Eugenio Damasio

Severe Aplastic Anaemia: Correlation of in Vitro Tests with Clinical Response to Immunosuppression in 20 Patients

Summary. Colony formation in agar (CFU‐c) was studied in 20 patients with severe aplastic anaemia by three different assays: (1) cultures of light density untreated marrow cells; (2) cultures of marrow cells manipulated in order to enhance colony formation (pretreatment with antilymphocytic globulin, ALG, or 6‐methylprednisolone, 6‐MPr, T cell depletion, adherent cell (AC) depletion, depletion of both AC and T cells), and (3) co‐culture of putative suppressor T cells with autologous T‐depleted marrow cells.

Prognostic value of serum IL-10 and soluble IL-2 receptor levels in aggressive non-Hodgkin's lymphoma.

Summary We investigated the prognostic significance of interleukin‐10 (IL‐10) and soluble interleuckin‐2 receptor (sIl‐2r) levles in the pretreatment serum of 105 individuals with newly‐diagnosed aggressive non‐Hodgkins lymphoma (NHL). Commercially available enzyem‐linked immunoassay kits were used for cytokine and receptor measurements. Detectable levels of IL‐10 were found in 42 (40%) patients at diagnosis, with no correlation with clinico‐haematological parameters, but in no control samples (P < 0.001).

Massive chemotherapy with non-frozen autologous bone marrow transplantation in 13 cases of refractory Hodgkin's disease

A group of 13 patients with advanced, diffuse Hodgkins disease, poorly responding to the most widely employed primary chemotherapy regimens, were treated with massive chemotherapy (MCH) followed by rescue with non-frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in 8/13 patients (61.5%) and partial remission in two. Hematopoietic recovery occurred in 12 cases. These preliminary results would seem to indicate that MCH with non-frozen ABMT may be successfully used in patients with resistant or relapsed Hodgkins disease.

4-Demethoxydaunorubicin (Idarubicin) in refractory or relapsed acute leukemias. A pilot study

Twenty‐five adults with previously treated acute leukemia were treated with 4‐demethoxydaunorubicin (Idarubicin) with a daily dose of 8 mg/m2 for 3 days intravenously. Complete remission was achieved in 3 of 18 patients with acute nonlymphoblastic leukemia (ANLL) and 2 of 6 with lymphoblastic leukemia. Complete remissions were observed in two of eight ANLL patients refractory to cytarabine, anthracycline, and m‐Amsa (amsacrine), indicating a lack of cross‐resistance between these drugs and Idarubicin. The median duration of remission was 8 weeks. The main major toxicity of Idarubicin therapy, severe myelosuppression, cannot be considered a toxic effect because it was desired in this case list. Our preliminary results indicate that Idarubicin has significant activity against refractory adult acute leukemia.

Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma

Abstract:  Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non‐Hodgkins lymphoma (NHL) treated by 4 cycles of an intensive multi‐agent chemotherapy regimen. Recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin‐2 (IL‐2), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐10 (IL‐10), the soluble IL‐2 receptor (sIL‐2r), the soluble transferrin receptor (sTf‐r), and neopterin, were observed in NHL patients as compared to controls (p< 0.001 for all molecules). sIL‐2r and sTf‐r levels correlated with tumor burden (p< 0.001 and p = 0.003, respectively) whereas IL‐6 was higher in patients presenting B symptoms (p< 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non‐responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM‐CSF, we observed the drastic increase of sIL‐2r, while lower elevations were recorded for a number of cytokines, including IL‐8, tumor necrosis factor‐α, interleukin‐1β, IL‐6, and IL‐2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM‐CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL‐10 and of sIL‐2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma.Identification of a subset at high risk of treatment failure

Background. This study explores the ability of the combined detection of soluble IL‐2 receptor (sIL‐2r) and interleukin‐10 (IL‐10) to predict treatment failure in patients with aggressive non‐Hodgkins lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).

