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Biomedical subjects

M Montillo

Publications and source records attributed to M Montillo.

At least 37 records · Page 2Linked to original sources

Two dosage interferon-alpha 2b maintenance therapy in patients affected by low-risk multiple myeloma in plateau phase: a randomized trial.

BACKGROUND AND OBJECTIVE: The role of interferon (IFN) in the remission phase of multiple myeloma (MM) is still an open question, particularly for its scheduling and the subset of patients who could benefit from this approach. The present randomized multicenter study was designed to compare two schedules of IFN maintenance therapy in order to assess the difference in effectiveness and tolerance. DESIGN AND METHODS: This prospective randomized multicenter study was attempted to assess the best schedule of IFN administration in the maintenance treatment of MM in plateau phase with regard to progression free survival (PFS) and toxicity. The second aim was defining the difference between the two schedules in overall survival (OS) and identifying the critical dose of IFN therapy needed to prolong plateau phase and survival. We enrolled 52 patients affected with low-risk MM (i.e. with serum beta 2-microglobulin < 6.0 mg/L and serum albumin > 3.0 g/dL); 27 patients (group A) were randomly assigned to receive IFN alpha-2b 3 megaunits (MU) subcutaneously three times a week and 25 patients (group B) 3 MU/day until disease progression. RESULTS: Median progression free survival (PFS) was 11.9 months in group A and 38.3 months in group B (p = 0.0038). Median survival was 63.2 months in group A and 61.9 months in group B (p = 0.489). However, those patients who were given an IFN dose > or = 30 MU/month experienced a significantly longer PFS and survival than the other patients. Seventeen patients (32.7%) discontinued therapy and sixteen patients (30.8%) reduced IFN alpha-2b dose because of severe side effects without having a significant difference between the two schedules. INTERPRETATION AND CONCLUSIONS: Our results show that patients treated with IFN alpha 3 MU/day had a significantly longer remission duration than patients treated with IFN alpha 3 MU three times weekly. Moreover, an IFN dose is probably critical for obtaining a longer survival in patients affected with low-risk MM. Since the patients' discomfort during a IFN maintenance therapy was frequently experienced the quality of their lives should be carefully taken into account.

Adult↗

Mucormycosis in patients with haematological malignancies: a retrospective clinical study of 37 cases. GIMEMA Infection Program (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto).

A retrospective study of 37 patients with haematological malignancy (21 acute myeloid leukaemia, 11 acute lymphoid leukaemia, two lymphoma, two hairy cell leukaemia, one Hodgkin's disease) and histologically documented mucormycosis was conducted to evaluate the clinical characteristics and ascertain the factors which influenced the outcome from mycotic infection. Patients were admitted to 18 haematology divisions in tertiary care or university hospitals in Italy between 1987 and 1995. Fever, thoracic pain, dyspnoea and cough were the most frequent presenting symptoms. At the onset, 89% patients were neutropenic (neutrophil counts < 0.5 x 10(9)/l) with a median duration of previous neutropenia of 14 d (range 6-60). The most frequent sites of infection were lungs (81%), CNS (27%), sinus (16%), liver (16%) and orbital space (10%). Only three patients were asymptomatic. A correct in vivo diagnosis was made in only 13 (35%) patients. When performed, thoracic and cranial CT scan were the most useful diagnostic investigations. Despite the fact that 26 febrile patients were treated with empirical antifungal treatment, 28 of the 37 patients (76%) died from fungal infection at a median time of 17 d from the onset of clinical symptoms. Nine patients were cured by antifungal therapy plus, in five cases, radical surgery procedures. An analysis of factors influencing outcome demonstrated that the resolution of chemotherapy-induced neutropenia and prolonged treatment with amphotericin B and, if feasible, radical surgical debridement treatment, were significantly correlated with recovery from infection. Mucormycosis, a rare filamentous fungal infection that occurs most frequently in neutropenic acute leukaemia patients, is characterized by a high mortality rate. Extensive and aggressive diagnostic and therapeutic procedures are essential to improve the prognosis in these patients.

Adolescent↗

Treatment of relapsed adult acute lymphoblastic leukemia with fludarabine and cytosine arabinoside followed by granulocyte colony-stimulating factor (FLAG-GCSF).

