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Biomedical subjects

M Valbonesi

Publications and source records attributed to M Valbonesi.

At least 73 records · Page 4Linked to original sources

Four-step high-dose sequential chemotherapy with double hematopoietic progenitor-cell rescue for metastatic breast cancer.

PURPOSE: High-dose chemotherapy produces high complete remission (CR) rates and some survival advantage in patients with metastatic breast cancer (BC). A current issue is the possibility that these patients may have an even better prognosis with multiple high-dose treatments. In this study, we evaluated the feasibility of a four-step, high-dose sequential chemotherapy (HDSC) with double autologous hematopoietic progenitor-cell rescue. We also tested the hypothesis that peripheral-blood progenitor cells (PBPCs) harvested following a single recruitment with cyclophosphamide (CY) and granulocyte-macrophage colony-stimulating factor (GM-CSF) allow the safe administration of the whole HDSC with closely timed repeated courses of several non-cross-resistant agents. PATIENTS AND METHODS: The treatment plan included CY 7 g/m2, followed by GM-CSF 5 to 7 micrograms/kg/d administered by continuous intravenous (i.v.) infusion on days 2 to 14; PBPCs with or without bone marrow (BM) harvest; mitoxantrone (NOV) 60, 75, or 90 mg/m2 plus melphalan (L-PAM) 140 to 180 mg/m2 with hematopoietic rescue; methotrexate (MTX) 8 g/m2 plus vincristine (VCR) 1.4 mg/m2; and etoposide (VP-16) 1.5 g/m2 plus carboplatin (PP) 1.5 g/m2 with hematopoietic rescue. RESULTS: All 15 patients enrolled completed the entire treatment and there were no toxic deaths. Hematologic reconstitution was good at each step. The median number of days with an absolute neutrophil count (ANC) less than 100/microL and platelet count less than 20,000/microL were 8 and 3, respectively, after NOV plus L-PAM, and 7 and 4, respectively, after VP-16 plus PP. The main non-hematologic toxicity was mucositis, while organ toxicity was mild and reversible. CONCLUSION: This regimen is feasible, with acceptable toxicity. GM-CSF and PBPCs have a pivotal role, as they hasten hematologic reconstitution, abate toxicity, and allow rapid recycling.

Adult↗

Intraoperative blood salvage (IOBS) in cardiac and vascular surgery.

The extensive application of IOBS has permitted a great reduction in the use of homoglous transfusion which presently represents the largest field of application of autologous systems. In cardiac and vascular surgery, IOBS is particularly useful to the goal of preventing the transmission of viral disorders and other adverse effects related to homologous transfusions. The apparatuses for IOBS may also be used to perform hemodilution and sequestration of a desired amount of platelet rich plasma. The appropriate usage of drugs in perioperative period and the promotion of hemostasis with IOBS are important costituents for the correct transfusional management of the patient. The feasibility and safety of IOBS is known and in expert hands it is an optimal method for the transfusional treatment of surgical patients.

Blood Transfusion, Autologous↗

Intraoperative blood salvage: a new artificial organ?

Optimal blood supply is critical to modern medical practice. Among the different possibilities of improving the quality and safety of blood, it is generally felt that autologous donation has played an important role and has contributed to changing transfusional practices, mainly since the appearance of HIV and HCV on the blood transfusion scene. At the San Martino Hospital Immunohematology Service, the autotransfusion era began in 1985. Autologous predeposit donation was the first to be introduced, followed by intentional perioperative hemodilution, intraoperative blood salvage with DFC apparatuses and lastly post-operative blood salvage. From about 200 autologous donations in 1985 we reached 5,372 in 1993 and more than 6,000 autologous donations are expected for 1994. Only 189 intraoperative blood salvages, were carried out in 1986, 593 in 1989, 1,207 in 1993 and more than 1,500 blood salvage sessions are anticipated for 1994. In the meantime, the total number of homologous RBC units employed in the Hospital dropped from 45,000 in 1985 to 18,000 in 1994, with the Onco-hematological Divisions using approximately 10,000 units of packed RBC.

Blood Platelets↗

Preparation and storage in Plasma-Lyte A of platelets collected with the cell separator CS3000 Plus equipped with the PLT30-separation and TNX6 collection chambers.

