In order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell (PBSC) transplantation, we compared 20 ...consecutive patients with lymphoma or multiple myeloma receiving a single 6-mg dose of Pegfilgrastim on day 1 posttransplant to an historical control group of 60 patients receiving daily Filgrastim 5 μg/kg starting on day 1 posttransplant. The duration of neutropenia was similar in the Pegfilgrastim group compared with the control group. There were no differences in time to neutrophil, erythroid, or platelet engraftment nor in the incidence of fever and infections. The duration of antibiotic therapy, transfusion support, and time to hospital discharge were similar in the two groups. However, after initial hematopoietic reconstitution, we observed significantly higher values of lymphocytes (e.g., 1660 ± 1000 versus 970 ± 460 on day 80,
p = 0.0002), neutrophils (e.g., 3880 ± 2030 versus 2420 ± 1500 on day 25,
p = 0.0004), reticulocytes (e.g., 148,160 ± 90,590 versus 87,140 ± 65,920 on day 25,
p < 0.0001), and platelets (e.g., 210,700 ± 116,090 versus 150,240 ± 58,230 on day 55,
p = 0.0052) up to day 100 in the Pegfilgrastim group compared with the Filgrastim group. These observations had no impact on clinical outcome of the patients after day 30 due to the low incidence of infectious events after engraftment in autologous PBSC transplantation. We conclude that the effect of Pegfilgrastim administrated on day 1 posttransplant is comparable to that of daily Filgrastim on initial hematopoietic reconstitution. The possibly superior effect of Pegfilgrastim on cell counts we observed after initial engraftment should be further tested in a prospective randomized trial.
The purpose of our study was to evaluate the capacities of cord blood (CB) CD34+ cells to proliferate and differentiate ex vivo into myeloid lineage in response to cytokines and to compare them with ...mobilized peripheral blood (MPB) cells. Briefly, 2.5 × 104 CD34+ cells, isolated from CB (n=10) and MPB (n= 9), were cultured in 5 ml MacoBiotech HP01 (Macopharma) with SCF, Flt3-L, IL-3 and G-CSF. At day 9, 106 cultured cells were replated for 5 additional days. Cells were counted and evaluated for their CD34, CD13 and CD15 expression. Differentiation into myeloid compartment was assessed by CD11b and CD16 coexpression on CD15+ cells. We observed that
leucocyte expansion was significantly higher in CB than in MPB at day 9 (24.3±3.8 vs 15.2±1.9) and at day 14 (224.7±54.2 vs 72.9±20.0). A similar difference was observed for CD34+ cell expansion (8.7±1.4 vs 3.4±0.5 at day 9 and 31.3±4.6 vs 7.6±2.4 at day 14).at day 9, despite superior CB leucocyte expansion, CD13+ and CD15+ cell number produced per CD34+ cell seeded at day 0 were similar in CB and in MPB (18.5±2.4 vs 14.4±2.5 for CD13+ and 7.1±1.3 vs 6.0±1.2 for CD15+). Increasing the culture period led to higher numbers of CD13+ and CD15+ cells in CB than in MPB. This increase was due to a total leucocyte expansion rather than to high CD13+ and CD15+ cell percentage.The distribution of CD11b−CD16−, CD11b+CD16− and CD11b+CD16+ subpopulations in CD15+ cells was comparable in CB and in MPB after 9 days of culture, with a majority of relatively immature CD11b−CD16− myeloid progenitor cells.
However, after 5 additionnal days of culture, MPB CD15+ cells expressed a more mature phenotype than CB CD15+ cells, with a dramatic increase of CD11b+CD16− cells (promyelocytes and myelocytes). In conclusion, our study suggests that, despite the high CB cell capacity of expansion in our culture conditions, CB CD34+ cell differentiation process into myeloid lineage appears to be slower. This difficulty of CB cells to reach maturation in vitro is likely to be related with the longer delay of neutrophil recovery after CB transplantation.
Introduction Transplant associated microangiopathy (TMA) is a severe complication occurring after allogeneic stem cell transplantation(alloSCT). It is recognized to have a poor prognosis and no ...effective treatment has been defined.
Methods and Population In this study, we analysed the outcome of patients who developed TMA after alloSCT in our institution from 1996 to 2007. A total 199 patients underwent allogeneic transplantation. To diagnose TMA, we used the criteria proposed by the International Working group of TMA: > 4% schistocytes in blood, de novo or prolonged thrombocytopenia, sudden and persistent increase in lactate dehydrogenase concentration, decrease in serum haptoglobin and decreased haemoglobin.
