoclonal antibody (MAb) BerEP4 and magnetic beads, and detected by reverse transcription-polymerase chain reaction using oligonucleotides derived from the cDNA sequences of cytokeratins 8, 19 and 20. The sensitivity of this assay was determined by spiking SW620 colon carcinoma cells in normal blood. Using cytokeratin 19 expression we were able to detect 1 epithelial tumor cell in 1 ml of whole blood. The clinical applicability of this technique was explored by evaluating patients with a colorectal carcinoma. Epithelial cells were detected in the blood of 12 out of 23 patients, 2 (20%) of 10 with Astler-Coller stage A or B, and 10 (77%) of 13 with stage C or D cancer. In conclusion, this test is a non-invasive, sensitive, and specific assay for detecting circulating epithelial cells in blood. It may be useful for the early diagnosis of disseminating disease, to determine whether the presence of micrometastatic cells at the time of surgery is correlated with an early relapse and for monitoring adjuvant therapeutic trials.

Adult↗

PubMed2005

Observation of circulating tumour cells in patients with non-small cell lung cancer by real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction in peroperative period.

PURPOSE: To assess whether surgical manoeuvre or resection of lung cancer could lead to haematogenous dissemination of malignant cells. In the mean time, the relationship between the sequence of vessel ligation and the haematogenous dissemination of cancer cells during operation was determined. METHODS: Exploiting cytokeratin 19 (CK19)/carcinoembryonic antigen (CEA) mRNA as markers, 69 peripheral blood samples were collected from 23 consecutive patients with non-small cell lung cancer (NSCLC) who underwent surgical resection with curative intention in preoperative, intraoperative and postoperative period, respectively. Before the operation, all patients were randomly assigned to one of the two surgical procedure groups according to the order of vessel ligation, PV-first group and PA-first group. Additionally, the ten patients with benign lung disease served as control subjects undergoing surgical resection. The quantity and timing of the shedding of lung cancer cells into the circulation of patients were also monitored by fluorescent quantitative-reverse transcriptase-polymerase chain reaction before, during and after surgery. RESULTS: (1) The CK19 diagnostic test: the value of CK19 mRNA in operation was significantly higher than that of preoperation (5.246+/-0.196 vs. 4.472+/-0.164, P=0.000) and postoperation (5.246+/-0.196 vs. 4.694+/-0.177, P=0.013). The values between adenocarcinoma and squamous carcinoma were strikingly different (4.9110+/-1.0315 vs. 4.1891+/-0.4126, t=2.364, P=0.028). The values between PV-first group and PA-first group during perioperative period appear to be different (4.503 vs. 5.085, P=0.086). Before operation, of the 23 cases studied, 14 cases were positive (60.9%). Surprisingly, circulating epithelial cells were detected in two patients resected for benign lung disease. (2) The CEA diagnostic test: the level of CEA mRNA ascended continuously within this period. The postoperative values were significantly higher than those of preoperation (4.874 vs. 4.483, P=0.000) and those of operative day (4.874 vs. 4.537, P=0.000). The values between PV-first group and PA-first group appear to reach statistical significance (4.397 vs. 4.817, P=0.075). At the same time, there was a correlation between preoperative T-stage and perioperative CEA mRNA (4.267 vs. 4.760, P=0.025). Among the 23 cases, 10 cases were positive (43.5%). Both patients with benign lung disease served as control subjects undergoing surgical resection and the volunteers were negative. CONCLUSIONS: A considerable proportion of patients who appear to have resectable NSCLC might be regarded as having systemic disease, which is often undetectable by current tumour staging method. In terms of a marker used for the NSCLC patients who undergo operation, CEA is more suitable than CK19. The CK19-expressing epithelial cells are released intraoperatively into the circulation, meanwhile CEA-expressing tumour cells are disseminated mostly postoperatively. Surgical manipulation could promote the release of tumour cells into the bloodstream, but the ligation of pulmonary vein before the ligation of the pulmonary artery may partly prevent such release during surgery.

Aged↗

PubMed2004

The natural course of cutaneous melanoma.

The natural course of cutaneous melanoma (CM) is determined by its metastatic spread and depends on tumor thickness, ulceration, gender, localization, and the histologic subtype of the primary tumor. CM metastasis develops via three main metastatic pathways and occurs as satellite or in-transit metastasis, as regional lymph node metastasis or as distant metastasis at the time of primary recurrence. About 50% of all CM patients with tumor progression firstly develop regional lymph node metastases. In the other 50% the first metastases are satellite or in-transit metastases (about 20%), or immediately distant metastases (about 30%). Development of distant metastasis appears to be an early event in metastatic spread and may in the majority of cases originate from the primary tumor, only few cases may develop secondarily to locoregional metastasis. Reporting of organ involvement in distant metastasis greatly differs between the results of imaging techniques and autopsy results in respect to the metastatic patterns detected, pointing out that there is a need of improved imaging systems. Proliferation, neovascularization, lymphangiogenesis, invasion, circulation, and embolism are important steps in the pathogenesis of CM metastasis, with tumor vascularity as an important independent significant prognostic factor. The expression of chemokine receptors in cancer cells associated with the expression of the respective chemokine receptor ligands in the target sites of the metastasis is an interesting observation which may stimulate the development of new therapeutic strategies.