The last five years have been characterized by the presentation of new cell separators the main task of which is the collection of high yield-high quality platelets. The CS3000 is an old apparatus which has undergone rejuvenation to sustain the assault of its new competitors. The CS3000 Plus Omnix system is the latest version to be offered along with a combination of TNX-6 separation/PLT30 collection chambers for optimal platelet collection. In this paper we present our results with this apparatus and configuration after its adaptation to the collection and storage of platelets in a non-plasma medium, the Baxter Plasma-Lyte A. After separation the platelet product (PC) was left in the collection chamber and resuspended with 200 ml of Plasma-Lyte A instead of being resuspended in autologous plasma as usual. Plasma was collected in a separate bag (400-450 ml) for transfusion or fractionation purposes. PC quality was assessed by evaluating the platelet yield (4.17 +/- 1.8 x 10(11), and the WBC contamination (4.8 +/- 2.6 x 10(5)). The presence of platelet aggregates (platelet count after aggregate fixation with formalin/platelet count after disaggregation in EDTA), the aggregation induced by ADP, collagen and ristocetin, the hypotonic shock response and the stability of membrane glycoproteins (CD 62 - 62 - 63 - 36- 42b - 51) were measured in the preapheresis samples and in the PC immediately after, 24 and 72 hours after collection. These results were totally satisfactory as was the post-transfusion survival measured as corrected count increment in 10 transfusions to non refractory patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Single-donor platelet concentrates produced along with packed red blood cells with the Haemonetics MCS 3p: preliminary results.

There has been an increasing interest in recent years over the qualitative superiority of single-donor platelets in the management of hemato-oncologic patients. The reasonable desire of both patients and physicians to limit the risks of transfusion along with the need for limiting the costs involved in this kind of therapy have led to application of multicomponent donations both in terms of double platelet concentrates and double products such as red blood cells (RBC) and platelets from the same donor. Single donor platelets and RBC have been collected in a semi-automated mode and only the very recent introduction of the Haemonetics MCS 3p with its SDP/RBC protocol provides a totally closed-system automated protocol for this combined collection. Twenty procedures have been carried out so far at our unit. In a mean of 87 minutes (6-7 passes), a mean of 3.1 x 10(11) platelets were collected along with approximately 220 mL of packed RBC. The leukocyte contamination of the platelet product was in the range of 0.4-1.1 x 10(7) (99% lymphocytes), and the quality of platelets was very satisfactory as measured by the hypotonic shock response, aggregation induced by ADP, collagen and ristocetin, morphology score, and membrane glycoproteins modifications. Equally satisfactory was the quality of the RBC concentrate, suspended in 80 mL of SAG-M, with a total hemoglobin (Hb) content approaching 55 g as compared to the normal Hb content of a standard RBC concentrate that is approximately 62 g.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intravenous immunoglobulin, plasmalymphocytapheresis and azathioprine in chronic progressive multiple sclerosis.

Five patients with a severe form of chronic progressive multiple sclerosis no longer responsive to steroid therapy were treated for six months with high-dose intravenous immunoglobulin associated with plasmalymphocytapheresis and azathioprine. In spite of an apparent initial stabilization of the course of the disease, EDSS assessment after six and twelve months of therapy revealed progressive disability in all patients.

Adult↗

[Consensus conference. Saving blood: which are still the doubts and the problems?].

The consensus conference on blood saving has allowed us to formulate some interesting guidelines. The autologous and homologous transfusion require the patient's consent. For volemic replacement crystalloid solutions are used for phlebotomies below 10-15%, and colloid solutions for those greater than 10-15% of the blood mass. Severe isovolemic hemodilution (Ht < 20%) necessitates the reduction of the dosage of some drugs. A limit of Hb around 9 g/dl after phlebotomy may be acceptable in the absence of cerebral and coronary vascular disease. Phlebotomies are therefore possible also when the Hb values are 10 g/dl (Ht 30%). Hb values around 7 g/dl in the late postoperative period (from day 3 to 6) may be accepted only if well tolerated. The blood salvaged during surgery and at the beginning of the postoperative phase must always be centrifugated, washed and microfiltered. Subsequently, in the first 8 hours it is possible to reinfuse red cells after sedimentation and microfiltration. The techniques of predeposit, hemodilution and recovery are valid especially if associated with careful control of postoperative bleeding by means of aspiration under controlled pressure (at minimum negative values and sometimes positive ones), monitoring of blood loss from drainage and application of elastic compression bandages.

Blood Loss, Surgical↗

Collection of peripheral blood hematopoietic progenitors (PBHP) from patients with severe aplastic anemia (SAA) after prolonged administration of granulocyte colony-stimulating factor.

