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See detailSoluble transferrin receptor as a potential determinant of iron loading in congenital anaemias due to ineffective erythropoiesis.
Cazzola, M.; Beguin, Yves ULg; Bergamaschi, G. et al

in British Journal of Haematology (1999), 106(3), 752-5

Congenital anaemias due to ineffective erythropoiesis may be associated with excessive iron absorption and progressive iron loading. We investigated whether the soluble transferrin receptor (TfR) level ... [more ▼]

Congenital anaemias due to ineffective erythropoiesis may be associated with excessive iron absorption and progressive iron loading. We investigated whether the soluble transferrin receptor (TfR) level was related to the degree of iron overload in 20 patients with thalassaemia intermedia, six patients with congenital dyserythropoietic anaemia type II (CDA II) and four patients with X-linked congenital sideroblastic anaemia (XLSA). All but two patients had increased serum ferritin levels (median 601 microgram/l, range 105-2855 microgram/l). Multiple regression analysis showed that 62% (P < 0.0001) of the variation in serum ferritin was explained by age and by changes in soluble TfR. [less ▲]

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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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See detailFactors determining the percentage of hypochromic red blood cells in hemodialysis patients.
Bovy, Christophe ULg; Tsobo, C.; Crapanzano, L. et al

in Kidney International (1999), 56(3), 1113-9

Factors determining the percentage of hypochromic red blood cells determines iron status in hemodialysis patients. BACKGROUND: Determination of the percentage of hypochromic red blood cells (RBC; %HYPO ... [more ▼]

Factors determining the percentage of hypochromic red blood cells determines iron status in hemodialysis patients. BACKGROUND: Determination of the percentage of hypochromic red blood cells (RBC; %HYPO) has been advocated as a sensitive index of functional iron deficiency during erythropoietin (EPO) therapy in hemodialyzed patients. METHODS: The significance of %HYPO in chronic renal failure was evaluated in 64 chronically hemodialyzed patients. The linear correlation was determined between %HYPO and 13 variables, including age, sex, weight, C-reactive protein (CRP), ferritin, transferrin (Tf), Tf saturation, soluble Tf receptor (sTfR), serum iron (SI), urea, parathormone, dialysis dose (Kt/V), dose of EPO administered (EPO), and absolute reticulocyte count. Multiple regression analyses were then performed to select the parameters that jointly provide the best prediction of %HYPO. RESULTS: Univariate analysis showed significant correlations between %HYPO and iron parameters (sTfR, Tf saturation, SI, and ferritin, in decreasing order), EPO, reticulocyte count, and CRP. Multivariate analysis yielded an equation showing that the variation of %HYPO is essentially associated with the combined changes in sTfR, CRP, and EPO dosage. CONCLUSIONS: %HYPO is a meaningful and inexpensive parameter that reflects the integrated effects of iron stores, inflammation, and erythropoietic stimulation on iron availability in hemodialyzed patients. Among iron exchange parameters, sTfR is the best predictor of %HYPO, followed by Tf saturation, SI, and ferritin. [less ▲]

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See detailInfluence of marrow erythropoietic activity on serum erythropoietin levels after autologous hematopoietic stem cell transplantation.
Beguin, Yves ULg; Baron, Frédéric ULg; Fillet, Georges ULg

in Haematologica (1998), 83(12), 1076-81

BACKGROUND AND OBJECTIVE: Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after ... [more ▼]

