CD34+ cell dose predicts costs after autologous peripheral blood stem cell transplantation for breast cancer.
Baron, Frédéric ; ; Baudoux, Etienne et al
in Haematologica (2004), 89(9), 1146-8
We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for ... [more ▼]
We assessed the effect of CD34+ cell dose on costs in breast cancer patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. Mean hospitalization costs were 26,992.9+/-9582.9 for patients receiving a CD34+ cell dose <5 x 10(6) cells/kg versus 22,339.4+/- 5471.1 for those receiving >5 x 10(6) CD34+ cells/kg (p=0.0065). [less ▲]Detailed reference viewed: 30 (7 ULg)
Low incidence of acute graft-versus-host disease after non-myeloablative stem cell transplantation with CD8-depleted peripheral blood stem cells: an update.
Baron, Frédéric ; Frere, Pascale ; Baudoux, Etienne et al
in Haematologica (2003), 88(7), 835-7Detailed reference viewed: 19 (3 ULg)
Long-term disease-free survival in patients with angioimmunoblastic T-cell lymphoma after high-dose chemotherapy and autologous stem cell transplantation.
; ; et al
in Haematologica (2003), 88(11), 1272-8
BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the ... [more ▼]
BACKGROUND AND OBJECTIVES: Patients with angioimmunoblastic T-cell lymphoma (AIL) have a poor prognosis with conventional treatment. DESIGN AND METHODS: We initiated an EBMT-based survey studying the impact of high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation in patients with AIL. Data on 29 patients, who were transplanted between 1992 and 1998 in 16 transplant centers, were collected on standardized documentation forms. RESULTS: The median age at transplantation was 53 years. HDCT was given as part of 1st-line therapy (N=14; 48%) or 2nd/3rd-line therapy (N=15; 52%). Regimens for the mobilization of peripheral blood stem cells (PBSC) included VIPE (N=7; 26%), DexaBEAM (N=6; 22%), CHOP-like regimens (N=6; 22%), other regimens (N=5; 19%) or alternatively growth factor alone (N=3; 11%). The median yield of PBSC was 3.8x106 CD34+cells/kg. Two patients received autologous bone marrow. The HDCT consisted of BEAM-type regimens in 16 patients, ICE-type regimens in 7, and other regimens in 6 patients. There was one treatment-related death. The rate of complete remissions increased from 45% before HDCT to 76% after HDCT. As of January 2003, after a median observation time of living patients of 5 years (range 2.5 to 10 years), 14 patients have died (13 from progressive disease), and 15 patients are alive. The probability of 5-year overall and event-free survival was 44% (95% CI, 22% to 66%) and 37% (95% CI, 17% to 57%), respectively. Long-term disease-free survival was observed in patients transplanted during 1st-line treatment as well as in the context of 2nd/3rd-line therapy. INTERPRETATION AND CONCLUSIONS: There is evidence that AIL is susceptible to high-dose chemotherapy. HDCT and autologous stem cell transplantation should be considered in selected patients with AIL. [less ▲]Detailed reference viewed: 81 (0 ULg)
Once weekly recombinant human erythropoietin therapy is very efficient after allogeneic peripheral blood stem cell transplantation when started soon after engraftment.
Baron, Frédéric ; Frere, Pascale ; Beguin, Yves
in Haematologica (2003), 88(6), 718-20Detailed reference viewed: 10 (2 ULg)
Non-myeloablative stem cell transplantation with low-dose total body irradiation and fludarabine for metastatic renal cell carcinoma.
