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Biomedical subjects

R Mazzara

Publications and source records attributed to R Mazzara.

At least 37 records · Page 2Linked to original sources
PubMed1997

Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood.

We have prospectively evaluated the feasibility and results of the biotin-avidin immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1), refractory anemia with excess of blasts in transformation (n = 3), histiocytosis X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L leukapheresis. PBPC were purified by positive selection of CD34+ cells using immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the patients as the sole source of progenitor cells. No growth factors were administered posttransplant. The median recovery of CD34+ cells after the procedure was of 65%. The median number of CD34+ cells infused in the patients was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted. Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6 to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient developed either grade II to IV acute or extensive chronic GVHD. After a median follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of them is again in hematologic and cytogenetic remission after infusion of the donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary aspergillosis and the other on day +251 of metastasic relapse of a previous breast cancer. Sixteen of the 20 patients are alive in remission after a median follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number of patients and limited follow-up, it appears that this method allows a high CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid engraftment without significant GVHD, and with low transplant related mortality.

Adolescent↗
PubMed1997

[Hemopoietic progenitor cell transplantation: 20 years' experience at the Hematology School "Farreras-Valentí"/Clinical Hospital of Barcelona].

BACKGROUND: Hemopoietic progenitor cell transplantation (HPCT) is acquiring an increasing role in the therapy for a variety of disorders. In this study, main characteristics and results of HPCT along 20 years are analyzed from the experience of Postgraduate School of Hematology "Farreras-Valentí" at the Hospital Clínic in Barcelona. PATIENTS AND METHODS: Six-hundred ninety-five patients transplanted between June 1976 and January 1996 were analyzed. Median age (range) were 33 (4-63) years. The following aspects were considered: donor type, source or progenitor cells, type of disease and disease-stage at transplantation, transplant related mortality and survival. RESULTS: A total of 714 HPCT were performed (448 allogeneic, 13 isogeneic, 253 autogeneic). Allogeneic HPCT were from an HLA-identical sibling in 408 cases, from other familial donors in 10, and from non-familial donors in 30. Most HPCT from non-familial donors (93%) were performed during the last five years of the study (1991-1995). The source of hemopoietic progenitor cells was bone marrow in 625 instances (88%), peripheral blood in 88 (12%), and fetal liver in one. During more than 15 years, the only source of progenitors was the bone marrow; in contrast, in the last 3 years (1993-1995) transplants using peripheral blood were predominant. Main indications for HPCT were the following: acute leukemias (n = 387) (54%), chronic leukemias (n = 134) (19%), severe aplastic anemia (n = 58) (8%), lymphomas (n = 80) (11%), multiple myeloma (n = 39) (5%) and myelodysplastic syndromes (n = 14) (2%). In patients with hematological malignancies (n = 656), HPCT was performed in first complete remission or in first chronic phase in 321 instances (49%), in subsequent remissions in 144 (22%), and in more advanced stages in the remaining 191 (29%). In the more recent years, a progressive decrease in the number of HPCT for acute leukemia or aplastic anemia was observed, contrasting with an increase in transplants for lymphoma, multiple myeloma and myelodysplastic syndromes. Of note, a significant decrease in transplant related mortality was evident along the years, both after autogeneic HPCT (21% during 1985-1992 and 6% thereafter) (p = 0.001) and after allogeneic transplantation (54%, 44%, and 20% during the periods 1976-1984, 1985-1992 and 1993-1995, respectively) (p = 0.004). The fact translated into an increase in the actuarial probability of survival after allogeneic HPCT (25%, 33% and 58% in the three mentioned periods, respectively) (p = 0.0003), and after autogeneic HPCT (33% in the interim 1985-1992, and 55% in the period 1993-1995) (p = 0.001). CONCLUSIONS: During the last 20 years, HPCT has significantly evolved in aspects such as type of donor, source of progenitor cells and indications. Remarkably, a progressive decrease in transplant related mortality has been observed translating into a improvement in survival after the procedure.

