Biomedical subjects
Publications and source records attributed to P Leoni.
A case of Hodgkin's disease with isolated cerebral relapse is reported here. The peculiar presentation features are reported and the difficulties related to the differential diagnosis are discussed.
Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985 and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1, were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily for a median of 5.7 months, produced a response of 93%, complete+partial response (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment variables were associated with the rate of response to IFN. However maintenance treatment of 3 MU/mq weekly given randomly had a slightly significant effect on failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%) obtained a new response with IFN. No differences in FFS were recorded between first and second response. At the third induction 7/11 patients were treated again with IFN, 4/7 obtaining some response, but the FFS was significantly worse. The overall survival is still 85%. We conclude that (1) IFN should be used as chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to prolong the disease free status and (3) continuous lymphoblastoid IFN administration seems not to be associated with the development of resistance to retreatment.
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We analyzed the results of 71 leukapheresis procedures performed in 21 patients to identify the best predictive factors affecting the yield of peripheral blood progenitors after high-dose chemotherapy followed by G-CSF administration. An average of 1 +/- 1 x 10(8) MNC/kg, 5 +/- 6 x 10(4) CFU-GM/kg and 4 +/- 6 x 10(6) CD34+ cells/kg was collected for each leukapheresis. When we defined > or = 5 x 10(4)/kg as the minimum number of CFU-GM per procedure for a 'satisfactory' collection, multiparameter analysis of clinical features and laboratory findings showed that the only factors that predicted the numbers of CFU-GM collected were prior treatment with the MOPP regimen and the number of mononuclear cells identified in the basophil channel of the H*1 = Technicon. A logistic regression analysis performed to generate a mathematical model revealed four predictive factors: the number of previous cycles of chemotherapy, previous MOPP chemotherapy, the interval from latest chemotherapy and the number of mononuclear cells/microliter. This model was valuable in defining the optimal time for the first leukapheresis procedure. In contrast, the number of circulating CD34+ cells did not correlate with CFU-GM numbers collected whereas the numbers of mononuclear cells did provide a simple and reliable index. Thus the principal factor affecting the efficiency of peripheral blood stem cell collection was prior therapy with MOPP.
In essential thrombocythemia patients alpha-IFN rapidly reduces platelet count, and it is also able to maintain a low count during long-term treatment. In order to verify if long-term IFN treatment can produce sustained remission in selected patients, we decided to suspend IFN treatment in two subsets of 21 patients on long-term alpha-IFN treatment: (a) all six patients who had shown a platelet count below 450 x 10(9)/l for at least 2 months with 3 MU once a week; (b) three patients who had shown the same platelet count for at least 2 months with 3 MU three times a week. After withdrawal of alpha-IFN treatment, a rapid increase in the platelet count was observed in all three patients requiring 3 MU three times a week. Three of the six patients treated with 3 MU once a week are still free of symptoms and have been in complete hematological remission (platelet count below 450 x 10(9)/l) for 9+, 13+, and 14+ months, respectively. As far as the three remaining cases are concerned, one was not assessable because of loss to follow-up, while the other two relapsed after 1 and 2 months. We believe that the three cases of sustained remission might be the result of a long-term tumor load reduction produced by the alpha-IFN treatment. Finally, the factor best able to predict sustained, unmaintained remission seems to be the clinical response to a low dose of alpha-IFN during the maintenance phase, rather than disease features prior to treatment.
Sera from patients with myelofibrosis were analysed for circulating antibodies against an antigenic determinant characterized by two molecules of galactose in alpha 1-3 linkage (anti-Gal antibodies). 50% of patients were found to have values above the 90th percentile of the values of control sera chosen as a cut-off. The median level of the antibodies was significantly higher than the value detected in normal controls, but no difference could be found between patients with idiopathic myelofibrosis and those with myelofibrosis associated to a chronic myeloproliferative disorder. Anti-Gal antibodies were found to correlate with disease activity and with platelet count whereas no correlation was detected with other haematological parameters. Furthermore, for evaluation of disease activity, determination of serum anti-Gal antibodies was a sensitive and specific parameter. We conclude that humoral immunity against Gal alpha 1-3Gal may provide a sensitive tool to detect disease activity in patients with idiopathic myelofibrosis and may be important for understanding its pathogenesis.
