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Biomedical subjects

F Mandelli

Publications and source records attributed to F Mandelli.

At least 199 records · Page 11Linked to original sources
PubMed1994

Interleukin-2 may induce prolonged remissions in advanced acute myelogenous leukemia.

The administration of interleukin-2 (IL-2) may induce complete remissions in acute myelogenous leukemia (AML) patients with a low proportion of residual bone marrow (BM) blasts. To confirm this preliminary observation, we treated 14 AML patients with advanced disease and with a residual BM blastosis that ranged between 7% and 24% with repeated 5-day cycles of high-dose recombinant IL-2 administered by daily continuous intravenous infusion. Patients who responded have been subsequently submitted to a monthly maintenance scheme with subcutaneous IL-2 at lower doses. While using this schedule and closely monitoring clinical and laboratory conditions, side effects were acceptable and no toxic deaths recorded. Eight of the 14 patients treated with high-dose IL-2 obtained a complete remission (CR). Five remain in persistent CR (four in third CR and one in fourth CR) after a median follow-up time of 32 months (14, 30, 32, 33, and 68 months, respectively). In all five patients, the IL-2-induced remission is the longest in the natural history of the disease. These findings show that IL-2 displays an antileukemic effect in AML with limited residual disease, and suggest that IL-2 should be considered a therapeutic option for resistant or relapsed AML patients.

Adolescent↗
PubMed1994

Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B.

OBJECTIVE: To compare the efficacy and tolerability of fluconazole and oral amphotericin B in preventing fungal infection in neutropenic patients with acute leukemia. DESIGN: A randomized, controlled, multicenter trial. SETTING: 30 hematologic units in tertiary care or university hospitals. PATIENTS: 820 consecutive, afebrile, adult patients with acute leukemia and chemotherapy-induced neutropenia. INTERVENTION: Patients were randomly assigned to receive fluconazole, 150 mg, as a once-daily capsule, or amphotericin B suspension, 500 mg every 6 hours. MEASUREMENTS: An intention-to-treat analysis was done for 820 patients: 420 treated with fluconazole and 400 treated with oral amphotericin B. RESULTS: Definite systemic fungal infection occurred in 2.6% of fluconazole recipients and 2.5% of amphotericin B recipients; suspected systemic fungal infection requiring the empiric use of intravenous amphotericin B occurred in 16% of fluconazole recipients and 21% of oral amphotericin B recipients, a difference of 5 percentage points (95% CI for difference, -0.02% to 10%; P = 0.07). Superficial fungal infection was documented in 1.7% of fluconazole recipients compared with 2.7% of amphotericin B recipients, a difference of one percentage point (CI of difference, -0.9% to 3%; P > 0.2). The distribution of fungal isolates in systemic and superficial fungal infection was similar in both groups. The overall mortality rate accounted for 10% in both groups. An excellent compliance was documented for 90% of patients treated with fluconazole compared with 72% of those treated with amphotericin B suspension, a difference of 18 percentage points (CI for difference, 13% to 23%). Side effects were documented less frequently in fluconazole than in amphotericin B recipients (1.4% compared with 7%, a difference of 5.6 percentage points; CI for difference, 2% to 8%; P < 0.01). CONCLUSION: Fluconazole was at least as effective as oral amphotericin B in preventing systemic and superficial fungal infection and the empiric use of amphotericin B in neutropenic patients with acute leukemia but was better tolerated.

Acute Disease↗
PubMed1994

Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Our aim was to study the prophylactic effect of high-dose intravenous acyclovir given around the time of BMT followed by oral acyclovir on CMV infection and survival. 310 BMT recipients at risk of developing CMV infection were randomised to one of three regimens in a double-blind and double-dummy design: intravenous acylclovir (500 mg/m2, three times a day) for 1 month followed by oral acyclovir (800 mg four times a day for a further 6 months) (intravenous/oral group); intravenous acyclovir followed by oral placebo (intermediate group); or low-dose oral acyclovir (200 or 400 mg, four times a day) followed by placebo ("controls"). Analysis was by intention-to-treat. Intravenous acyclovir significantly reduced the probability of and delayed the onset of CMV infection. There was no further reduction in infection risk with the addition of long-term oral acyclovir. Time to CMV viraemia was delayed in the intravenous/oral acyclovir group compared with controls. Extending the prophylaxis with oral acyclovir significantly improved survival: 79 of 105 recipients were still alive at 7 months compared with 60 of 102 controls (p = 0.012). Although the intravenous/oral acyclovir group did significantly better than controls in terms of survival, the difference between the intravenous/oral acyclovir group and the intermediate group was of borderline statistical significance (p = 0.054). Adverse events that were possibly treatment related were similar in all three groups. The most commonly reported events were nausea, vomiting, elevated creatinine, and renal failure. High-dose intravenous followed by oral acyclovir improved survival and was of benefit in prophylaxis against the effects of CMV after BMT. Interpretation of CMV infection was made difficult because an intermediate treatment (intravenous acyclovir followed by oral placebo) was as effective as high-dose intravenous/oral acyclovir.

