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Biomedical subjects

M Valbonesi

Publications and source records attributed to M Valbonesi.

At least 37 records · Page 2Linked to original sources

Cascade filtration (CF) with the Haemonetics MCS+: a new technical adaptation.

CF was introduced in clinical medicine in 1980. Up to now, exclusively two-vein procedures have been carried out with some limitations to expansion of this technique. In this report we describe the very first application of single-needle CF carried out with Haemonetics MCS + apparatus. Twenty procedures were completed without any untoward effect in patients suffering from TTP, post-hepatitic cryoblobulinemia, familial hypercholesterolemia and acute Guillan-Barrè Syndrome. From 1 to 4 sessions were carried out per patient with the expected laboratory and clinical results. The only limit is the procedure time that averages 231 +/- 48 min., approximately 40% longer than two needle procedures.

Cryoglobulinemia↗

Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma.

PURPOSE: To investigate the use of a nonmyeloablative fludarabine-based immunosuppressive regimen to allow engraftment of HLA-sibling donors' mobilized stem cells and induction of a graft-versus-lymphoma effect for patients with advanced resistant Hodgkin's disease and non-Hodgkin's lymphoma. PATIENTS AND METHODS: Fifteen patients with Hodgkin's disease (n = 10) and non-Hodgkin's lymphoma (n = 5) were studied. All patients received cyclophosphamide and granulocyte colony-stimulating factor to mobilize autologous hematopoietic stem cells (HSCs). Subsequently, they received high-dose therapy with carmustine, etoposide, cytarabine, and melphalan and reinfusion of HSCs. At a median of 61 days after engraftment, patients were given fludarabine 30 mg/m(2) with cyclophosphamide 300 mg/m(2) daily for 3 days. Donor-mobilized HSC collections were prepared for fresh infusion and were not T-cell depleted. Methotrexate and cyclosporine were used to prevent graft rejection and as graft-versus-host disease (GVHD) prophylaxis. RESULTS: Combined treatment was well tolerated. After mini-allografting, hematologic recovery was prompt. Thirteen patients had 100% donor cell engraftment. Eleven patients achieved complete remission (CR) after the combined procedure. Nine patients, who were in partial remission after autografting, achieved CR after mini-allografting. Seven patients developed >/= grade 2 acute GVHD (aGVHD) and two developed extensive chronic GVHD (cGVHD). Three patients who received the highest number of donor lymphocyte infusions (DLIs) developed grade 3 GVHD (two patients) and extensive cGVHD (one patient). Ten patients are currently alive, and five are in continuous CR. Seven patients received DLI, with five CRs. Five patients died: one of progressive disease, two of progressive disease combined with aGVHD or cGVHD, one of extensive cGVHD, and one of infection. CONCLUSION: Fludarabine/cyclophosphamide was well tolerated and allowed consistent engraftment in lymphoma allografted patients. Response rates were high in this group of refractory and heavily pretreated patients. This dual procedure seems to be most promising in patients with end-stage malignant lymphomas.

Adult↗

Clinical application of therapeutic erythrocytapheresis (TEA).

Therapeutic erythrocytapheresis (TEA) has been used in different diseases such as polycythemia vera (PV), secondary erythrocytosis or hemochromatosis as a process of the less cumbersome but more expensive phlebotomy. TEA is preferred in emergency conditions such as thrombocytosis or in conditions such as porphyria cutanea tarda (PCT) or erythropoietic porphyria when plasma exchange (PEX) is often combined with TEA to reduce extracellular levels of uroporphyrin which contribute to plasma hyperviscosity. TEA is often combined with drug therapy that varies from etoposide in PV to EPO and desferoxamine which are used to mobilize and reduce iron stores in hemochromatosis. Benefits from this combination may be more long lasting than expected. Nonetheless for TEA, there is no standard protocol and, clinical experience with this therapy remains highly anecdotal. Therapeutic red cell-exchange (TREX) has been used with much interest over the years, starting with the management of hemolytic disease of the newborn and later used to correct severe anemia in thalassemia patients thereby preventing iron overload. It has also been used for the management of complications of sickle cell disease such as priapism, chest syndrome, stroke, retinal, bone, splenic and hepatic infarction or in preparation for surgery by reducing HbS to less than 30%. Automated apheresis has also favored the use of TREX in conditions such as paroxysmal nocturnal hemoglobinuria and aniline poisoning, arsenic poisoning, Na chlorate intoxications and CO intoxications, hemoglobinopathies, autoimmune hemolytic anemia, reactions due to ABO incompatibility, in preparation for ABO incompatible bone marrow transplantation or for preventing anti-D immunization after the transfusion of D(+) cells to D(-) recipients. Another field of application has been in the emergency management of intraerythrocytic parasite infections such as malaria and babesiosis. Application of TREX may be wide but its real use remains limited. In our personal experience, in 16 years, only 167 TREX procedures have been carried out in a total of 13,747 therapeutic procedures. This represents only 1.21% of the total.

