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.

Infusion of lymphocytes obtained from a donor immunised with the paraprotein idiotype as a treatment in a relapsed myeloma.

A 48-year-old patient with IgA k multiple myeloma received a BMT from his HLA-matched sibling. After transplantation, the disease relapsed. Melphalan therapy followed by reinfusion of haemopoietic blood stem cells collected from the patient led to the improvement of the clinical status, although mixed chimerism and an elevated serum IgA persisted. Successful donor immunisation against an immunogenic preparation of the recipient monoclonal protein was performed before the infusion of donor T lymphocytes (DLI) into the patient. Ten weeks after the lymphocyte infusions, no monoclonal band was evidenced and donor complete chimerism was detected. The patient did not develop GVHD. Once complete remission was achieved, the idiotype vaccine was administered to the patient. Nineteen months after DLI, the patient remains in remission. Bone Marrow Transplantation (2000).

[Determination of the cytokine level during storage of partially leukocyte-depleted (<0.5 x 10(9)) or totally leukocyte-depleted (<0.5 x 10(6)) platelets]. / Determinación del nivel de citocinas durante el almacenamiento de plaquetas parcialmente desleucocitadas (< 0.5 x 10(9)) o "totalmente" desleucocitadas (< 0.5 x 10(6)).

PURPOSE: To evaluate the levels of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) during the storage of pools of PCs obtained after removing the buffy-coat, in comparison with the amount of leukocytes present in these components. MATERIAL AND METHODS: Blood was collected in quadruple-bag-system containing 63 mL of CPD as anticoagulant and 100 mL of SAG-M solution as additive for the red cells. Approximately twelve hours after collection, blood separation was made automatically by Compomat (NPBI) and platelet concentrates were prepared from the buffy-coat fraction. Five or six PCs were mixed to obtain a pool (n = 28). Eight pools were WBC reduced by filtration (PXL-8, Pall España). Before storage a sample of each pool was obtained in order to count platelets and WBC as basal values. All kind of pools were stored at room temperature with continuous agitation during a period of 10 days. Volumes were measured by weight and specific gravity. Platelets and leukocytes were counted in the Coulter-counter (STKR Counter. Izasa) or in Nageotte chamber for the filtered products. On days 1, 4 and 7 interleukins were measured by ELISA (EASIA Kits, Medgenix Diagnostics, Brussels), Lecture was done at 450 nm using a spectophotometer (ANTHOS 2001). Lower limits of sensitivity were 2 pg/mL for IL-1 beta and 3 pg/mL for IL-6 and TNF-alpha according to the manufacturer. Wilcoxon test was used for statistical analysis. RESULTS: The average volume of the pools was 460 mL and 374 for the filtered ones. The total platelet amount was 3.63 x 10(11) and 2.8 x 10(11) respectively, with a WBC contamination of 380 x 10(6) and 0.54 x 10(6) for the filtered. The yield of platelets after filtration was 84% with a loss of 99.90% of WBC (3-log). The measures of interleukins were not homogeneous, but a great variability was found shown among the different pools, not always in relationship with the amount of leukocytes. The levels of IL-1 beta were 3.58 pg/mL on day 1, 6.36 pg/mL on day 4 and 8.76 pg/mL on day 7 (p < 0.005). For the IL-6 we found 13.08 pg/mL on day 1, 15.43 pg/mL on day 4 and 19.77 on day 7 (p < 0.05). For the TNF-alpha, 13.65 pg/mL an day 1,24.33 pg/mL on day 4 and 30.10 pg/mL on day 7 (p < 0.05). In the filtered pools the detections of IL-1 beta and IL-6 were always under the sensibility threshold, but there was an increment of TNF-alpha on day 7 (16.91 pg/mL). Microbiologic cultures were always negative. CONCLUSION: The accumulation of IL-1 beta, IL-6 and TNF-alpha is not prevented by the fact of removing the buffy-coat layer when preparing PCs, although these levels are considerably lower in comparison with those obtained by the PRP technic. Filtration of pooled PCs avoids the presence of these cytokines except TNF-alpha, where a low amount can be detected.

[Hospital use of fresh frozen plasma]. / Uso hospitalario del plasma fresco congelado.

