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Biomedical subjects

E E Damasio

Publications and source records attributed to E E Damasio.

At least 19 recordsLinked to original sources

Alpha-interferon as induction and maintenance therapy in hairy cell leukemia: a long-term follow-up analysis.

Although in recent years the use of purine analogues has increased the percentage of long-term complete response the effect on overall survival of patients with hairy cell leukemia (HCL) is not yet clear. This study aimed to evaluate the long-term outcome (mean follow up of 92 months) of 64 patients receiving IFN as first-line therapy. IFN was well tolerated and effective. The overall response rate was 91% (PR 65%, CR 13%, GPR 13%). Forty-one patients (63%) received IFN 3 MU/ wk as maintenance therapy. The 10-yr projected survival rate of responding patients (CR and GPR 100%; PR 95%) and non-responders (SD, PD 80%) clearly shows that type of response does not affect survival. Patients receiving IFN maintenance had a statistically higher PFS than those who did not (p <0.01). This study shows that IFN is still one of the standard therapies for this disease, that achieving CR has no primary relevance for the control of the disease, and that good utilization of therapeutic resources may assure HCL patients a survival rate comparable to that of a normal, healthy population.

Adult↗

Five day intermittent vs seven day continuous 2-chlorodeoxyadenosine infusion for the treatment of hairy cell leukemia. A study by Italian Group for the Hairy Cell Leukemia.

The new purine-analogue 2-chlorodeoxyadenosine (2-CdA) has proved to induce an high CR rate and a long lasting disease free survival. In this study we compare the efficacy and toxicity of 2-CdA employed in two different schedules (A and B). Forty-one patients have been enrolled from 1994: 22 p. (group A) were treated with a single cycle of 2-CdA given as two hour i.v. infusion on 5 consecutive days (0.15 mg/kg/die); while 19 p. (group B) with continuous i.v. infusion for 7 consecutive days (0.10 mg/kg/die). Response criteria were those proposed by NCI. The Hairy Cell Index (HCI) was calculated using DBA44 MoAb. At three months, the responses in group A (19/22) were: 5 CR (26.3%), 6 GPR (31.5%), 5 PR and 3 NR.; in group B (17/19): 6 CR (35.3%), 3 GPR (17.6%), 4 PR and 4 NR. Overall response at six months was respectively 84.2% and 76.5%. At six months the responses were: in group A (18/22): 9 CR (50%), 4 GPR (22.2%), 3 PR, 2 NR; in group B (16/19): 4 CR (25%), 6 GPR (37.5%), 3 PR, 3 NR. Overall response at 6 months was respectively 88.8% (group A) and 81.2% (group B). The 5 day intermittent schedule appears efficient, well tolerated and suitable for out-patient treatment. DBA44 MoAb appears useful to better define the HCI and to distinguish CR from GPR.

Adult↗

Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with HCL diagnosed over 25 years. We analysed this large series of patients with the aim of providing an evaluation of changes in clinical presentation, impact of initial therapy and modifications in prognostic factors over the period of two decades. Over time, a progressive down-staging of the disease at the onset, along with a reduction of patients with severe anemia and marked splenomegaly, has been observed. A second malignancy was found in 3.7% of patients, mostly detected several years after the onset of HCL. A striking improvement of survival rates has been observed, from 58.9% survival at five years for patients diagnosed before 1985 to 87.5% at five years for patients diagnosed after 1985 (p < 0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas after 1985, clinical stage and the number of leukocytes correlated better with patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy, steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9% (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our findings suggest that IFN has improved the prognosis of HCL, and that it must be considered a good initial treatment for patients with HCL.

Adult↗

Splenectomy following complete response to alpha interferon (IFN) therapy in patients with hairy cell leukemia (HCL): results of the HCL88 protocol. Italian Cooperative Group for the Study of Hairy Cell Leukemia (ICGHCL).

