Impact of cord blood banking technologies on clinical outcome: a Eurocord/Cord Blood Committee (CTIWP), European Society for Blood and Marrow Transplantation and NetCord retrospective analysis
; ; et al
in Transfusion (2016), 56(8), 2021-2029
BACKGROUND Techniques for banking cord blood units (CBUs) as source for hematopoietic stem cell transplantation have been developed over the past 20 years, aimed to improve laboratory efficiency without ... [more ▼]
BACKGROUND Techniques for banking cord blood units (CBUs) as source for hematopoietic stem cell transplantation have been developed over the past 20 years, aimed to improve laboratory efficiency without altering the biologic properties of the graft. A large-scale, registry-based assessment of the impact of the banking variables on the clinical outcome is currently missing. STUDY DESIGN AND METHODS A total of 677 single cord blood transplants (CBTs) carried out for acute leukemia in complete remission in centers affiliated with the European Society for Blood and Marrow Transplantation were selected. An extensive set of data concerning CBU banking were collected and correlations with clinical outcome were assessed. Clinical endpoints were transplant-related mortality, engraftment, and graft-versus-host disease (GVHD). RESULTS The median time between collection and CBT was 4.1 years (range, 0.2-16.3 years). Volume reduction (VR) of CBUs before freezing was performed in 59.2% of available reports; in half of these the frozen volume was less than 30 mL. Cumulative incidences of neutrophil engraftment on Day 60, 100-day acute GVHD (II-IV), and 4-year chronic GVHD were 87, 29, and 21 ± 2%. The cumulative incidence of nonrelapse mortality (NRM) at 100 days and 4-year NRM were, respectively, 16 ± 2 and 30 ± 2%. Neither the variables related to banking procedures nor the interval between collection and CBT influenced the clinical outcome. CONCLUSION These findings indicate a satisfactory validation of the techniques associated with CBU VR across the banks. Cell viability assessment varied among the banks, suggesting that efforts to improve the standardization of CBU quality controls are needed. [less ▲]Detailed reference viewed: 52 (15 ULg)
Infusion of clinical-grade enriched regulatory T cells delays experimental xenogeneic graft-versus-host disease
Hannon, Muriel ; LECHANTEUR, Chantal ; et al
in Transfusion (2014), 54(February), 353-363Detailed reference viewed: 88 (37 ULg)
Routine Fetal Rhd Genotyping with Maternal Plasma: A Four-Year Experience in Belgium
; Gerard, Christiane ; et al
in Transfusion (2008), 48(2), 373-81
BACKGROUND: The objective was to evaluate the diagnostic value of RHD fetal genotyping from the plasma of D- mothers as soon as 10 weeks' gestation in a routine clinical practice in Belgium. STUDY DESIGN ... [more ▼]
BACKGROUND: The objective was to evaluate the diagnostic value of RHD fetal genotyping from the plasma of D- mothers as soon as 10 weeks' gestation in a routine clinical practice in Belgium. STUDY DESIGN AND METHODS: A prospective study was conducted between November 2002 and December 2006. DNA extraction was performed in an automated closed tube system. Fetal RHD/SRY genotypes were detected in the plasma of 563 pregnant mothers by real-time polymerase chain reaction (PCR) targeting multiple exons 4, 5, and 10 of the RHD gene and targeting an SRY gene sequence. These were compared to the D phenotypes determined in the 581 babies they delivered. RESULTS: By combining amplification of three exons, the concordance rate of fetal RHD genotypes in maternal plasma and newborn D phenotypes at delivery was 100 percent (99.8% including one unusual false-positive). The presence of nonfunctional RHD genes and the absence of a universal fetal marker, irrespective of fetal sex, did not influence the accuracy of fetal RhD status prediction. The RHD genotyping from 18 twin pregnancies was also assessed. Five weak D women were excluded from the RHD fetal genotyping prediction. Three discrepant results (0.5%) between predicted fetal genotype and cord blood phenotype were not confirmed by the baby phenotypes from venipuncture blood. CONCLUSION: Prenatal prediction of fetal RHD by targeting multiple exons from the maternal plasma with real-time PCR is highly sensitive and accurate. Over 4 years, this experience has highly modified our management of D- pregnant women. [less ▲]Detailed reference viewed: 90 (11 ULg)
An unusual false-positive fetal RHD typing result using DNA derived from maternal plasma from a solid organ transplant recipient
; ; Schaaps, Jean-Pierre et al
in Transfusion (2006), 46(8), 1454-1455Detailed reference viewed: 26 (0 ULg)
Increased iron absorption during autologous blood donation supported by recombinant human erythropoietin therapy.
Bovy, Christophe ; Baudoux, Etienne ; Salmon, Jean et al
in Transfusion (2006), 46(9), 1616-23
BACKGROUND: Recombinant human erythropoietin (rHuEPO) therapy improves the success of autologous blood (AB) donation programs before elective surgery. The aim of this study was to evaluate iron absorption ... [more ▼]
BACKGROUND: Recombinant human erythropoietin (rHuEPO) therapy improves the success of autologous blood (AB) donation programs before elective surgery. The aim of this study was to evaluate iron absorption during an AB donation program with or without rHuEPO. STUDY DESIGN AND METHODS: Thirty-two patients were randomly assigned among placebo (Group 1) or 300 (Group 2) or 600 UI per kg rHuEPO (Group 3) on the first, second, and third donation visits. All patients also received daily oral iron (200 mg Fe(+)). RESULTS: The number of units collected in Group 3 was higher than in Group 1 (4.6 +/- 0.5 vs. 3.6 +/- 0.8 units; p < 0.01). Red blood cell (RBC) production increased in a rHuEPO dose-dependent manner. With rHuEPO, the RBC volume collected per unit presented a lower decrease with number of donated units than with placebo and was similar to that of homologous blood units. Storage iron did not influence the number of units collected, whereas circulating mobilizable iron was the limiting factor. Oral iron absorption increased in a rHuEPO dose-dependent manner (12-fold with 600 UI/kg rHuEPO) and was proportional to erythropoietic activity. CONCLUSION: rHuEPO does not only improve the number of AB units collected but also their quality. Storage iron cannot meet marrow iron requirements, but rHuEPO strongly increased oral iron absorption in a dose-dependent fashion through stimulation of erythropoietic activity. [less ▲]Detailed reference viewed: 26 (0 ULg)
Phase III randomized study comparing 5 or 10 microg per kg per day of filgrastim for mobilization of peripheral blood progenitor cells with chemotherapy, followed by intensification and autologous transplantation in patients with nonmyeloid malignancies.