Baron, Frédéric ; Frere, Pascale ; Baudoux, Etienne et al
in Haematologica (2003), 88(4), 478-80Detailed reference viewed: 19 (1 ULg)
Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients.
in Haematologica (2002), 87(11), 1209-21
BACKGROUND AND OBJECTIVES: The majority of cancer patients suffer from chronic anemia. While recombinant human erythropoietin (rHuEPO) offers many of the advantages of blood transfusions, response rates ... [more ▼]
BACKGROUND AND OBJECTIVES: The majority of cancer patients suffer from chronic anemia. While recombinant human erythropoietin (rHuEPO) offers many of the advantages of blood transfusions, response rates to this treatment are variable and in some trials a large proportion of patients (30 50%) did not respond. This failure may be due to factors related to the underlying disease, the chemotherapy given or functional iron deficiency. An accurate means of predicting response to rHuEPO would be beneficial to both healthcare providers and patients. EVIDENCE AND INFORMATION SOURCES: Data were identified by searches of the published literature, including PubMed, references from relevant reviews, and abstracts presented at recent international oncology and hematology meetings. Only papers in English published between 1990 and 2002 were included. References were selected according to direct relevance to the topic discussed and availability. STATE OF THE ART: The best algorithms for predicting response appear to be those combining an assessment of the adequacy of endogenous erythropoietin production together with some early indicators of erythropoietic marrow response. Further characterization of the dose-response relationship of erythropoietic agents may allow better understanding of ways in which response may be enhanced. Adequate iron availability could also contribute to better response rates. PERSPECTIVES: Further characterization of the predictors of response for current and upcoming erythropoietic agents may enhance the management of anemia associated with cancer, and provide more convenient, effective, and flexible therapy. [less ▲]Detailed reference viewed: 6 (0 ULg)
Increased platelet reactivity to collagen in transgenic mice overexpressing the P2X1 ion channel.
Oury, Cécile ; ; et al
in Haematologica (2002), 87Detailed reference viewed: 7 (2 ULg)
P2X1-mediated activation of Ca2+-calmodulin leads to myosin light chain and ERK2 phosphorylation in human platelets.
; Oury, Cécile ; et al
in Haematologica (2002), 87Detailed reference viewed: 8 (2 ULg)
Ca2+ influx via the platelet P2X1 ion channel contributes to collagen-induced platelet activation.
; Oury, Cécile ; et al
in Haematologica (2002), 87Detailed reference viewed: 10 (1 ULg)
Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation.
Baron, Frédéric ; ; Schaaf-Lafontaine, Nicole et al
in Haematologica (2002), 87(1), 78-88
BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood ... [more ▼]
BACKGROUND AND OBJECTIVES: To maximize graft-versus-leukemia (GVL) effects while minimizing the risk of graft-versus-host disease (GVHD), we undertook a study of allogeneic CD34-selected peripheral blood stem cell (PBSC) transplantation followed by CD8-depleted donor lymphocyte infusion (DLI). DESIGN AND METHODS: Twenty-four patients with advanced hematologic malignancies were included. PBSC were collected in matched (N=16) or one-mismatch (N=8) related donors and CD34-selected. On day 60, donors donated lymphocytes that were CD8-depleted and separated into 3 aliquots containing 2 x 10(6), 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 1-13) or into 2 aliquots containing 1 x 10(7) and 5 x 10(7) CD3+ cells/kg (patients 14-24). The 1st aliquot was infused on day 60 and the other 1 (2) cryopreserved and infused on days 100 (and 140). RESULTS: An average of 100%, 100% and 84% of the scheduled dose could be administered in DLI 1, 2 and 3, respectively. Although the study group was at very high risk of GVHD, the actuarial incidence of grade II-IV acute GVHD was 28% (13% for HLA-identical siblings) with only 1 patient developing grade III-IV GVHD (after DLI). The actuarial 2-year probability of extensive chronic GVHD was similarly low (13% for all patients and 0% for HLA-identical siblings). Individual cases as well as a 30% relapse rate (0% for standard-risk patients versus 55% for high-risk patients) indicated preservation of the GVL effect. INTERPRETATION AND CONCLUSIONS: We conclude that allogeneic transplantation of CD34-selected PBSC followed by pre-emptive CD8-depleted DLI is feasible with rapid engraftment and minimizes the risk of severe GVHD. Large prospective trials are required to prove that it preserves the GVL effect fully. [less ▲]Detailed reference viewed: 20 (3 ULg)
Combination of nonmyeloablative stem cell transplantation and Imatinib in accelerated phase CML.
