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See detailWhole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease.
Jerusalem, Guy ULg; Beguin, Yves ULg; Fassotte, Marie-France ULg et al

in Haematologica (2001), 86(3), 266-73

BACKGROUND AND OBJECTIVES: Accurate staging is essential in order to determine appropriate treatment in Hodgkin's disease (HD). (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) offers ... [more ▼]

BACKGROUND AND OBJECTIVES: Accurate staging is essential in order to determine appropriate treatment in Hodgkin's disease (HD). (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) offers the advantage of metabolic imaging that is largely independent of morphologic criteria. In the present study we evaluated the role of (18)F-FDG PET compared to routine procedures for the staging of patients with HD. DESIGN AND METHODS: Thirty-three patients with HD underwent standard staging procedures (clinical examination, laboratory screening, chest X-ray, computed tomography (CT) of the chest and abdomen and bilateral bone marrow biopsies) and a whole-body (18)F-FDG PET study. In clinical examination, an isolated lymph node > 1 cm or multiple lymph nodes > or = 1 cm in size were considered abnormal. Positive findings at both clinical examination or CT and (18)F-FDG PET were regarded as actual locations of disease. Negative findings with both methods were regarded as true negative (no involvement by HD). In cases of discrepancy, response to treatment and follow-up data were used to assess the overall accuracy of the patient's original evaluation. RESULTS: Completely concordant results in lymph node staging were observed in 20 patients. The two staging procedures indicated complementary information in 1 patient. Conventional staging indicated more pathologic lymph node areas in 6 patients (at least 1 false positive). (18)F-FDG PET showed more sites in 6 patients. The sensitivity of (18)F-FDG PET in detecting all known pathologic lymph nodes was 83% for peripheral lymph nodes, 91% for thoracic lymph nodes and 75% for abdominal and pelvic lymph nodes. Conventional staging procedures and (18)F-FDG PET indicated the same tumor stage in 26 patients. Based on (18)F-FDG PET, downstaging was suggested in 4 patients, including a biopsy-proven case. However in 1 of these cases this was incorrect. (18)F-FDG PET suggested upstaging in 3 patients. Based on conventional staging or (18)F-FDG PET the same treatment strategy was defined in 32 patients. In one patient (18)F-FDG PET downstaged disease extension (stage IIIA-->IIA) that would have suggested radiotherapy as a possible treatment option. INTERPRETATION AND CONCLUSIONS: (18)F-FDG PET provides an easy and efficient whole-body method for the evaluation of patients with HD. (18)F-FDG PET never missed tumor masses >1 cm. (18)F-FDG PET detected additional sites of disease not seen by conventional procedures and identified absence of disease in some sites suspected to be involved. However, in our patients this did not translate into changes in treatment strategy. [less ▲]

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See detailPositron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for the staging of low-grade non-Hodgkin's lymphoma (NHL).
Jerusalem, Guy ULg; Beguin, Yves ULg; Najjar, F. et al

in Annals of Oncology (2001), 12(6), 825-30

BACKGROUND: Although PET has been shown to be highly sensitive in the primary staging of lymphoma, previous studies with small numbers of patients indicated that low-grade NHL may not always be adequately ... [more ▼]

BACKGROUND: Although PET has been shown to be highly sensitive in the primary staging of lymphoma, previous studies with small numbers of patients indicated that low-grade NHL may not always be adequately detected by PET. We undertook this study to determine factors influencing the detection of lesions by PET in low-grade NHL and to evaluate the utility of PET in this indication. PATIENTS AND METHODS: Forty-two patients underwent conventional staging procedures (clinical examination, oto-rhino-laryngologic examination, computed tomography of the chest, abdomen and pelvis, gastroscopy and bone marrow biopsy as well as whole-body non-attenuation corrected 18F-FDG-PET RESULTS: PET detected 40% more abnormal lymph node areas than conventional staging in follicular lymphoma but was inappropriate for the staging of small lymphocytic lymphoma where it detected less than 58% of abnormal lymph node areas. PET showed more lesions than conventional staging for peripheral (34% more lymph node areas detected) and thoracic lymph node (39% more) areas but not for abdominal or pelvic lymph nodes (26% fewer areas detected). The sensitivity to detect bone marrow infiltration was unacceptably low for PET. In contrast, PET was as effective as standard procedures for the detection of other extranodal localizations, although a few localizations were detected only by PET and a few others only by conventional procedures. CONCLUSIONS: PET may contribute to the management of patients with low-grade follicular NHL. For the other low-grade lymphoma subtypes, the role of PET is less evident. Further studies using PET to evaluate the results of treatment or to diagnose disease recurrence are warranted in low-grade follicular NHL. [less ▲]