Acyclovir↗
PubMed1994

Hair dye use and other risk factors for leukemia and pre-leukemia: a case-control study. Italian Leukemia Study Group.

A case-control study was carried out to examine the relation of three subtypes of leukemia cells and refractory anemia with excess of blasts to selected behavioral and environmental factors. Cases aged 15 years or older were recruited in three hospitals located in Rome, Bologna, and Pavia, respectively. Outpatients who were either normal or had nonneoplastic hematologic disorders and were seen in the same hospitals as the cases were enrolled as controls. Two hundred fifty-two patients with acute myeloid leukemia, 100 with acute lymphocytic leukemia, 111 with refractory anemia with excess of blasts, 156 with chronic myeloid leukemia, and 1,161 controls were included in the study. Refractory anemia with excess of blasts and chronic myeloid leukemia were included because they are regarded as forms of pre-leukemia. Odds ratio estimates were generally imprecise, but associations were suggested between specific case subtypes and exposure to dark hair dye, selected occupations (shoemaker, painter, electrician, child care), residence in houses built with tuff, and smoking. Although the exploratory nature of the study and its limited statistical power preclude firm conclusions, its results are consistent with those of previous studies, and are in general biologically plausible.

Adolescent↗
PubMed1994

Peripheral neuroectodermal tumor of the chest (Askin tumor) as secondary neoplasm after Hodgkin's disease: a case report.

The authors present the case of a 20-year-old woman who developed a peripheral neuroectodermal neoplasm of the thoracopulmonary region (Askin tumor) 7 years after achieving complete remission of stage-IV Hodgkin's disease. The previous treatment had consisted of eight courses of alternating MOPP/ABVD combined with involved-field 20-Gy radiotherapy. The second neoplasm appeared in a nonirradiated area of the chest wall, with erosion of the ribs as shown by sonography and computed tomography. The histological pattern was in accordance with a generic diagnosis of a malignant small cell tumor; the immunostaining positivity of the neoplastic cells for the neuron-specific enolase allowed us to make the diagnosis of a tumor with a neuroectodermal origin. Partial resection of the neoplasm and four courses of chemotherapy including adriamycin, cisplatin, and ifosfamide induced a complete remission, confirmed by surgical restaging. She is alive and well 10 months after the completion of therapy. The clinical, radiological, and microscopic features of this tumor occurring as a secondary neoplasm after Hodgkin's disease are described.

Adult↗
PubMed1994

Myelodysplastic syndromes in childhood: description of seven cases.

Seven children with a primary myelodysplastic syndrome were seen at our center over a 9-year period. Two presented with refractory anemia, three with refractory anemia with excess of blasts, and two with refractory anemia with excess of blasts in transformation. All children received supportive therapy, including blood transfusions in five of them. Three patients developed acute myeloid leukemia and were treated with intensive chemotherapy, followed by allogeneic or autologous marrow transplantation in the two responders. All three died of either infection or progressive disease. The other four patients are still alive a median of 71 months (range 38-130) after diagnosis. These results confirm the difficulties in managing patients with myelodysplastic syndromes.

Anemia, Refractory↗
PubMed1994

The interferons in haematological malignancies.

Interferons (IFNs) are a family of biological response modifiers with a broad spectrum of action on cellular proliferation as well as immunoregulation. In the last decade, these properties have prompted several investigations of the effect of IFNs on various haematological malignancies. IFNs-alpha have been used most extensively. The response rate is dependent on the type of the disease. The most striking effects have been observed in hairy cell leukaemia and chronic myeloid leukaemia. In both these malignancies the results are well consolidated and indicate that IFNs-alpha have modified the natural history of the disease. Results of IFN therapy in low grade lymphoma, cutaneous T-cell lymphoma and multiple myeloma suggest a beneficial role of IFNs-alpha in the induction, as well as the maintenance, phase. The efficacy of IFNs is now widely confirmed in treating patients with essential thrombocythaemia or polycythaemia vera. However, the role of IFNs in the management of chronic lymphocytic leukaemia and myelofibrosis with myeloid metaplasia is still controversial.

Humans↗
PubMed1994

Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study.

