Measuring cyclosporin in plasma.
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Biomedical subjects
Publications and source records attributed to G Visani.
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In the cryopreservation procedures intended for autotransplantation of human bone marrow a controversial point is represented by the methods of reconstruction of the cellular suspension after thawing and before infusion into the patient. To evaluate how the dilution rate after thawing affects bone marrow viability, we cryopreserved the bone marrow from 16 hematologically normal patients in DMSO at a concentration of 10%. After thawing, the cells were diluted according to three different techniques and their viability was tested by the growth of CFU-GM in methylcellulose. The average recovery of CFU-GM, in comparison with that of fresh cells, was satisfactory and not affected by the type of dilution. In conclusion, if we accept that the resistance to osmotic stress due to the cryoprotectant is similar for stem cells and CFU-GM, we can maintain that a slow, gradual dilution is not a necessary condition to assume the staminality of bone marrow designed for autotransplantation.
Twelve adult patients with acute lymphoblastic leukemia (ALL) received lithium carbonate, 300 mg, three times a day during induction treatment. They were compared to 12 similar patients consecutively treated with the same induction regimen; patients and controls were comparable for age, degree and presence of splenomegaly, hemoglobin level, blast cell count, polymorphonuclear (PMN) cell count and platelet count at diagnosis. All patients developed a severe neutropenia. PMN count at nadir was slightly higher in the lithium group, but not at a level of statistical significance (p = 0.100). The median number of days with PMN less than 1 x 10(9)/liter was 4 in the lithium group and 14.5 in the non-lithium group (p = 0.014), while the median number of days with PMN less than 0.5 x 10(9)/liter was 0 and 2 days, respectively (p = 0.004). Duration of thrombocytopenia was similar in the 2 groups and so was the remission rate; 2 infective episodes occurred, one in the lithium group and one in the controls.
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Results in the treatment of mostly Gram-negative infections of the respiratory apparatus (30 subjects) and the urinary apparatus (20 subjects) with ribostamycin are reported. These were regarded as good overall, as shown by the bacteriological findings. An extremely high sensitivity to the antibiotic was noted in isolated germs from both types of infection. This good response in vitro was matched by an equally encouraging bacteriological result in vivo.
Total serum lactate dehydrogenase (LDH) activity was measured in 514 adult patients with de novo acute non-lymphocytic leukemia (ANLL) prior to any treatment and was compared with several disease features, with response to induction treatment, and with relapse-free survival. LDH was higher in the M4 and M5 FAB cytological subtypes and was positively correlated with the white blood cell count (WBC). The proportion of remissions, of deaths during induction, and of failure, and the duration of relapse-free survival, were clearly unrelated to LDH activity, in the whole series as well as in different age groups (below 40 years, and 40 to 60 years) and in any FAB cytological subtype. Multivariate analysis showed that only WBC and sex (female better than male) were marginally related with relapse-free survival. These data provide conclusive evidence that LDH does not help in defining the prognosis of adult ANLL, either because enzyme activity fails to reflect the number and proliferation rate of leukemic cells efficiently, or because with current standard treatment these features are of borderline importance, in contrast with acute lymphocytic leukemia and malignant lymphomas.
BACKGROUND: Recombinant (r) human (h) granulocyte/macrophage colony stimulating factor (rh GM-CSF) has been shown to increase the number of peripheral blood (PB) neutrophils, eosinophils and monocytes in myelodysplastic syndromes (MDS). The aims of this study were: 1) to evaluate the effect of rh GM-CSF therapy on the in vitro growth of granulocyte-erythroid-macrophage-megakaryocyte colonies (CFU-GEMM), erythroid colonies (BFU-E), and granulocyte-macrophage colonies (CFU-GM) in patients with MDS; 2) to assess in these patients, while they are being treated in vivo with rh GM-CSF, the possible additive effect of rh IL-3 and rh G-CSF on the in vitro growth of haematopoietic progenitors. METHODS: The in vitro growth of CFU-GEMM, BFU-E and CFU-GM was studies in 10 myelodysplastic (MDS) patients, before and after in vivo administration of rh GM-CSF. RESULTS: After rh GM-CSF administration, the number of CFU-GM increased in all standard risk MDS patients. In 2 out of 5 cases, this effect was more pronounced and persisted up to 30 days after the end of rh GM-CSF treatment. On the other hand, the number of CFU-GEMM and BFU-E was substantially unchanged. When rh GM-CSF, rh G-CSF and rh IL-3 were added in vitro alone or in combination as the source of colony stimulating activity, no significant increase of the CFU-GM colony number was noticed. CONCLUSIONS: Rh GM-CSF therapy appears useful for increasing the number of peripheral blood granulocytes and of marrow CFU-GM in standard-risk MDS patients. High-risk MDS patients are far less responsive to rh GM-CSF treatment, probably reflecting a more aggressive and/or advanced disease.