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See detailAdministration of erythopoietin and granulocyte colony-stimulating factor in donor/recipient pairs to collect peripheral blood progenitor cells (PBPC) and red blood cell units for use in the recipient after allogeneic PBPC transplantation.
Sautois, Brieuc ULg; Baudoux, Etienne ULg; Salmon, Jean ULg et al

in Haematologica (2001), 86(11), 1209-18

BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more ... [more ▼]

BACKGROUND AND OBJECTIVES: It may be useful to reduce the exposure of transplant recipients to homologous blood. This may be achieved by procuring donor-derived red blood cell (RBC) units, collecting more peripheral blood progenitor cells (PBPC) with a combination of granulocyte colony-stimulating factor (G-CSF) + recombinant human erythropoietin (rHuEpo) and by administering rHuEpo post-transplantation. DESIGN AND METHODS: Eight ABO-compatible donors were treated with rHuEpo and intravenous iron to collect 12 RBC units for use in their recipients. PBPC were collected after mobilization with rHuEpo and G-CSF in the same donors. The recipients received G-CSF and rHuEpo post-transplantation. A control group of 10 donor/recipient pairs received G-CSF alone for PBPC mobilization and after the transplantation. RESULTS: Eighty-six out of 91 planned RBC units were collected in the donors without significant decrease in hematocrit because of a 4-fold increase in RBC production despite functional iron deficiency. After 2 leukaphereses, the cumulative yields of NC and CFU-GM were lower in the study group while those of BFU-E, CFU-Mix and CD34+ cells were similar. However, erythroid recovery was significantly accelerated in the study group. INTERPRETATION AND CONCLUSIONS: Collection of 12 RBC units within 6 weeks is feasible with rHuEpo and intravenous iron; this strategy allows a dramatic reduction in recipient exposure to homologous blood; rHuEpo has no synergistic effect with G-CSF for mobilization of PBPC in normal donors and may even be deleterious; and rHuEpo in the recipient may enhance erythroid engraftment. [less ▲]

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See detailNouvelles approches thérapeutiques puor l'hypernéphrome métastasique
Sylvestre, Rose-Marie; Jerusalem, Guy ULg; Sautois, Brieuc ULg et al

in Médecine et Hygiène (2001), 59

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See detailPlace de la tomographie d'émission de positons dans le suivi thérapeutique du cancer du sein
Jerusalem, Guy ULg; Belhocine, Tarik; Silvestre, Rose-Marie et al

in Médecine Nucléaire : Imagerie Fonctionnelle et Métabolique (2001), 25(6), 341-346

La tomographie à émission de positons (TEP) au 18F-fluorodeoxyglucose (FDG) fait l'objet d'un nombre croissant d'applications cliniques en oncologie surtout dans le bilan d'extension et le bilan de fin de ... [more ▼]

La tomographie à émission de positons (TEP) au 18F-fluorodeoxyglucose (FDG) fait l'objet d'un nombre croissant d'applications cliniques en oncologie surtout dans le bilan d'extension et le bilan de fin de traitement. Un domaine très prometteur mais peu étudié est l'utilisation de la TEP dans l'évaluation thérapeutique précoce. Nous passons en revue les données de la littérature concernant la place de la TEP dans l'évaluation précoce de la réponse thérapeutique chez des patientes atteintes de cancer du sein. La TEP permet d'identifier précocement les patientes qui ont une grande probabilité de présenter une réponse tumorale facorable à une chimiothérapie néoadjuvante (chimiothérapie première). Cependant, non propres travaux chez des patientes atteintes de cancer du sein métastatique sont moins prometteurs. La poursuite des travaux de recherche est indispensable pour mieux connaître le bénéfice réel et les limites d'une évaluation thérapeutique précoce. [less ▲]

