Successful 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.
; Sautois, Brieuc ; Baudoux, Etienne 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 ▲]Detailed reference viewed: 87 (10 ULg)
Clinical course and predictive factors for cyclosporin-induced autologous graft-versus-host disease after autologous haematopoietic stem cell transplantation.
Baron, Frédéric ; Gothot, André ; Salmon, Jean et al
in British Journal of Haematology (2000), 111(3), 745-53
The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome ... [more ▼]
The administration of cyclosporin A (CyA) after autologous haematopoietic stem cell transplantation (HSCT) induces a systemic autoimmune syndrome mimicking graft-vs.-host disease (GVHD). This syndrome, termed autologous GVHD has notable anti-tumour activity in animal studies. We intended to induce autologous GVHD with CyA in patients undergoing an autologous HSCT. We prospectively studied 118 patients with miscellaneous malignancies undergoing an autologous HSCT with low-dose CyA to characterize the clinical syndrome, its frequency and clinical course, and to determine the factors affecting its incidence. Patients received CyA from d -1 through to d 28, first starting at 2 mg/kg intravenously and then orally as soon as feasible. The dose was adjusted to achieve pre-dose blood levels around 100 ng/ml. A skin biopsy was performed when a skin rash was observed. Thirty-three percent of the patients developed clinical GVHD: clinical stage 1 in 21 patients, stage 2 in seven patients, and stage 3 in three patients. Although total body irradiation (TBI) or high-dose cyclophosphamide were previously thought to be needed, autologous GVHD occurred in five out of 12 patients (42%) after a preparative regimen with high-dose melphalan alone. Autologous GVHD was significantly more frequent in patients older than 33 years, in patients who had received high doses of granulocyte-macrophage colony forming units (CFU-GM) and in those with a diagnosis of myeloid malignancy, compared with those with lymphoid malignancies or solid tumours. A significant negative association was also found with HLA-DR6. In lymphoma patients, GVHD occurred more frequently in advanced disease than in first or second complete remission (CR1-2) patients. All other factors studied were not predictive for GVHD. In conclusion, CyA-induced GVHD is reproducibly and safely induced with doses of CyA adapted to achieve blood levels around 100 ng/ml. In retrospective analysis, there was no survival advantage for patients with GVHD. Phase III trials with this approach are needed to evaluate its anti-tumoral effect. [less ▲]Detailed reference viewed: 24 (0 ULg)
Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.
Sautois, Brieuc ; ; Baudoux, Etienne et al
in Haematologica (1999), 84(4), 342-9
BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify ... [more ▼]
BACKGROUND AND OBJECTIVE: Peripheral blood progenitor cells (PBPC) are now widely used to restore hematopoiesis following high dose chemotherapy in patients with malignancies. We sought to identify parameters that could predict the yield of PBPC after mobilization with chemotherapy (CT) with or without granulocyte colony-stimulating factor (G-CSF) in cancer patients. DESIGN AND METHODS: One hundred and fifty patients underwent 627 PBPC collections during the recovery phase following CT with (n = 469) or without (n = 142) G-CSF. Hemogram, CFC-assays and CD34+ cell count were performed on peripheral blood and leukaphereses products. After log transformation of the data, differences between groups were assessed with the unpaired t-test or one-way analysis of variance. RESULTS: Seventeen and two patients required 2 and 3 mobilization cycles respectively to reach our target of 15x10(4) CFU-GM/kg. In patients with lymphoma but not in those with leukemia, the yields of both CFU-GM and CD34+ cells/kg were dramatically increased when G-CSF was added to CT for mobilization. In collections primed with CT and G-CSF, better yields were obtained in patients with breast cancer or small-cell lung carcinoma (SCLC) as opposed to other solid tumors and leukemia. Among potential predictive factors of CT- and G-CSF-primed harvests, we found that the CD34+ cell count in peripheral blood (PB) was strongly correlated with both the CFU-GM and CD34+ cell yields. Except in leukemia patients, more than 1x10(6) CD34+ cells/kg were harvested when the CD34+ cell count in blood was above 20x10(6)/L. Similarly, better results were obtained in collections performed when the percentage of myeloid progenitors in blood on the day of apheresis was above 5 % or when the leukocyte count in blood was above 5x10(9)/L. INTERPRETATION AND CONCLUSIONS: A diagnosis of breast cancer or SCLC, a leukocyte count in PB of more than 5x10(9)/L, more than 5% myeloid progenitors or more than 20x10(6) CD34+ cells/L in PB were associated with higher yields of PBPC in collections mobilized with CT+G-CSF. [less ▲]Detailed reference viewed: 60 (10 ULg)
Delayed massive immune hemolysis mediated by minor ABO incompatibility after allogeneic peripheral blood progenitor cell transplantation.
Salmon, Jean ; ; 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 ▲]Detailed reference viewed: 67 (4 ULg)
Le cas clinique du mois. Association d'une maladie de Hodgkin et d'un syndrome nephrotique.
Baron, Frédéric ; ; Fassotte, Marie-France 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 ▲]Detailed reference viewed: 79 (4 ULg)
Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin: results in young normal controls.
Sadzot, Bernard ; Lemaire, Christian ; Maquet, Pierre et al
in Journal of Cerebral Blood Flow & Metabolism (1995), 15(5), 787-97
Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the ... [more ▼]
Changes in serotonin-2 receptors have been demonstrated in brain autopsy material from patients with various neurodegenerative and affective disorders. It would be desirable to locate a ligand for the study of these receptors in vivo with positron emission tomography (PET). Altanserin is a 4-benzoylpiperidine derivative with a high affinity and selectivity for S2 receptors in vitro. Dynamic PET studies were carried out in nine normal volunteers with high-specific activity (376-1,680 mCi/mumol) [18F]altanserin. Arterial blood samples were obtained and the plasma time-activity curves were corrected for the presence of labeled metabolites. Thirty minutes after injection, selective retention of the radioligand was observed in cortical areas, while the cerebellum, caudate, and thalamus had low radioactivity levels. Specific binding reached a plateau between 30 and 65 min postinjection at 1.8% of the injected dose/L of brain and then decreased, indicating the reversibility of the binding. The total/nonspecific binding ratio reached 2.6 for times between 50 and 70 min postinjection. The graphical analysis proposed by Logan et al. allowed us to estimate the binding potential (Bmax/KD). Pretreatment with ketanserin was given to three volunteers and brain activity remained uniformly low. An additional study in one volunteer showed that [18F]altanserin can be displaced from the receptors by large doses of ketanserin. At the end of the study, unchanged altanserin was 57% of the total plasma activity. These results suggest that [18F]altanserin is selective for S2 receptors in vivo as it is in vitro. They indicate that [18F]altanserin is suitable for imaging and quantifying S2 receptors with PET in humans. [less ▲]Detailed reference viewed: 41 (5 ULg)