Actuarial Analysis↗
PubMed1997

In vitro evaluation of the hemostatic effectiveness of non viable platelet preparations: studies with frozen-thawed, sonicated or lyophilized platelets.

OBJECTIVES: Because of the limited life span of platelets in regular storage systems, we were interested in investigating the effects on hemostasis of nonliving platelet derivatives. METHODS: We evaluated the effects of different platelet preparations on primary hemostasis in a well-established perfusion model. Studies were carried out with blood anticoagulated with low molecular weight heparin. Similar amounts of frozen-thawed, sonicated or lyophilized platelets were added to normal blood or to blood which had been experimentally depleted of platelets. Platelet interaction with the subendothelium and fibrin deposition were morphometrically evaluated. RESULTS: Addition of nonviable platelet preparations to thrombocytopenic blood always promoted a statistically significant increase in the deposition of fibrin on the subendothelium, but only lyophilized platelets retained some ability to interact with the subendothelium. Flow cytometry studies demonstrated the presence of GPIb, GPIIIa and P-selectin on lyophilized platelets. CONCLUSIONS: Preparations containing nonviable platelets may still retain some hemostatic properties.

Animals↗
PubMed1997

[Staphylococcal sepsis associated with platelet transfusion: report of a new case and review of the literature].

Bacterial contamination of blood components is an infrequent although potentially fatal event. Bacterial contamination rate of platelet concentrates (PC) varies between 1/900 to 1/2,000 random donor units. However the risk of symptomatic bacteriemias is lower (between 1/2,000 to 1/12,000 random donor units). The organisms most commonly implicated in contaminated PC are gram-positive bacteria such as coagulase negative Staphylococci, Bacillus cereus or Propionibacterium acnes, although gram-negative organisms are also found that generally are associated to a higher mortality. Here, a fatal case of sepsis due to Staphylococcus carnosus associated to transfusion of a contaminated random donor platelet unit is reported.

Bacteremia↗
PubMed1996

[Allogeneic transplant of peripheral blood hematopoietic progenitors. Preliminary experience].

Myeloablative treatment followed by allogeneic transplantation of peripheral blood hemopoietic progenitors (alloPBT) was administered to five leukemia patients with a high risk of relapse. The donors subcutaneously received 10 micrograms/kg/day of G-CSF for five days. The tolerance to this medication was good with only complaints of moderate bone pain. Two of the peripheral blood donors had previously been bone marrow donors and both expressed their preference for the new method. The product of peripheral blood leukapheresis contained from one to four-fold more hemopoietic progenitors and approximately ten-fold more T-lymphocytes than the bone marrow received from normal donors. Prophylaxis of the graft versus host disease (GVHD) consisted of cyclosporine A (CsA) in one case and CsA and methotrexate (MTX) in four cases. The bone marrow implantation was verified with a neutrophil count of up to more than 0.5 x 10(9)/l between days 12 to 21 after transplant and a platelet count higher than 20 x 10(9)/l from days 11 to 41 after transplant. Acute GVHD was clinical grade O (two cases), II (one case) and grade III (two cases). In conclusion, alloPBT may be more safely and comfortably performed to the donor. This method may provide rapid recovery of neutrophils and platelets in patients without an apparent increase in the risk of developing graft versus host disease.

Adolescent↗
PubMed1996

Effects of G-CSF administration and peripheral blood progenitor cell collection in 20 healthy donors.

