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Biomedical subjects

S Sica

Publications and source records attributed to S Sica.

At least 91 records · Page 5Linked to original sources
PubMed1997

Interleukin-2 therapy in relapsed acute myelogenous leukemia.

PURPOSE: Several studies have been conducted in Italy to assess the activity of recombinant interleukin-2 (rIL-2) in patients with relapsed-refractory acute myelogenous leukemia (AML) and in AML patients in second complete remission (CR) who are not eligible for standard therapy. We report here the updated results of those studies. PATIENTS AND METHODS: Since 1988, a total of 24 patients with relapsed-refractory AML and < or = 30% bone marrow blasts (median blastosis, 15%), who were not suitable for further chemotherapy, were treated with a daily dose-escalating protocol of rIL-2 (8-18 x 10(6) IU/m2 x 5 days) by continuous intravenous infusion with a 72-hour rest period between each cycle. Patients achieving a response to induction therapy received subcutaneous maintenance rIL-2 therapy at lower doses for 5 days/month. Based on these encouraging results, a prospective randomized trial was initiated by the Italian cooperative groups GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto) and AIEOP (Associazione Italiana Ematologie e Oncologia Pedietrica) to assess the efficacy of this rIL-2 regimen in AML patients in second CR. Of 264 AML patients enrolled, 146 patients (55%) achieved a second CR in response to mitoxantrone, etoposide, and cytarabine; 32 patients who were not eligible for transplantation were randomized to rIL-2 (15 patients) or no treatment (17 control patients). Accural goals were never reached, however, due to low recruitment. RESULTS: In the pilot study, 13 patients (54%) obtained a CR, which persists in eight patients with a median follow-up of 64 months (range, 1-110 months) on maintenance rIL-2. In the randomized study, a trend in favor of improved disease-free survival was observed in the rIL-2 arm. CONCLUSIONS: Encouraging results have been obtained with rIL-2 therapy in AML patients with relapsed-refractory disease and limited blastosis and in patients in second CR. These results have prompted a large, multicenter, randomized study to evaluate the efficacy of high-dose rIL-2 therapy in AML patients with advanced disease but limited blastosis in relapse following cytoreductive chemotherapy or autologous transplantation.

Adolescent↗
PubMed1996

Hypereosinophilia during 2-chlorodeoxyadenosine treatment for hairy cell leukaemia.

A 43-year-old male with newly diagnosed hairy cell leukaemia underwent a single course of 2-chlorodeoxyadenosine (2-CdA). Skin rash, facial swelling and marked eosinophilia developed 20 d after treatment and were resolved by 7 d of steroid therapy. Eosinophil peak in peripheral of the eosinophil population showed a high expression of the IL-2 receptor alpha-chain (CD25), representing up to 94% of gated cells. HLA-DR and CD4 antigens were constantly negative; eosinophils strongly reacted with the secretory form of the eosinophil cationic protein (ECP), recognized by EG2 monoclonal antibody. IL-5 serum levels were markedly elevated at the onset of eosinophilia, returned to normal levels after its disappearance and positively correlated with eosinophil count (r = 0.94, P = 0.016). Eosinophilia is an uncommon finding after treatment with 2-CdA. It is unclear whether these phenomena represented a true allergic reaction to the drug or the effect of massive tumour cell lysis and haemopoietic pancytopenia with immunosuppression, which induced the release of IL-5 and possibly other cytokines.

Adult↗
PubMed1996

rhG-CSF in healthy donors: mobilization of peripheral hemopoietic progenitors and effect on peripheral blood leukocytes.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16 micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG-CSF was administered s.c. for 5 days. No side effects were encountered except for moderate bone pain and lumbago. Mobilization was effective, reaching a peak median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3) colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak values were obtained at a median of 4 days of rhG-CSF and represented, respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007 and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59). Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2-fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1 x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3-fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar changes were observed in lymphocytes collected in leukapheresis product. T helper and T suppressor subsets displayed a similar increase. Thus, besides the anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an unexpected and still unexplained modification of lymphocyte subsets in peripheral blood.

Adolescent↗
PubMed1996

Localization of aspergillosis to the central nervous system among patients with acute leukemia: report of 14 cases. Gruppo Italiano Malattie Ematologiche dell'Adulto Infection Program.