BACKGROUND AND OBJECTIVE: Serum erythropoietin (sEpo) concentration depends primarily on the rate of renal production in response to hypoxia. However, sEpo levels increase inappropriately after conditioning for autologous stem cell transplantation (ASCT) before progressively returning to adequate levels. We investigated the possible influence of erythropoietic activity on these observations. DESIGN AND METHODS: Forty patients undergoing an ASCT, 8 with bone marrow (BMT) and 32 with peripheral blood stem cells (PBSC), were separated into 3 groups. Group 1 was formed of the 8 BMT patients (median time to 1% reticulocytes: 39 days), group 2 of 16 PBSC patients with relatively slow erythroid engraftment (> or = 15 days to 1% reticulocytes, median 19 days) and group 3 of 16 PBSC patients with prompt erythroid recovery (< 15 days to 1% reticulocytes, median 13 days). Marrow erythroid activity was assessed by serum transferrin receptor levels (sTfR). Serum Epo (sEpo) levels were expressed in relation to the degree of anemia as observed/predicted (O/P) ratios of (O/P) log (sEpo). RESULTS: Serum sTfR levels decreased by more than 50% in all 3 groups after conditioning, reaching their nadir on day 7. Nadir values doubled by day 28 in group 3, day 60 in group 2, but not within 100 days in group 1. O/P sEpo ratios increased inappropriately in all 3 groups after conditioning but then declined at very differing speeds in the 3 groups. In group 1, ratios remained above 1.10 through to day 28 and above 1.00 through to day 42, before leveling off at around 1.00 thereafter. In group 2, ratios remained above 1.00 through to day 14, than decreased to a minimum of 0.89 by day 42 before returning to 1.00 by day 100. In group 3, ratios decreased to 0.84 by day 21 and remained below 0.90 thereafter. INTERPRETATION AND CONCLUSIONS: We conclude that sEpo levels are not only influenced by tissue oxygenation but also depend on the mass of erythroid precursors in the bone marrow. This may be the main explanation for the observed changes in sEpo levels during ASCT. [less ▲]

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See detailMyasthenia gravis without chronic GVHD after allogeneic bone marrow transplantation.
Baron, Frédéric ULg; Sadzot, Bernard ULg; Wang, François-Charles ULg et al

in Bone Marrow Transplantation (1998), 22(2), 197-200

A 20-year-old man with aplastic anemia developed myasthenia gravis (MG) 7 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched sister. Proximal muscle weakness (predominant in ... [more ▼]

A 20-year-old man with aplastic anemia developed myasthenia gravis (MG) 7 months after bone marrow transplantation (BMT) from an HLA one locus-mismatched sister. Proximal muscle weakness (predominant in the lower limbs) and dysphagia occurred without any other sign of graft-versus-host disease (GVHD), 1 month after cessation of immunosuppression with cyclosporine. The diagnosis of MG was based on clinical symptoms and on neurophysiologic investigations showing a significant increase of the Jitter in single-fiber electromyography and a significant decremental response during repetitive stimulation at slow rates, but antibodies against the acetylcholine receptor (AchRab) were negative. All clinical and neurophysiological signs normalized within 1 month of treatment with low-dose prednisolone and pyridostigmine, and the patient is perfectly well 1 year after cessation of all therapy. All cases of BMT-associated MG previously published are reviewed in comparison with ours. The originality of this new observation is that this case is the only one not associated with chronic GVHD and negative for AchRab. Alternatively, MG may have been the sole manifestation of chronic GVHD in this patient. [less ▲]

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See detailBronchiolitis obliterans organizing pneumonia and ulcerative colitis after allogeneic bone marrow transplantation.
Baron, Frédéric ULg; Hermanne, Jean-Philippe; Dowlati, A. et al

in Bone Marrow Transplantation (1998), 21(9), 951-4

A 37-year-old man with acute myeloblastic leukemia in first remission developed ulcerative colitis and bronchiolitis obliterans organizing pneumonia (BOOP) 7 months after bone marrow transplantation (BMT ... [more ▼]

