Immunological abnormalities in treated hemophiliacs (an Italian study).
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
F Mandelli
Publications and source records attributed to F Mandelli.
Coagulation factor VII. (Biochemistry, role in blood coagulation, methods of assay, congenital deficiencies and relationship with thrombosis).
Factor VII is a trace plasma protein which is very reactive and can be activated through several enzymatic pathways. It has been postulated that factor VII has all the features of an initiator of the clotting mechanism. The severe congenital deficiency of factor VII is characterized by a clinical picture which is not distinguishable from that observed in hemophilias. The presence of factor alpha-VIIa in the circulation in clinical conditions associated with thrombosis leads to the assumption that this factor, when activated, may play an important role in thrombogenesis. The variants of factor VII congenital deficiency and the methods currently employed to assay factor VII in various conditions are reviewed.
Blood Coagulation↗
Sequential combination of methotrexate and L-asparaginase in the treatment of refractory acute leukemia.
Seventy-six patients with advanced acute leukemia refractory to conventional chemotherapy were treated with a sequential combination of methotrexate (MTX) and L-asparaginase (L-ASP), based on the reported schedule-dependent synergism between the two drugs in human leukemic cells in vitro. On Day 1, patients received 60 mg/m2 of MTX iv, followed 24 hours later by L-ASP at a dose of 10,000 IU/m2 iv. This sequence was repeated weekly with 50% escalations in the dose of MTX with each course. Overall, 31 of 76 patients (40.7%) achieved complete remission after a median of three courses; the response rate was 35.5% in patients with acute nonlymphocytic leukemia (21 of 59 patients) and 58.8% in patients with acute lymphocytic leukemia (ten of 17). Increasing the starting dose of MTX to 200 mg/m2 did not improve the response rate. Maintenance therapy with the same combination given every 2 weeks produced a median complete remission of 10 weeks. Toxicity was manifested by: acute hypersensitivity reactions to L-ASP (five patients), stomatitis (36 patients), and mild liver abnormalities (five patients). MTX in doses up to 200 mg/m2 caused minimal myelosuppression. We conclude that the MTX-L-ASP combination is a well-tolerated, highly effective induction regimen for refractory acute leukemia.
Acute Disease↗
The PML/RAR alpha fusion gene in the diagnosis and monitoring of acute promyelocytic leukemia.
The acute promyelocytic leukemia (APL)-specific t(15;17) chromosome abnormality is characterized at the molecular level by rearrangement of the PML and RAR alpha genes, resulting in fusion PML/RAR alpha mRNA and a chimeric protein. Besides its relevance in the pathogenesis of the disease, this hybrid gene represents a specific tumor marker that is rapidly detectable by reverse transcriptase-polymerase chain reaction (RT-PCR) in the RNA extracted from leukemic blasts. Several studies have highlighted the clinical relevance of PML/RAR alpha detection, which provides a specific diagnosis, prognostic information, and prediction of relapse when monitoring residual disease during the follow-up. In fact, this hybrid gene is detected in 100% of APLs. Rare cases of patients with a morphological diagnosis of FAB M3 AML who lack the specific PML/RAR alpha abnormality have been reported as being unresponsive to differentiation treatment. Finally, all the studies reported so far on PCR monitoring in APL have documented that the identification of small amounts of residual disease at remission strongly predicts impending relapse. Thus, RT-PCR of the hybrid PML/RAR alpha gene is currently performed prospectively as part of cooperative clinical trials aimed at better addressing post-remission treatment in APL.
Adolescent↗
Granulocyte colony stimulating factor (G-CSF) as adjunct therapy in relapsed-resistant high-grade non-Hodgkin's lymphoma.