The aim of the present study was to evaluate the efficacy of the combination of fludarabine 30/mg/m2 + cytarabine 2g/m2 followed by the administration of G-CSF to achieve a complete remission (CR) in patients with relapsed acute lymphoblastic leukemia (ALL). We treated twelve patients in first relapse, overall 10 patients achieved a second CR, one patient showed resistant disease and one patient died during remission induction. The regimen was well tolerated and we observed a short period of neutropenia with a low incidence of myelosuppression-associated problems. Eight patients in second CR received the same chemotherapeutic regimen as consolidation used for the reinduction. In six patients the chemotherapeutic regimen was well tolerated, two patients died, (cerebral hemorrhage in one patient and sepsis in the other). In conclusion the combination of fludarabine, cytarabine and G-CSF has significant antileukemic activity and non hematological toxicities were acceptable. The addition of G-CSF reduced the period of neutropenia obtaining a low incidence of myelosuppression-associated problems.

Adolescent↗

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↗

[Prognostic factors in acute nonlymphoid leukemias].

Our retrospective study was aimed at assessing parameters affecting the prognosis of acute non lymphoid leukemia (ANLL). Since 1988 to 1994 we observed 84 patients: 52 males, 32 females. For each patient we considered at diagnosis: age, fever, performance status, platelets, hemoglobin and white blood cell count, extramidollary disease, bone marrow blastosis, phenotype and cytogenetic abnormalities of blasts cells. All the parameters listed above were correlated with the time to achieve the complete remission (CR), CR duration and the overall survival. Statistical tests as t-student and chi square test were used. Statistical analysis of the parameters considered revealed that the only value affecting the achievement of a CR was the age. The prognostic significance of immunophenotyping in ANLL has been a controversial issue, with a number of conflicting reports. In our study only the terminal deoxynucleotidyl transferase was significantly associated with prognosis. Our study, as data reported in literature, confirms that the prognostic impact of the various parameters in ANLL is controversial. The study of prognostic factors and of the immunophenotype is important to identify the clinical and the biologic profile of the disease and to evaluate the optimal post-remission treatment.

Adult↗

Fatal haemoptysis in pulmonary filamentous mycosis: an underevaluated cause of death in patients with acute leukaemia in haematological complete remission. A retrospective study and review of the literature. Gimema Infection Program (Gruppo Italiano Malattie Ematologiche dell'Adulto)

A retrospective study on a consecutive series of 116 patients affected by acute leukaemia with documented pulmonary filamentous mycosis (FM) admitted between 1987 and 1992 to 14 tertiary-care hospitals in Italy was made in order to evaluate the characteristics of those patients who developed fatal massive haemoptysis. In 59/116 cases of pulmonary FM the infection was the principal cause of death and in 12 of these patients a massive haemoptysis was responsible for death. The diagnosis of FM infection was made ante-mortem in only four out of these 12 patients. The autopsy was performed in 11/12 patients and documented a FM infection. The mycetes isolated were: Hyphomycetes spp. (three patients), Mucorales spp. (two patients), Aspergillus spp. (seven patients). At the time of the massive haemoptysis the mean neutrophil count was 7.2 x 10(9)/l, and no patient had relevant thrombocytopenia (mean 184 x 10(9)/l, range 28-350) or coagulative abnormalities. The mean time which elapsed between resolution of chemotherapy-induced neutropenia (WBC < 10(9)/l) and occurrence of haemoptysis was 7 d. No signs or symptoms predictive of this fatal complication were identified. Massive haemoptysis can be the cause of death in patients with acute leukaemia and pulmonary FM which in the majority of patients was not diagnosed in vivo. This complication occurs most frequently shortly after the recovery from chemotherapy-induced aplasia. The mechanism of lesion is unknown, but it may involve the vascular tropism of FM and the release of leucocyte enzymes. Better preventive and therapeutic antifungal treatments are needed to avoid this serious, albeit rare, complication.

Acute Disease↗

Value of antigen and antibody detection in the serological diagnosis of invasive aspergillosis in patients with hematological malignancies.

In a study to determine the value of antigen and antibody detection in the serological diagnosis of invasive aspergillosis in patients with hematological malignancies, 436 sequential serum samples from 79 neutropenic patients were tested. Circulating galactomannan antigen was detected with a latex agglutination method (Pastorex Aspergillus) and antibody to Aspergillus fumigatus with an immunodiffusion test on agar gel. Among the 79 patients 18 cases of invasive aspergillosis were detected (4 proven, 6 highly probable, 3 probable, 5 suspected). Antigen was detected in 7 of these 18 patients. The sensitivity of the antigen test was 38.8% and the specificity 95%. The antibody test showed 55.5% sensitivity and 100% specificity. In this study the antigen test was less sensitive than previously reported but highly specific and might serve as a supplementary diagnostic test.