A 37-year-old man with acute myeloblastic leukemia in first remission developed ulcerative colitis and bronchiolitis obliterans organizing pneumonia (BOOP) 7 months after bone marrow transplantation (BMT) from an HLA-matched brother who suffered from severe Crohn's disease. BOOP occurred 20 days after idiopathic interstitial pneumonia, in the context of severe ulcerative colitis. Lung and colon biopsies showed no signs of CMV infection or GVHD. The patient was treated with oral methylprednisolone 1 mg/kg/day and his clinical status and chest X-ray improved slowly. Remarkably, the symptoms of colitis also resolved with prednisone therapy and he is now symptom-free. We hypothesize that ulcerative colitis may have been transmitted from donor to recipient (adoptive autoimmunity) and that it was complicated by BOOP. However, other factors such as CMV may have contributed to the occurrence of BOOP. [less ▲]

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See detailEpidermal Calprotectin Expression in Lymphocyte-Depleted Cutaneous Graft-versus-Host Reaction
Pierard, Gérald ULg; Nikkels, Nazli ULg; Nikkels, Arjen ULg et al

in Archivos Argentinos de Dermatologia (1998), 48

One of the most important complications associated with bone marrow transplantation (BMT) is graft-versus-host reaction (GVHR) altering different organs. The immunosuppressive regimen frequently abates ... [more ▼]

One of the most important complications associated with bone marrow transplantation (BMT) is graft-versus-host reaction (GVHR) altering different organs. The immunosuppressive regimen frequently abates the severity of cutaneous lesions to a peculiar lymphocyto-depleted GVHR (LD-GVHR) with scant recognizable inflammatory cells and almost absence of epidermal injury. The recently revisited histological criteria for cutaneous GVHR are of little help in diagnosing such LD-GVHR. As calprotectin (L1-protein) has been reported to be expressed in several types of stressed epithelia, we assessed the epidermal calprotectin expression during LD-GVHR. Calprotectin expression was studied by immuno-histochemistry using the Mac 287 moAb in 50 cases of LD-GVHR and 40 cases of toxic reactions due to the conditioning regimens or to post-transplant drugs. Calprotectin was evidenced in normal looking keratinocytes of all cutaneous LD-GVHR cases and in the vast majority of cytotoxic drug-induced dermatitis. It is concluded that calprotectin immunoreactivity appears to be a diagnostic clue in LD-GVHR. The epidermal calprotectin expression occurs early in GVHD, irrespective of the histological grading. However, it cannot be used alone to distinguish early LD-GVHR from drug-induced dermatitis. [less ▲]

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See detailAnemia in children with cancer is associated with decreased erythropoietic activity and not with inadequate erythropoietin production.
Corazza, Francis; Beguin, Yves ULg; Bergmann, Pierre et al

in Blood (1998), 92(5), 1793-8

A defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect ... [more ▼]

A defect in erythropoietin (EPO) production has been advocated as being the main cause of anemia presented at time of diagnosis or during treatment by adults with solid tumors. On the basis of this defect, anemic cancer patients, both adults and children, have been treated with recombinant human EPO (rHuEPO). To further elucidate the pathophysiology of anemia in children with cancer, we measured serum soluble transferrin receptor (sTfR), a quantitative marker of erythropoiesis, and serum EPO at time of diagnosis and during chemotherapy in children suffering from solid tumor or leukemia. We determined serum EPO in 111 children (55 leukemia, 56 solid tumors) at time of diagnosis. In the last 44 patients (23 leukemia and 21 solid tumors), sTfR levels were also measured. Serum EPO together with sTfR levels were also determined in 60 children receiving chemotherapy (29 leukemia, 31 solid tumors). These results were compared with those obtained from appropriate control groups. In all patients, we found a highly significant correlation between the logarithm of EPO (log[EPO]) and the hemoglobin (Hb) level. In all subsets of patients, sTfR levels were inappropriately low for the degree of anemia. Neither leukemic nor solid tumor groups showed a significant inverse relationship between log(sTfR) and the Hb level as would be expected in anemic patients with appropriate marrow response. Thus, in children with cancer, anemia is associated with a decreased total bone marrow erythropoietic activity which, in contrast to what has been reported in anemic cancer adults, is not related to defective EPO production. [less ▲]