High-dose non ablative chemotherapy followed by growth factors efficiently mobilizes and amplifies Peripheral Blood stem Cells (PBSC). Cytofluorimetric PBSC monitoring reduces the number of leukapheresis needed to collect sufficient amounts of progenitors to restore hemopoiesis after myeloablative therapy. Twenty-eight patients, affected by lymphoproliferative disorders, were primed with non myeloablative chemotherapy followed by G-CSF 5 micrograms/kg/die subcutaneously, until leukapheresis. A total number of 90 leukaphereses was performed (median: 3 per patient) using blood cell separator CS 3000 Plus Baxter; we collected 1 +/- 0.8 x 10(8)/kg mononuclear cells (MNC), 6 +/- 9 x 10(4)/kg CFU-GM and 4 +/- 5 x 10(6) CD34+ cells for each procedure. The statistical analysis showed that the number of progenitors collected was dependent on the age, number and type of previous chemotherapies and interval between the last chemotherapy and the priming; the type of priming, type and status of disease, sex, and bone marrow involvement were not significant. Duration of neutropenia after megachemotherapy was very short; in two cases platelet support was necessary and only two patients needed hospitalization. Our experience shows that high-dose non ablative chemotherapy followed by G-CSF is safe and yields large amounts of PBSC; several factors influence the quality of collections mainly regarding age and the previous treatment.
The Myelo-Dysplastic Syndromes are a heterogeneous group of diseases which includes patients with different prognosis. There is no agreement about the management and the therapeutic strategy must be based on many individual parameters, particularly the age of the patients and their performance status. The therapeutic options range from no cytotoxic therapy for low-risk patients up to more aggressive treatment for high-risk patients, with disappointing results except for the very few cases eligible for allogenic bone marrow transplantation. The leukaemic cell can be induced to differentiate, so losing its self-maintenance potential; different drugs such as Interferon, vitamin D3, retinoids and arabinosyl-cytosine (low doses) have shown a differentiating action on myeloid blasts in "vitro". We summarize the general strategy in the treatment of myelo-dysplastic syndromes based on literature data, and on our results about the efficacy and tolerance of a combination of the above mentioned differentiating drugs, in a group of 27 elderly patients affected by myelodysplastic syndrome with poor prognosis. We obtained 14 objective responses (52%), and the median overall survival of these patients have been compared with that of 25 patients with severe myelodysplastic syndrome treated with a conventional regimen. In the 27 patients receiving the differentiating combination the median survival was found to be 14.7 months, versus 8.4 months for the control group. The results obtained are encouraging about the tolerance and the efficacy of this combination in elderly patients with a poor MDS prognosis. Further randomized studies are necessary to establish whether this treatment can really improve the survival in this group of patients.
The increase of survival in patients with Hodgkin's disease (HD) has made appear the problem of secondary neoplasms, included acute leukemias. The authors evaluate the incidence of acute leukemias in 205 HD with a follow-up more than 12 months (mean 92 months). With regard to these latter, 18 (8.7%) were treated with radiotherapy alone, 69 (33.6%) with chemotherapy alone and 118 (57.5%) with a combination of radiotherapy and chemotherapy. Chemotherapy consisted of 2-12 courses of MOPP alone or in combination with ABVD. The relative risk of acute leukemias is 96.7 (CI 95%: 44.2-183.6): nine cases against an expectancy of 0.093. The risk changes during five-years periods, but not significantly, and it not declines after ten years from the diagnosis. Only the alkylating chemotherapy seems to be important to favour the onset of acute leukemias. Among the patients who received a number of courses of MOPP less or equal than 6 (177), seven developed an acute leukemia (relative risk 85.3; CI 95%: 34.3-175.9); among those who received more than 6 (9), two developed an acute leukemia (relative risk 333.3; CI 95%: 40.3-1204.1). Neither the addition of radiotherapy nor the stage nor the splenectomy nor the histotype favour the onset of acute leukemia.
There are many reports concerning the morphology of hairy cell leukemia (HCL), but, to our knowledge, there are no data on the ultrastructural modifications of HCL during interferon therapy. The ultrastructural modifications of neoplastic cells in peripheral blood in a case of HCL were investigated before and 2 and 4 months after beginning treatment with human lymphoblastoid alpha-interferon. Before therapy, hairy cells displayed the typical cytoplasmic projections, and 4% contained ribosome-lamellae complexes (RLC) (the cells contained up to 7 RLC). Two months from the beginning of therapy, hairy cells had shorter projections, RLC had disappeared, and tubuloreticular structures (TRS) had appeared in 2.2% of the elements. Four months from the beginning of therapy, TRS persisted in 2.3% of hairy cells, cylindrical confronting cisternae (CCC) appeared in 6.8% of the cells, and uncommon RLC, in close contact with the rough endoplasmic reticulum and nuclear membrane, were found in 1.5% of the elements. The cells contained up to 3 RLC. Our data confirm that interferon stimulates the synthesis of TRS and CCC, whereas the reappearance of uncommon forms of RLC could reflect their neosynthesis, possibly related to the interferon therapy. The frequent findings of a close contact between RLC and nuclear membrane support the view that RLC are derived not only from rough endoplasmic reticulum, but also from the nuclear membrane.