The aim of this study was to test whether prolonged administration of granulocyte colony-stimulating factor (G-CSF) would allow the collection by leukapheresis of PBHP in patients with SAA. For this purpose, nine SAA patients, 7 to 46 years old, six of whom were enrolled at diagnosis of their disease and three after previous immunosuppression had failed, were treated with antilymphocyte globulin (ALG) (day 1 to 5), cyclosporin A (5 mg/kg/d orally) (day 6 to 90) and G-CSF 5 micrograms/kg/d (day 6 to 90). A total of 40 leukaphereses were performed, (range 2 to 7 per patient), between days +10 and +168 from G-CSF treatment. White blood cell count at the time of harvest ranged from 1.2 to 18.1 x 10(9)/L. Results can be summarized as follows: the median number of cells collected per patient was 5.0 x 10(8)/kg (range 2.6 to 18.7), the median number of CD34+ cells was 1.8 x 10(6)/kg (range 0.27 to 3.8) and the median number of colony-forming units granulocyte-macrophage (CFU-GM) was 3.9 x 10(4)/kg (range 0 to 39). Twenty leukaphereses performed between days +33 and +77 of G-CSF treatment grew granulocyte macrophages and erythroid colonies in vitro. No colony growth was obtained from 20 leukaphereses performed before day +33 or after day +80. In six patients the total number of CFU-GM recovered were in the range described for autologous peripheral blood stem cell grafts. (2.6 to 39 x 10(4)/kg). In conclusion, this study suggests that circulating hematopoietic progenitors can be recovered after ALG priming and after at least 1 month of G-CSF treatment in a proportion of patients with SAA. Whether these cells will be suitable for autologous transplantation remains to be determined.

Adolescent↗

Hemopoietic stem cells: technical and methodological considerations.

Peripheral blood cells containing large numbers of granulocyte-macrophage colony forming units (CFU-GM) can be collected by leukapheresis. The number of aphereses needed to collect 2-7 x 10(8) mononuclear cells (MNC)/Kg and 2-50 x 10(4) CFU-GM/Kg during rapid hematopoietic recovery following cytotoxic chemotherapy-induced myelosuppression depends on type of disorder, type of chemotherapy, patients' clinical conditions, cell precounts, concomitant growth factor administration, optimal timing of leukapheresis, vascular access apheresis machines, and type of technique used. Because of the advent of growth factors, a broader window for collection of progenitors has been provided. This has determined an increasing interest for peripheral blood stem cell (PBSC) autotransplants, along with increasing problems due to the number and types of procedures to be performed and the quality and purity of the products. Presently most of the basic technical problems are solved and an array of third generation cell separators is offered for collection of progenitors. Their common features are safety controls, closed circuits, automation, and mechanical and electrical reliability. Performance and quality of the product may be totally different depending not only on the apparatus, but also on the patients' clinical conditions. These technical aspects will be rapidly discussed having in the due considerations the expected increase in the number of procedures.

Bone Marrow Transplantation↗

Excel: a new cell separator in its very first clinical application.

BACKGROUND: The evolution of technology has been one of the most interesting features that has accompanied thrombocytapheresis throughout the years. In this presentation we report on the preliminary results obtained with Excel, a third-generation cell separator that is presently in its early experimental phase. MATERIAL AND METHODS: So far only 15 thrombocytapheresis procedures, 2 of which of the single-needle type, were carried out on 15 healthy donors processing 4 liters of blood (2.8 liters in single needle). RESULTS AND CONCLUSIONS: The results were satisfactory since the average platelet yield was 4.7 x 10(11). The leukocyte contamination was 0.8 x 10(6) and the RBC contamination 0.4 x 10(7). The platelet efficiency per minute was 6.5 x 10(9), and the run time average 72 min. As to the quality of the product the very first results of platelet aggregation, relative to pre-apheresis, were 78% in response to ADP 6 microM; 106 and 102% in response to collagen 4.5 micrograms/ml and ristocetin 1.5 mg/ml, respectively. Essentially no platelet aggregates were found in the platelet products (Wu-Hoak ratio: 0.91).

Adult↗

Donors thrombocytapheresis with last generation cell separators.

An exciting, fast moving and promising field remains the use of plasma-free synthetic medium for platelet storage (10, 11), that along with the potential for getting more plasma for therapeutic needs, might also improve the quality of stored platelets. Addition of acetate to solution, may be the way to obtain these results. An astonishing fact is that citrate remains the only anticoagulant for platelet collection, and remains as well the only real cause of donor discomfort during thrombocytapheresis.

Blood Donors↗

Plasma exchange: the cost/benefit ratio and the critical revision of indications.

The number of conditions that can benefit from Plasma-Exchange (PE) continues to grow. We have recently added to the list the Cyclosporin-A induced hypertrygliceridemia and myoglobinuric acute renal insufficiency. Such as any therapeutic measure for PE, four evolutive phases can be recognized: the discovery and research, the confirmation of indications, the routine applications and the decline, when new more powerful tools are offered by culture or technology. We have participated in the first three phases during the last 20 years. Not necessarily all experiences were favourable. Nonetheless, we feel that, for the time being, a hemapheresis unit is an absolute necessity for a medium - sized hospital even if only therapeutic procedures are carried out. The phase four, decline of interest and applications, cannot be foreseen. Finally the ability of PE to shorten substantially the length of hospital stays along with the ease with which procedure can be performed on ambulatory patients, substantiate a favourable cost/benefit ratio for this therapeutic modality.