BACKGROUND: Granulocyte colony stimulating factor (G-CSF) safely stimulates the production of neutrophils in normal people and neutropenic patients. Phase II studies have been completed that explored the role of G-CSF in either abrogating or accelerating recovery from chemotherapy-induced neutropenia. METHODS: Fourteen patients with resistant/relapsed high-grade non-Hodgkin's lymphoma were treated with a dexamethasone, cytarabine and cisplatin (DHAP) regimen, and with G-CSF between chemotherapeutic courses. RESULTS: All patients showed a rise in neutrophil count; none was neutropenic when hospitalized for subsequent DHAP courses. Furthermore, the interval between cycles was decreased in 11 of the 14 patients. The overall response rate was 86%, with 4 patients obtaining complete remission. CONCLUSIONS: Administration of G-CSF was associated with an acceleration of neutrophil recovery, indicating its potential to reduce the risk of infection and to maintain planned chemotherapy doses.
Adolescent↗
Prognostic value of bone marrow histology in chronic lymphocytic leukemia. A study of 335 untreated cases from a single institution.
BACKGROUND AND METHODS: A significant correlation between bone marrow (BM) histology, survival and disease progression (DP) probability has been observed by several authors in chronic lymphocytic leukemia (CLL). The prognostic value of BM histologic patterns on survival and disease progression probability was investigated in 335 B-CLL patients. RESULTS: Actuarial survival probability estimated by univariate analysis proved to be significantly influenced by stage (p < 0.0001), BM histology (p = 0.01), and by the following parameters: anemia (p = 0.0005), splenomegaly (p < 0.001), CLL-related symptoms (p < 0.01), thrombocytopenia (p < 0.01), number of involved nodal areas (p = 0.01) and peripheral lymphocyte count over 30 x 10(9)/L (p < 0.05). In this series we did not detect a discriminating prognostic effect for BM histology within the individual stages. Cox multivariate regression analysis failed to demonstrate a significant value for BM histology, while stage and anemia emerged as the best prognostic variables. Actuarial DP free probability in 294 untreated patients with A and B stages was significantly related to stage (p < 0.00001) and to BM pattern (p = 0.01). CONCLUSIONS: Despite the clear correlation between the D pattern of BM involvement and advanced and early progressive disease, we were unable to demonstrate an independent prognostic value for BM histology. These findings suggest that stage emerged as the best predictive factor of survival probability in our B-CLL patients.
Adult↗
Pure red cell aplasia following peripheral stem cell transplantation: complete response to a short course of high-dose recombinant human erythropoietin.
We studied a patient who developed pure red cell aplasia (PRCA) following peripheral stem cell transplantation for non-Hodgkin lymphoma. Serum erythropoietin was appropriate for the degree of anemia. Corticosteroid treatment was ineffective. Four months after transplantation rHuEpo was administered subcutaneously at a dose of 150 U/Kg per day, five days a week for 8 weeks. Treatment induced an erythropoietic response and corrected anemia. Response was maintained following discontinuation of rHuEpo. This study and previous reports indicate that high doses of rHuEpo given over a short time can resolve PRCA following autologous or allogeneic stem cell transplantation.
Dose-Response Relationship, Drug↗
[Platelet transfusions].
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Blood Transfusion↗
[Transfusions of leukocyte concentrates].
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Blood Transfusion↗
Fludarabine and prednisone in pretreated and refractory B-chronic lymphocytic leukemia (B-CLL) in advanced stages.
BACKGROUND: The use of fludarabine, an analog of vidarabine with significant lymphocytolytic activity, has provided encouraging results in the treatment of patients with non Hodgkin's lymphoma (NHL) and sometimes in phase II studies of solid tumors and acute leukemias. Fludarabine has also been shown to be effective in B-CLL. Some studies referred results using fludarabine in high-risk untreated or pretreated CLL patients. METHODS: We report treatment results with fludarabine and prednisone in 22 pretreated B-CLL patients in progressive disease, refractory to CHL and other regimens. RESULTS: One patient obtained a complete response (CR), 8 obtained a partial response (PR). Thirteen failed to respond to treatment. Among the partial responders, 1 patient had fatal pneumonia while neutropenic, another died of disease progression. Among the non responders, 7 died of progressive disease, and 3 evolved into high-grade NHL. Three are still alive in disease progression. CONCLUSIONS: We confirm the effectiveness of fludarabine in pretreated and resistant B-CLL, but in the light of the considerable toxicity observed in this series, we believe that the drug would be better employed as a first-line approach to "younger" untreated B-CLL patients.