Baron, Frédéric ; Frere, Pascale ; Herens, Christian et al
in Haematologica (2002), 87(12), 43Detailed reference viewed: 3 (0 ULg)
Reticulocyte transferrin receptor (TfR) expression and contribution to soluble TfR levels.
R'Zik, Samir ; ; Beguin, Yves
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 ▲]Detailed reference viewed: 79 (1 ULg)
Administration 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 ; Baudoux, Etienne ; Salmon, Jean 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 ▲]Detailed reference viewed: 35 (1 ULg)
Whole-body positron emission tomography using 18F-fluorodeoxyglucose compared to standard procedures for staging patients with Hodgkin's disease.
Jerusalem, Guy ; Beguin, Yves ; Fassotte, Marie-France 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 ▲]Detailed reference viewed: 11 (1 ULg)
Treatment of leukemia relapse after allogeneic hematopoietic stem cell transplantation by donor lymphocyte infusion and STI-571.
Baron, Frédéric ; Frere, Pascale ; Fillet, Georges et al
in Haematologica (2001), 86(9), 993-4Detailed reference viewed: 11 (0 ULg)
Differential Expression of Cellular Prion Protein on Human Blood and Tonsil Lymphocytes
Antoine, Nadine ; ; Coumans, Bernard et al
in Haematologica (2000), 85(5), 475-80
BACKGROUND AND OBJECTIVE: The expression of cellular prion protein (PrPc) on the surface of peripheral lymphocytes has been previously reported, but little is known about its expression on lymphoid cells ... [more ▼]
BACKGROUND AND OBJECTIVE: The expression of cellular prion protein (PrPc) on the surface of peripheral lymphocytes has been previously reported, but little is known about its expression on lymphoid cells from secondary lymph organs. In this report, we compare the surface expression of PrPc on human blood lymphocytes and tonsil lymphocytes. DESIGN AND METHODS: This analysis was performed by cytometry on live lymphocytes isolated from healthy donors or from the tonsils of adults or children. RESULTS: Human peripheral lymphocytes and tonsillar lymphoid cells, but not erythrocytes or granulocytes, express PrPc at their surfaces. Interestingly, we found significantly less PrPc on freshly isolated tonsil lymphocytes, both B and T, than on blood cells. Although tonsil cells bear less PrPc than circulating blood lymphocytes, they are able to express high quantities of PrPc on their surface when placed in culture. However, contrary to previous results, mitogen stimulation does not affect this expression on B- or T-cells. INTERPRETATION AND CONCLUSIONS: We suggest that the PrPc expression by lymphocytes may be modified by interactions occurring during intratissular migration or during cell-to-cell contacts. Whether PrPc plays a role in intracellular communication at this location, as it does in the nervous system, remains an open question. [less ▲]Detailed reference viewed: 29 (4 ULg)
ADP-induced activation of the extracellular-regulated kinase/mitogen-activated protein kinase pathway via the ionotropic P2X1 receptor in platelets.
Oury, Cécile ; ; et al
in Haematologica (2000), 85Detailed reference viewed: 4 (1 ULg)
Persistent tumor 18F-FDG uptake after a few cycles of polychemotherapy is predictive of treatment failure in non-Hodgkin's lymphoma.
Jerusalem, Guy ; Beguin, Yves ; Fassotte, Marie-France 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 ▲]Detailed reference viewed: 16 (2 ULg)
The belgian experience in unrelated donor bone marrow transplantation: identification of center experience as an important prognostic factor.