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See detailHaematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium.
Vermylen, C.; Cornu, G.; Ferster, Aline et al

in Bone Marrow Transplantation (1998), 22(1), 1-6

Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for ... [more ▼]

Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for transplantation. Group 1 included 36 permanent residents of a European country who, retrospectively, met the inclusion criteria accepted at a consensus conference held in Seattle in 1990, wherein children were selected because they already had evidence of a morbid course. Group 2 included 14 patients who were transplanted earlier, had not received more than three blood transfusions and were transplanted because they had decided to return to their country of origin. Kaplan-Meier estimates of overall survival, event-free survival and disease-free survival at 11 years of the whole grafted population are 93, 82 and 85%, respectively. In group 1, overall survival, EFS and DFS were 88, 76 and 80% and in group 2, 100, 93 and 93%, respectively. Clinical manifestations of the disease, as well as disease associated haemolytic anaemia, disappeared in all successfully treated patients. Recovery of spleen function was present in seven out of 10 evaluated patients. Adverse events (death, absence of engraftment, mixed chimerism and relapse) occurred more frequently in group 1 than in group 2 (25% vs 7%, P< 0.001). Acute graft-versus-host disease (GVHD) was present in 20 patients (grade I or II, 19; grade III, 1), chronic GVHD in 10 (limited, 7; extensive, 3). One patient developed an acute myeloid leukaemia. Gonadal dysfunction was present in all patients (six boys and eight girls) transplanted close to or after puberty, although transient in one adolescent girl. [less ▲]

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See detailIron metabolism and erythropoiesis after surgery.
van Iperen, C. E.; Kraaijenhagen, Rob J.; Biesma, D. H. et al

in British Journal of Surgery (1998), 85(1), 41-5

BACKGROUND: This was a prospective study comparing the effect of major and minor surgery on haematological variables concerning erythropoiesis, iron metabolism and acute-phase response proteins. METHODS ... [more ▼]

BACKGROUND: This was a prospective study comparing the effect of major and minor surgery on haematological variables concerning erythropoiesis, iron metabolism and acute-phase response proteins. METHODS: Thirty-one otherwise healthy patients, 15 having major orthopaedic surgery and 16 undergoing minor surgery, were studied. Blood samples were taken before surgery and 1, 4, 10 and 28 days after operation. RESULTS: Haemoglobin concentration was decreased for up to 4 weeks after surgery. Serum erythropoietin concentration and reticulocyte count were raised after major surgery only. Serum iron concentration dropped the day after major (to 23 per cent of its preoperative level) and minor (to 46 per cent of its preoperative level) surgery and remained lower for up to 28 days after major surgery. Serum transferrin concentration and transferrin saturation decreased after both types of surgery while ferritin concentration increased. Serum transferrin receptor concentration increased only 4 weeks after major surgery (P < 0.01). The interleukin 6 peak (day 1) was greater after major than minor surgery, as was the C-reactive protein peak (day 4). CONCLUSION: Both major and minor surgery induce a state of hypoferraemia in the presence of adequate iron stores. The degree of this transient form of 'anaemia of chronic disease' is related to the extent of surgery. Iron supplementation in the first weeks after surgery (if iron stores were normal before operation) is ineffective. [less ▲]

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See detailRed blood cell precursor mass as an independent determinant of serum erythropoietin level.
Cazzola, M.; Guarnone, R.; Cerani, P. et al

in Blood (1998), 91(6), 2139-45

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors ... [more ▼]

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells. [less ▲]

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See detailTreatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients.
Hellstrom-Lindberg, E.; Ahlgren, T.; Beguin, Yves ULg et al

in Blood (1998), 92(1), 68-75

Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of ... [more ▼]