Anemia, Sickle Cell↗

PCR testing for HCV in anti-HCV negative blood donors involved in the so called HCV +ve post-transfusion hepatitis.

UNLABELLED: Although it is infrequent, post-transfusion HCV infection may occur if the donors blood is collected in the window period between exposure and anti-HCV detectability by ELISA testing. STUDY DESIGN: In these last years, despite of routine application of anti-HCV testing, our blood transfusion center has been involved in 53 cases of alleged post-transfusion HCV hepatitis and look-back programs were set up with the goal of finding out the donors possibly involved in viral transmission. Most of these patients were hematological cases with multiple transfusions given because of aplastic anemia (3 cases), leukemia with or without bone marrow transplantation (5/4 cases) but necessitating long-term platelet support, leukemia and solid cancer patients undergoing autologous PBSC transplantation (3/4 cases) and TTP (2 cases). Only 32 patients were of the simple medical or surgical type, 9 transfused because of cardiac or vascular surgery, 8 because of spine surgery, 5 for different diseases and 5 for different types of cancer surgery. Donor's infectivity was determined by ELISA anti-HCV testing, by recombinant immunoblotting assay, and by nucleic acid testing. RESULTS AND CONCLUSION: No donors out of 267 traced of a total of 359 involved was found with anti-HCV seroconversion, or positive on PCR testing. This suggests that the responsibility for HCV transmission can only hypothetically be related to blood or blood components and that other transmission routes should be found out.

Blood Donors↗

The supply of blood products in 10 different systems or countries.

Countries vary greatly in their ability to produce their own blood products including albumin and IVIgG. Part of this variability depends on the supply of plasma within the country. As has been seen most recently in the UK, the quality of the plasma and its acceptability for plasma fractionation must also be considered. Therefore concerns regarding the quality of the plasma have been added to those regarding the quantity.Only a few countries are nationally self sufficient in plasma. This has a marked effect on blood product availability and therefore the ability to treat patients. Unlike most pharmaceuticals, the plasma fractionation industry must rely, for its raw products, on plasma obtained from blood donors. As such this puts it in a potentially compromised situation since neither the supply nor the quality of the raw material can be assured and both of those will vary with time. This paper reviews the processes through which blood products are made available in 10 different systems including: Canada, England, France, Italy, Norway Scotland, Sweden, Switzerland, South Africa and USA. A series of specific questions were posed and the responses received from the various coauthors and other respondents provide comparative data on blood product availability in different areas of the world.

Blood Banks↗

Early total white blood cell recovery is a predictor of low number of apheresis and good CD34(+) cell yield.

OBJECTIVE: We analysed peripheral blood progenitor cell (PBPC) mobilisation and collection in order to assess the main factors related to CD34(+) cell yields in patients affected by haematological malignancies. PATIENTS AND METHODS: The features of CD34(+) cell mobilisation of patients with haematological malignancies that underwent autologous bone marrow transplantation were examined. Mobilisation chemotherapy consisted mainly of cyclophosphamide (CY) 4 or 7 g/m(2) followed by growth factors. Leukapheresis was started when the WBC counts reached 1.0x10(9)/l with the aim to collect at least 5x10(6) CD34(+) cells/kg body weight. The aphereses were performed on continuous-flow blood cell separators. The analysed variables were: age, diagnosis, CT mobilisation regimen, type of growth factor, number of previous CT lines, prior radiotherapy, days for WBC recovery and number of aphereses procedures to achieve the target of CD34(+) cells. RESULTS: There were 41 consecutive patients (26 M/15 F): 21 non-Hodgkin's lymphoma (NHL), 15 Hodgkin's disease (HD), two chronic myeloid leukaemia (CML) and three multiple myeloma (MM). Eleven patients could not collect the proposed threshold of CD34(+) cells. CY 4 mobilised patients recovered WBC counts in less days (P=0.03). By ANOVA, the days to WBC recovery had a linear function of the predictors "number of aphereses" and "type of mobilisation CT" (coefficients: 0.86 and 0.95, respectively). For the number of aphereses and WBC recovery after CT mobilisation, we obtained a correlation coefficient of 0.36 (P=0.02). CONCLUSION: This study shows that it is feasible to mobilise and collect PBPC in patients previously treated with CT with or without RT. There was a linear correlation between the days for WBC recovery and the number of aphereses needed to collect the target number of CD34(+) cells. The study suggests that early WBC recovery, using mainly CY 4 mobilisation chemotherapy, is an important predictor of a low number of aphereses to achieve a good CD34(+) yield.