Humans↗

PubMed2002

[Micrometastases in colonic cancers: diagnostic methods and prognostic elements].

Micrometastasis are defined by the existence of cells or groups of cells in target organs. In the particular cas of colon cancers, although lymph node involvement is frequent, metastatic medullary involvement (while rarely at the origin of identified metastasis) can also be observed. Furthermore, micrometastatics cells can be identified in the circulating blood. This research relies on recent technics of immunocytochemistry with image analysis or molecular biology technics (generally PCR or RT-PCR). It is essential to have a specific reliable marker of metastatic cells. The prognostic value of identifying micrometastasis in organs also remains to be defined.

Biomarkers, Tumor↗

PubMed1993

Detection of circulating monoclonal lymphocytes in multiple myeloma patients by analysis of gene rearrangements: correlation with progressive disease.

Multiple myeloma is characterized by the proliferation of a monoclonal plasma cell population that essentially spreads in the bone marrow. However, immunological data and studies on clonal gene rearrangements have provided evidence for circulating malignant B-lymphocytes. Herein, we report on the detection and clinical significance of monoclonal lymphocytes in the peripheral blood of multiple myeloma patients. Applying the analysis of immunoglobulin gene rearrangements, clonal circulating lymphocytes were found in 8 out of 37 patients. In three of these eight patients, DNA from the bone marrow could be examined as well, and the same gene rearrangement as in peripheral blood was detected. This observation indicates that the monoclonal lymphocytes in the peripheral blood are part of the malignant plasma cell clone in the bone marrow. There was a strong correlation between progressive stage III disease and the detection of circulating tumour cells, whereas neither in stable stage III nor stage I disease could clonal gene rearrangements be detected. Our findings indicate the high incidence of monoclonal lymphocytes in the peripheral blood from patients with progressive multiple myeloma. This may be of importance with respect to cell harvesting strategies for autologous peripheral stem cell transplantation in multiple myeloma.

Aged↗

PubMed1975

Techniques for inhibiting tumor metastases.

Of the four major biological mechanisms of cancer spread, hematogenous dissemination is perhaps the most significant, as it usually heralds a fatal outcome for the patient. Recent experimental approaches have shown ways of altering the metastatic process and even totally inhibiting it in some animal models. It appears that these models may be applicable to certain human cancers. To prevent hematogenous metastasis formation the process must be inhibited at any one of four levels: 1) growth of the primary; 2) invasion of vessel walls; 3) release of viable tumor cells; or 4) entrapment and growth in distant organs. Judicious handling of the primary can decrease metastasis by minimizing the shedding of tumor cells. New experimental agents prevent the release of tumor cells from the primary by normalizing the blood vessels of the tumor. Warfarin, heparin, and fibrinolytic agents inhibit the entrapment of circulating tumor cells, presumably by their effect on coagulative mechanisms. A better understanding of the benefits of combined approaches to cancer using chemotherapy, irradiation, and immunotherapy, alone and as adjuncts to surgery, offers new opportunity to study methods of controlling metastatic disease.

Animals↗

PubMed2004

Immunomagnetic enrichment, genomic characterization, and prognostic impact of circulating melanoma cells.

PURPOSE: The finding of melanoma cells in the peripheral blood, thus far mainly inferred from the PCR-based demonstration of tyrosinase mRNA, has been associated with metastatic melanoma. Neither the malignant nature nor the prognostic significance of circulating cells could be established. To address this question, we analyzed immunomagnetically isolated circulating melanoma cells for chromosomal aberrations and performed a clinical follow-up study of the enrolled patients. EXPERIMENTAL DESIGN: In a prospective study, blood samples were taken from 164 melanoma patients and 50 donors without malignant disease. Circulating melanoma cells were enriched by immunomagnetic cell sorting using a murine monoclonal antibody against the melanoma-associated chondroitin sulfate proteoglycan. To prove the malignant origin of the positive cells and to define their chromosomal aberrations, we analyzed the genomes of 15 individually isolated cells from seven patients by single-cell comparative genomic hybridization (SCOMP). RESULTS: Absolute and relative frequencies of circulating melanoma cells were associated with stage and with the presence or absence of detectable tumor. The detection of two or more cells correlated significantly with a reduced survival of patients with metastatic melanoma. All of the cells that were analyzed by SCOMP displayed multiple chromosomal changes and carried aberrations typical for melanoma. CONCLUSIONS: Immunomagnetic enrichment enables isolation and genomic characterization of circulating melanoma cells. The prognostic impact on survival of metastatic patients apparently reflects the aggressiveness of an ongoing tumor spread. Direct genomic analysis of the enriched and isolated cells will help to clarify the molecular-genetic basis of the establishment of generalized melanoma.

