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See detailPersistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma.
Jerusalem, Guy ULg; Beguin, Yves ULg; Fassotte, Marie-France ULg et al

in Haematologica (2000), 85(6), 613-8

BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve ... [more ▼]

BACKGROUND AND OBJECTIVE: Early recognition of the ineffectiveness of chemotherapy could result in lower cumulative drug toxicity and tumor burden at the start of salvage therapy, which might improve clinical outcome. Therefore, we studied the value of (18)F-FDG PET for early evaluation of response in patients with non-Hodgkin's lymphoma (NHL). DESIGN AND METHODS: We studied 28 patients by (18)F-FDG PET after a median of 3 cycles of polychemotherapy. The presence or absence of abnormal (18)F-FDG uptake was correlated to clinical outcome (median follow-up: 17.5 months, range 4-47 months). RESULTS: Five of 28 patients still had increased (18)F-FDG uptake in one or more sites previously shown to be involved by lymphoma at baseline evaluation. Only one of these five patients entered complete remission (CR), whereas among the 23 patients with negative (18)F-FDG PET studies, two died of toxicity during chemotherapy and all the others entered clinical CR (p<0.00001). All five patients with and 7/21 patients without residual abnormal (18)F-FDG uptake relapsed or reprogressed (positive predictive value for relapse: 100%, negative predictive value: 67%). By Kaplan-Meier analysis, progression-free survival (PFS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive patients and 81+/-9% and 62+/-12% for (18)F-FDG PET negative patients (p=0.0001). Overall survival (OS) at 1 and 2 years was respectively 20+/-18% and 0% for (18)F-FDG PET positive and 87+/-7% and 68+/-11% for (18)F-FDG PET negative patients (p<0.0001). INTERPRETATION AND CONCLUSIONS: Persistent tumoral (18)F-FDG uptake after a few cycles of polychemotherapy is predictive of CR, PFS and OS in NHL. Further studies are warranted to determine whether (18)F-FDG PET has a predictive value independent from conventional prognostic factors. However, the sensitivity of qualitative (18)F-FDG PET imaging in identifying patients with a poor outcome was insufficient. Earlier evaluation after only one cycle of chemotherapy and quantitative analysis might increase the sensitivity of 18F-FDG PET is predicting treatment failure. [less ▲]

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See detailSuccessful mobilization of peripheral blood HPCs with G-CSF alone in patients failing to achieve sufficient numbers of CD34+ cells and/or CFU-GM with chemotherapy and G-CSF.
Fraipont, V.; Sautois, Brieuc ULg; Baudoux, Etienne ULg et al

in Transfusion (2000), 40(3), 339-47

BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures ... [more ▼]

BACKGROUND: Mobilization with chemotherapy and G-CSF may result in poor peripheral blood HPC collection, yielding <2 x 10(6) CD34+ cells per kg or <10 x 10(4) CFU-GM per kg in leukapheresis procedures. The best mobilization strategy for oncology patients remains unclear. STUDY DESIGN AND METHODS: In 27 patients who met either the CD34 (n = 3) or CFU-GM (n = 2) criteria or both (n = 22), the results obtained with two successive strategies-that is, chemotherapy and G-CSF at 10 microg per kg (Group 1, n = 7) and G-CSF at 10 microg per kg alone (Group 2, n = 20) used for a second mobilization course-were retrospectively analyzed. The patients had non-Hodgkin's lymphoma (5), Hodgkin's disease (3), multiple myeloma (5), chronic myeloid leukemia (1), acute myeloid leukemia (1), breast cancer (6), or other solid tumors (6). Previous therapy consisted of 10 (1-31) cycles of chemotherapy with additional chlorambucil (n = 3), interferon (n = 3), and radiotherapy (n = 7). RESULTS: The second collection was undertaken a median of 35 days after the first one. In Group 1, the results of the two mobilizations were identical. In Group 2, the number of CD34+ cells per kg per apheresis (0.17 [0.02-0.45] vs. 0.44 [0.11-0.45], p = 0. 00002), as well as the number of CFU-GM (0.88 [0.00-13.37] vs. 4.19 [0.96-21.61], p = 0.00003), BFU-E (0.83 [0.00-12.72] vs. 8.81 [1. 38-32.51], p = 0.00001), and CFU-MIX (0.10 [0.00-1.70] vs. 0.56 [0. 00-2.64], p = 0.001134) were significantly higher in the second peripheral blood HPC collection. However, yields per apheresis during the second collection did not significantly differ in the two groups. Six patients in Group 1 and 18 in Group 2 underwent transplantation, and all but one achieved engraftment, with a median of 15 versus 12 days to 1,000 neutrophils (NS), 22 versus 16 days to 1 percent reticulocytes (NS), and 26 versus 26 days to 20,000 platelets (NS), respectively. However, platelet engraftment was particularly delayed in many patients. CONCLUSION: G-CSF at 10 microg per kg alone may constitute a valid alternative to chemotherapy and G-CSF to obtain adequate numbers of peripheral blood HPCs in patients who previously failed to achieve mobilization with chemotherapy and G-CSF. This strategy should be tested in prospective randomized trials. [less ▲]

