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Biomedical subjects

G Meloni

Publications and source records attributed to G Meloni.

At least 109 records · Page 6Linked to original sources
PubMed1992

Use of recombinant human granulocyte-macrophage colony-stimulating factor in patients with lymphoid malignancies transplanted with unpurged or adjusted-dose mafosfamide-purged autologous marrow.

The neutropenia-related morbidity and mortality occurring after autologous bone marrow transplantation (ABMT) is increased by marrow purging procedures. While phase I through III clinical trials showed the enhancing activity of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on neutrophil recovery after ABMT with unpurged marrow, controversial results have been reported when purged marrow was used. Therefore, it was the aim of the present study to evaluate the efficacy of rhGM-CSF administration in a group of patients (n = 15) with lymphoid malignancies transplanted in complete remission with mafosfamide-purged (n = 10) or unpurged (n = 5) marrow. Mafosfamide concentrations used for marrow purging were evaluated on an individual basis by means of a recently described technique that destroys the granulocyte-macrophage (granulocyte-macrophage colony-forming units [CFU-GM]) compartment, but spares 50% of the more primitive stroma adherent colony-forming cells (CFU-Blast). rhGM-CSF (10 micrograms/kg/d) was started within 24 hours of ABMT and administered in a 4-hour infusion daily until the absolute neutrophil count (ANC) reached 500 x 10(6)/L and then for 7 more days. Patients receiving mafosfamide-purged or unpurged marrow failed to show any difference in terms of median number of days required to achieve an ANC > or = 500 x 10(6) (13 v 14.0, P > .4) cells/L. As compared with retrospective controls, granulocytic recovery was reduced by a median time of 11 (P < or = .0005) and 5 (P < or = .0005) days for patients grafted with purged and unpurged marrow, respectively. The number of CFU-GM (mean +/- SD) infused per kilogram of body weight was significantly lower in patients who received purged autografts as compared with those receiving unpurged autografts (0.85 +/- 0.79 x 10(4) v 15.7 +/- 9.2 x 10(4), P < or = .0005). The dose of CFU-GM progenitors infused per kilogram of body weight did not correlate (r = .031, P > .05) with the time required to reach an ANC > or = 500 x 10(6) cells/L. The number of CFU-Blast (mean +/- SD) infused per kilogram of body weight was not significantly different between patients who received purged or unpurged autografts (5.05 +/- 2.51 x 10(3)/kg v 6.18 +/- 2.66 x 10(3)/kg, P < or = .375). A statistically significant correlation (r = -.658, P < or = .05) was observed between the number of CFU-Blast infused and the number of days required to reach an ANC > or = 500 x 10(6) cells/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Pretransplant conditioning with busulfan and cyclophosphamide in acute leukemia patients: neurological and electroencephalographic prospective study.

A neurological and electroencephalographic (EEG) prospective study was performed in 34 leukemic patients receiving busulfan (BU) plus cyclophosphamide (CY) before bone marrow autologous transplant. During BU treatment and briefly thereafter, all patients were given anticonvulsant prophylaxis with phenobarbital. Neurological evaluations were performed daily and EEGs, recorded one week before and soon after the end of the BU regimen, were re-evaluated two months later. Basal EEGs were normal in 23 of the 34 patients, focal abnormalities were detected in 9 cases, and generalized epileptic discharges were present in one (one subject was not studied). EEGs performed at the end of BU administration showed generalized spike/polyspike-and-wave discharges in 21 of the 34 patients, with associated myoclonic epilepsy in 10 subjects appearing on the 3rd or 4th day of treatment. Focal abnormalities were present in 6 patients and constant EEG normality in 7. It is known that myoclonic epilepsy can be induced by drugs. Oral administration of high-dose BU is followed by a high-dose cerebrospinal fluid concentration of the drug. Therefore, myoclonic epilepsy and/or paroxysmal epileptiform EEG discharges may be observed in leukemic patients undergoing high-dose BU therapy.

Acute Disease↗
PubMed1992

Treatment of primary refractory or relapsed acute lymphoblastic leukemia (ALL) in children.

Thirty-one intensively pretreated children with ALL in first bone marrow relapse or refractory to initial therapy were treated with a combination of intermediate-dose Ara-C and idarubicin (IDA). Twenty-four patients (77%) achieved complete remission (CR), 8 patients relapsed early and 2 were removed from the study. Fourteen (45% of the original 31 patients) underwent bone marrow transplant (BMT) and 7 of them (22%) are still in continuous CR (CCR) with a median follow-up of 18 months. These results confirm that it is possible to achieve CR even in ALL children who failed on an initial intensive regimen. Newer modalities of post-remission therapy, especially for children lacking an HLA donor, should be considered.

Adolescent↗
PubMed1992

Has IL2 a role in the management of minimal residual disease for acute leukemia?