Adult↗
Haematological monitoring of acute lymphoblastic leukemia by automated flow cytochemistry (Bayer/Technicon H*1).
UNLABELLED: BACKGROUND AND METHODS. The usefulness of hematological parameters provided by the Technicon H*1 was investigated for the diagnosis of acute lymphoblastic leukemias (ALL) and for the identification of blast cells in peripheral blood samples. RESULTS AND CONCLUSIONS: When automated blast detection was compared with microscopic examination in 62 samples with 4-98% morphologically recognizable lymphoblasts on peripheral blood smears, a false-negative result occurred in 28% (17/62) of the ALL cases. However, in 14 of these 17 false-negative cases the H*1 generated an output listing that would require microscopic evaluation in any event. The H*1 output listing interpretation (based on abnormal leukograms, blast flags and bicytopenia) led us to suspect the presence of ALL in 76% (47/62) of the cases. Three ANLL were recognized as ALL. In three out the 62 ALL, the H*1 output listing interpretation missed identify a leukemic process. In most cases (77%) we noted a characteristic deformation of the mononuclear population profile in the baso/lobularity display, and the cloud of analytical points was shifted toward to the left, in keeping with the presence of a large number of hypodense nuclei.
Adolescent↗
Epidemiology of acute promyelocytic leukemia.
BACKGROUND: The estimated incidence of acute promyelocytic leukemia (APL) is approximately 6 cases per 10 million people per year with no apparent differences between sexes. The age of APL cases is younger than that of other acute myeloid leukemias (AML). Spatial and temporal clusters of APL have been reported. These observations suggest a possible selective role for environmental and/or occupational factors in APL development. METHODS: A multicenter case-control study was carried out on risk factors for acute leukemias and preleukemias. In this report data related to APL are selectively analyzed from the larger study to identify specific risk factors. RESULTS: The case-control study on 38 cases of APL showed a strong association with shoemaking (odds ration 6.3, 95% confidence interval 1.3-31.1). A moderate leukemogenic effect from living in houses built with tuff, a polous building material containing gamma-emitting radionuclides and having a high radon concentration, and from using hair dyes was also suggested. CONCLUSIONS: These data, together with the reported spatial and temporal clustering of APL, support the hypothesis of specific environmental and/or occupational risk factors for APL among other AML subtypes and indicate the need for additional ad hoc multicenter studies.
Adolescent↗
Long-term results of treatment of childhood and adolescent Hodgkin's disease in 73 patients: the experience of the Departments of Radiology and Hematology of the University of Rome "La Sapienza".
PURPOSE: Various experiences show no substantial differences between children and adults in the treatment of Hodgkin's disease. In consideration of some peculiar characteristics of these cases which might influence the therapeutical choice, particularly regarding long-term survival and therapeutical complications, we report the results of a series of 73 children and adolescents with Hodgkin's disease treated at the University of Rome "La Sapienza". METHODS: Between 1976 and 1983, 73 untreated pediatric cases of stage I-IV Hodgkin's disease were treated with radiotherapy, alone or associated with chemotherapy, using high doses and extended fields. RESULTS: Fifty-six patients (77%) were in continuous complete remission in April 1995 and seventeen (23%) had died. CONCLUSIONS: The authors confirm the excellent results in the treatment of pediatric Hodgkin's disease, both in terms of overall and relapse free survival, in spite of a high incidence of complications caused by the aggressive treatment used in this series. Therefore the majority of authors suggest combined alternating low-dose radiation administered with small portals and short-term chemotherapy. These procedures provide optimal results together with a significant reduction of complications. Consequently, it is very important to evaluate all patient characteristics accurately in order to tailor optimal treatment and select cases with risk factors which might be undertreated and therefore undergo a higher risk of recurrence.
Adolescent↗
Analysis of the risk of solid tumor following Hodgkin's disease.