BACKGROUND: Despite the fact that granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are increasingly used in clinical practice, little is known of their endogenous production, especially in myeloproliferative disorders such as chronic myelogenous leukemia (CML). METHODS: In order to define serum levels of GM-CSF and G-CSF in subjects affected by CML, the sera of 17 patients with CML in chronic phase treated either with hydroxyurea or interferon-alpha were tested by specific enzyme immunoassays. Fifteen age- and sex-matched healthy volunteers were used as normal controls. RESULTS: Eight out of the 17 patients (44%) with CML showed detectable (> 3 pg/mL) serum levels of GM-CSF (range 3.9-55 pg/mL). Detectable levels (> 50 pg/mL) of G-CSF were observed in 9 of these patients (52%) (range 150-2,830 pg/mL). On the contrary, among the normal controls only one had detectable GM-CSF concentrations, and none had detectable G-CSF concentrations. The highest concentrations of both GM-CSF and G-CSF were seen in patients with the highest white blood cell counts, although a linear correlation between the levels of these growth factors and the number of circulating leukocytes was not demonstrated. CONCLUSIONS: Our data indicate that significant amounts of both endogenous GM-CSF and G-CSF are detectable in the serum of a substantial percentage of patients with CML in chronic phase. The pathophysiological meaning of this finding remains to be determined.
In vitro clonogenic assays may be useful for determining the sensitivity of leukemic cells to chemotherapeutic agents. We evaluated the antileukemic effect of Bisantrene (an anthracene derivative now undergoing phase II clinical trials in relapsed/resistant acute non lymphoid leukemias-ANLL) using the ANLL cell clonogenic assay. Fifteen cases were studied (9 newly diagnosed, 5 relapsed and 1 refractory ANLL). Normal CFU-GM sensitivity was tested in a subset of 10 normal controls. A wide range of concentrations (from 0.01 to 10 micrograms/ml) at 3 durations of exposure (30 min, 120 min, continuous) was employed. Bisantrene proved effective in 12 out of 15 ANLL cases, inhibiting blast colony growth (50% at 1 micrograms/ml; nearly 100% at 10 micrograms/ml) in a dose-dependent, time-independent way. Three cases were unresponsive both in vitro and in vivo. Normal CFU-GM were inhibited at lower doses (50% at 0.5 micrograms/ml; 100% at 5 micrograms/ml). We conclude that: 1) Bisantrene is active in vitro on leukemic clonogenic cells at doses corresponding to plasmatic levels achievable in patients, with a parallel activity in vivo in 3 relapsed cases. It should be tested in vitro before therapeutic use in order to avoid, if possible, improper use in resistant patients. 2) Normal CFU-GM are more sensitive than clonogenic leukemic cells. This must be taken into account, in view of possible prolonged neutropenias after therapy. 3) The time-independent effect of the drug should be evaluated in the design of new therapeutic schedules.
Human recombinant granulocyte-macrophage colony-stimulating-factor has been employed, on a compassionate basis, in 14 hematological patients in order to reduce the duration of the neutropenic period after high-dose chemotherapy for the treatment of hematological malignancies (7 traditional CHT courses, 7 autologous bone marrow transplantations). The compound was administered intravenously by 6-hour infusion at a dose of 5 microgram/kg/day until the patient reached at least 1000 PMN in the peripheral blood. Eleven out of the 13 evaluable patients showed a significative improvement in hemopoietic recovery, even though in CHT patients hematological reconstitution was higher in terms of PMN counts. The ABMT patients, however, showed a faster myeloid recovery than that obtained both in a group of 14 NHL and in a series of 8 MM previously submitted to ABMT in our Institution. Moreover the increase in peripheral neutrophils appeared to be stable, since it was maintained throughout one month after the end of rhGM-CSF therapy. We did not observe effects on platelet or erythrocyte recovery. We conclude that rhGM-CSF is active in accelerating the recovery of myelopoiesis, without significant toxic or collateral effects.