Humans↗

The organization of the autotransfusion-perioperative blood salvage at San Martino Hospital.

Autologous transfusion is playing an important role in modern transfusion medicine. At San Martino hospital we use a combination of manual and mechanical techniques in order to improve autotransfusion procedures, control the hypertransfusion and avoid waste. Our autotransfusion program has determined a 55% reduction in the red cell concentrates used (from 42,000 in 1985 down to 19,400 in 1992). Proper training, cultural improvements and new applications on autotransfusion procedures will permit a better use of blood with less transfusion related complications, until a suitable substitute for blood will be available.

Blood Loss, Surgical↗

Single-needle thrombo-cytapheresis with the Fresenius AS 104.

BACKGROUND: The Fresenius AS 104 cell separator has recently met some popularity in European apheresis units for the quality of the platelets obtained with the totally automated double-needle procedure. MATERIALS AND METHODS: Taking advantage of the machine's flexibility we have developed a new automated procedure for single-needle thrombocytapheresis (SNP). So far 61 SNP were carried out. From donors having a platelet precount of 2.74 x 10(5) an average of 3.8 x 10(11) cells were collected by processing 2.5 liters of blood in a run time of 83 min. RESULTS AND CONCLUSIONS: The leukocyte and erythrocyte contaminations were 2.7 x 10(7) and 3.5 x 10(7), respectively. Only 2 products did contain less than 3.5 x 10(11) platelets, and 7 procedures were complicated by minor signs of hypocalcemia. With minor modifications this SNP is presently offered on a routine basis to our platelet donors.

Adult↗

Apheresis for severe malaria complicated by cerebral malaria, acute respiratory distress syndrome, acute renal failure, and disseminated intravascular coagulation.

Malaria has become a very uncommon disease in Italy. Recently a variety of circumstances, such as travel to tropical countries as well as immigration from Asia and Africa, have combined to increase the number of malaria cases recorded annually. In this report we describe the use of red cell exchange transfusion and plasma exchange in the treatment of a patient with hyperparasitemic malaria (51% erythrocytes or more parasitized). When first observed the patient was in shock and had signs of cerebral malaria, disseminated intravascular coagulation, and acute respiratory distress syndrome, which in the following 2 days were complicated by acute renal failure. After mefloquine therapy combined with 3 red blood cell exchanges, 2 plasma exchanges, and 10 dialysis sessions over 14 days, the patient recovered completely. This case of severe malaria with multiple complications, treated with mefloquine in conjunction with both exchange transfusion and plasmapheresis, had a successful outcome and lends further support to the possible beneficial role of exchange transfusion in complicated malaria.

Acute Disease↗

Intensive conventional chemotherapy can lead to a precocious overshoot of cytogenetically normal blood stem cells (BSC) in chronic myeloid leukemia and acute lymphoblastic leukemia.

Forty patients with Ph-positive blastic phase (BP) (28 patients) or chronic phase (CP)-CML (3 patients) and relapsed adult acute lymphoblastic leukemia (ALL) (9 patients) with cytogenetical translocations [t(8;14):2 patients; t(4;8):2 patients; t(4;11):3 patients; t(9;22):2 patients], received an intensive conventional chemotherapy. During early recovery from marrow aplasia, when WBC reached 0.3-1.5 x 10--9/L, peripheral blood stem cells (BSC) were collected by 4-8 leukapheresis consecutively. BSC collected from the 2/3 patients with CP-CML resulted Ph-negative and PCR negative. In 8 out of 26 BP-CML patients, BSC resulted Ph-negative and in two cases PCR negative. Of the nine ALL patients, 6 patients lost the cytogenetic translocations, one patient died during aplasia, two patients did not have cytogenetic modifications and died in few weeks of leukemia and one patient out of six responding patients relapsed before transplant. After complete recovery, 15 patients (BP-CML:8 patients; CP-CML:2 patients; ALL:5 patients) were subsequently given high-dose therapy (VP-16 +/- Cy+TBI in single dose) followed by reinfusion of "normal" BSC. Both the patients in CP-CML and 5/5 patients with ALL maintain clinical and cytogenetic remission; all the patients transplanted in BP-CML relapsed 5-18 months post-transplant. It is concluded that intensive conventional chemotherapy employed in CML and ALL can lead to a precocious overshoot of cytogenetically normal BSC.

Adolescent↗