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G Adorno

Publications and source records attributed to G Adorno.

At least 19 recordsLinked to original sources

Accurate prediction of autologous stem cell apheresis yields using a double variable-dependent method assures systematic efficiency control of continuous flow collection procedures.

BACKGROUND AND OBJECTIVES: Stem cell collection is a standard procedure for the procurement of autologous grafts to rescue myelosuppression induced by high-dose treatments. Accurate prediction of collection yields may contribute to optimize planning and quality control of collection. MATERIALS AND METHODS: Data of 313 autologous haematopoietic stem cell (AHSC) evaluable collections performed in 208 patients with haematologic and non-haematologic neoplasms from seven centres were prospectively analysed to test the accuracy of yield predictions generated by a formula that required the input of peripheral blood (PB) CD34+ cell precount and desired PB volume to be processed. Data were matched in a standard linear regression, in a zero-point regression analysis and tested for prediction accuracy. Further 165 AHSC collections were analysed on a single-centre basis, using yield predictions as reference standards. RESULTS: Analysis showed high levels of correlation between measured collection yields (my) and predictions (py) (R = 0.85; P = 0.000000) as well as high degree of prediction accuracy (my vs. py at paired t-test: P = 0.114781; median my/py ratio = 1.23). Analysis of additional 165 AHSC collections on a single-centre basis showed that the analysed centres had 70% or more measured yields comprising the 0.6-1.8 interval of the my/py ratio. The observance of the 'efficiency' my/py interval assured collection quality control in these centres confirming the reliability of the method. CONCLUSIONS: This prediction method generates accurate and immediate yield predictions allowing collection planning and rapid efficiency control. As a consequence of our study, four centres out of seven use the described method to plan both leukapheresis number and single-procedure blood processing volume while the remaining three centres plan leukapheresis number on the basis of our predictions, maintaining a fixed single-procedure 200 ml/kg blood volume processing, according to their centre AHSC collection policy.

Adolescent↗

Enumeration of CD34+ hematopoietic progenitor cells for clinical transplantation: comparison of three different methods.

Three different methods for determination of CD34+ cells in G-CSF-mobilized peripheral blood were compared. The methods were: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cells enumeration and our own protocol. The procedure we have adopted is essentially a Milan/Mulhouse protocol-derived methodology combined with a multiparametric approach using the PAINT-A-GATE software analysis program. The samples were collected from 70 patients affected by acute leukemia, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myeloma and breast cancer who were scheduled to receive autologous PBSC transplantation. PBSC collection was performed following mobilization with subcutaneous G-CSF at 5-10 microg/kg/day. A minimum target of 2 x 10(6)/kg CD34+ cells was considered an acceptable harvest to ensure a safe transplant. On average, three aphereses per patient were performed and a total of 204 apheresis samples were analyzed. Regression analysis of the percentage and absolute number of CD34+ cells, as calculated with each method, achieved an excellent correlation in spite of methodological differences. In fact, both CD34+dim and CD34+CD45- events were included in our gating strategy. In the setting of a triple staining associating CD34, CD38 and CD45, we identified a variable fraction of CD34+CD38+CD45- cells which would be otherwise undetected due to its CD45 negativity. To this end, we used a new technology referred to as laser-scanning cytometry (LSC) which allowed the isolation and morphological identification of CD34+CD45- cells. By comparing CD34+CD45+ and CD34+CD45- cells, we found that they share a common morphology, thus confirming the hypothesis that the latter are to be considered for CD34+ cell calculation. The median number of CD34+ cells/kg, as calculated by the three methods, was: 4.79 x 10(6)/kg (range 1-570) for the Milan/Mulhouse protocol, 3.9 x 10(6)/kg (range 0.8-498) for the ISHAGE one, and 5.17 x 10(6)/kg (range 2-599) for our protocol. The median time to ANC and PLT engraftment was 11 (range 9-24) and 20 (range 10-70) days, respectively. Our protocol achieved the best correlation between CD34+ cells/kg and time to ANC/PLT recovery according to the Spearman's rank test (r = -40 and P < 0. 015 for ANC, r= -46 and P = 0.005 for PLT). We conclude that (1) CD45 does not appear the ideal partner of HPCA-2 for determination of hematopoietic progenitors in mobilized peripheral blood; and (2) for clinical application, a single staining with 8G12 appears simple, reliable and feasible when rigorous procedures for sample preparation and acquisition are followed and an adequate software for multiparametric analysis is available.