Dresse, Marie-Françoise ; ; et al
in Haematologica (1999), 84(7), 637-42
BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality ... [more ▼]
BACKGROUND AND OBJECTIVE: We reviewed all unrelated donor bone marrow transplants (UDBMT) performed in Belgium up to December 1995 to identify prognostic factors for relapse, transplant-related mortality and survival. DESIGN AND METHODS: A total of 163 UDBMT were performed in 92 males and 71 females aged 1-55 (median 26) years. Patients were transplanted for ALL (n=35), AML (n=34), CML (n=51), other myeloid malignancies (n=14), SAA (n=21) or miscellaneous other diseases (n=8). Most patients had advanced disease; a few patients were in CR1 (n=10) or early chronic phase (CP) of CML (n=5). RESULTS: Overall survival at 5 yrs was 17% (95% confidence interval: 8-32%), but survival was significantly better for patients with non-malignant disorders (55% at 4 yrs). The relapse rate +/-SE was projected to be 40 (28-54)% at 5 yrs, 36 (20-56)% for standard-risk and 68 (43-85)% for high-risk malignancies (p=0.0029). There was no relapse in CML patients transplanted in 1st CP compared to 68% at 4 yrs with more advanced CML (p=0.0033). Grade II-IV acute graft-versus-host disease (aGVHD) occurred in 55% by day 100 and was strongly modulated by age, ranging from 41% in <20-yr-old to 80% in >40-yr-old patients (p=0. 0021). Transplant-related mortality (TRM) was projected to be 72 (52-87)% at 5 yrs including 2 very late deaths from lung fibrosis and secondary cancer. Main causes of death were original disease in 27, secondary malignancy in 2, GVHD in 28, interstitial pneumonia in 21, other infections in 19, and miscellaneous toxic causes in 21 patients. In multivariate analysis, the relapse rate was strongly dependent on the disease status (p=0.0029), TRM being significantly worse with older age (p=0.0049), and overall survival being significantly worse in more advanced disease (p=0.0006), after a second transplant (p=0.0166), in centers of smaller size (p=0.0316) and in older patients (NS). INTERPRETATION AND CONCLUSIONS: Although results have improved somewhat in recent years, UDBMT remains a procedure with a high TRM. UDBMT should be performed in patients with less advanced diseases and in centers with more experience, particularly in the treatment of adult patients. [less ▲]Detailed reference viewed: 79 (6 ULg)
Erythropoietin and platelet production.
in Haematologica (1999), 84(6), 541-7
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is the primary growth factor for the red cell lineage but treatment with recombinant human Epo (rHuEpo) has been shown to increase platelet counts. In ... [more ▼]
BACKGROUND AND OBJECTIVE: Erythropoietin (Epo) is the primary growth factor for the red cell lineage but treatment with recombinant human Epo (rHuEpo) has been shown to increase platelet counts. In several animal species treatment with rHuEpo stimulated platelet production, but platelet counts tended to normalize after 1-2 weeks and large, chronic doses even caused thrombocytopenia. This paper aims to review the evidence about the effects of Epo on megakaryopoiesis. INFORMATION SOURCES: I examined the literature published in journals covered by Medline(R)a concerning the effects of Epo, hypoxia and iron deficiency on megakaryopoiesis and platelets. The reference list of each article was reviewed to try to identify further contributions. STATE OF THE ART: In vivo data have shown that moderate Epo stimulation, i.e. that produced by standard doses of rHuEpo, short-term hypoxia or moderate iron deficiency, causes a moderate elevation of platelet counts, whereas intense Epo stimulation, as produced by high doses of rHuEpo, prolonged hypoxia or severe iron deficiency, causes some degree of thrombocytopenia. In the latter case, there appears to be a diphasic response to Epo, the initial positive response (a stimulation of platelet production) being followed by thrombocytopenia. Contrarily to the thrombocytopenia due to increased platelet destruction induced by other growth factors, Epo-induced thrombocytopenia is the result of an inhibition of platelet production. CONCLUSION AND PERSPECTIVE: Stem-cell competition between erythroid and platelet precursors appears to be the cause of these phenomena in situations of prolonged, intense stimulation by Epo. In vitro data support the existence of a common erythrocytic and megakaryocytic precursor. It remains to be determined whether these effects of rHuEpo are a result of the dose itself or of the magnitude of the erythropoietic effect of that dose. It is not known whether a lower dose given in a patient with decreased marrow function would bring about the same biological effects as those induced by high doses of rHuEpo in the presence of a normal marrow function. Caution should be exercised before using high doses of hematopoietic growth factors. [less ▲]Detailed reference viewed: 24 (0 ULg)