BACKGROUND AND OBJECTIVE: This study examines the occurrence of solid tumor (ST) in relation to the different types of therapy (radiotherapy, chemotherapy and radiochemotherapy; splenectomy or splenic irradiation vs no splenectomy-no splenic irradiation) received by patients treated for Hodgkin's disease (HD). METHODS: The study included 1,045 HD patients treated at the Department of Radiation Oncology, the Institute of Radiology and the Department of Human Biopathology, Hematology Section, University of Rome, "La Sapienza", from 1972 to 1992. For 23% of the patients the follow-up period was longer than 10 years. The average follow-up period was 72 months. For a more accurate calculation of the risk of ST occurrence, the patients were first divided into 3 subgroups according to initial treatment and then according to the total treatment they had received. Moreover, to establish a probable connection between solid tumor and splenic treatment the patients were also divided into 3 subgroups (splenectomy, splenic irradiation and no splenectomy/no splenic irradiation). RESULTS: We recorded twenty-four cases of ST after initial treatment. Secondary solid tumor showed a cumulative risk of 0.2% and 13.4% at 5 and 20 years, respectively. After initial treatment with radiotherapy (RT) alone, the cumulative risk was 1.7% and 5.2% at 10 and 20 years, respectively; in the chemotherapy (CT) group, it was 2.4% and 18.1%; in the CT(+)RT group, it was 1.7% and 9%. No statistically significant differences were observed among the different types of treatment (splenectomy, splenic irradiation or no splenectomy/no splenic irradiation) as regards the occurrence of ST. According to multivariate analysis, the most important factor in the risk of ST was age (> 40). Relative risk was 5.2, p = 0.0001. INTERPRETATION AND CONCLUSIONS: We conclude that an age of over 40 at diagnosis and treatment with CT alone greatly increase the risk of solid tumor occurrence.
Adolescent↗
Use of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with hydroxyurea as post-transplant therapy in chronic myelogenous leukemia patients autografted with unmanipulated hematopoietic cells.
BACKGROUND AND OBJECTIVE: Allogeneic bone marrow transplantation remains the only potentially curative treatment for CML, but more than 70% of patients will be ineligible for allogeneic marrow transplant either because they do not have a suitable HLA-matched related or unrelated donor or because they are more than 50 years old. Several experimental and clinical findings support a role for autologous stem cell transplantation (ASCT) in CML. It has been suggested that in the early phase following autografting the Ph-negative clone has a proliferative advantage over the Ph-positive clone. We hypothesized that post-transplant GM-CSF administration could reactivate the functional activity of quiescent normal progenitors and prolong the duration of the post-transplant proliferative advantage of Ph-negative over Ph-positive progenitors. In order to evaluate the effect of post-transplant GM-CSF administration, a pilot clinical study was performed in which CML patients resistant to IFN-alpha therapy were autografted with unmanipulated marrow or blood cells and given prolonged GM-CSF therapy post-transplant. METHODS: Five adult CML patients conditioned with the BAVC regimen were reinfused with either marrow (n = 2) or blood (n = 3) cells and given granulocyte-macrophage colony-stimulating factor (GM-CSF). Recombinant GM-CSF was initially administered at standard dosage (5 micrograms/kg/day) until a white blood cell count > or = 2 x 10(9)/L was achieved on two consecutive examinations, and thereafter at a low dose (1 microgram/kg/day) for 5 to 9 months. On a weekly basis, GM-CSF was discontinued and hydroxyurea (1,000 mg/d) was given for two days. RESULTS: Evidence of trilineage engraftment was observed in all cases. At autografting, 3 out of the 5 patients revealed 8-9% Ph-negative metaphases. During the initial phase of hematopoietic regeneration, direct cytogenetic analysis revealed 81% and 100% Ph-negative metaphases in two cases; nonleukemic hematopoiesis progressively decreased and was no longer detectable at +9 months. One patient showed cyclic Ph-negative hematopoiesis that appeared 3 months following autografting and peaked at +4 and +8 months. The fourth patient showed a low percentage (20%) of Ph-negative metaphases 1 month after ASCT, followed by a significant expansion of nonleukemic hematopoiesis, which could be detected up to month +13. No evidence of Ph-negative hematopoiesis could be detected in one patient. Three patients are in chronic phase 28, 30 and 31 months after autografting, respectively, and two patients evolved into blast crisis. INTERPRETATION AND CONCLUSIONS: This pilot study demonstrates that combined GM-CSF and hydroxyurea therapy seems to be effective in inducing and/or prolonging a transient period of Ph-negative hematopoiesis. The late appearance of Ph-negative hematopoiesis detected in two patients suggests an antileukemic activity of the combined GM-CSF/hydroxyurea therapy rather than an antileukemic effect of the conditioning regimen.