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See detailEffective treatment of Jo-1-associated polymyositis with T-cell-depleted autologous peripheral blood stem cell transplantation.
Baron, Frédéric ULg; Ribbens, Clio ULg; Kaye, O. et al

in British Journal of Haematology (2000), 110(2), 339-342

A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an ... [more ▼]

A patient with Jo-1 antibody-associated polymyositis (Jo-1 PM) had a Karnofsky score of 40% and severe muscle, liver and lung damage that was refractory to standard therapy. The female patient received an autologous T-cell-depleted haematopoietic stem cell transplant (HSCT) after myeloablative conditioning. The transplant procedure was complicated by severe adult respiratory distress syndrome (ARDS) and adenovirus-associated haemorrhagic cystitis as well as cytomegalovirus (CMV) reactivation. The patient's creatinine phosphokinase (CPK) and alanine transaminase (ALT) values were normal on day 21. The patient's strength has improved remarkably and her dyspnoea is subjectively improved. At 15 months after the transplant, the patient was well with a Karnofsky score of 80% and had been off any therapy, including steroids, for 14 months. [less ▲]

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See detailPhase II study of docetaxel alternating with cisplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer
Mattson, Karin; Vansteenkiste, Johan; Stupp, Roger et al

in Anti-Cancer Drugs (2000), 11

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See detailApproches thérapeutiques du cancer ovarien
Bonnet, Christophe ULg; Jerusalem, Guy ULg; Bours, Vincent ULg et al

in Médecine et Hygiène (2000), 58

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See detailTraitement des myélomes réfractaires par la Thalidomide
Sautois, Brieuc ULg; Scerbo, Franca; Beguin, Yves ULg et al

in Médecine et Hygiène (2000), 58

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See detailHyperammonemia after high-dose chemotherapy and stem cell transplantation.
Frere, Pascale ULg; Canivet, Jean-Luc ULg; Gennigens, Christine ULg et al

in Bone Marrow Transplantation (2000), 26(3), 343-5

We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the ... [more ▼]

We report a patient with multiple myeloma who suffered from hyperammonemia after a second stem cell autograft. This syndrome is not well known but is associated with a high mortality rate. Considering the possibility of this diagnosis in patients developing confusion and neurological degradation with respiratory alkalosis after intensive chemotherapy, could allow earlier treatment and perhaps improved survival. Possible mechanisms and potential therapies are discussed. With rapid recognition and treatment of the syndrome, the patient fully recovered. One and a half years later, she is still alive and well, on interferon for persisting myeloma. [less ▲]

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See detailClinical course and predictive factors for cyclosporin-induced autologous graft-versus-host disease after autologous haematopoietic stem cell transplantation.
Baron, Frédéric ULg; Gothot, André ULg; Salmon, Jean ULg et al

in British Journal of Haematology (2000), 111(3), 745-53

The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome ... [more ▼]

The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome, termed autologous GVHD has notable anti-tumour activity in animal studies. We intended to induce autologous GVHD with CyA in patients undergoing an autologous HSCT. We prospectively studied 118 patients with miscellaneous malignancies undergoing an autologous HSCT with low-dose CyA to characterize the clinical syndrome, its frequency and clinical course, and to determine the factors affecting its incidence. Patients received CyA from d -1 through to d 28, first starting at 2 mg/kg intravenously and then orally as soon as feasible. The dose was adjusted to achieve pre-dose blood levels around 100 ng/ml. A skin biopsy was performed when a skin rash was observed. Thirty-three percent of the patients developed clinical GVHD: clinical stage 1 in 21 patients, stage 2 in seven patients, and stage 3 in three patients. Although total body irradiation (TBI) or high-dose cyclophosphamide were previously thought to be needed, autologous GVHD occurred in five out of 12 patients (42%) after a preparative regimen with high-dose melphalan alone. Autologous GVHD was significantly more frequent in patients older than 33 years, in patients who had received high doses of granulocyte-macrophage colony forming units (CFU-GM) and in those with a diagnosis of myeloid malignancy, compared with those with lymphoid malignancies or solid tumours. A significant negative association was also found with HLA-DR6. In lymphoma patients, GVHD occurred more frequently in advanced disease than in first or second complete remission (CR1-2) patients. All other factors studied were not predictive for GVHD. In conclusion, CyA-induced GVHD is reproducibly and safely induced with doses of CyA adapted to achieve blood levels around 100 ng/ml. In retrospective analysis, there was no survival advantage for patients with GVHD. Phase III trials with this approach are needed to evaluate its anti-tumoral effect. [less ▲]