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See detailReticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels.
R'Zik, Samir ULg; Loo, Martine; Beguin, Yves ULg

in Haematologica (2001), 86(3), 244-51

BACKGROUND AND OBJECTIVES: Transferrin receptor (TfR) expression in erythroid cells is regulated by a number of factors, including iron status and erythropoietin (Epo) stimulation. However, the impact of ... [more ▼]

BACKGROUND AND OBJECTIVES: Transferrin receptor (TfR) expression in erythroid cells is regulated by a number of factors, including iron status and erythropoietin (Epo) stimulation. However, the impact of these factors on reticulocyte TfR expression in vivo has never been studied. A soluble form of TfR (sTfR) is present in serum in proportion to the mass of cellular TfR. Although sTfR shedding by reticulocytes and erythroblasts has been demonstrated in vitro, the contribution of reticulocyte TfR to serum sTfR has never been evaluated in vivo. DESIGN AND METHODS: We measured directly the total number of reticulocyte TfR in normal rats of different age and iron status, as well as in animals experiencing various conditions and treatments aimed at altering erythropoietic activity and iron status, including rHuEpo therapy, hemolytic anemia, phlebotomies, hypertransfusions, thiamphenicol-induced red cell aplasia or inflammation. In addition, we examined the impact of repeated hypertransfusions with normal, reticulocyte-poor and reticulocyte-rich blood on serum sTfR levels. RESULTS: The number of TfR molecules per reticulocyte was around 50,000 in young rats but was around 100,000 in older animals. These values remained constant in most conditions and in particular were not influenced by iron supplementation or iron overload. However, functional iron deficiency as well as rHuEpo therapy resulted in increased reticulocyte TfR expression. In addition, TfR numbers in reticulocytes were elevated in the early phase of recovery after acute hemolysis or red cell aplasia but normalized soon after. Hypertransfusion experiments clearly demonstrated that reticulocytes can contribute substantially to sTfR levels in vivo. INTERPRETATION AND CONCLUSIONS: TfR numbers are regulated in vivo by the same factors as in vitro, in particular iron deficiency and erythropoietin stimulation. Circulating reticulocytes contribute significantly to serum sTfR levels. [less ▲]

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See detailSerum soluble transferrin receptor concentration is an accurate estimate of the mass of tissue receptors.
R'Zik, Samir ULg; Beguin, Yves ULg

in Experimental hematology (2001), 29(6), 677-85

OBJECTIVE: Serum levels of the soluble transferrin receptor (sTfR) vary depending on the erythropoietic activity and iron status. In vitro, sTfR shed in the incubation medium correlates well with cellular ... [more ▼]

OBJECTIVE: Serum levels of the soluble transferrin receptor (sTfR) vary depending on the erythropoietic activity and iron status. In vitro, sTfR shed in the incubation medium correlates well with cellular TfR, but this relationship has never been established in vivo. To determine the value of serum sTfR as a quantitative marker of the body mass of tissue TfR, we designed experiments to examine the correlation between serum sTfR and tissue TfR in rats with various degrees of erythropoietic activity or iron status. MATERIALS AND METHODS: We studied changes in erythropoietic activity in normal rats as well as in animals experiencing hemolysis, phlebotomy-induced iron deficiency, transfusion- or thiamphenicol-induced erythroid aplasia, or inflammation. At the end of follow-up, ferrokinetic studies were performed and animals were sacrificed. Organs were isolated and homogenized to determine the total mass of tissue TfR from the sum of tissue solubilized TfR in the bone marrow, spleen, liver, and blood cells (direct method). An indirect method was developed to derive the corporeal mass of tissue TfR from a representative marrow sample. RESULTS: As expected, serum sTfR and total mass of tissue TfR varied as a function of iron status and erythropoiesis. Relative erythroid expansion in the spleen was greater than in the bone marrow. With the exception of phlebotomized animals, the indirect method correlated very well with direct measurements of the total mass of tissue TfR (r = 0.97, p < 0.0001). There was a close relationship between the total mass of tissue TfR and the total mass of serum sTfR (r = 0.79, p < 0.0001). Serum sTfR represented approximately 5-6% of the total mass of tissue TfR in most experimental situations, but this ratio was twice as high during iron-restricted erythropoiesis. In addition, the ratio could be higher or lower in nonsteady-state situations, because changes in tissue TfR occurred faster than those of serum sTfR. CONCLUSIONS: Serum sTfR represents a constant proportion of the total mass of tissue TfR over a wide range of erythropoietic activity. However, iron deficiency results in a higher proportion of serum sTfR, and the pace of change in serum sTfR levels is slower than that of tissue TfR mass. [less ▲]