Adult↗
Hematopoiesis and growth factors in elderly cancer patients.
Hemopoietic Growth Factors (GF) are glycoprotein hormones that regulate the proliferation and differentiation of hematopoietic progenitor cells and of mature blood cell function. In last years GFs have moved from the laboratory study to the clinical area, and most of them have been produced on a large scale through recombinant DNA technology. Hemopoiesis and GF sensitivity of marrow cells declines with age, impairing the ability of elderly people to increase the production of GFs under stress conditions. In elderly cancer patients chemotherapy-associated neutropenia very frequently causes fever or infection with dose delay and increased morbidity and mortality rate, therefore in this setting beneficial effects of adjunct treatment with GFs have been proposed. Since reduction in neutropenia and in the risk of infection does not necessarily result in improved remission rate and long-term survival, some recommendations on the use (or abuse) of GFs are reviewed in this paper.
Aged↗
A single high dose of idarubicin combined with high-dose ABA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University La Sapienza of Rome.
BACKGROUND AND OBJECTIVE: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance. METHODS: In a clinical phase II study the combination of a single high dose (HD) idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L). RESULTS: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections. INTERPRETATION AND CONCLUSIONS: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD- ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
Adolescent↗
A single high dose of idarubicin combined with high-dose ARA-C (MSKCC ALL-3 protocol) in adult and pediatric patients with acute lymphoblastic leukemia. Experience at the University "La Sapienza" of Rome.
BACKGROUND AND OBJECTIVE: The anthracycline analogue idarubicin, either alone or in combination with other antineoplastic drugs, has shown antileukemic activity in relapsed and refractory acute lymphoblastic leukemia (ALL). In an attempt to minimize the non-hematologic toxicity and obtain a potent antileukemic effect, MSKCC activated a pilot study in previously treated adult ALL, using HD-ARA-C combined with idarubicin administered as a single high-dose infusion. We herein report our experience with a series of pediatric and adult high risk ALL and NHL patients treated with the protocol above, which confirms its feasibility, response rate and individual compliance. METHODS: In a clinical phase II study, the combination of a single high dose (HD) of idarubicin and HD cytosine-arabinoside (ARA-C), as designed at the Memorial Sloan Kettering Cancer Center, was applied to 70 adults and children with refractory or early relapse acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic non-Hodgkin's lymphoma (NHL). Therapy consisted of HD-ARA-C 3 g/m2/d on days 1-5, idarubicin 40 mg/m2 on day 3, prophylactic intrathecal methotrexate on days 1 and 4, and G-CSF 5 mg/kg/d s.c. from day 7 to hematopoietic reconstitution (PMN > 0.5 x 10(9)/L). RESULTS: Fifty-five of the 70 patients (78%) achieved complete remission (CR), four died in aplasia due to infection and 11 were non-responders. Recovery of blood counts occurred at a median of 21 days from the start of treatment. Non-hematologic side effects were extremely limited and consisted predominantly of infections. INTERPRETATION AND CONCLUSIONS: In view of the highly unfavorable series of patients selected, this study confirms the feasibility and antileukemic activity of the HD-idarubicin + HD-ARA-C combination in patients with refractory and early relapse ALL and NHL. The excellent tolerance to this regimen does not preclude bone marrow transplantation as post-remission treatment.
Adolescent↗