Treatment with erythropoietin (epo) may improve the anemia of myelodysplastic syndromes (MDS) in approximately 20% of patients. Previous studies have suggested that treatment with the combination of granulocyte colony-stimulating factor (G-CSF) and epo may increase this response rate. In the present phase II study, patients with MDS and anemia were randomized to treatment with G-CSF + epo according to one of two alternatives; arm A starting with G-CSF for 4 weeks followed by the combination for 12 weeks, and arm B starting with epo for 8 weeks followed by the combination for 10 weeks. Fifty evaluable patients (10 refractory anemia [RA], 13 refractory anemia with ring sideroblasts [RARS], and 27 refractory anemia with excess blasts [RAEB]) were included in the study, three were evaluable only for epo as monotherapy and 47 for the combined treatment. The overall response rate to G-CSF + epo was 38%, which is identical to that in our previous study. The response rates for patients with RA, RARS, and RAEB were 20%, 46%, and 37%, respectively. Response rates were identical in the two treatment groups indicating that an initial treatment with G-CSF was not neccessary for a response to the combination. Nine patients in arm B showed a response to the combined treatment, but only three of these responded to epo alone. This suggests a synergistic effect in vivo by G-CSF + epo. A long-term follow-up was made on 71 evaluable patients from both the present and the preceding Scandinavian study on G-CSF + epo. Median survival was 26 months, and the overall risk of leukemic transformation during a median follow-up of 43 months was 28%. Twenty patients entered long-term maintenance treatment and showed a median duration of response of 24 months.The international prognostic scoring system (IPSS) was effective to predict survival, leukemic transformation, and to a lesser extent, duration of response, but had no impact on primary response rates. [less ▲]

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See detailPrediction of response to optimize outcome of treatment with erythropoietin.
Beguin, Yves ULg

in Seminars in Oncology (1998), 25(3 Suppl 7), 27-34

Recombinant human erythropoietin (EPO; epoetin) has been shown to be effective in improving anemia in a proportion of cancer patients. The response rate is approximately 60%, but varies considerably ... [more ▼]

Recombinant human erythropoietin (EPO; epoetin) has been shown to be effective in improving anemia in a proportion of cancer patients. The response rate is approximately 60%, but varies considerably according to baseline hematocrit and transfusion needs, as well as the response criteria used. Response is not greatly influenced by the type of tumor, except in situations of major marrow involvement and limited residual hematopoiesis, or in the presence of specific mechanisms of anemia, such as hemolysis, splenomegaly, bleeding, hemodilution, or ineffective erythropoiesis. Stem cell damage by previous therapy as well as marrow suppression by current intensive chemotherapy can impair response. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications, such as infections, bleeding, or nutritional deficiencies, may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency (ie, an imbalance between iron needs in the erythropoietic marrow and iron supply), which depends on the level of iron stores and its rate of mobilization. Functional iron deficiency is best monitored by the percentage of hypochromic red blood cells, and oral or intravenous iron supplements should be given when this percentage increases above 10%. All these factors explain why the response rate to epoetin is only approximately 60%. Therefore, it would be interesting to develop models that could help predict response to epoetin to help select the most appropriate cancer patients for this therapy. Few baseline parameters have been shown to be highly predictive of response in patients with solid tumors, although most studies in patients with myeloma or lymphoma have indicated that patients with a low baseline serum EPO level will respond better. Early changes after 2 to 4 weeks of treatment are also of great interest. Among these early changes, increments of soluble transferrin receptor, reticulocytes, and hemoglobin, as well as the persistence of elevated ferritin or EPO levels, have all shown some predictive value. Combination of baseline serum EPO and the 2-week increment of soluble transferrin receptor or hemoglobin may provide the best prediction of response. [less ▲]

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See detailHematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells.
Beguin, Yves ULg; Baudoux, Etienne ULg; Sautois, Brieuc ULg et al

in Transfusion (1998), 38(2), 199-208

BACKGROUND: A study of CD34+ cell selection and transplantation was carried out with particular emphasis on characteristics of short- and long-term hematopoietic recovery. STUDY DESIGN AND METHODS ... [more ▼]