Castleman's lymphoma is a rare clinicopathological entity and is often difficult to classify nosographically. From the histopathological point of view two variants are recognized, one hyalino-vascular and one plasma cellular. Moreover Castleman's lymphoma may be multifocal or unifocal (located within the thorax in 70% of patients). The plasma cellular variant is often associated with systemic symptoms such as fever, sweating, organomegaly, polyneuropathy, and mono- or polyclonal gammopathy. We describe a rare case of unifocal, plasma cellular-type Castleman's lymphoma located in the mediastinum, asymptomatic at onset but later dominated by neurological symptoms (chronic isolated polyneuropathy whose clinical expression was predominantly motor). A brief review is presented of the main clinico-histological characteristics of Castleman's lymphoma together with some hypotheses about the pathogenesis of the associated neuropathy.
A varying percentage from 40 to 60% of patients having lymphoplasmacytic dyscrasias with a monoclonal component shows a clinical or subclinical polyneuropathy. From a different viewpoint, a monoclonal gammopathy has been detected in 10% of patients effected by chronic idiopathic polyneuropathy. A case study of 38 patients with lymphoplasmacytic dyscrasia subjected to clinical, immunohematological and electrophysiological examination revealed a high prevalence of polyneuropathy (84%), mainly axonal (72%) and often subclinical. The neuropathy was evenly distributed between patients having malignant and benign lymphoplasmacytic dyscrasias. No statistically significant correlation was found between the presence of neuropathy and the main clinical and immunohematological data. This supports the concept that the pathogenesis of polyneuropathy associated with lymphoplasmacytic dyscrasias may be multifactorial. Nor can it be ruled out that the paraprotein may in fact be secondary to the polyneuropathy or sometimes a simple coincidence.
The increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease.
A-EEG is an important recent technologic innovation in EEG recording that facilitates long-term monitoring. The system consists of a miniature cassette tape recorder and a video play-back unit, which permits the taped EEG to be reviewed (Brain Spy CH24, Micromed). Because it is extremely lightweight and portable, the system permits unrestricted activity during recording. On the other hand, this predisposes the recording to more artifacts than are seen in routine recordings. We examined 103 patients, aged 3 months-24 years, between July 1988 and July 1990. Patients were divided into three groups: group 1 included 61 subjects with evidence of epilepsy and clinically definite seizures; group 2 included 29 patients with recurrent episodes that were not clearly epileptic (suspected "pseudo epileptic"); group 3 included 13 subjects with psychiatric disorders. We found that the clinical utility of A-EEG in epileptic children was: 1) obtain better clinical and EEG characterization and circadian distribution of seizures in 17 cases (28%); 2) quantify epileptiform generalized abnormalities and their variations during the sleep in 6 cases (10%); 3) verify the efficacy of specific drug treatment such as Bzd and ACTH in 12 cases (20%). The role of A-EEG in non-epileptic children with pseudoseizures was to establish the epileptic or non epileptic nature of some ictal events by detecting EEG seizure patterns in 11 cases (38%). As to regard the group 3, A-EEG has permitted to study sleep architecture and REM sleep measures, especially in depressed children compared to normal children. We discuss advantages, drawbacks and clinical applications of A-EEG in child neurology and psychiatry vs conventional EEG.
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We treated 35 patients affected with essential thrombocythemia (ET) with interferon (IFN) alpha-2b. Our treatment scheme consisted of (a) a 6-month induction phase and (b) a continuous maintenance phase. During the induction phase, our results showed that using 21 million units (mu) of IFN weekly platelet counts fell below 600 x 10(9)/1 in about 90% of patients. These data demonstrate that well-tolerated doses of IFN can rapidly correct excessive thrombocytosis. During the continuous maintenance phase, 61% of patients required 3 mu three times a week, 15% once a week, and 24% daily. Thus the minimal IFN doses able to maintain platelet count below 600 x 10(9)/l varied between 3 and 21 mu per week. During long-term treatment, subjective side effects were tolerable, especially using 3 mu three times a week. We conclude that IFN alpha-2b is an effective drug in the long-term treatment of ET.
To answer the question of whether interferon (IFN) should replace splenectomy, we reviewed the Italian HCL Registry: the records of 450 patients with hairy cell leukemia (HCL), seen from 1975 to 1988 were analysed. Of these, 321 were considered for the study: 231 had been splenectomized, 46 of them receiving subsequently IFN and 90 patients had IFN as initial therapy. Patients treated with splenectomy showed different survival according to Jansen and Hermans' staging system, which identified two risk groups: stage 1 and stages 2 and 3, p = 0.0329. On the contrary, patients treated with IFN did not show significantly different survival according to stage. By the comparison of stage 1 patients, either treated with splenectomy or with IFN, no statistical difference in survival was registered. Different survivals emerged for patients stage 2 + 3, which improved when treated with IFN, p = 0.0324. The median failure free survival (FFS) after splenectomy resulted in 89 months versus 33 months after IFN. In conclusion, splenectomy still remains the primary therapy for HCL patients stage 1. For high risk patients, stages 2 and 3, IFN should be adopted as first line therapy, improving substantially the survival. The short duration of response to IFN suggests a sequential combination of the two treatments for this group of patients, IFN reducing tumor mass quite safely and splenectomy assuring long lasting stable disease.