; Baudoux, Etienne ; et al
in Transfusion (2003), 43(1), 50-7
BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic ... [more ▼]
BACKGROUND: It is not known whether increasing the dose of filgrastim after mobilizing chemotherapy improves collection of peripheral blood progenitor cells (PBPC) and leads to faster hematopoietic engraftment after autologous transplantation. STUDY DESIGN AND METHODS: A randomized, open-label, multicenter trial was carried out in patients with breast cancer, multiple myeloma, and lymphoma, in which patients were randomized to receive 5 or 10 microg per kg per day of filgrastim after standard chemotherapy to mobilize PBPCs. After high-dose chemotherapy, the components from the first two leukapheresis procedures were returned, and all patients received 5 microg per kg day of filgrastim after transplantation. RESULTS: A total of 131 patients were randomized, of whom 128 were mobilized (Group A, 5 microg/kg, n = 66; Group B, 10 microg/kg, n = 62) and 112 were transplanted. Only six patients were not transplanted because of insufficient CD34+ cell numbers. The median number of CD34+ cells collected in the first two leukapheresis procedures tended to be higher in Group B than in Group A (12.0 vs. 7.2 x 10(6)/kg, NS), but after transplantation there was no significant difference in median times to platelet (9 days in both groups) or neutrophil (8 days in both groups) engraftment or the number of platelet transfusions (three in both groups). A subsequent subgroup analysis separating patients transplanted after first- or second-line chemotherapy also showed no measurable impact of filgrastim dose on the median CD34+ cell yield or on platelet engraftment in either subgroup. CONCLUSION: PBPC mobilization with chemotherapy and 5 microg per kg of filgrastim is very efficient, and 10 microg per kg of filgrastim does not provide additional clinical benefit. [less ▲]Detailed reference viewed: 148 (6 ULg)
Adoptive immunotherapy with donor lymphocyte infusions after allogeneic HPC transplantation.
Baron, Frédéric ; Beguin, Yves
in Transfusion (2000), 40(4), 468-76Detailed reference viewed: 9 (1 ULg)
Donor lymphocyte infusion to eradicate recurrent host hematopoiesis after allogeneic BMT for sickle cell disease.
Baron, Frédéric ; Dresse, Marie-Françoise ; Beguin, Yves
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 ▲]Detailed reference viewed: 29 (3 ULg)
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: 109 (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: 81 (4 ULg)
Hematopoietic recovery in cancer patients after transplantation of autologous peripheral blood CD34+ cells or unmanipulated peripheral blood stem and progenitor cells.
Beguin, Yves ; Baudoux, Etienne ; Sautois, Brieuc 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 ▲]Detailed reference viewed: 51 (9 ULg)
A moderate transfusion regimen may reduce iron loading in beta-thalassemia major without producing excessive expansion of erythropoiesis.
; ; et al
in Transfusion (1997), 37(2), 135-40
BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is ... [more ▼]
BACKGROUND: Hypertransfusion with a baseline hemoglobin of 10 to 12 g per dL is still considered by many to be the mainstay of conservative therapy for beta-thalassemia major. However, this regimen is frequently associated with manifestations of transfusion iron overload, despite regular chelation therapy with subcutaneous desferoxamine. STUDY DESIGN AND METHODS: To verify whether a transfusion regimen with a target pretransfusion hemoglobin level between 9 and 10 g per dL can allow a significant reduction in blood consumption, while still effectively suppressing erythropoiesis, the records were reviewed of 32 beta-thalassemia major patients, who were maintained at a pretransfusion hemoglobin of 11.3 +/- 0.5 g per dL between 1981 and 1986. These patients were switched at the beginning of 1987 to a transfusion regimen with pretransfusion hemoglobin of 9.4 +/- 0.4 g per dL. The degree of erythroid marrow activity was evaluated in these patients and in 32 subjects with beta-thalassemia intermedia through the simple measurement of serum transferrin receptor. RESULTS: After the adoption of the moderate transfusion regimen, transfusion requirements decreased from 137 +/- 26 to 104 +/- 23 mL per kg per year of red cells (p < 0.0001), and mean serum ferritin decreased from 2448 +/- 1515 to 1187 +/- 816 micrograms per L (p < 0.0001), with one-half of patients achieving serum ferritin levels lower than 1000 micrograms per L. The proportion of patients having spontaneous pubertal development increased significantly (p < 0.01), as a result of less iron-related gonadotropin insufficiency. At the lower pretransfusion hemoglobin, erythroid marrow activity did not exceed two to three times normal levels in most subjects. CONCLUSION: As compared with hypertransfusion, moderate transfusion may allow more effective prevention of iron loading, with higher likelihood of spontaneous pubertal development and without producing excessive expansion of erythropoiesis. [less ▲]Detailed reference viewed: 37 (3 ULg)