Anaplastic Large Cell Lymphoma: A Clinicopathologic Study of 53 Patients

Fifty-three consecutive cases of adult CD30+ anaplastic large cell lymphoma (ALCL) have been analyzed. Thirty-six were classified as Hodgkins disease like variety (HL) (67%) and seventeen as so-called common type (CT) (33%). All cases strongly expressed the CD30/Ki-1 antigen; the neoplastic cells expressed CD15, CD45 and EMA in 60%, 44% and 33% of cases, respectively; T. B and null phenotypes were found in 37%, 17% and 46% of cases. Bulky mediastinal, B symptoms, and extranodal disease at diagnosis were present in 36%, 49% and 25% of cases. EBV encoded latent membrane protein (LMP-1) was found in 10 cases. Of the 13 tested cases only 4 expressed a weak positivity of the CD40 molecule, in a fraction of the tumor cells; in the same cases CD21 was never found. Patients were treated with various protocols; of the 50 evaluable patients, 39 (78%) obtained a complete remission (CR), 3 (6%) a partial remission (PR) and 8 (16%) did not respond. The projected overall disease free survival (DFS) at 36 months is 70%. Only patients with advanced disease stage (III-IV) showed a statistically decreased DFS and survival. Only symptomatic and extranodal disease significantly appeared to influence survival. This study confirms the good outcome of this group of lymphomas and differs from other reports for some clinical (lower percentage of advanced stage, extranodal disease and skin infiltration) and pathological (HL/CT ratio and immunophenotype) features.

First line Fludarabine treatment of symptomatic chronic lymphoproliferative diseases: clinical results and molecular analysis of minimal residual disease

Abstract: Fludarabine (25 mg/m2 for 5 d, every 4 wk, for 6 courses) was administered as first line therapy in 32 symptomatic chronic lymphoproliferative diseases. All CLL patients achieved at least partial response (5 CR, 2 nPR, 9 PR) but 44% of patients relapsed. In LG‐NHLs response and relapse rate were similar. Haematological toxicity was low. VDJ rearrangement PCR analysis was performed on marrow samples at diagnosis and at the time of response evaluation. In the 3 patients who underwent high dose therapy with peripheral blood progenitor cell rescue analysis was also performed on apheresis samples and on marrow samples at the end of the procedure. Clonal VDJ rearrangement was always evident after Fludarabine therapy even in those patients who achieved histological and immunophenotypic complete remission, whereas it disappeared in 2 of 3 patients who underwent HDT. Our data confirm that Fludarabine monotherapy can reduce the neoplastic mass to a subclinical level and suggest the possibility that high dose therapy might produce true complete remission.

A to O Bone Marrow Transplantation in Severe Aplastic Anaemia: Dynamics of Blood Group Conversion and Demonstration of Early Dyserythropoiesis in the Engrafted Marrow

Summary. A to O bone marrow transplantation was performed in a 25‐year‐old male affected with severe aplastic anaemia, the donor being an HLA compatible brother. Three plasma exchanges had to be performed with an Aminco separator to remove the original and recurring anti‐A isohaemagglutinins. The dynamics of O to A blood group conversion were followed by means of differential agglutination. An early wave of marked dyserythropoiesis was observed in the engrafted marrow. Mild to moderate GvHD was treated successfully with MTX, bolus high dosage 6‐methyprednisolone and, at relapse, with intravenous ALG.

High-dose chemotherapy and non-frozen autologous bone marrow transplantation in relapsed advanced lymphomas or those resistant to conventional chemotherapy

Ten patients with advanced, diffuse Hodgkins and non‐Hodgkins lymphomas responding poorly to the most widely employed primary chemotherapy regimens were treated with a high‐dose chemotherapy (HDC) followed by rescue with non‐frozen autologous bone marrow infusion (ABMT). Complete remission (CR) was obtained in seven of ten patients (70%) and partial remission in two. Hemopoietic recovery occurred in nine cases. These preliminary results appear to indicate that HDC and non‐frozen ABMT may be successfully used in patients with resistant or relapsed lymphomas.