Based on pre-clinical findings and on more recent preliminary in vivo data it has been suggested that immunotherapy with Interleukin 2 (IL2) may be employed in the treatment of acute leukemia patients. Here we shall discuss the biological and clinical observations which indicate that this innovative therapeutic approach may play a role in the management of minimal residual disease.

Acute Disease↗
PubMed1992

Early deaths in children after BMT. Bone Marrow Transplantation Group of the Italian Association for Pediatric Hematology and Oncology (AIEOP) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

In order to determine the incidence and causes of death during the first 100 days after BMT (early deaths) in a pediatric population we have examined data reported in the AIEOP BMT Registry. Up to July 1990, data on 486 children who underwent allogeneic (180) or autologous (306) BMT were evaluable. The children had acute lymphoblastic leukemia (148 cases), acute non-lymphoblastic leukemia (127 cases), neuroblastoma (82 cases), chronic myelogenous leukemia (15 cases), aplastic anemia (nine cases), solid tumors, lymphoma, immunodeficiency or storage diseases. The overall survival is 55% for allogeneic HLA matched and 38% for autologous transplants at 5 years, 24% for HLA mismatched graft at 2 years. Out of the 486 children, 70 (14%) died during the first 100 days after BMT: 33/306 (11%) after autologous BMT, 24/150 (16%) after allogeneic matched BMT and 13/30 (43%) after mismatched BMT. Causes of early death were as follows: disease progression: 12 children (10/306 after autologous and 2/180 after allogeneic BMT); infection: 12 children (five after autologous and seven after allogeneic BMT); interstitial pneumonitis: 21 children (seven after autologous and 14 after allogeneic BMT); cardiac failure: five children (four after autologous BMT); veno-occlusive disease: eight children (three after autologous, five after allogeneic BMT); acute renal failure: three children (one after autologous and two after allogeneic BMT); multiple organ failure: two cases (one after autologous BMT); cerebral hemorrhage: three children (one after autologous BMT); hypertension: one child; acute GVHD: three children (12% of early deaths after allogeneic BMT).

Adolescent↗
PubMed1992

Interleukin 2 (IL2) in the management of acute myeloid leukemia: clinical and biological findings.

In this paper we review some of the preclinical findings which have led us to believe that immunotherapy with interleukin 2 (IL2)/lymphokine activated killer (LAK) cells may be a feasible approach in the management of acute myeloid leukemia. The main clinical and biological results so far obtained with IL2 treatment, and the currently ongoing protocols and strategies are discussed.

Acute Disease↗
PubMed1992

Autologous bone marrow transplantation followed by interleukin-2 in children with advanced leukemia: a pilot study.

In an attempt to prolong disease-free survival in children with acute leukemia, we tested the feasibility of interleukin-2 (IL-2) administration after an autologous bone marrow transplantation (ABMT). We report the clinical and biological data obtained in three children with acute myelocytic leukemia (AML) in second complete remission (CR) and in seven children with acute lymphocytic leukemia (ALL) in second or subsequent CR, who received IL-2 at a median interval of 78 days (range 38-125) from ABMT. Patients were treated with 1-2 cycles of IL-2 given by continuous infusion over a 5-day period using a daily escalating protocol, from 100 micrograms/m2 per day to the maximum tolerated dose, followed after 3 weeks by low-dose IL-2 for 5 days monthly over a 6-h infusion on an out-patient basis. Side effects greater than grade 2 (WHO system), consisting of thrombocytopenia, fever, cutaneous rash, nausea and vomiting, diarrhoea were common during the high-dose IL-2 cycles, but resolved 24-48 h after stopping IL-2. Only one patient developed liver toxicity (grade 3, WHO) on day +3 of the first cycle which prompted us to stop the administration of IL-2. An increase in lymphocytes and eosinophils was also observed. IL-2 treatment was followed by a normalization of NK function and by the generation of a high proportion of endogenous LAK cells. All seven ALL patients relapsed at a median of 5 months (range 1-23). Two AML patients relapsed at 1 and 11 months, while the other is still in continuous CR at 23 months after IL-2 treatment. Our IL-2 schedule for treatment of leukemia in children after ABMT is thus feasible but its efficacy requires further investigation.

Adolescent↗
PubMed1991

Peripheral blood and bone marrow immunophenotypic and functional modifications induced in acute leukemia patients treated with interleukin 2: evidence of in vivo lymphokine activated killer cell generation.