Antibodies, Monoclonal↗

PubMed1997

Detection of circulating prostate carcinoma cells via an enhanced reverse transcriptase-polymerase chain reaction assay in patients with early stage prostate carcinoma. Independence from other pretreatment characteristics.

BACKGROUND: Circulating prostate cells can be detected in the venous blood of patients with clinically localized prostate carcinoma by applying reverse transcriptase-polymerase chain reaction (RT-PCR) techniques using primers specific for the prostate specific antigen (PSA) gene. This study evaluates whether the detection of circulating cells correlates with established prognostic factors, treatment, and pathologic stage. METHODS: Two hundred and twenty-seven patients with clinically localized adenocarcinoma of the prostate had an RT-PCR assay performed as part of their staging evaluation. No treatment decisions were made on the basis of the RT-PCR results. Of these, 156 patients were treated with radical prostatectomy (RP) and 71 with radical external beam radiotherapy (EBRT). Forty-eight patients were treated with hormonal therapy prior to RP (n = 39) or EBRT (n = 9). The prognostic factors analyzed for their relationship to RT-PCR were clinical stage, pretreatment serum PSA levels, Gleason score of the biopsy specimen, and Gleason score of the surgical specimen. An analysis of the relationship between treatment and RT-PCR results was also performed. Multivariate logistic regression analysis of predictors of RT-PCR positivity was performed as well. In addition, univariate and multivariate analyses of predictors of pathologic stage, including RT-PCR, were performed. RESULTS: Sixty-one patients (26.9%) had a positive RT-PCR assay. There was no relationship between clinical stage, pretreatment PSA, biopsy Gleason score, or surgical Gleason score and RT-PCR positivity. In univariate analysis, patients treated with RP had a higher rate of RT-PCR positivity than patients treated with EBRT (P = 0.054). However, in multivariate logistic regression analysis no factor, including treatment with RP, was a significant predictor of RT-PCR positivity. RT-PCR and pretreatment PSA predicted pathologic stage in univariate and multivariate analyses (P < 0.0001 and P = 0.002, respectively). CONCLUSIONS: The detection of circulating prostate cells using RT-PCR occurs in approximately 25% of early stage prostate carcinoma patients and is independent of other established prognostic factors. In addition, a positive RT-PCR assay is a strong predictor of pathologic upstaging in patients with clinically organ-confined disease.

Analysis of Variance↗

PubMed2003

Dynamics of circulating t(14;18)-positive cells during first-line and subsequent lines of treatment in follicular lymphoma.

In follicular lymphoma the t(14;18) might be useful as a tumor marker in predicting the quality of the response to treatment. We investigated whether analyzing numbers of t(14;18)-positive cells in peripheral blood correlated with remission status in individual patients receiving a variety of treatments. Numbers of circulating t(14;18)-positive cells were determined by real-time polymerase chain reaction (PCR) technique. Disease parameters and response to treatment were related to the pre- and post-treatment numbers of circulating t(14;18)-positive cells for 53 follicular lymphoma patients. In these 53 patients, 70 treatment episodes were investigated. A content of more than 328 t(14;18)-positive cells per 75,000 cells prior to therapy correlated with the more advanced stage IV disease ( P=0.01), bone marrow involvement ( P<0.01), and overt leukemic lymphoma ( P=0.04). Therapy episodes that cleared circulation from t(14;18)-positive cells with more than one log resulted in a significantly longer progression-free survival than treatment episodes with less than one log decline (26 versus 12 months, respectively) ( P<0.01). After first-line treatment episodes, numbers of circulating t(14;18)-positive cells declined in fairly all cases, irrespective of the clinical response. However, for second or later lines of treatment, declining numbers of lymphoma cells correlated with a clinical remission, whereas increasing numbers of lymphoma cells were associated with clinically stable or progressive disease. From this, we conclude that quantitation of circulating t(14;18)-positive cells in peripheral blood is of only limited clinical significance in predicting treatment efficacy for the individual follicular lymphoma patient.

Antineoplastic Combined Chemotherapy Protocols↗