Antigens, CD34↗

Femoral catheters: safety and efficacy in peripheral blood stem cell collection.

Central venous access is necessary in patients candidate for peripheral blood stem cell (PBSC) collection. We report our experience with a dual lumen femoral catheter (Gamcath, 11 french), initially designed for hemodialysis. We studied 147 patients and performed 488 collections after mobilization with either G-CSF alone or chemotherapy + G-CSF, when the white blood cell count exceeded 1 x 10(9)/L, or when a measurable population of CD34+ cells (20/microL) was detected in peripheral blood. All patients received systemic anticoagulation with a low weight heparin and ultrasound examination was performed after the removal of the catheter. Seven patients developed thrombosis (4.7%), ten experienced hematomas at the site of catheter placement (6.8%) despite prophylactic platelet transfusions, while only one patient (0.6%) had a catheter-related infection. In conclusion, the short-term use of large bore femoral catheters in setting up PBSC collection seems to be associated with minimal risk of infection and low thrombotic incidence.

Catheterization, Peripheral↗

Red blood cell depletion of cord blood using hydroxyethylstarch double sedimentation: analysis of 40 cases.

Cord blood has been shown to successfully reconstitute haematopoiesis following allogeneic transplantation in a variety of disorders. A major drawback of cord blood has been the risk of transfusion reaction secondary to ABO incompatibility and reduction in the stem cell pool if cord blood is manipulated to remove red cells. We report our experience on red blood cell depletion of cord blood (CB) with hydroxyethylstarch (HES) double sedimentation. The nucleated and mononucleated cell recovery passed from 78.4% at 90 min to 92.9% at 180 min and from 85% at 90 min to 96% at 180 min, respectively. The overall recovery of CCD34+ cells and of haemopoietic progenitors (CFU-GM) was 90.5% and 83.8%, respectively. The data indicate that HES double sedimentation is a simple and effective technique for cord blood manipulation, but further studies are necessary to evaluate the clonogenic progenitor recovery after thawing.

Cell Separation↗

Multiparametric analysis for the enumeration of CD34+ cells from bone marrow and stimulated peripheral blood.

Determination of CD34+ cells was performed in bone marrow and G-CSF mobilised peripheral blood samples. We adopted three different protocols of analysis: the Milan/Mulhouse protocol, the ISHAGE guidelines for CD34+ cell determination and our own protocol based upon the use of PAINT-A-GATEPRO software analysis program. An excellent correlation was demonstrated between the three methods (r2 0.98); however the analysis of variance showed a statistically significant difference between the results generated with the three methods (P=0.001). The differences between the three procedures are discussed with a special focus on the value of CD34+dim cells and the role of CD45 in the setting of a double staining. We have in fact identified a minor subset (CD34+CD38+CD45-) which would go unrecognised based upon its CD45 negativity.

Antigens, CD34↗

Efficacy and safety of human leucocyte interferon-alpha treatment in patients younger than 60 years of age with polycythaemia vera.

OBJECTIVES: To evaluate the therapeutic activity and toxicity of human leucocyte interferon-alpha (lIFN-alpha) in patients with polycythaemia vera (PV) aged less than 60 years. DESIGN: An open clinical study. SETTING: Department of Medical Sciences, Regina Apostolorum Hospital, Albano Laziale, and Chair of Haematology, University of Rome 'Tor Vergata', S. Eugenio Hospital, Rome, Italy. SUBJECTS: Fourteen patients with PV and aged < 60 years who had active disease as indicated by the need for phlebotomy and/or cytoreductive therapy. INTERVENTIONS: lIFN-alpha administered subcutaneously at the starting dose of 3 MU thrice weekly. The interferon dose could be escalated to six MU thrice weekly if it was well tolerated and disease was not controlled after three months of treatment at the lower dose. MAIN OUTCOME MEASURES: Change in phlebotomy requirements, spleen size, pruritus score and haematological parameters after 6 months of treatment. Evaluation of lIFN-alpha side effects. RESULTS: Complete or partial disease control was achieved in 13 patients. Six patients achieved a complete response (CR) and four a partial response (PR) after 3 months of therapy. Dose escalation in partial or nonresponders resulted in two patients switching from a status of PR to CR, and three other patients achieving a partial response after being unresponsive to the lower dosage. Human leucocyte interferon-alpha therapy significantly improved (P < 01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and MCV values, and platelet and leucocyte counts. A mild flu-like syndrome (low-grade fever, nausea and myalgias) appeared during the early phase of therapy in the majority of patients, but no patient had to discontinue lIFN-alpha because of intolerance. CONCLUSIONS: Subcutaneous human leucocyte interferon-alpha appears an effective and well tolerated therapy in the management of PV-associated myeloproliferation and pruritus in patients aged less than 60 years.

