Value of FDG-PET in detecting residual or recurrent nonsmall cell lung cancer.
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In order to evaluate the usefulness of 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of therapeutic effects, a study was performed before and after therapy in 126 patients with non-small cell lung cancer (NSCLC) codified stage I to stage IIIB. Treatment with an early curative result was given in 58 patients, whereas in 68 cases it was limited to palliation. During the treatment follow-up period (8-40 months), each patient was evaluated every 3 months by clinical examination and < or =6 months by imaging techniques (PET and computed tomography (CT)). A diagnosis of persistent or recurrent tumour was established by means of pathological analysis in 31 patients and by clinical evolution and subsequent imaging progression in 29 other patients. PET showed increased FDG uptake in all cases (n = 60) of persistent or recurrent tumour, whereas CT was nonspecific in 17 cases. Conversely, there were five false positive cases via PET imaging and three via CT. In detecting residual or recurrent NSCLC, PET had a sensitivity of 100% and specificity of 92%, whereas CT had a sensitivity and specificity of 71% and 95% respectively. In conclusion, 18-fluorodeoxyglucose positron emission tomography correctly identified response to therapy in 96% (121 of 126) of patients. Positron emission tomography appears to be more accurate (p = 0.05) than conventional imaging in distinguishing persistent or recurrent tumour from fibrotic scar in patients undergoing treatment for non-small cell lung cancer. (+info)
Successful peripheral blood stem cell transplantation for myelodysplastic syndrome.
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Wilms' tumor (WT1) gene expression is increased in patients with leukemia as well as myelodysplastic syndrome (MDS) and is useful for detection of minimal residual disease (MRD). A 47-year-old man given a diagnosis of refractory anemia with excess of blasts in transformation (RAEB-T) received myeloablative therapy followed by autologous peripheral blood stem cell transplantation (PBSCT). MRD by WT1 expression was not detected in the graft. The patient has been in CR for 25 months after PBSCT. These observations suggest that PBSCT is feasible for patients with RAEB-T and analysis of WT1 expression can be applied for patients with high risk MDS. (+info)
Local relapse in primary breast cancer patients with unexcised positive surgical margins after lumpectomy, radiotherapy and chemoendocrine therapy.
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BACKGROUND: Inadequate surgical excision with residual involvement of resection margins by tumour after breast conservation results in increased local recurrence rates. To reduce this risk positive margins are, therefore, usually excised. Systemic treatment with tamoxifen or chemotherapy reduces local recurrence, along with radiotherapy. However, no studies to date have examined the correlation between chemoendocrine treatment, together with radiotherapy, and local relapse in patients with unexcised involved resection margins, having had breast conservation treatment. PATIENTS AND METHODS: The histopathology reports were reviewed of 184 patients who were treated from June 1991 to August 1995 within our randomised study of neoadjuvant versus adjuvant chemoendocrine therapy with mitozantrone and methotrexate (2M) +/- mitomycin-C (3M) and tamoxifen, used concurrently with radiation following conservation surgical treatment. Histological resection margin was considered positive if ductal carcinoma in situ (DCIS) or invasive carcinoma was present microscopically less than 1 mm from the excision margin. RESULTS: Although 38% of patients had unexcised microscopically involved margins, local relapse rate as first site of relapse was only 1.9% after a median follow up of 57 months. There was no difference in distant relapse (P = 0.2) and survival (P = 0.5) between the positive and negative margins groups. CONCLUSIONS: The presence of positive unexcised margins does not have a significant effect on outcome in patients who are treated with chemoendocrine therapy together with radiotherapy. Further clinical trials are required. (+info)
Rapid molecular response during early induction chemotherapy predicts a good outcome in childhood acute lymphoblastic leukemia.
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Early response to therapy is an independent prognostic factor in childhood acute lymphoblastic leukemia. Although most patients have rapid early responses, as detected by morphology, 15% to 20% of patients have relapses. The authors evaluated residual disease by molecular methods on day 15 of minimal residual disease (MRD) therapy and compared these data with their recently established MRD-based risk stratification, defined by MRD levels 5 weeks after induction treatment and before consolidation. All 68 children treated according to current Berlin-Frankfurt-Munster (BFM) protocols went into morphologically complete remission after induction. There was a significant difference in outcome between children with rapid disease clearance and those with high levels of day-15 MRD (P =.035). Among patients with high levels of day-15 MRD, only the MRD-based risk stratification was predictive of the outcome. All patients with negative or low day-15 MRD had excellent prognoses and were in the MRD-based low-risk group. Thus, after only 2 weeks of treatment, the authors were able to identify a patient population of 20% who may benefit from the least intensive treatment. (+info)
Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.
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One of the most common translocations in acute myeloid leukemia (AML) is the t(8;21), which produces the fusion gene AML1-MTG8. We have developed a sensitive competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for AML1-MTG8 transcripts, coupled with a competitive RT-PCR for the ABL transcript as a control to accurately estimate the level of amplifiable RNA. We have shown that AML1-MTG8 and ABL transcripts have equal degradation rates. Thus, this method is useful for multicenter studies. We studied 25 patients with t(8;21) AML by means of serial analysis done on bone marrow (BM) and peripheral blood (PB) samples from 21 patients. Our analysis showed that, in general, a successful induction chemotherapy produces a reduction of 2 to 3 log in the level of AML1-MTG8, followed by a further 2 to 3 log after consolidation/intensification chemotherapy. Levels up to 1 x 10(3) and 1 x 10(2) molecules/microg of RNA in BM and PB, respectively, were compatible with durable remission. On the other hand, 5 patients with levels of 0.71 x 10(5) to 2.27 x 10(5) molecules/microg of RNA in BM and 2.27 x 10(3) to 2.27 x 10(4) molecules/microg of RNA in PB had hematologic relapse within 3 to 6 months. Our data indicate that serial quantitation of AML1-MTG8 transcripts is useful in identifying patients at high risk of relapse and may offer an opportunity for clinical intervention to prevent hematologic relapse. This approach was applied successfully in a patient who had an allogeneic BM transplantation. We also suggest that PB may be used an alternative to BM for quantitating AML1-MTG8 transcripts. (+info)
Myeloma progenitors in the blood of patients with aggressive or minimal disease: engraftment and self-renewal of primary human myeloma in the bone marrow of NOD SCID mice.
