An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment.

BACKGROUND: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. METHODS: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. RESULTS: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (> or = Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. CONCLUSIONS: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity.

Primordial role of CD34+ 38- cells in early and late trilineage haemopoietic engraftment after autologous blood cell transplantation.

In order to better define which cell subset contained in graft products might be the most predictive of haemopoietic recovery following autologous blood cell transplantation (ABCT), the relationships between the amounts of reinfused mononuclear cells (MNC), CFU-GM, total CD34+ cells and their CD33 and CD38 subsets. and the successive stages of trilineage engraftment kinetics, were studied in 45 cancer patients, using the Spearman correlation test, a linear regression model and a log-inverse model. No relationship was found between the infused numbers of MNC, CD33+ and CD33- subsets observed and the numbers of days to reach predetermined absolute neutrophil (ANC), platelet and reticulocyte counts. The infused numbers of CFU-GM, CD34+ and CD34+ 38+ cells correlated inconstantly with haemopoietic recovery parameters. The strongest and the most constant correlations were significantly observed between the infused numbers of CD34+ 38- cells and each trilineage engraftment parameter. The log-inverse model determined a threshold dose of 0.05 x 10(6) (= 5 x 10(4)) CD34+ 38- cells/kg, below which the trilineage engraftment kinetics were significantly slower and unpredictable. Post-transplant TBI-conditioning regimens increased the low cell dose-related delay of engraftment kinetics whereas post-transplant administration of haemopoietic growth factors (HGF) seemed to abrogate this delay. This would justify clinical use of HGF only in patients transplanted with CD34+ 38- cell amounts lower than the proposed threshold value. This study suggests that the CD34+ 38- subpopulation, although essentially participating in late complete haemopoietic recovery, is also composed of committed progenitor cells involved in early trilineage engraftment.

Role of the CD34+ 38- cells in posttransplant hematopoietic recovery.

Using three different statistical tests in parallel, we showed in a preliminary study that neither mononuclear cells, CD34+ 33+ or 33- cells, nor CD34+ 38+ cells significantly correlated with engraftment kinetics following autologous blood cell transplantation (ABCT). We additionally demonstrated here, in a series of patients suffering from malignant diseases, that the graft content in CD34+ 38- cells is individually a more sensitive indicator of the earliest, as well as the latest post-ABCT trilineage hematopoietic recovery than the colony-forming units-granulocyte-macrophage and even the total CD34+ cell content. This suggests that the CD34+ 38- cell population is itself subdivided into two more subsets, one being already lineage-committed and responsible for short-term engraftment, the other containing only very primitive hematopoietic cells responsible for sustained engraftment. Strong arguments favor the probability that these subsets correspond to HLA-DR+ and DR cells, respectively. We also defined an optimal threshold value of 0.05 x 10(6) CD34+ 38- cells/kg of the patient's body weight (b.w.) above which a rapid and sustained trilineage engraftment safely occurs. In fact, infusion of lower numbers of cells seems to have a more significant impact on long-term compared to short-term neutrophil recovery and on platelet kinetics engraftment. We additionally looked for the eventual influence on engraftment time of the type of disease, and of post-ABCT administration of hematopoietic growth factors (HGF). When the type of disease appeared to have no influence on the engraftment time, posttransplant HGF administration significantly reduced the time to trilineage engraftment in patients transplanted with < 0.05 x 10(6) CD34+ 38- cells, thus justifying it in case of reinfusion of low numbers of CD34+ 38- cells. On the other hand, the administration of HGF after infusion of more than 0.05 x 10(6) CD34+ 38- cells/kg b.w. did not hasten more, or only very little, the engraftment time, thus becoming not only unprofitable for the patients but costly as well.