Thrombotic events have been reported in acute lymphoblastic leukaemia patients, especially during or after L-asparaginase administration. A so-called L-asparaginase associated coagulopathy has been well recognized, being characterized by a hypercoagulable state (decrease of antithrombin III, plasminogen, protein C, protein S and increase of prothrombin fragment F1 + 2, thrombin-antithrombin complexes and fibrinopeptide A). The aim of this study was to determine whether the supplementation of antithrombin III (AT-III) concentrates could improve the L-asparaginase associated coagulopathy, thereby blocking the activation of the haemostatic system. In 25 adult patients with acute lymphoblastic leukaemia (M 19, F6, mean age 34 years) antithrombin III (AT-III) concentrates were administered at daily doses of 50 U/kg for 10 consecutive days from the beginning of L-asparaginase therapy (6,000 U/m2/day s.c. for 7 days), given according to the GIMEMA ALL 0288 trial. A marked increase of antithrombin III was recorded on days IV-VIII-XI (P < 0.001). No changes in protein C, protein S, plasminogen, alpha 2-antiplasmin, factor VII and platelet count were observed and there was no increase in markers of hypercoagulability. There was no evidence of disseminated intravascular coagulation. In conclusion, AT-III concentrate supplementation during L-asparaginase therapy, by the achievement of high levels of antithrombin III, is associated with a lack of activation of the haemostatic system and appears to overcome the complex coagulopathy associated with L-asparaginase.

Adolescent↗
PubMed1994

High-dose therapy and autologous bone marrow transplantation for intermediate and high grade non-Hodgkin's lymphoma in patients aged 55 years and over: results from the European Group for Bone Marrow Transplantation. The EBMT Lymphoma Working Party.

The results of high-dose therapy and autologous BMT for patients with intermediate/high grade NHL were analysed in 82 patients aged > or = 55 years, identified from the EBMT lymphoma database. These were compared with the results for 82 patients aged < 55 years who were matched on the basis of disease status at transplantation, presence of bone marrow or CNS involvement and closest date of transplantation. The 5 year actuarial progression-free survival (PFS) for patients aged < 55 years was 33% compared with 37% for the > or = 55 year group (p = 0.08). Corresponding figures for overall survival (OS) were 39% and 38%, respectively (p = 0.19). No difference in outcome was observed according to histological subtype. Although the number of patients receiving total body irradiation (TBI) is small, a significantly lower PFS was observed in patients > or = 55 years receiving TBI-based high-dose regimens compared with younger patients. This difference was due to a higher toxic death rate in the older patient group. In this retrospective matched analysis, age > or = 55 years was not associated with lower PFS or OS following high-dose therapy and autologous BMT. The increased toxic death rate in patients receiving TBI suggests that this should be avoided in older patients, who should receive chemotherapy only high-dose regimens.

Adolescent↗
PubMed1994

Treatment of patients with acute promyelocytic leukemia. The EORTC-LCG experience. EORTC Leukemia Cooperative Group.

Acute promyelocytic leukemia (M3) is, as one of the FAB subtypes of AML, included in the EORTC/GIMEMA AML-8A and 8B randomized trials. In these trials 1519 patients were included, 477 of them in non-Italian EORTC-LCG centers and 1042 in GIMEMA centers. A total of 80 patients were classified as M3 including 18 patients with M3-variant. Thirty-nine were male and 41 female. Ages ranged from 15 to 59 years; 25 (31.3%) of them were younger than 30, 34 (42.5%) between 30 and 45, and 21 (26.3%) older than 45 years of age. 56.3% of the patients had leukocytes less than 5 x 10(9)/l at the time of diagnosis vs. 24.9% of the patients belonging to the other FAB subtypes. Remission induction consisted of a standard protocol with 3 days daunorubicin and 7 days of cytosine arabinoside. Forty-three patients (53.8%) achieved a complete remission compared to 64.6% of the remaining AML patients. After salvage treatment this percentage increased to 70%, which is the same as for the other AML subtypes. Thirteen (16.3%) patients died during remission induction, mainly due to hemorrhagic complications. This percentage is significantly higher than the death rate (9.1%) in the other FAB subtypes of AML. All patients received one course of consolidation treatment. Post consolidation treatment could be either standard maintenance, intensive consolidation courses, autologous or allogeneic transplantation, according to the guidelines of the treatment protocols. At present, relapses almost all in the bone marrow, are seen in only 34.9% of the M3 patients, compared to 48.4% in the remaining AML patients. Disease-free survival for patients less than 45 years of age with the M2 and M3 subtypes was approximately 50% at 3 years compared to 30-40% for the other FAB subtypes. Despite the higher death rate during induction, the long-term survival results were better for M3 patients in comparison with the remaining AML patients. The projected survival at 3 years was 50% for M3 patients vs. 38% for remaining patients.

Adolescent↗
PubMed1994

Acute promyelocytic leukemia in children: experience of the Italian Pediatric Hematology and Oncology Group (AIEOP).