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See detailPrediction of response to rHuEpo
Beguin, Yves ULg

in Bokemeyer, C.; Ludwig, H. (Eds.) ESO Scientific Upadtes, Vol. 6 Anaemia in cancer (2001)

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See detailSerum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria.
Verhoef, H.; West, C. E.; Ndeto, P. et al

in American Journal of Clinical Nutrition (2001), 74(6), 767-75

BACKGROUND: Serum transferrin receptor concentrations indicate both erythropoietic activity and the deficit of functional iron in the erythron. In contrast with serum ferritin concentrations, serum ... [more ▼]

BACKGROUND: Serum transferrin receptor concentrations indicate both erythropoietic activity and the deficit of functional iron in the erythron. In contrast with serum ferritin concentrations, serum transferrin receptor concentrations are not or are only marginally influenced by the inflammatory response to infection. OBJECTIVE: We assessed iron status and examined the relation between serum transferrin receptor concentrations and malaria in children aged 2-36 mo who were asymptomatic for malaria. DESIGN: This was a community-based cluster survey (n = 318). RESULTS: Prevalences of malaria, anemia (hemoglobin concentration <110 g/L), iron deficiency (serum ferritin concentration <12 microg/L), and iron deficiency anemia were 18%, 69%, 53%, and 46%, respectively. Malaria was associated with lower mean hemoglobin concentrations (92.7 compared with 104.1 g/L; P = 0.0001) and higher geometric mean serum concentrations of transferrin receptor (11.4 compared with 7.8 mg/L; P = 0.005), ferritin (21.6 compared with 11.9 microg/L; P = 0.05), and C-reactive protein (12.5 compared with 6.8 mg/L; P = 0.004). There was no evidence for an association between serum concentrations of C-reactive protein and transferrin receptor. Children with malaria had higher serum transferrin receptor concentrations than expected for the degree of anemia, even after adjustment for inflammation indicated by serum C-reactive protein concentration quartiles (P = 0.02). CONCLUSIONS: Our findings are consistent with the notion that malaria-induced hemolysis is accompanied by increased erythropoiesis. Serum transferrin receptor concentration is not useful for detecting iron deficiency in individuals with malaria. Individuals with high concentrations of serum C-reactive protein or similar acute phase reactants should be excluded from analysis if serum ferritin concentrations <12 microg/L are to be used to measure iron deficiency in malaria-endemic areas. [less ▲]

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See detailCessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia.
Piron, Maude ULg; Loo, Martine; Gothot, André ULg et al

in Blood (2001), 97(2), 442-8

Little information is available on the evolution of erythropoiesis after interruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overloaded rats received 20 daily injections of rHuEpo ... [more ▼]

Little information is available on the evolution of erythropoiesis after interruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overloaded rats received 20 daily injections of rHuEpo. During treatment, reticulocytes, soluble transferrin receptor (sTfR), and hematocrit increased progressively. This was accompanied by a substantial expansion of spleen erythropoiesis but a decrease in the bone marrow. Five weeks after treatment, rats developed a significant degree of a regenerative anemia. Erythropoietic activity, as assessed by reticulocytes, sTfR, erythroid cellularity, iron incorporation into heme, and the number of erythroid colonies, was severely depressed 3 weeks after cessation of rHuEpo. This was followed by regeneration of erythroblasts and reticulocytes at weeks 6 to 7 post-Epo, but erythroid progenitors recovered only partially by that time. The anemia was definitely corrected 2 months after cessation of rHuEpo treatment. Serum Epo levels remained elevated for several weeks, but the sensitivity of marrow erythroid precursors to Epo was preserved. No rat antibodies to rHuEpo were detected, and serum from post-Epo animals did not exert any inhibitory activity on erythropoiesis. In conclusion, after cessation of intensive rHuEpo therapy, there was a strong inhibition of erythropoietic activity with secondary anemia followed by late recovery. This was not due to antibodies or other soluble inhibitory factors, a defect in endogenous Epo production, or a loss of sensitivity to Epo. This may rather represent intrinsic erythroid marrow exhaustion, mostly at the level of erythroid progenitors but also at later stages of erythropoiesis. [less ▲]