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The myelomagenic capacity of clonotypic myeloma cells in G-CSF mobilized blood was tested by xenotransplant. Intracardiac (IC) injection of NOD SCID mice with peripheral cells from 5 patients who had aggressive myeloma led to lytic bone lesions, human Ig in the serum, human plasma cells, and a high frequency of clonotypic cells in the murine bone marrow (BM). Human B and plasma cells were detected in BM, spleen, and blood. Injection of ex vivo multiple myeloma cells directly into the murine sternal BM (intraosseus injection [IO]) leads to lytic bone lesions, BM plasma cells, and a high frequency of clonotypic cells in the femoral BM. This shows that myeloma has spread from the primary injection site to distant BM locations. By using a cellular limiting dilution PCR assay to quantify clonotypic B lineage cells, we confirmed that peripheral myeloma cells homed to the murine BM after IC and IO injection. The myeloma progenitor undergoes self-renewal in murine BM, as demonstrated by the transfer of human myeloma to a secondary recipient mouse. For 6 of 7 patients, G-CSF mobilized cells from patients who have minimal disease, taken at the time of mobilization or after cryopreservation, included myeloma progenitors as identified by engraftment of clonotypic cells and/or lytic bone disease in mice. This indicates that myeloma progenitors are mobilized into the blood by cyclophosphamide/G-CSF. Their ability to generate myeloma in a xenotransplant model implies that such progenitors are also myelomagenic when reinfused into patients, and suggests the need for an effective strategy to purge them before transplant. (+info)
The detection of wt-1 transcripts is not associated with an increased leukemic relapse rate in patients with acute leukemia after allogeneic bone marrow or peripheral blood stem cell transplantation.
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We studied the role of wt-1 as a minimal residual disease (MRD) marker in 46 patients with acute leukemia (AL) (1st CR n = 24; 2nd CR n = 9, in relapse n = 13) after allogeneic bone marrow or peripheral blood stem cell transplantation. Prior to allogeneic transplant, wt-1 transcripts were detected by PCR in 38 of 46 patients (83%) with AL. After transplant, in 14 of 38 patients (37%) wt-1 transcripts were detected in at least one PCR assay at a median of 12 months post transplant (range 1-89 months). Twelve of the 38 patients relapsed after transplant, but only seven of the 12 were wt-1 positive after transplant. In five relapsing patients the wt-1 test remained negative 0 to 3 months prior to relapse. On the other hand, only seven of 14 patients with a positive test for wt-1 after transplant, relapsed consecutively. In 17 of the 46 study patients chromosomal abnormalities had been found prior to transplant (AML-M4eo with inv16 n = 7, AML-M2 with t(8;21) n = 3, AML-M3 with t(15;17) n = 1, AML-M5 with t(4;11) n = 1, ALL with t(9;22) n = 5). In these 17 patients, we analyzed the wt-1 transcript simultaneously with a specific chimeric transcript characteristic for the corresponding chromosomal abnormality. In 32 of 45 samples (71%) the results for the MRD marker and wt-1 transcript were concordant, but differed in 13 patients. We conclude that detection of wt-1 transcripts does not predict leukemic relapse reliably and is therefore not a suitable MRD marker in patients with acute leukemia after allogeneic BM or PBSC transplantation. Bone Marrow Transplantation (2000) 25, 91-96. (+info)
Purging in BCR-ABL-positive acute lymphoblastic leukemia using immunomagnetic beads: comparison of residual leukemia and purging efficiency in bone marrow vs peripheral blood stem cells by semiquantitative polymerase chain reaction.
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Twenty autologous bone marrow (BM) and 25 peripheral blood stem cell (PBSC) grafts were collected from a total of 40 consecutive patients with BCR-ABL+ acute lymphoblastic leukemia (ALL) in first (n = 37) or second (n = 3) complete morphological remission and subsequently purged with a cocktail of anti-CD19, -CD10, AB4 MoAbs and immunomagnetic beads (IMB). Residual BCR-ABL-positive cells before purging were detected in 19 of 20 BM grafts at a median of 4 (range 0-6) logs and in 17 of 25 evaluable PBSC grafts at a median of 1 (range 0-3) log above the limit of detection assessed by a semiquantitative limiting log10-dilution RT-PCR (P < 0.0001). IMB purging depleted a median of 2.5 (range 1-4) log of residual BCR-ABL+ cells from BM and a median of 1 (range 0-2) log from PBSC grafts, achieving RT-PCR negativity in 1/20 BM and 12/25 PBSC grafts after purging. Cell recoveries were 62% and 86% (P < 0.0001) of MNC and 74% and 97% (P = 0.065) of CD34+ cells after BM and PBSC purging, respectively. BM purging was superior using the triple MoAb cocktail which depleted 2.64 +/- 0.4 log (n = 14) compared to 1.6 +/- 0.4 log (n = 5) using the MoAb cocktail not including AB4 (P = 0. 02). We conclude that unpurged BM grafts contain 2-3 log more residual BCR-ABL+ cells than unpurged PBSC grafts and that purging efficacy is superior in BM compared to PBSC grafts, but median titers in purged BM grafts still exceed those in purged PBSC grafts. Bone Marrow Transplantation (2000) 25, 97-104. (+info)