Adolescent↗

Therapeutic hemapheresis as of 2000.

The main task of therapeutic hemapheresis remains doing the right thing and doing the right thing right. If objective results have been slow to take hold it is in large part because several physicians have resisted continuous improvement since therapeutic apheresis was considered so efficient to boomerang preventing elimination of unnecessary procedures and treatments. The right thing to do is treating patients who may respond in a specific phase of their disease, frequently along with the right drugs. Doing right the right thing is to take advantage of the new technologies and, medical culture which have led apheresis to the recent complexity and efficacy. In the following pages we are trying to update the state-of-the-art and new trends which characterize therapeutic apheresis at the beginning of 2000.

Blood Component Removal↗

Acute intravascular hemolysis in two patients transfused with dry-platelet units obtained from the same ABO incompatible donor.

Since 1989 we have been collecting dry-platelets on a routine basis. Dry-platelets are those collected along with 25-30 ml of contaminating plasma cell with separators such as the Amicus, AS 104 and the Excel Pro. Platelets are resuspended in non plasma media for storage and for at least 60 hours their viability and functionality are not impaired. In this article we report on two hemolytic crises determined by two O Rh D + units of single donor platelets (SPD) taken from the same donor in a double-apheresis session. The two split units were administered to two A Rh D + patients suffering from metastatic breast cancer and severe aplastic anemia (SAA) respectively. In both cases the hemolytic reaction was of the intravascular type, with a drop in hemoglobin (Hgb) level from 8.6 to 5.4 and from 8.8 down to 5.3 g/dl respectively. From the patients' RBC only alpha agglutinins were eluted and donor's indirect antiglobulin test (IAT) was negative with extended panel RBCs. In the first case the clinical course after erythroexchange (Erex) was uneventful whereas in the second one, that suffering from SAA, after Erex, acute renal failure and shock did complicate the clinical course and the patient died seven days after the incriminated platelet transfusion.

ABO Blood-Group System↗

[Preoperative autologous blood donation and transfusion in gynecology].

BACKGROUND: Autologous transfusions reduce the risk of alloimmune and infectious complications of allogenic blood transfusions. We have evaluated preoperative autologous blood donation practice in relation to patients characteristics and surgical technique. METHODS: In the Obstetrics and Gynecology Department of Genoa University, we enrolled 462 patients in an autologous transfusion program during 1997. We did not analyze 105 patients who underwent minor surgery. Patients with hemoglobin lower than 11 g/dl or with other risks related to autotransfusion have been excluded; 284 (79.5%) patients have been able to make preoperative autologous blood donations. Patients who did not undergo predeposit have utilised type screen or cross reaction for a possible who did eterologous transfusion. We have analysed the two groups of patients for kind of pathology, for number of heterologous blood units used, for number of transfused patients and we have considered the mean of the units received by each of them. RESULTS: 44 of the 284 predeposited blood units were reinfused while 10 patients, who did not undergo predeposit, were transfused. Heterologous transfusion was done in 1.06% of the cases that underwent predeposit. Oncologic patients underwent predeposit in 83% of the cases. CONCLUSIONS: We have concluded that autologous blood donation reduces the risk of allogenic blood transfusion especially in oncologic surgery.

Adolescent↗

Dry platelets with the Dideco Excel apparatus.