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See detailCell cycle activation of hematopoietic progenitor cells increases very late antigen-5-mediated adhesion to fibronectin.
Giet, Olivier ULg; Huygen, Sandra; Beguin, Yves ULg et al

in Experimental hematology (2001), 29(4), 515-24

Recent studies suggested that trafficking of hematopoietic progenitor cells is related to cell cycle status. We studied whether adhesion of progenitor cells to extracellular matrix proteins was modulated ... [more ▼]

Recent studies suggested that trafficking of hematopoietic progenitor cells is related to cell cycle status. We studied whether adhesion of progenitor cells to extracellular matrix proteins was modulated by cell cycle transit.Mobilized peripheral blood CD34+ cells were stimulated ex vivo for 48 hours with stem cell factor, flt-3 ligand, and thrombopoietin and fractionated by adhesion to fibronectin or vascular cell adhesion molecule-1 (VCAM-1). Adherent and nonadherent cells were assayed for cell cycle status, long-term culture-initiating cell frequency, and integrin function. Binding to fibronectin, but not to VCAM-1, displayed a cell cycle selectivity as the adherent fraction to fibronectin was enriched in cycling CD34+ cells and in cycling long-term culture-initiating cells compared to the nonadherent fraction. Combined cell cycle and phenotypic analysis showed that the expression of VLA-5 was upregulated during S/G2+M but that of VLA-4 remained constant. The selective binding of cycling CD34+ cells to fibronectin was reverted by anti-VLA-5 but not by anti-VLA-4 blocking antibodies. Also, cycling CD34+ cells preferentially adhered to the VLA-5 binding domain but not to the VLA-4 binding domain of fibronectin. Adhesion of cycling CD34+ cells to fibronectin was a reversible process modulated by cell cycle progression, because adherent cells could exit the cell cycle and return to a nonadhesive state within an additional 48-hour culture period.The results indicate that the enhanced binding capacity of cycling progenitor cells to fibronectin is mediated by VLA-5. [less ▲]

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

in Médecine et Hygiène (2000), 58

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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 detailDonor lymphocyte infusion to eradicate recurrent host hematopoiesis after allogeneic BMT for sickle cell disease.
Baron, Frédéric ULg; Dresse, Marie-Françoise ULg; Beguin, Yves ULg

in Transfusion (2000), 40(9), 1071-3

BACKGROUND: Donor lymphocyte infusion (DLI) is currently standard therapy for relapse of malignancies after allogeneic BMT. Several observations suggest that both normal and leukemic progenitor cells of ... [more ▼]

BACKGROUND: Donor lymphocyte infusion (DLI) is currently standard therapy for relapse of malignancies after allogeneic BMT. Several observations suggest that both normal and leukemic progenitor cells of host origin constitute effective target cells for donor-derived lymphocytes. To prevent relapse of sickle cell disease (SCD), a child with evidence of decreasing mixed chimerism received DLIs 8 months after allogeneic BMT for SCD. CASE REPORT: A 4-year-old child who was homozygous for SCD underwent a transplantation of bone marrow from his fully HLA-matched sister. Routine detection of sex chromosomes in bone marrow cells evidenced decreasing mixed chimerism, which heralded a probably imminent recurrence of the disease. The patient received two DLIs in graded incremental doses on Days 234 and 267. One month later, he developed grade 2 acute GVHD that responded well to corticosteroids and cyclosporine. RESULTS: DLI resulted in complete donor chimerism within 2 months of the second infusion. Now, 2 years after the second DLI, the patient is in excellent condition, with normal Hb and excellent growth and development. CONCLUSION: This is the first report of successful use of DLI in a patient with probable imminent SCD recurrence after allogeneic BMT. It shows that DLI can displace residual host HPCs in case of recurrence of nonmalignant disease after allogeneic BMT. [less ▲]

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