The effects of both daily G-CSF administration and subsequent peripheral blood progenitor cell collection (PBPCC) by apheresis on 20 healthy adult donors were studied. All received daily G-CSF (filgrastim) 10 micrograms/kg for 5-7 days by subcutaneous injection. G-CSF administration was well tolerated, except for moderate bone pain and headache. Peak values of CD34+ cells were observed on days 5 (n = 12) or 6 (n = 8). In all donors a significant increase in CD3+, CD4+, CD8+, CD19+, and NK cells was observed on day 5 in relation to the baseline values. CD4/CD8 lymphocyte ratio was unmodified by G-CSF. None of the donors required a central venous line for PBPCC. Immediately after PBPCC, a platelet count below 100 x 10(9)/1 was observed in nine of 18 cases, although in all donors platelet counts were over 100 x 10(9)/1 7 days later. A lymphocytopenia on day 7 following PBPCC was observed, although there was a tendency to achieve baseline values 30-90 days after the procedure. Mean numbers ( +/- SD) of collected cells x 10(6)/kg after a median of two (1-4) apheresis sessions and a median of 20 1 (10-40) processed were: CD34+ 5.5 ( +/- 2.3), CD3+ 326 ( +/- 105), CD4+ 207 ( +/- 64), CD8+ 164 ( +/- 60), CD19+ 88 ( +/- 32), and NK cells 32 ( +/- 14). We conclude that G-CSF administration to healthy donors is a well-tolerated procedure which is associated with (a) obtaining a high number of hematopoietic progenitor cells, and (b) a significant increase in T, B, and NK cells in donors' blood. In addition, PBPCC by apheresis results in a moderate, rapidly reversible, and clinically irrelevant thrombocytopenia and a moderate lymphocytopenia, which tends to resolve within 3 months following the procedure.

Adolescent↗
PubMed1996

Procoagulant effect of incompatible platelet transfusions in alloimmunized refractory patients.

The clinical effectiveness of platelet transfusion in refractory patients is still a subject of debate. We have evaluated the possible hemostatic effect of platelet transfusion in 16 alloimmunized thrombocytopenic patients whose platelet counts were less than 20,000/microliters. Platelet concentrates were always obtained by apheresis procedures from incompatible donors. The posttransfusion platelet recovery was greater than 15% only in 3 cases. In the first 6 patients, measurements of bleeding time performed immediately before transfusion were in all cases longer than 30 min and did not change significantly 10 and 60 min after platelet transfusions. In all patients, ex vivo perfusion experiments with Baumgartner's platelet adhesion model, using native nonanticoagulated blood, were performed immediately before and 10 and 60 min after transfusion. No difference in platelet deposition onto the subendothelial surface was observed after platelet transfusion. Unexpectedly, the deposition of fibrin on the subendothelial surface was statistically augmented in the posttransfusion studies. Quantification of thrombin-antithrombin complexes (TAT) in plasma showed statistically significant elevations (p < 0.01) in the posttransfusion samples (31.9 +/- 12.6 vs. baseline 5.8 +/- 1.7 ng/ml), not justified by TAT levels in the transfused material (2.3 +/- 0.17 ng/ml). Transfusion of incompatible platelets to refractory patients may activate coagulation mechanisms in the absence of an increase in peripheral platelet count.

Blood Group Incompatibility↗
PubMed1996

Allogenic transplants with peripheral blood progenitor cells: a report of six cases.

Six patients with high-risk leukaemia received a myeloablative regimen followed by allogeneic peripheral blood progenitor cells transplantation (PBPCT) from an HLA-identical sibling donor. Donors received 10-12 mu g/kg/day of G-CSF subcutaneously for 5 days. G-CSF was well tolerated except for moderate bone pain. Peripheral blood leukapheresis product contained 1-4 times more CD34+ cells and approximately a log more of T lymphocytes than marrow grafts from normal donors. In the two first cases the leukapheresis product was partially depleted of T-lymphocytes using counterflow centrifugation. No growth-factors were administered post-transplant. GVHD prophylaxis consisted of cyclosporin A (CyA) in one case, and CyA and methotrexate in five cases. All patients engrafted with a neutrophil count reaching more than 0.5 x 10(9)/L by day 12 to 21 post-transplant and a platelet count above 20 x 10(9)/L by day 6 to 41 post-transplant. Acute GVHD was clinical grade 0 (n = 2), I (n = 1), II (n = I), grade III (n = I) and grade IV (n = 1). One case presents an extensive chronic cutaneous GVHD and is currently being treated with methylprednisolone. In conclusion, allogeneic transplants using PBPC can be performed safely. This may result in a rapid neutrophil and platelet engraftment, without an apparent increased risk of GVHD.

Acute Disease↗
PubMed1995

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a multivariate analysis of factors predicting the response to plasma exchange.