We retrospectively studied a consecutive series of 100 patients with acute leukemia and aspergillosis to evaluate the clinical findings and risk factors for colonization of the central nervous system (CNS) by Aspergillus species. The diagnosis of CNS aspergillosis was made in 14 patients on the basis of the following criteria: neurological signs of CNS involvement (13 of 14 patients); cerebral CT scan findings (9 of 12); microbiological findings (6 of 12); and histological findings at autopsy (11 of 11). The majority of patients had severe neurological complications (i.e., hemiparesis or seizures), due mainly to brain abscesses or mycetomas. Autopsies were performed on 11 of 14 patients and provided evidence that CNS localization was secondary to invasive aspergillosis; in each case, the most likely primary focus of infection was the lung. Although all patients had received oral antimycotic prophylaxis and had received timely empirical antifungal treatment, they all died within a median time of 5 days from the onset of neurological symptoms. Analysis of the characteristics of patients with invasive aspergillosis did not reveal any difference between those with CNS localization and those without CNS localization.

Acute Disease↗
PubMed1996

Non-Hodgkin's lymphoma: a case report of a secondary bladder involvement.

Bladder secondary involvement rate in non-Hodgkin's lymphoma (NHL) reaches 13%. Nevertheless, clinical evidence of such an involvement is very rare (less than 0.5%). We report a case of a NHL arising from the Peyer's plaques of the gut and involving secondly the bladder. The onset symptomatology was urologic. Pathophysiology and clinical features of secondary bladder lymphoma are discussed.

Adult↗
PubMed1996

Flow cytometric detection of CD44 (H-CAM) in hairy cell leukemia.

Hairy cell leukemia (HCL) is a rare clonal B-cell disorder characterized by a distinctive pattern of infiltration of hairy cells (HCs) in the bone marrow (BM), hepatic sinusoids and splenic red pulp. HCs express a wide spectrum of matrix-binding integrins, which influence their migratory behaviour and subsequent tissue localization. CD44 distribution and staining intensity on HCs from the BM and peripheral blood (PB) were investigated using dual-color flow cytometry. HCs from all cases expressed CD44, but the staining intensity of the positive population was significantly higher than normal residual lymphocytes (p < 0.0005) and medullary HCs in those patients exhibiting additional hairy cell dissemination in the peripheral blood. It is of interest to speculate that the BM microenvironmental may deliver signals which down-regulate CD44 expression on resident HCs compared to HCs recirculating in peripheral blood. CD44 expression on HCs may help clarify their homing mechanisms in the bone marrow and to define phenotypic subsets with different clinical and pathological behaviours.

Adult↗
PubMed1996

Plasmodium vivax malaria after autologous bone marrow transplantation: an unusual complication.

We report the case of unusually early infection by Plasmodium vivax after autologous bone marrow transplantation in a 20-year-old female from Bangladesh affected by acute myelogenous leukemia in first complete remission (CR) who underwent autologous bone marrow transplantation in our center. During the aplastic phase she became febrile; broad spectrum antibiotics and antifungal therapy were without effect. Blood smears were examined and Plasmodium vivax was detected despite a very low number of red cells infected. Cloroquine therapy for 3 days was given followed by primaquine for 2 weeks in order to avoid possible cloroquine resistance. Fever disappeared within 48 h from initial treatment and the patient was discharged having completely recovered at day +30. Primary malaria infection in non-endemic areas is a very rare event. In this particular case, after excluding primary infection or blood transfusion-mediated infection, malaria was attributed to a recrudescence of a primary unidentified infection.

Adult↗
PubMed1995

Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia.

The mechanisms underlying acute promyelocytic leukemia (APL) coagulopathy and its reversal by administration of all-trans retinoic acid (ATRA) have been investigated. Bone marrow promyelocytic blasts from nine patients with APL were cultured with or without ATRA 1 mumol/L. Cultured blasts (days 0, 3, 6, and 9) were washed, resuspended in phosphate buffer, lysed by freezing and thawing, and then assayed for procoagulant activity (PCA), elastase activity, tissue factor (TF) antigen, tissue-type plasminogen activator (t-PA) antigen and urokinase-type plasminogen activator (u-PA) antigen. PCA was determined by a recalcification assay. Elastase was measured by an amidolytic assay (S-2484). TF, t-PA, and u-PA antigens were measured by an enzyme-linked immunosorbent assay (ELISA). Malignant promyelocytes isolated from the patients had increased levels of PCA and TF as compared with the control polymorphonucleates, and low levels of elastase, t-PA, and u-PA; the patient blast PCA level was significantly related to the degree of hypofibrinogenemia. In this system, blast PCA depended on the tissue factor and was significantly correlated to the TF antigen values. In the cultures without ATRA, PCA, TF, and u-PA progressively increased, whereas elastase and t-PA levels remained essentially unchanged. In the presence of ATRA, all parameters (except u-PA) decreased during the culture time. Thus, a major role of the promyelocytic blast cell PCA in the pathogenesis of M3-related coagulopathy is suggested; the ATRA effect on coagulopathy seems mainly mediated by a downregulation of the PCA.

Adolescent↗