BACKGROUND: A study of CD34+ cell selection and transplantation was carried out with particular emphasis on characteristics of short- and long-term hematopoietic recovery. STUDY DESIGN AND METHODS: Peripheral blood stem and progenitor cells (PBPCs) were collected from 32 patients, and 17 CD34+ cell-selection procedures were carried out in 15 of the 32. One patient in whom two procedures failed to provide 1 x 10(6) CD34+ cells per kg was excluded from further analysis. After conditioning, patients received CD34+ cells (n = 10, CD34 group) or unmanipulated (n = 17, PBPC group) PBPCs containing equivalent amounts of CD34+ cells or progenitors. RESULTS: The yield of CD34+ cells was 53 percent (18-100) with a purity of 63 percent (49-82). The CD34+ fraction contained 66 percent of colony-forming units--granulocyte-macrophage (CFU-GM) and 58 percent of CFU of mixed lineages, but only 33 percent of burst-forming units-erythroid (BFU-E) (p < 0.05). Early recovery of neutrophils and reticulocytes was identical in the two groups, although a slight delay in platelet recovery may be seen with CD34+ cell selection. Late hematopoietic reconstitution, up to 1.5 years after transplant, was also similar. The two groups were thus combined for analyses of dose effects. A dose of 40 x 10(4) CFU-GM per kg ensured recovery of neutrophils to a level of 1 x 10(9) per L within 11 days, 15 x 10(4) CFU of mixed lineages per kg was associated with platelet independence within 11 days, and 100 x 10(4) BFU-E per kg predicted red cell independence within 13 days. However, a continuous effect of cell dose well beyond these thresholds was apparent, at least for neutrophil recovery. CONCLUSION: CD34+ cell selection, despite lower efficiency in collecting BFU-E, provides a suitable graft with hematopoietic capacity comparable to that of unmanipulated PBPCs. In both groups, all patients will eventually show hematopoietic recovery of all three lineages with 1 x 10(6) CD34+ cells per kg or 5 x 10(4) CFU-GM per kg, but a dose of 5 x 10(6) CD34+ cells or 40 x 10(4) CFU-GM per kg is critical to ensure rapid recovery. [less ▲]

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See detailPrediction of response to treatment with recombinant human erythropoietin in anaemia associated with cancer.
Beguin, Yves ULg

in Medical Oncology (Northwood, London, England) (1998), 15 Suppl 1

The anaemia associated with cancer can be effectively treated with recombinant human erythropoietin (rHuEpo) in about 60% of the patients. However, the response rate varies according to treatment ... [more ▼]

The anaemia associated with cancer can be effectively treated with recombinant human erythropoietin (rHuEpo) in about 60% of the patients. However, the response rate varies according to treatment modalities as well as the response criteria used. A number of disease- or chemotherapy-related factors determines the probability of response. Several specific mechanisms of anaemia, such as haemolysis, splenomegaly, bleeding, haemodilution, or ineffective erythropoiesis can seriously interfere with response. However, the type of tumor, in particular haematologic versus non-haematologic, is not critical, except in situations of major marrow involvement and limited residual haematopoiesis. Stem cell damage by previous therapy, reflected by low platelet counts or high transfusion needs, will impair response. In addition, marrow suppression by current intensive chemotherapy will also have a negative impact. Besides its intensity, the type of chemotherapy may not be critical, although patients undergoing platinum-based chemotherapy may respond faster than those receiving non-platinum regimens. Complications such as infections, bleeding or nutritional deficiencies may have a major negative impact on outcome. An important response-limiting factor is functional iron deficiency, i.e. an imbalance between iron needs in the erythropoietic marrow and iron supply, which depends on the level of iron stores and its rate of mobilisation. Therefore, oral or preferably intravenous iron supplements should be given when serum ferritin is below 40-100 micrograms/l, reflecting the absence of iron stores, or when the percentage of hypochromic red cells rises above 10%, indicating functional iron deficiency even in the presence of adequate storage iron. Because up to 40% of the patients will not respond to rHuEpo, it is of utmost importance to develop models that could help predict response to rHuEpo and thus select the most appropriate cancer patients for this therapy. Most studies of patients with myeloma or lymphoma have indicated that patients with a low baseline serum Epo level will respond better, but this is not true of patients with solid tumors. Also of considerable interest are early changes of erythropoietic parameters after 2 to 4 weeks of treatment, including increments of serum transferrin receptor (sTfR), reticulocytes and haemoglobin, as well as the persistence of elevated ferritin or Epo levels. Combination of baseline serum Epo and the 2-week increment of sTfR or haemoglobin may provide the best prediction of response. [less ▲]