Scanty information is available on acute promyelocytic leukemia (APL) in children, and whether differences are present with respect to the adult form. The experience of the Italian Pediatric Hematology and Oncology Group (AIEOP) will be presented with respect to the following aspects: 1. Incidence of APL. The incidence of APL is generally considered to account for 3-9% of acute myelogenous leukemia (AML) in children and approximately 10-15% in adults. Recently a single Italian pediatric institution reported that APL constituted one third of observed acute nonlymphocytic leukemia (AnLL) cases. Data from the AIEOP cooperative study group have confirmed that APL in Italy is more frequently observed in children as compared to other countries. Environmental and/or genetic factors should be considered to explain such differences. 2. Diagnosis of M3v. The clinical and biological features of the largest series of childhood M3v will be presented and the problems encountered in the proper separation of 'classic' M3 and M3v in children will be discussed. 3. Clinical Aspects. The clinical features of the APL patients enrolled in the AIEOP study groups since 1989, will be presented with emphasis on the recent experience with the use of all-trans retinoic acid. 4. Analysis of PML/RAR alpha Fusion Transcripts. An RT-PCR analysis of 32 pediatric APL cases from cryopreserved bone marrow samples has been performed. It is concluded that APL in children did not differ significantly from the adult form, with the exception of a higher incidence of PML bcr3 breakpoint.

Age Factors↗
PubMed1994

Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical and biological results of two different regimens.

The use of alpha interferon (alpha IFN) and, more recently, of the purine analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has dramatically improved the prognosis of patients affected by hairy cell leukemia (HCL). DCF has been shown to induce an higher and more durable response rate than IFN, with only moderate myelosuppression and relatively few side effects. In this paper, we report our experience with dCF in a series of 38 HCL patients who had progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha (TNF alpha) levels were also evaluated before, both during and after treatment in order to monitor clinical response. Two schedules of treatment were employed: 23 patients were treated with the EORTC protocol and the following 15 with the NCI regimen. The overall response rate was 94.7%; no significant differences in response rates were observed between the two schedules. In respect to toxicity, we recorded nausea and in two cases a cutaneous rash. Four patients experienced localized herpes zoster and one had a fungal pneumonia. Median overall survival after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC schedule and 77% of those who received the NCI program are currently in CCR at 3 years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment, while no significant changes in serum TNF alpha levels were observed. In our study, dCF was confirmed as an effective agent in HCL, inducing an high response rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

HLA typing in hairy cell leukemia.

In HCL patients some cases of familial occurrence of the disease were reported, without an association with a specific haplotype or HLA antigen. In a series of a non familial HCL patients an increase in DR11 frequency was reported. We performed HLA class I and class II antigens in a series of 38 consecutive HCL patients. An increased frequency of B17 (10/38-27%) and DR11 (22/38-57%) antigens compared with the normal Caucasian population was recorded. As clinical characteristics, no significant differences were recognized between DR11 positive and DR11 negative patients. In response to IFN treatment, a complete response (CR) was achieved in 20% of DR11 patients and in 46% of DR11 negative patients. In this study an increase frequency of B17 and DR11 antigens was found; furthermore DR11 positive patients seem to be less responsive to IFN treatment but a larger series of patients will have to be studied in the future in order to establish this observation with more certainty.

Adult↗
PubMed1994

European survey of bone marrow transplantation in acute promyelocytic leukemia (M3). Working Party on Acute Leukemia of the European Cooperative Group for Bone Marrow Transplantation (EMBT).

Acute promyelocytic leukemia (M3) is a distinct subtype of AML considered to have better response to chemotherapy and a higher cure rate than other subtypes. We analyzed the outcome for 362 M3 patients transplanted in Europe from November 1979 to December 1992 and reported to the acute leukemia registry of the European Cooperative Group for Bone Marrow Transplantation (EMBT). Of these 362 patients, 187 received an autograft, 129 in first remission (CR1) and 58 in second remission (CR2), and 175 an allograft, 142 in CR1 and 33 in CR2. Patients autografted in CR1 had at 7 years a leukemia-free survival (LFS) of 48 +/- 5%, a relapse rate (RR) of 41 +/- 5% and a probability of transplant-related mortality (TRM) of 18 +/- 6%. Patients allografted in CR1 had a LFS of 42 +/- 6%, a RR of 28 +/- 5% and a TRM probability of 42 +/- 8%. For patients transplanted in CR2, the respective figures after auto and allotransplantation were: LFS: 31 +/- 7% and 22 +/- 8%, RR: 54 +/- 8% and 64 +/- 11%, TRM: 23 +/- 9% and 40 +/- 9%. These data, which do not permit comparison between autologous and allogeneic BMT, indicate that roughly 45% of M3 patients achieving CR1 may be cured by a marrow transplant. Since the recent use of transretinoic acid-containing induction regimens has increased early control for patients with AML M3, it will be important to find out how these results affect outcome following allogeneic or autologous BMT.

Adolescent↗