In December 1987, the Italian Cooperative Study Group for Hairy Cell Leukemia (ICGHCL) started a multicenter trial designed with the aim of investigating the possible role of splenectomy in HCL patients responding to initial treatment with a-IFN. Patients aged less than 65 years, diagnosed within 6 months, were included into the trial and treated with a-IFN (3 MU/daily) for 3 additional months after the achievement of CR or for a maximum of 12 months, regardless of the quality of the response. Patients in CR could undergo splenectomy while patients achieving PR after 12 months of treatment were randomized between splenectomy and maintenance therapy. By June, 1992, the trial closed, with 182 enrolled patients. Nine were subsequently determined to be not eligible while nine additional patients were lost at follow up. One hundred and sixty-nine patients were assessable for both response and survival. At the end of the induction therapy with a-IFN (mean time of treatment 16.9 months), 29 CR (17.7%), 100 PR (61.0%), 26 minor responses (MR) (15.8%) and 9 (5.5%) treatment failures occurred. At the last follow up (March, 1993), with a mean follow up of 39 months, 5 patients had died and the overall survival rate at 4 years was 96%. Twelve patients underwent splenectomy after CR. After a mean follow up of 8.6 months, 8 relapses occurred. Thirty-one out of 100 were randomized between splenectomy (16 cases) and maintenance therapy (15 cases). The low accrual was mostly due to the rejection of randomization by the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Hairy-cell leukemia].

This is a review of current opinions on all aspects of diagnosis and treatment of hairy-cell leukemia. First, the authors report a concise but complete description of clinical and hematological characteristics of the disease with particular attention to peripheral blood and bone marrow morphological, cytochemical and cytogenetic features. Still concerning the diagnostic phase, the authors report a brief description of splenic, hepatic and lymph nodal histological pictures and some informations about immunophenotypic diagnosis with monoclonal antibodies. A space is then given to differential diagnosis and prognostic factors which have remarkably changed over the years. The second part of this review concerns current treatments for hairy-cell leukemia and analyses all the aspects of the different therapeutic strategies. Data, for this analysis were obtained from the Italian Cooperative Group's Studies and from other published series. Special attention was given to the impact of splenectomy, alpha-interferon therapy and new drugs such as purine analogues (2-CdA, 2-dCF) on the management of the disease. The last section concerns minimal residual disease, second neoplasia and the most common causes of death. A whole paragraph is dedicated to hairy-cell leukemia variants.

Biopsy, Needle↗

Splenectomy after initial therapy with alpha-IFN in patients with hairy-cell leukemia (HCL): a multi-center study by the Italian Cooperative Group for HCL. Preliminary results.

Since December 1987, 115 patients with HCL have been enrolled in a prospective multicenter study to evaluate the role of splenectomy after an induction therapy with alpha interferon. The group of patients was divided into two categories: those younger and those older than 65 years. The schedule of treatment with IFN was, respectively, 1.8 MU/sm/daily and 1.0 MU/daily, 33 patients were treated with r-alpha-2a, 34 with r-alpha-2b, and 25 with alpha-Ly. To date, 92 patients are fully evaluable. The response was assessed every 3 months by bone marrow trephine biopsy. Patients in CR continued IFN therapy for 3 months and, if they were still in CR, could undergo an optional splenectomy. Patients in PR continued therapy for 12 months and subsequently were randomized for splenectomy or observation only. In these preliminary results of an ongoing protocol, CR was obtained in 5 cases (6%), PR in 59 (64%), MR in 25 (27%), NR in 3 (3%). Only 2 of the 5 patients in CR underwent splenectomy and are still in CR. Of the 59 patients in PR, only 15 completed 12 months of therapy. 9 patients in Group A were randomized, 4 were splenectomized and 5 were in the observation arm. All patients were splenectomized safely and no complications occurred. These preliminary results suggest that splenectomy could be effective in consolidating the response obtained with IFN.

Adult↗

Human lymphoblastoid interferon for hairy cell leukemia: results from the Italian Cooperative Group.