Results From 1996 to 2006, the overall incidence of TMA in our institution was 19%(37/199). According to the type of transplant, the incidence of TMA was: 18%(14/79) for sibling myeloablative SCT(MSCT); 27%(10/37) for unrelated MSCT; 22.5%(9/40) in haploidentical SCT; 20%(2/10) for sibling non myeloablative SCT(NMSCT) and 20%(2/10) for unrelated NMSCT. Median age of patients was 37 years (range: 16–63). Male to female sex ratio was 1:1.8. As conditioning for transplantation, 60% of patients had received total body irradiation (49% for the alloSCT and 11% for previous treatments). At time of diagnosis of TMA, 35% of patients presented with neurological symptoms (unexplained headache, epilepsy, impaired concentration, drowsiness and/or confusion). Fourty-nine percent (49%) of patients also had cytomegalovirus reactivation; 54% were treated with steroids for acute Graft-versus-host disease and 100% of patients were treated with ciclosporine. The overall mortality rate in the TMA group was 86%, but TMA related mortality was 46%. In patients who died from TMA, median survival post-TMA diagnosis was 16 days(range: 4–60). 88% of those patients had been treated with plasma exchange, 12% by defibrotide. Four of the six patients(66%) treated with defibrotide died from haemorrhagic complications. Only 1 patient treated with defibrotide achieved a complete remission (CR). Of those patients who did not achieve complete remission, 65% had been conditioned with TBI versus 41% in patients who achieved CR.
Conclusion: In our series, the incidence of TMA is significant (19%). The most important risk factors of developing TMA are use of cyclosporine, steroid treatment, CMV reactivation, the use of TBI as conditioning and unrelated donor transplantation. From this study we are unable to define the most effective treatment for TMA. The use of defibrotide was associated with a high risk of haemorrhage in our series and should be used with caution. Because of its incidence and poor prognosis, randomized trials should be utilised to define effective treatment.
In order to assess the effect of Pegfilgrastim on the duration of neutropenia and clinical outcome of patients after autologous peripheral blood stem cell transplantation (PBSCT), we compared 20 ...consecutive patients with lymphoma or multiple myeloma receiving a single 6 mg dose of Pegfilgrastim on day 1 posttransplant to a historical control group of 60 patients receiving daily Filgrastim 5 μg/kg starting on day 1 posttransplant. There were 54 M and 26 F, 30 patients with lymphoma and 50 with myeloma, 26 in CR and 54 not in CR. Mean age was 55±10 yrs and 25 had already received a previous autologous transplant. The two groups were matched for disease and disease status, transplant number, age and sex. Cell dose infused tended to be higher in the Pegfilgrastim group (7.16±3.82 vs 10.03±6.25 x106 CD34+ cells/kg, p=0.0575). There were no differences (p>0.05) in time to 0.5 (8 vs 9 days) or 1 (9 vs 9 days) x109/L neutrophils; to 1 % reticulocytes (13 vs 15 days) or 9 (12 vs 14 days) or 10 (30 vs 25 days) g/dL Hb; to 20 (9 vs 9 days) or 100 (20 vs 31 days) x 109/L platelets. The number of days with fever (2.7±2.3 vs 2.3±2.4 days), incidence of infections (all infections; bacteremia; bacterial, fungal or viral infections; FUO), duration of antibiotic therapy (8.7±5.9 vs 8.4±5.9 days), RBC (1.1±1.6 vs 0.9±1.6) and platelet (1.0±1.7 vs 1.2±1.8) transfusions, and time to hospital discharge (14.5±5.3 vs 15.4±5.8 days) were similar in the Pegfilgrastim compared to the Filgrastim group. However, after initial hematopoietic recovery, several differences between the groups became apparent, with the group always showing higher counts compared to the Filgrastim group (p values <0.05 to <0.001). Neutrophils remained significantly higher in the Pegfilgrastim group between days 14–30, lymphocytes between days 56–90, monocytes between days 21–24, reticulocytes between days 17–42 and platelets between days 35–90, respectively. These differences had no impact on clinical outcome after day 30 due to the low incidence of infectious events after engraftment. We conclude that Pegfilgrastim administrated on day 1 posttransplant facilitates early hematopoietic reconstitution comparable to daily Filgrastim. However, despite a trend towards fewer CD34+ cells transplanted, the Pegfilgrastim group enjoyed higher trilineage cell counts for some time after initial engraftment. This should be further tested in prospective randomized trials.
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