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See detailEvaluation thérapeutique précoce par tomographie à émission de positrons
Jerusalem, Guy ULg; Beguin, Yves ULg; Fassotte, Marie-France ULg et al

in Médecine et Hygiène (2000), 58

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See detailTranslocation (2;3)(P21;Q26) as the Sole Anomaly in a Case of Primary Myelofibrosis
Herens, Christian ULg; Hermanne, J. P.; Tassin, Françoise ULg et al

in Cancer Genetics & Cytogenetics (1999), 110(1), 62-4

Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with ... [more ▼]

Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis. [less ▲]

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See detailA propos d'un cas de rhabdomyolyse aigue
Rorive, Andrée ULg; Fraipont, V.; Quatresooz, Pascale ULg et al

in Revue Médicale de Liège (1999), 54(3), 143-8

A 83 years old patient was admitted with a complex clinical picture including cutaneous rash, muscular pain, rhabdomyolysis and renal failure. The clinical picture suggests a dermatopolymyositis. Despite ... [more ▼]

A 83 years old patient was admitted with a complex clinical picture including cutaneous rash, muscular pain, rhabdomyolysis and renal failure. The clinical picture suggests a dermatopolymyositis. Despite of high dose corticotherapy, the patient died on day 22. The anatomical examination shows a cholangiocarcinoma disseminated locally as well as in the lungs and bones. [less ▲]

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See detailWhole-Body 18f-Fdg Pet for the Evaluation of Patients with Hodgkin's Disease and Non-Hodgkin's Lymphoma
Jerusalem, Guy ULg; Warland, V.; Najjar, F. et al

in Nuclear Medicine Communications (1999), 20(1), 13-20

Whole-body metabolic information provided by 18F-FDG PET could help in the evaluation of lymphoma patients at diagnosis and follow-up. We studied 60 patients, 42 at initial presentation and 18 for disease ... [more ▼]

Whole-body metabolic information provided by 18F-FDG PET could help in the evaluation of lymphoma patients at diagnosis and follow-up. We studied 60 patients, 42 at initial presentation and 18 for disease recurrence (23 aggressive non-Hodgkin's lymphoma, 21 low-grade non-Hodgkin's lymphoma and 16 Hodgkin's disease). All patients underwent a clinical examination, computed tomography (CT) and a non-attenuated PET scan within 1 week. The patients received 222-296 MBq (6-8 mCi) 18F-FDG intravenously and emission scans were recorded 45-90 min later. 18F-FDG PET detected more lymph nodes than the clinical examination or CT, but this rarely resulted in upstaging (two patients). The concordance between PET and CT for the evaluation of the spleen, liver and digestive tract was quite good. Discordance was noted in 12 patients for the evaluation of bone marrow infiltration, but confirmation by MRI or focal biopsy was not always obtained. We conclude that non-attenuated 18F-FDG PET is an easy and efficient whole-body method for the evaluation of patients with lymphomas. Compared with conventional techniques, however, it does not appear to offer much improvement for staging but provides a satisfactory base for follow-up. [less ▲]

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See detailLes tumeurs malignes d'origine indéterminée
Rezaei Kalantari, Hassan ULg; Jerusalem, Guy ULg; Bours, Vincent ULg et al

in Revue Médicale de Liège (1999), 54(1), 39-42

Cancers of unknown origin form a specific clinical entity. The diagnostic procedure has to be guided by the therapeutical possibilities and requires a biopsy. Immunohistology, electron microscopy and ... [more ▼]

Cancers of unknown origin form a specific clinical entity. The diagnostic procedure has to be guided by the therapeutical possibilities and requires a biopsy. Immunohistology, electron microscopy and cytogenetics are informative for carcinomas and poorly differentiated adenocarcinomas. The clinical status and the histology allow the definition of groups of patients who can benefit from a specific therapy and have a better prognosis. For the other patients, the prognosis is severe and there is no efficient therapy available. Such tumors are usually characterized by a very aggressive behaviour. [less ▲]

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See detailWhole-body positron emission tomography using 18F-fluorodeoxyglucose for posttreatment evaluation in Hodgkin's disease and non-Hodgkin's lymphoma has higher diagnostic and prognostic value than classical computed tomography scan imaging.
Jerusalem, Guy ULg; Beguin, Yves ULg; Fassotte, Marie-France ULg et al

in Blood (1999), 94(2), 429-33

A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron ... [more ▼]