The effect of treatment with interleukin 2 (IL2) on the phenotypic and functional immune system of acute leukemia patients was investigated. Fifteen acute myeloid leukemia and acute lymphoid leukemia patients with evidence of persistent disease were further subdivided into two groups according to the percentage of bone marrow (BM) blasts: group a had 6-15% blasts and group b had 30-65%. Following two cycles of IL2 (Glaxo Imb, Geneva, Switzerland) given i.v. by continuous infusion at escalating doses, no major changes in the proportion of CD3-, CD4-, and CD8-positive cells were encountered in the blood or in the marrow of either group of patients. When these could be retested after four cycles of IL2, a significant increase of CD3+ and CD4+ cells was documented in the peripheral blood (PB), as well as a significant increase of CD3+ cells in the BM. Irrespective of the number of cycles administered, the proportion of CD16+ cells increased significantly in the blood in both groups of patients and in the marrow of group a patients only. The expression of CD25 was significantly enhanced in all samples tested. Following IL2 administration, an enhancement of the natural killer compartment was documented. This was consistently more evident in patients with more limited disease. A significant amplification of the in vitro-induced lymphokine-activated killer function was noted in the BM of the treated patients. Furthermore, we documented the presence both in the PB and in the BM of "spontaneous" lymphokine-activated killer cells generated in vivo following IL2 administration. These results demonstrate that in acute leukemia of both myeloid and lymphoid origin, treatment with IL2 is capable of inducing profound immunophenotypic and functional modifications in PB and in BM lymphocytes, particularly in patients with more limited disease. The evidence of the in vivo activation of cytotoxic cells, particularly in the BM, may help to explain the clinical responses preliminarily observed in individual acute leukemia patients.

Acute Disease↗
PubMed1991

Fluconazole treatment of Blastoschizomyces capitatus meningitis in an allogeneic bone marrow recipient.

The first known case of Blastoschizomyces capitatus meningitis occurring in an allogeneic bone marrow recipient on steroid and cyclosporine therapy for chronic graft-versus-host disease is reported. An 11-month course of treatment with oral fluconazole resulted in resolution of the meningeal syndrome and eradication of Blastoschizomyces capitatus from the cerebrospinal fluid. Three months after discontinuation of fluconazole the patient died due to idiopathic interstitial pneumonia and bilateral pneumothorax, without clinical signs of meningitis. Post mortem examination showed meningeal fungus invasion consistent with Blastoschizomyces capitatus infection. Oral fluconazole treatment thus did not eradicate the fungal infection, but achieved significant control of the meningitis on an outpatient basis.

Adolescent↗
PubMed1991

Treatment of acute myeloid leukaemia patients with recombinant interleukin 2: a pilot study.

Twelve patients with acute myeloid leukaemia (AML) with evidence of resistant disease were treated with recombinant interleukin 2 (rIL2) given intravenously by continuous infusion. No objective response to rIL2 alone was documented in the seven patients with advanced disease (20-90% resistant blasts in the marrow), except for a partial response to rIL2 plus chemotherapy in one. Of the five patients with limited disease (8-15% marrow blasts), three obtained a complete disappearance of the blasts following two to four 5d courses of rIL2 alone. One patient persists in fourth complete remission (CR) 30 months later, another obtained a third CR for 4 months, and the last remained in third CR for 9 months before relapsing. This latter patient achieved a fourth CR with low-dose cytarabine. The remissions have been maintained with low-dose monthly courses of rIL2 given on an out-patient basis. Two AML did not respond to rIL2 alone; one, however, obtained a fourth CR with chemotherapy and rIL2. Administration of rIL2 was accompanied by organomegaly and leucocytosis, with a frequent lymphocytosis and increase in eosinophils and large granular lymphocytes, both in the blood and in the marrow. Side effects, though often severe, were controllable using a daily dose escalating protocol and never required intensive care treatment. The results of this pilot study indicate that treatment of AML patients with rIL2 is feasible and may result in the disappearance of chemotherapy-resistant blasts in patients with limited but detectable disease. Further controlled trials in AML in CR appear warranted.

Acute Disease↗
PubMed1991

Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia.

Thirty-two patients with refractory acute myeloid leukemia (AML) received salvage therapy with a single course of mitoxantrone 6 mg/m2 intravenous (IV) bolus, etoposide 80 mg/m2 IV for a period of 1 hour, and cytarabine (Ara-C) 1 g/m2 IV for a period of 6 hours daily for 6 days (MEC). Eighteen patients were primarily resistant to conventional daunorubicin and Ara-C induction treatment; eight patients had relapsed within 6 months from initial remission; six patients had relapsed after a bone marrow transplantation (BMT) procedure. Overall, 21 patients (66%) achieved a complete remission (CR), two (6%) died of infection during induction, and nine (28%) had resistant disease. Age greater than 50 years was the only factor predictive for a significantly lower response rate (P = .03). The median remission duration was 16 weeks; the overall median survival was 36 weeks. Severe myelosuppression was observed in all patients resulting in fever or documented infections in 91% of patients. Nonhematologic toxicity was minimal. We conclude that the MEC regimen has significant antileukemic activity and acceptable toxicity in salvage AML. Its benefit in front-line AML therapy is being investigated.

Adolescent↗