Since April 1985, 82 patients with HCL entered a multicenter study using lymphoblastoid alpha-interferon; 51 (including 15 who failed splenectomy and 24 with substantial splenomegaly) enrolled before April 1986 are evaluated in this study. The patients were treated with 3 mega units daily subcutaneously until complete or partial response and were thereafter randomly allocated to a maintenance regime of 3 mega units/week or to observation only. Ten cases had a complete response, 18 a partial response, and 15 a minimal response. Two patients had no response, two interrupted therapy due to major toxicity (toxic hepatitis and thrombocytopenia), six died before completing 1 month of therapy of sepsis, and two died of myocardial infarction. In the two groups of splenectomized and nonsplenectomized patients the mean time to hemoglobin recovery was 8.5 and 6.5 weeks, respectively, the neutrophil count recovery was 6.5 and 9.3 weeks, and the time to platelet count recovery was 4.0 and 5.4 weeks, respectively. No significant differences in recovery time and response rate were observed between the two groups. In 31 out of 32 patients with substantial splenomegaly the spleen became either inpalpable (18) or significantly smaller (13). This study confirms the responsiveness of HCL to IFN in nonsplenectomized patients with high tumor burdens and is therefore recommended as a first-line therapy.

Humans↗

Hairy cell leukemia: a retrospective study of 235 cases by the Italian Cooperative Group (ICGHCL) according to Jansen's clinical staging system.

This is a report from a cooperative study on hairy cell leukemia (HCL) involving 20 Hematology Departments in Italy. Data for the patients was collected between January 1967 and December 1981 and included 235 cases of which 203 could be evaluated; 160 were males (78.8%) and 43 females (21.2%) with an M:F ratio of about 3:1; mean age was 54 years (range 26-82 yrs). The diagnostic criteria of admission were: typical aspect of hairy cells, in peripheral blood and bone marrow smears, tartrate resistant acid phosphatase (TRAP) positivity, typical bone marrow, spleen, liver and/or lymph node histology, and/or electronmicroscopy. On the basis of hemoglobin level and spleen size at the time of diagnosis, three stages could be distinguished according to Jansen: 51 patients, 27 of which splenectomized, were in stage I; 67 patients, of which 44 splenectomized, were in stage II; 85 patients of which 60 splenectomized, were in stage III. The actuarial survival curves of these patients showed clear distinction between the three stages. In the first stage the difference in survival, between splenectomized and nonsplenectomized groups, was not statistically significant (p less than 0.5): on the contrary, in stages II and III the difference in survival was statistically significant (stages II and III; p less than 0.01).

Aged↗

Treatment of severe aplastic anemia with sequential immunosuppression.

Forty-two patients with severe aplastic anemia (SAA) were treated with immunosuppressive therapy (IS) consisting of one or more courses of the following regimens: a) high dose bolus 6 methylprednisolone (BMPr); b) horse antilymphocytic globulin (HALG); c) rabbit ALG (RALG); d) ALG followed by the infusion of haploidentical marrow (ALG +/- BM); e) BMPr in combination with HALG; f) ALG in combination with androgens. All patients received one initial course of IS: 16 (38%) showed hematologic reconstitution and required no further transfusions, of 26 refractory patients 4 died, and 22 received a second course of IS 60 days after the first course. Of these 22, 6 (27%) responded, and of the 16 refractory patients, 9 died, and 7 received a third course of IS 60 days after the second course. Two of these responded (28%), 3 died and 2 are alive but pancytopenic. The overall response rate is 24/42 patients (57%): all of these patients are transfusion independent 6-60 months post-treatment, and 17 are off maintenance therapy with low dose steroids. The actuarial 5 year survival is currently 60%; 13/26 surviving patients have been followed for more than 3 years. The present study confirms that over 50% of patients with SAA can recover from their aplasia following IS treatment, and this is of relevance for patients who can not be offered a bone marrow transplant.

Adolescent↗

Lymphoid antigens on blast cells in the agranular metamorphosis of chronic myelogenous leukaemia.

Undifferentiated blasts from a Ph'-positive chronic myelogenous leukaemia (CML) in terminal metamorphosis were reacted in an indirect immunofluorescence test with antilymphocytic globulins (AHLGs), raised against cultured lymphoblasts, thoracic duct and peripheral blood lymphocytes from healthy donors. After proper myeloid and/or monocytic absorptions the AHLGs interacted strongly with the undifferentiated blasts of CML, while this was not true for parallel controls with non-lymphoid leukaemias, both acute and chronic. The intensity of fluorescence, as determined by the use of a microfluorimeter, on these agranular blasts was comparable to the positivity of lymphoid cells from acute and chonic lymphatic leukaemias. These findings lend further support to the conception of a lymphoblast-like variety of terminal blastic crisis in chronic myelogenous leukaemia.

Antigens, Surface↗