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See detailA risk-benefit assessment of epoetin in the management of anaemia associated with cancer.
Beguin, Yves ULg

in Drug Safety : An International Journal of Medical Toxicology & Drug Experience (1998), 19(4), 269-82

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated ... [more ▼]

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant benefits in patients with cancer. [less ▲]

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See detailLe cas clinique du mois. Association d'une maladie de Hodgkin et d'un syndrome nephrotique.
Baron, Frédéric ULg; Hermanne, J. P.; Fassotte, Marie-France ULg et al

in Revue Médicale de Liège (1998), 53(11), 651-3

The nephrotic syndrome is a rare complication of Hodgkin's disease. The majority of the cases do not respond to corticosteroids but are cured by the treatment of the lymphoma. We describe a patient with a ... [more ▼]

The nephrotic syndrome is a rare complication of Hodgkin's disease. The majority of the cases do not respond to corticosteroids but are cured by the treatment of the lymphoma. We describe a patient with a nephrotic syndrome at the time of diagnosis of mixed cellularity Hodgkin's disease and the resolution of this nephrotic syndrome by MOPP-ABV chemotherapy. [less ▲]

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See detailIron management in patients on rHuEpo
Cavill, I.; Macdougall, I. C.; Gokal, R. et al

in British Journal of Renal Medicine (1997), 2

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See detailAcute Functional Iron Deficiency in Obese Subjects During a Very-Low-Energy All-Protein Diet
Beguin, Yves ULg; Grek, Vincent; Weber, Georges ULg et al

in American Journal of Clinical Nutrition (1997), 66(1), 75-9

We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 ... [more ▼]

We examined whether a very-low-energy all-protein diet (VLED) would produce detectable changes in iron as well as in other trace elements. Twenty-five obese patients consumed for 2 wk a VLED containing 70 g protein after a 1-wk period during which total daily energy intake was progressively reduced to 1.26 MJ. Serum iron fell sharply by approximately equal to 50% (P < 0.0001), and despite a small decrease in total-iron-binding capacity, transferrin saturation decreased from 30 +/- 11% to 18 +/- 5% (P < 0.0001). Serum ferritin did not change significantly but serum soluble transferrin receptor (sTfR), an indicator of iron deficiency, increased progressively from 4630 +/- 1110 to 6070 +/- 1390 micrograms/L (P < 0.0001). Changes in sTfR correlated inversely with prior changes in serum iron. Changes in iron metabolism did not translate into changes in erythropoiesis or red cell indexes, but the white blood cell count decreased from 7.3 +/- 1.6 to 6.2 +/- 1.9 x 10(9)/L (P < 0.002). There was no evidence of deficiency for the other trace elements and minerals tested. Daily supplementation with 200 mg Fe in 18 other subjects only partially corrected these observations despite some increase in iron stores. These results indicate that during a 2-wk VLED serum iron is significantly depressed, inducing functional tissue iron deficiency too short in duration to produce alterations in red blood cell indexes. These changes are not mediated by absolute iron deficiency, inflammation, or protein malnutrition but could be related to alterations in the iron storage and release behavior of the reticuloendothelial cell during energy deprivation alone. [less ▲]

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