Antibodies, Fungal↗

Meningioma-like cerebral relapse of Hodgkin's disease.

A case of Hodgkin's disease with isolated cerebral relapse is reported here. The peculiar presentation features are reported and the difficulties related to the differential diagnosis are discussed.

Antineoplastic Combined Chemotherapy Protocols↗

Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group.

Ninety-seven patients with refractory or relapsed acute myelogenous leukemia (AML), median age 37 years, received as salvage therapy a single course of idarubicin 6 mg/m2 as an intravenous (i.v.) bolus daily for 5 days, cytarabine (Ara-C) 600 mg/m2 i.v. for a period of 2 hours daily for 5 days and etoposide (VP-16) 150 mg/m2 for a period of 2 hours daily for 3 days (ICE protocol). Thirty-six patients were primarily resistant to standard inductive therapy with daunorubicin and Ara-C; 50 patients were in first relapse, three patients in second or third relapse, and eight patients in relapse after transplants. Forty-two (43%) out of 97 patients achieved complete remission, 11 patients died of infection or hemorrhage during induction, and 44 patients (45%) had resistant disease. Of the various variables examined, only disease status (i.e. refractory versus relapsed AML) was predictive for a significantly lower response rate. The median remission duration was 16 weeks; the overall median survival was 10 weeks. Nausea, vomiting, and oral mucositis were common but were rarely severe. No patient experienced treatment-related cardiac toxicity. In conclusion, the ICE protocol is a tolerable regimen providing effective antileukemic activity in patients with advanced AML. The evolution of this protocol in previously untreated patients with AML appears indicated.

Adolescent↗

[Differentiating agents in myelodysplastic syndromes. Analysis of personal cases].

The Myelo-Dysplastic Syndromes are a heterogeneous group of diseases which includes patients with different prognosis. There is no agreement about the management and the therapeutic strategy must be based on many individual parameters, particularly the age of the patients and their performance status. The therapeutic options range from no cytotoxic therapy for low-risk patients up to more aggressive treatment for high-risk patients, with disappointing results except for the very few cases eligible for allogenic bone marrow transplantation. The leukaemic cell can be induced to differentiate, so losing its self-maintenance potential; different drugs such as Interferon, vitamin D3, retinoids and arabinosyl-cytosine (low doses) have shown a differentiating action on myeloid blasts in "vitro". We summarize the general strategy in the treatment of myelo-dysplastic syndromes based on literature data, and on our results about the efficacy and tolerance of a combination of the above mentioned differentiating drugs, in a group of 27 elderly patients affected by myelodysplastic syndrome with poor prognosis. We obtained 14 objective responses (52%), and the median overall survival of these patients have been compared with that of 25 patients with severe myelodysplastic syndrome treated with a conventional regimen. In the 27 patients receiving the differentiating combination the median survival was found to be 14.7 months, versus 8.4 months for the control group. The results obtained are encouraging about the tolerance and the efficacy of this combination in elderly patients with a poor MDS prognosis. Further randomized studies are necessary to establish whether this treatment can really improve the survival in this group of patients.

Aged↗

[Hodgkin's lymphoma and secondary leukemias].

The increase of survival in patients with Hodgkin's disease (HD) has made appear the problem of secondary neoplasms, included acute leukemias. The authors evaluate the incidence of acute leukemias in 205 HD with a follow-up more than 12 months (mean 92 months). With regard to these latter, 18 (8.7%) were treated with radiotherapy alone, 69 (33.6%) with chemotherapy alone and 118 (57.5%) with a combination of radiotherapy and chemotherapy. Chemotherapy consisted of 2-12 courses of MOPP alone or in combination with ABVD. The relative risk of acute leukemias is 96.7 (CI 95%: 44.2-183.6): nine cases against an expectancy of 0.093. The risk changes during five-years periods, but not significantly, and it not declines after ten years from the diagnosis. Only the alkylating chemotherapy seems to be important to favour the onset of acute leukemias. Among the patients who received a number of courses of MOPP less or equal than 6 (177), seven developed an acute leukemia (relative risk 85.3; CI 95%: 34.3-175.9); among those who received more than 6 (9), two developed an acute leukemia (relative risk 333.3; CI 95%: 40.3-1204.1). Neither the addition of radiotherapy nor the stage nor the splenectomy nor the histotype favour the onset of acute leukemia.

Acute Disease↗

[The soluble IL-2 receptor in malignant hemopathies].

The increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease.

Adult↗