Adult↗

Minimally differentiated acute myeloid leukemia (AML-M0): a distinct clinico-biologic entity with poor prognosis.

FAB proposals for the diagnosis of AML-M0 represent the formal recognition of a distinct entity which has been described over the past few years by several authors and called minimally differentiated acute myeloid leukemia. By definition, AML-M0 includes acute leukemias which do not fit morphological and cytochemical criteria for the diagnosis of AML, and for which myeloid lineage assignment can be made by immunological assay showing positivity for MPO, CD13, and CD33 and negativity for lymphoid markers. Involvement of an early myeloid progenitor in the leukemic process is a possible theory hypothesized to explain the existence of such a form. Validity of this assumption has been based on the observation that AML-M0 frequently bears "stem cell" markers such as CD34, HLA-DR, Tdt, CD7, and promiscuous IgH/TCR gene rearrangements, which are thought to occur in uncommitted cells. Finally, AML-M0 very frequently carries cytogenetic abnormalities common to MDS or secondary AML, such as -5/5q- or -7/7q- deletions and or complex karyotype. In our experience, AML-M0 is also very often associated with the MDR phenotype, which in turn has been found strictly linked to "stem cell" features, especially in MDS. These biological aspects, altogether, translate into a very unfavorable prognosis, confirming even from a clinical point of view that AML-M0 is a distinct entity. In conclusion, "stem cell" markers, MDR phenotype, complex chromosome lesions, frequent occurrence in elderly patients, and intrinsic chemoresistance characterize AML-M0 and indicate the need for tailored treatments, possibly involving the use of MDR modulators and/or differentiating agents.

Humans↗

First report of t(8;21)(q22;q22) in a case of de novo acute monoblastic leukemia.

Here we describe the case of a 30-year-old man with a diagnosis of de novo acute monoblastic leukemia (FAB M5a), whose karyotype analysis revealed the presence of the translocation (8;21)(q22;q22) as the sole chromosome anomaly. In spite of the rather good prognosis patients suffering from acute leukemia and carrying this translocation are supposed to have, our patient had a very poor outcome, including an early relapse resistant to any treatment and meningeal localization. Death occurred within 5 months from diagnosis. To our knowledge this is the first report of t(8;21)(q22;q22) in de novo acute monoblastic leukemia.

Adult↗

Treatment of multiple myeloma with autologous blood stem cell transplantation. Preliminary results of an Italian multicentric pilot study.

Starting from May, 1991, 35 untreated myeloma patients entered a multicentric pilot study to evaluate the feasibility of a program of PBSC transplantation for previously untreated myeloma patients. The schedule was as follows: 2 cycles of VAD followed by CY, 7 g/mq+G-CSF (Granulokine, Roche) for 14 days, to increase and collect PBSC. The subsequent conditioning regimen was Melphalan+Busulfan followed by G-CSF. As maintenance R alpha-2 IFN was given, until relapse. The median follow-up is 14 months (4-22). On April 1993, 34 patients received at least 2 cycles of VAD, 27 were submitted to PBSC collection, 22 received conditioning regimen plus PBSC and 16 of them are in the maintenance treatment with IFN. Considering 28 patients for an intention to treat evaluation (35-7 in treatment), responding patients are 71% with 46% who achieved CR. White cells and platelets raised to > 1000/mmc and > 50,000/mmc after a median period of 10 and 13 days, from CY, and 11 and 14 days from transplant, respectively. Two patients relapsed, 2 others died while in PR because of CMV epatitis and candida pneumonia. The median number of CD34+ cells and CFU-GM was 24.75 x 10(6)/kg b.w. and 28.1 x 10(4)/kg b.w. respectively. In conclusion this treatment seems to be feasible and with low toxicity, but a longer follow-up is needed to evaluate the progression free survival of the high proportion of responding patients that we observed.