A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) offers the advantage of functional tissue characterization that is largely independent of morphologic criteria. We compared 18F-FDG PET to computed tomography (CT) in the posttreatment evaluation of 54 patients with Hodgkin's disease (HD) or intermediate/high-grade non-Hodgkin's lymphoma (NHL). Residual masses on CT were observed in 13 of 19 patients with HD and 11 of 35 patients with NHL. Five of 24 patients with residual masses on CT versus 1 of 30 patients without residual masses presented a positive 18F-FDG PET study. Relapse occurred in all 6 patients (100%) with a positive 18F-FDG PET, 5 of 19 patients (26%) with residual masses on CT but negative 18F-FDG PET, and 3 of 29 patients (10%) with negative CT scan and 18F-FDG PET studies (P </=.0001). We observed a higher relapse and death rate in patients with residual masses at CT compared with patients without residual masses at CT (progression-free survival at 1 year: 62 +/- 10 v 88 +/- 7%, P =. 0045; overall survival at 1 year: 77 +/- 5 v 95 +/- 5%, P =.0038). A positive 18F-FDG PET study was even more consistently associated with poorer survival: compared with patients with a negative 18F-FDG PET study, the 1-year progression-free survival was 0% versus 86% +/- 5% (P <.0001) and the 1-year overall survival was 50% +/- 20% versus 92% +/- 4% (P <.0001). The detection of vital tumor by 18F-FDG PET after the end of treatment has a higher predictive value for relapse than classical CT scan imaging (positive predictive value: 100% v 42%). This could help identify patients requiring intensification immediately after completion of chemotherapy. However, 18F-FDG PET mainly predicts for early progression but cannot exclude the presence of minimal residual disease, possibly leading to a later relapse. [less ▲]

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See detailPeripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.
Sautois, Brieuc ULg; Fraipont, V.; Baudoux, Etienne ULg et al

in Haematologica (1999), 84(4), 342-9

BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify ... [more ▼]

BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and CD34+ cell count were performed on peripheral blood and leukaphereses products. After log transformation of the data, differences between groups were assessed with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and two patients required 2 and 3 mobilization cycles respectively to reach our target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically increased when G-CSF was added to CT for mobilization. In collections primed with CT and G-CSF, better yields were obtained in patients with breast cancer or small-cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among potential predictive factors of CT- and G-CSF-primed harvests, we found that the CD34+ cell count in peripheral blood (PB) was strongly correlated with both the CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6) CD34+ cells/kg were harvested when the CD34+ cell count in blood was above 20x10(6)/L. Similarly, better results were obtained in collections performed when the percentage of myeloid progenitors in blood on the day of apheresis was above 5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+ cells/L in PB were associated with higher yields of PBPC in collections mobilized with CT+G-CSF. [less ▲]

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See detailActualités thérapeutiques dans le traitement du cancer colorectal
Jerusalem, Guy ULg; Bours, Vincent ULg; Fillet, Georges ULg

in Médecine et Hygiène (1999), 57

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See detailClinical Activity and Benefit of Irinotecan (CPT-11) in Patients with Colorectal Cancer Truly Resistant to 5-Fluorouracil (5-FU)
Van Cutsem, Eric; Cunningham, D.; Ten Bokkel Huinink, W. W. et al

in European Journal of Cancer (1999), 35

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See detailDelayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation.
Salmon, Jean ULg; Michaux, S.; Hermanne, J. P. et al

in Transfusion (1999), 39(8), 824-7

BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor-derived ABO antibodies. This reaction may be more ... [more ▼]

BACKGROUND: Bone marrow transplantation with minor ABO incompatibility may be followed by moderate delayed hemolysis of the recipient's red cells by donor-derived ABO antibodies. This reaction may be more severe after transplantation of peripheral blood progenitor cells (PBPCs). CASE REPORT: A 16-year-old boy underwent an allogeneic PBPC transplant from his HLA-mismatched mother as treatment for acute myeloblastic leukemia that had proved resistant to induction chemotherapy. Transfusion of the unmanipulated PBPCs proceeded without any complication, despite the difference in ABO blood group (donor, O Rh-positive; recipient, A Rh-positive). On Day 7, a rapid drop in hemoglobin to 4 g per dL was observed, which was attributed to a massive hemolysis. All the recipient's group A red cells were destroyed within 36 hours. This delayed and rapidly progressive hemolytic anemia was not associated with the transfusion of the donor's plasma. Rather, the anti-A titer increased in parallel with marrow recovery, which suggested an active synthesis of these antibodies by immunocompetent cells from the donor against the recipient's red cells. The mother's anti-A titer was retrospectively found to be 2048. Her unusually high titer is probably due to prior sensitization during pregnancies. On Day 12, the patient developed grade IV graft-versus-host disease, which proved resistant to all treatments instituted and led to his death on Day 35. CONCLUSION: PBPC transplantation with minor ABO incompatibility may be associated with significant risk of massive delayed hemolysis. [less ▲]

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