Several clinical observations have shown that alpha-IFN is presently the most interesting investigational agent for the treatment of Ph+ chronic myeloid leukemia (CML). Gamma-IFN is also effective, and experimental data as well as preliminary clinical observations suggest that the combination of the two IFNs is worth investigating. No comparative data are available on the effects of the two IFNs, given alone, in the same patients. In this study 11 patients with PH+ CML were first treated with gamma-IFN, up to a maximum period of 35 weeks, and after a short rest period were retreated with alpha-IFN. Both IFNs were ineffective in 3 patients in accelerated or instable chronic phase. Both IFNs were equally effective in 8 patients in stable chronic phase, but none of these patients achieved a karyotypic conversion with either IFN. This study did not show any measurable differences in the therapeutic response to gamma-IFN and alpha-IFN given consecutively to the same patients.
A 55-year-old woman developed Sweet's syndrome (acute febrile neutrophilic dermatosis, AFND) 5 years after a diagnosis of chronic lymphocytic leukemia (CLL). Two months later she developed a scirrhous carcinoma of the breast. The patient died 7 months later from sepsis. To our knowledge, this is the first case of an association among a cancer of the breast, CLL and Sweet's syndrome.
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Pretreatment serum total lactate dehydrogenase (LDH) activity was measured in 341 adult patients (greater than 15 years old) with acute lymphocytic leukemia (ALL) in order to assess its prognostic value. Failure, death during induction and remission were not related to LDH. In contrast, a negative and continuous relationship was found between LDH and relapse-free survival. Though LDH activity was significantly higher in cases with already established risk factors such as high WBC count, FAB L3 cytotype, mature B-cell phenotype, and central nervous system involvement, LDH was confirmed to be the strongest predictor of remission duration by multivariate analysis. This study provides a definitive confirmation of the negative prognostic value of LDH in adult ALL.
Human immunodeficiency virus (HIV-1) can be transmitted by blood transfusions. A recent report focused on the relativey high risk of HIV-1 infection in American patients treated for leukemia and multiply transfused as a consequence of therapy. We therefore conducted a retrospective study on the presence of HIV-1 antibodies among 91 acute leukemia patients diagnosed between 1978 and 1985, before the onset of routine tests for HIV-1 contamination of blood products. The transfusion requirement (platelet units, red blood cell concentrates) involved almost 7,000 donors. We did not find any case of seropositivity in patients transfused with units from the donor pool. The only case of HIV-1 seropositivity was due to a bone marrow transplant donor, retrospectively found to be HIV-1 seropositive. These results differ from the American data previously cited. This is probably due both to differences in diffusion of the HIV-1 infection in the two countries and to differences in the selection of the two donor populations. We conclude that the risk of contracting HIV-1 infections before 1985 through multiple transfusions from registered donors in our Italian area was very low, if not absent, not only for leukemia patients but reasonably for other categories of heavily transfused groups.
In an attempt to reduce the risk of leukemic relapse, different post-remission intensifications based on high-dose Ara-C (HiDAC) and autologous bone marrow transplantation (ABMT) were evaluated in patients with acute non lymphocytic leukemia in first remission and compared as to response and toxicity. Between September, 1985 and May, 1987, 34 patients in complete remission were eligible for our study. Induction therapy consisted of one or two courses of daunorubicin (DNR) and Ara-C (schedule 3 + 7). Fourteen patients receiving intensive post-remission chemotherapy with DNR + Ara-C (schedule 2 + 5), HiDAC + DNR, and ABMT following pretransplant BAVC conditioning entered the first pilot study. A high toxicity was observed and only 5 of them completed the full treatment plan. Thus the second pilot study used a single post-remission intensive course with HiDAC + m-AMSA and ABMT following cyclophosphamide plus TBI or BAVC. This approach was more feasible. The preliminary results show the usefulness of intensive post-remission therapy: in fact, all patients but one who completed the treatment program are still in continuous complete remission. A large number of patients and a longer follow-up are required to draw final conclusions.