The aim of this study was to investigate pretreatment prognostic factors that could be useful in predicting the response to plasma exchange in thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Thirty-two patients with TTP/HUS, treated with plasma exchange at our institution from 1980 to 1994, were studied. The main clinical and laboratory data at the beginning of plasma exchanges were analyzed by the Cox stepwise logistic regression, applied to either treatment failure or death. Seventeen (53%) patients attained a complete remission and 22 (69%) survived (five in advanced renal failure and long-term hemodialysis). Longer delay in initiating plasma exchanges, presence of stupor or coma, and higher creatinine levels at the beginning of plasma exchanges were independent predictors of treatment failure. Stupor or coma at the beginning of plasma exchanges was the only predictor of mortality from unremitted TTP/HUS. Hemoglobin levels, platelet count, and LDH activity, traditionally envisaged as markers of disease activity, neither correlated with previous duration of TTP/HUS nor had any prognostic value. Early diagnosis of TTP/HUS and prompt initiation of intensive plasma exchange emerged from this study as the most effective interventions for improving the prognosis of TTP/HUS patients.

Adolescent↗
PubMed1995

Platelet concentrates promote procoagulant activity: evidence from experimental studies using a perfusion technique.

BACKGROUND: Evaluation of the hemostatic effectiveness of platelet transfusions is difficult. Perfusion methods have been employed to test the quality and function of platelet concentrates, allowing differentiation between platelet-platelet and platelet-surface interactions. STUDY DESIGN AND METHODS: A study was performed to investigate platelet adhesive and cohesive properties as well as the formation of fibrin when aliquots of platelet concentrates were added to thrombocytopenic blood. Blood previously anticoagulated with low-molecular-weight heparin (20 U/mL) underwent platelet and white cell reduction by filtration. Perfusates were prepared by adding to filtered blood platelets obtained from standard concentrates (stored for 1, 3, and 5 days). The final platelet count in these perfusates was standardized at 80,000 per microL. After perfusions, platelet-subendothelium interaction and fibrin formation were analyzed morphometrically. Results were always compared with those obtained in unfiltered blood (> 150,000 platelets/microL). RESULTS: A slight impairment in the ability of stored platelets to interact with the subendothelium was noticed during the storage period. However, the presence of fibrin was significantly greater than that observed in studies with unfiltered blood (Day 1 = 23.48 +/- 9.43%*; Day 3 = 26.99 +/- 6.74%*; Day 5 = 17.95 +/- 9.06% vs. unfiltered blood = 12.60 +/- 3.08%; *p < 0.05). The lower platelet counts (80,000/microL) in the perfusates containing platelets from concentrates could account for the reduced platelet-subendothelium interactions, but they cannot explain the increments in fibrin formation. CONCLUSION: While the preparation and storage of platelets have a detrimental effect on platelet adhesiveness, such procedures can positively influence the platelet procoagulant activity necessary to platelet hemostasis.

Animals↗
PubMed1993

Anti-Sa cold agglutinin of IgA class requiring plasma-exchange therapy as early manifestation of multiple myeloma.

The case of a patient (Col) with multiple myeloma presenting as chronic cold agglutinin (CA) syndrome is reported. The CA (Col) was a monoclonal IgA/k paraprotein which recognizes an antigen fully expressed in adult and newborn erythrocytes, sialidase sensitive and partially resistant to proteases. Hemagglutination-inhibition studies showed that immunodominant N-acetylneuraminic acid bound alpha 2-->3 to O-glycans of glycophorins represents the CA(Col) epitope. These serological and biochemical findings fit with the anti-Sa specificity, of which only two previous examples are known. The clinical manifestations of CA (Col) were characterized by marked acrocyanosis, generalized livedo reticularis, and incapacitating dyspnea, but only mild hemolysis. Plasma-exchange therapy was effective in quickly removing the CA and relieving the associated clinical manifestations, but such benefit was only temporary. This is the first reported example of anti-Sa CA of IgA isotype and the first case of IgA CA syndrome treated by plasma exchange.

Anemia, Hemolytic, Autoimmune↗