PURPOSE: The aim of this work is double. On the one hand, to assess if the measures to strictly control the clinical indications of fresh-frozen plasma (FFP) transfusion may lead to a decrease of its use, and on the other to assess the importance of FFP with regard to other blood components, along with disclosing the number and characteristics of the more patients and those who receive only FFP. MATERIAL AND METHODS: Starting from data of the blood bank and the hospital records, an analysis of the use of FFP in the General Hospital was carried out, and it was correlated with the use of other blood components, mostly red cells (RC), and the hospital indices expressed as DRG. An analysis was also performed of the use of FFP in 1996 with regard to the number of transfused patients, mean consumed units in general and according to patient-groups, association with RC use and identification of high-use patients (defined as requiring over 3 FFP units). RESULTS: A decrease in the use of FFP between 1992 and 1996 was appreciated, from 1,385 to 760 units. This decrease, when correlated with the use of RC, was from 17.8 to 9.2 FFP units/ 100 RC units during this period. The FFP units/100 RC units varied from 6 to 2 in three years; this index has been stable since then. With regard to the use in 1996, 162 patients received FFP, which represents 4% of all the transfusions in the hospital. Of these, 15 patients received only plasma (9% of the patients receiving FFP and 0.3% of all transfusions). Other blood components, mainly RC, were associated to FFP in 96% of the cases. The patients consuming more FFP units were those of heart surgery and intensive care units, with significant differences with respect to others. CONCLUSIONS: This study shows a steady decrease in the use of FFP, which is stable in the last years. The patients receiving only FFP represented a low number with respect to all the patients transfused. The follow-up of these patients might provide valuable data about the benefit of adding additional security processes to standard FFP.

[Changes in total and differential leukocyte counts during heart surgery with extracorporeal circulation]. / Variación en el recuento y fórmula leucocitarios durante la cirugía cardíaca con circulación extracorpórea.

The changes in leukocyte overall and differential counts during anesthesia and surgery were evaluated in 24 patients scheduled for cardiac surgery with cardiopulmonary bypass. All the end of cardiopulmonary bypass a marked and sustained leukocytosis was found (10.2 and 11.1 x 10(9).l-1), which was significantly different from baseline values (6.7 x 10(9).l-1), the values previous to cardiopulmonary bypass (6.2 and 6.4 x 10(9).l-1, and the values 30 minutes after it (5.3 x 10(9).l-1). In the differential count there were significant increases in neutrophils, associated with band and immature forms, corresponding with significant reductions in lymphocytes. There was no significant association of leukocyte variability during and after cardiopulmonary bypass and the perfusion time, the type of oxygenator or the need for intraoperative transfusion. All the reported changes tended to become normal during the first postoperative days.

Immunotherapy of glioblastoma with intratumoural administration of autologous lymphocytes and human lymphoblastoid interferon. A further clinical study.

A clinical trial of an immunotherapy which consisted of intratumoural injections of autologous lymphocytes with human lymphoblastoid interferon was evaluated in 31 patients with intracranial glioblastoma. Immunotherapy was performed after stereotactic biopsy or surgical resection. The treatment was tolerated well by all patients. Three patients showed positive response to immunotherapy as documented by transient regression or stabilization of the tumour size on computed tomography. Nevertheless, there is no significant difference in the survival time of the patients treated with immunotherapy and those not treated. We conclude that this immunotherapeutic regimen is not beneficial in patients with glioblastoma when used as single treatment after tumoural biopsy or resection.

Histological changes in glioblastoma after intratumoral injection of autologous lymphocytes and human lymphoblastoid interferon.

Seven glioblastomas were studied between 1 and 6 months after intratumoral injection of autologous lymphocytes and human lymphoblastoid interferon. Morphological study showed a great number of lymphocytes within the tumor tissue, and interactions between lymphocytes and glioblastoma cells, suggesting a killing phenomenon. These data support the potential usefulness of adoptive immunotherapy in patients with glioblastoma by means of intratumoral administration of activated lymphoid cells.

[Interstitial pneumonia in bone marrow transplantation. Preventive and therapeutic aspects. Our experience and review of the literature]. / Neumonía intersticial en el trasplante de medula ósea. Aspectos profilácticos y terapéuticos. Nuestra experiencia y revisión de la literatura.