Dry platelets are required to prevent hemolytic and nonhemolytic febrile reactions after transfusion to ABO mismatched recipients, to reduce the risk of HLA immunization and to prevent allergic or anaphylactic reactions. Previously we have shown that the collection of single donor platelets almost free of plasma is possible with different cell separators. With the systems we described for the CS 3000+/Amicus and AS 104-204 apparatuses collection of dry platelets implies their resuspension in non plasma solutions after opening the circuit. With the new system developed by Dideco for the Excel apparatus this moreover is no longer required since the platelet bag can be connected to the resuspending medium through a dedicated line with an antibacterial filter. Platelets are collected cyclically and the resuspending solution is added when the procedure is over. In this study 53 collections were evaluated, 21 of which were erythrothrombocytapheresis. In 60-65 min 4.21 of anticoagulated blood (1/12) were processed with platelet collection automatically done after 6-700 ml cycles. The platelet yield averaged 4.67 +/- 0.7 x 10(11), with a platelet efficiency per minute of 7.18 +/- 0.9 x 10(9). The WBC contamination averaged 2.6 +/- 0.7 x 10(5) and contamination did not exceed 0.87 x 10(6). The quality of platelets was satisfactory as measured by aggregation, morphology score, and CD 62 membrane glycoprotein externalization. These results were comparable to those obtained with three other Excel apparatuses used in the conventional way to collect platelets resuspended in plasma or with the Amicus used to collect dry platelets using an open system.

Cell Separation↗

Automatic volumetric capillary cytometry in the routine of an apheresis unit involved in multicomponent collection.

In apheresis, leukodepletion by secondary filtration of the platelet components or by the primary use of special high efficiency apparatuses is widely used to meet current clinical practice. Leukodepletion of RBC is mandatory for hematooncological patients and new filters for plasma are progressively being introduced in the routine of European blood banks. However, since the monitoring of leukodepletion efficiency continues to be carried out manually using the Nageotte or the microdroplet fluorescence assay (MFA), inaccuracy and labour-intensity of counting will limit the possibility of satisfying the increasing demand for leukodepletion monitoring. Volumetric capillary cytometry (VCC) is a totally automated system that has been shown to correlate well with Nageotte, MFA and flow-cytometric countings of residual leukocytes in platelet and RBC product. In this article we describe the application of VCC in the quality control program of our hemapheresis unit in which all apheresis donations are of the multicomponent collection type.

Automation↗

Autoapheresis and intraoperative blood salvage in oncologic surgery.

Transfusion of predeposit or salvaged autologous blood has continued to grow since the 1980s. Issues such as the indications for use and cost effectiveness as well as the safety of autologous blood salvaged during cancer surgery have emerged and should be addressed. The concern for possible contamination of autologous RBC with cancer cells responsible for metastasis has limited the use of autologous salvaged blood in cancer patients. Nevertheless, clinical experience has been gained on the use of salvaged blood in patients with colorectal, gastric, renal, hepatic, breast, bladder and lung cancer. No evidence has been reported showing an increase in metastasis or a decrease in patient survival, in spite of the obvious demonstration that salvaged blood is contaminated with viable tumor cells which are not washed out of the RBC layer during intraoperative blood salvage (IOBS). However, a number of limitations have hampered the widespread use of IOBS in these patients and the technique is not well established. Increasing knowledge of the deleterious effects of allogeneic blood transfusion both in terms of the increased number of viral or bacterial infections and the down-regulation of the patient's immune system have recalled attention to IOBS and to the techniques such as filtration, which might reduce the risk of reinfusion of cancer cells, or totally eliminate the risks such as irradiation has been proposed by Hansen's group. This paper reviews the topic with some emphasis on our personal experience with gamma and X-ray irradiation of salvaged blood in a large reference hospital, where IOBS and filtration of salvaged blood were established for use in cancer patients in 1993 and 1996.

Blood↗

Cascade filtration for TTP: an effective alternative to plasma exchange with cryodepleted plasma.

TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that compares sufficiently well with those required by our historical control group of 47 cases (14 +/- 13). Of course the patient's exposure to allogenic plasma was significantly lower for patients in the CF only group (1.4 +/- 1.2 plasma U/session) compared to the PE + CF group (4.4 +/- 2.3 plasma U/session) or for the controls treated by PE only (10.8 +/- 4.6 plasma U/session). There were no deaths in the CF or PE + CF groups and no untoward effect was observed. On the contrary there were 5 deaths (1 on the day of presentation) in the PE group, and 1 HBV and 2 HCV infections as well as 4 severe allergic reactions to plasma proteins (or passive antibody infusion). We conclude that CF is presently the best treatment to offer to patients suffering from sporadic TTP and that CF may contribute to expanding the knowledge of the pathogenetic mechanisms of this uncommon multisystem disorder.

Adult↗