Adult↗

Concentration of human hematopoietic stem cells in bone marrow transplantation: results of a multicenter study using Baxter CS 3000 plus cell separator.

Preliminary BM processing to produce an enriched MNC fraction from large BM volumes improves subsequent pharmacological and/or immunological "ex vivo" treatment and cryopreservation. We detail on a multicenter study (6 Transplant Centers) performed to establish an effective and reliable protocol using a CS 3000 continuous flow separator on a large series of BM processed for autologous (96) and allogeneic (12) transplantation. The reduction in volume was 78.6 + 7.2% while 28.9 + 12.4% of the original nucleated cells were found in the final product. A mean of 84.3 + 13.2% of the staring MNC was yielded in a fraction containing over 81% MNC. Cloning efficiency indicated than the final graft was highly enriched in progenitor cells committed to the granulocyte/macrophage pathway (> 100%) as assessed in vitro (CFU-GM). Removal of RBC and PLT was 98.3 + 1.1 and 37.7 + 14.6%, respectively. The mean dose of MNC and CFU-GM was 0.6 + 0.37 x 10(8) and 0.96 + 1 x 10(5) recipient weight. The entire process was accomplished in 87.5 + 20 min. We concluded that this automated device is a simple and reproducible method for BM processing suitable as first step for further "ex vivo" automated negative and/or positive cell selections.

Adolescent↗

A metastatic breast carcinoma presenting as autoimmune hemolytic anemia.

The authors describe the case of a 75-year-old female who was hospitalized for anemia of unknown origin. Physical examination revealed a swelling in the right mammary region, where a mastectomy scar was present from surgery for a breast carcinoma. On admission, laboratory tests disclosed anemia (Hb, 8.5 g/dl), with a reticulocyte count of 65,000/mm3 and slightly increased bilirubin. Immunohematologic study revealed the presence of a red cell autoantibody with anti-D specificity in the serum and in the eluate from the patient's erythrocytes. A biopsy of the swelling was performed and histologic examination showed the presence of metastatic cells of breast carcinoma. The patient was given chemotherapy and radiotherapy. At this writing the anemia was absent, the immunohematologic study was negative, the swelling was greatly reduced, and no other metastatic lesions of breast carcinoma were present.

Aged↗

Bone marrow processing with a gravity sedimentation technique: experience of 13 cases.

The experience of 13 bone marrow processings is reported: 7 patients were affected by Acute Leukemias, 4 by Non Hodgkin's Lymphomas, 1 by Chronic Myelogenous Leukemia in complete remission after induction chemotherapy, 1 by Ewing's Sarcoma. Gravity sedimentation technique with 6% hydroxyethyl starch was used in all cases. A mean value of 0.754 x 10(8)/kg body weight mononuclear cells was harvested after sedimentation, with a mean recovery of 74.554%. Mean CFU-GM value was 0.543 x 10(4)/kg body weight. Only one evaluable patient, affected by ANLL, underwent Autologous Bone Marrow Transplantation and a full engraftment was noted on day +14. Results are discussed and further studies are proposed to clarify the relationship between the in vitro CFU-GM growth and the bone marrow engraftment.

Adolescent↗

A second example of hemolysis due to IgA autoantibody with anti-e specificity.

A case of warm autoimmune hemolytic anemia due to IgA antibody is described. The patient had clinical and hematologic signs of hyperhemolysis, but all specific tests were negative. The direct antiglobulin test was positive only when it was performed with anti-IgA monospecific antiserum. The autoantibody eluted from the patient's red cells showed anti-e specificity. The sensitivity of broad-spectrum antiglobulin serum and the possible hemolytic mechanisms of IgA-coated red cells are discussed.

Adult↗