From June/82 through November/85 bone marrow transplant recipients in our Institution were given only trimethoprim-sulfamethoxazole as prophylaxis against interstitial pneumonia. In December/85 we began a program of administration of passive immunoprophylaxis with hyperimmune plasma or cytomegalovirus-specific gamma globulin and transfusion of seronegative blood products to all bone marrow transplant recipients whether they were seropositive or seronegative prior to transplant. Nine of 36 patients in the historical control group and 9 of 32 patients in the study group developed an interstitial pneumonia. Interstitial pneumonia, once established, was treated empirically. The 9 patients in the control group received trimethoprim-sulfamethoxazole +/- adenine arabinoside, acyclovir, amphotericin B and anti-bacterial antibiotics; all died. Post-mortem study was performed in 7 (4 CMV, 3 idiopathic). The 9 patients in the study group received high dose cytomegalovirus-specific gamma globulin + acyclovir or ganciclovir in addition to the above measures. Four were cured, one relapsed and responded to treatment again. Five died (1 CMV, 1 candida, 3 idiopathic). We conclude that the prophylactic measures, as applied at our Institution, were inefficient. By contrast, therapy with specific immunoglobulin + acyclovir or ganciclovir can control a high percentage of patients. We compare this experience with reports from other centers.

[Evolution of antibodies and ABH plasmatic transferases in transplants with ABH difference between the recipient and donor]. / Evolución de los anticuerpos y de las transferasas plasmáticas ABH en los trasplantes con diferencia ABH entre receptor y donante.

Another important aspect of these transplants is the possibility of assessing the variations in the activity of serum ABH transferases in receptors of organs with ABH typing different from theirs. The antigenicity of these enzymes has been proven, antitransferase antibodies being found in BMT with minor mismatch, A-group receptors of O-group bone-marrow, and in SOT with major mismatch, O-group receptors of B-group liver. The study of the properties of such antibodies is of great interest in the course of GVHD or HVGD, in either form of transplant, as well as in the knowledge of the biochemical and immunologic characteristics of these ABH enzymes.

Intratumoural injection of autologous lymphocytes plus human lymphoblastoid interferon for the treatment of glioblastoma.

Preliminary experience with a clinical trial of immunotherapy for glioblastoma, by means of intratumoural injection of autologous lymphocytes (AL) mixed with low doses of human lymphoblastoid interferon (HLI) is presented. In two of twelve patients, a transient reduction of tumoural volume was obtained. Morphological studies showed that injected lymphocytes remain within the tumour, and suggest tumoural lysis due to activity of natural killer (NK) cells. Clinically no significant prolongation of survival time could be achieved and, as in other series, patients with additional radiation therapy survived longer. But the morphological findings suggest that immunotherapy carrying NK-cells to contact with tumoural cells might be useful in some patients with glioblastoma. Actually no explanation can be given why only two of our cases responded positively. Regarding the otherwise poor prognosis it seems justified to continue these studies.

Presence of antibody to A- and B-transferases in minor incompatible bone marrow transplant.

The contribution of the bone marrow to plasma A- or B-transferase activities has been studied in patients who underwent incompatible bone marrow transplantation (BMT). As deduced from major incompatibility (group O recipient/A donor), the contribution of the marrow to these plasma activities was c. 5-10% of the total activity. In cases of minor incompatible transplants (A recipient/O donor), normal plasma activity was present in two patients, while no activity was found in a further two in whom a potent antitransferase was detected. The antibody inhibited both A- and B-transferase activities to a high titre. The patients in whom this antibody arose exhibited severe graft-versus-host disease.

Intrathecal injection of autologous leucocytes in glioblastoma: circulatory dynamics within the subarachnoid space and clinical results.

In part I of this report, the CSF circulatory dynamics of autologous leucocytes labelled with indium-111 and injected in the subarachnoid space, in patients operated on for glioblastoma, were studied. In the Part II, a series of 11 patients with recurrent glioblastoma was studied for evaluating the efficacy of intrathecal injection of autologous leucocytes. Six patients previously had radiotherapy. The results in Part I show that after intrathecal injection of autologous leucocytes, these cells follow throughout the subarachnoid space and pass to the systemic blood circulation, showing no evidence of colonization of the tumour or deposit in the tumoural region. The mean survival of the patients studied in Part II was 8 months. Those six patients who received radiotherapy had a mean survival of 11.4 months, and those five who received only intrathecal injection of autologous leucocytes after surgery, had a mean survival of 4 months. This results seem to demonstrate that immunotherapy, as used in this study, is ineffective in patients with glioblastoma.