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Biomedical subjects

F Zaja

Publications and source records attributed to F Zaja.

At least 55 records · Page 3Linked to original sources
PubMed1996

Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/- radiotherapy) and autologous bone marrow transplantation.

Few series of adult patients with primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma (ALCL) are reported in the literature; most of them have been treated with combination chemotherapy (CHT), with only an occasional patient being autotransplanted, mainly after relapsing. The remission rate ranges from 60% to 90%, but relapses are frequent (up to 60%) and precocious (mainly in the first 24 months). The aim of our study was to analyze the outcome of a series of adult patients affected by primary systemic ALCL that were treated at our institution with a sequential intensive therapeutic program including CHT, radiotherapy (RT), and autologous bone marrow transplantation (ABMT). Sixteen consecutive, unselected patients with ALCL were identified. All of them were treated with the 5-fluorouracil, methotrexate, cytosine arabinoside, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) regimen; 9 of 16 (56.2%) reached a complete remission (CR). In six cases with residual mediastinal disease, involved-field RT was performed, allowing three additional patients to become free of disease. All 16 were then autotransplanted with bone marrow stem cells after conditioning with the cytosine arabinoside, etoposide, cyclophasphamide, and carmustine (BAVC) regimen. A present, 16 of 16 patients are alive and in CR. The actuarial overall survival is 100% at a median of 45.5 months, and the actuarial disease-free survival is 100% at a median of 33.5 months. These data suggest that ALCL can be successfully managed with a sequential intensive treatment (CHT +/- RT + ABMT) that prevents early relapses and projects these patients as long-term survivors.

Adolescent↗
PubMed1996

Neutralizing anti-interferon-alpha antibodies and response to treatment in patients with Ph+ chronic myeloid leukaemia sequentially treated with recombinant (alpha 2a) and lymphoblastoid interferon-alpha.

Neutralizing anti-IFN alpha antibodies (nIFN alpha Abs) occur in a significant proportion of patients with hairy cell leukaemia, hepatitis or solid tumours treated with recombinant IFN alpha (IFN alpha 2a or IFN alpha 2b), but information on their incidence in chronic myeloid leukaemia (CML) is scanty and their clinical relevance is not yet completely defined. By using an IFN alpha antiviral neutralization bioassay, the frequency of nIFN alpha 2a Abs was evaluated in 67Ph+ CML patients during IFN alpha 2a therapy at doses ranging from 6 to 9 MU/d. 15 patients (22%) developed nIFN alpha 2a Abs (titre ranging from 1:40 to 1:20480) and 11/15 (73%) were haematologically and/or karyotypically unresponsive to treatment. 52 patients did not develop antibodies and 11 of them (21%) were unresponsive. The negative relationship between the positivity for nIFN alpha 2a Abs and the response to treatment was highly significant (P = 0.0001). In nine nIFN alpha 2a Abs positive patients, treatment was changed from recombinant IFN alpha 2a to lymphoblastoid IFN alpha (IFN alpha-ly), at the same dose and schedule. After 9 months of IFN alpha-ly treatment a haematological response was achieved in 4/7 cases who were non-responsive to prior IFN alpha 2a therapy and was maintained in the other two patients previously responsive to IFN alpha 2a. However, no karyotypic response was observed. This data shows that a significant proportion of Ph+ CML patients receiving treatment with IFN alpha 2a can develop neutralizing antibodies and that these antibodies are associated with a loss of IFN alpha 2a efficacy. Changing the patients to treatment with lymphoblastoid IFN alpha may restore haematological response but it is not likely to induce a karyotypic response.

Adult↗
PubMed1996

More on false thrombocytopenias: EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect.

We report herein the case of a 54-year-old woman with a moderate bleeding tendency, diagnosed as an EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect. The patient, at the age of 12, had a misleading diagnosis of idiopathic thrombocytopenic purpura and all the recurrent bleeding problems she had during her life were referred to that disease. The recent correct diagnosis of a false thrombocytopenia stimulated further laboratory investigation on the cause of the patient's bleeding tendency with the consequent identification of a congenital platelet deficiency of the arachidonic acid pathway. This finding is of relevant importance for the management of the patient in case of elective surgery or hemorrhagic emergency.

Arachidonic Acid↗
PubMed1995

Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive outpatient population referred for isolated thrombocytopenia.

Among 111 patients referred to our outpatient clinic for isolated thrombocytopenia during a 24-month period, 17 (15.3%) cases of EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) were identified. EDTA-PTCP represented the second most frequent cause of thrombocytopenia in this population. The diagnosis was confirmed by the following findings: (a) normal platelet numbers immediately after blood withdrawal; (b) progressive fall of platelet counts and evident platelet clumping over time, only in EDTA-anticoagulated blood. A simple, inexpensive and quick diagnostic method was devised, that consists in evaluating the platelet number in a blood sample anticoagulated with EDTA immediately after blood withdrawal and 4 h later.

Adult↗
PubMed1995

Granulocyte colony-stimulating factor (G-CSF) allows the delivery of effective doses of CHOP and CVP regimens in non-Hodgkin lymphomas.

The aim of this study was to evaluate the role and potential benefit of G-CSF administered following standard regimen chemotherapy (CHT) in non-Hodgkin lymphomas. Twenty patients with NHL were given CHOP or CHOP/CVP CHT every 21 days. None was given G-CSF after the first cycle. After each cycle, G-CSF was administered only for: 1) ANC < 1 x 10(9)/L between cycles; or 2) delay in cycle schedule due to ANC < 1 x 10(9)/L on the planned day of treatment; or 3) development of a febrile syndrome or a documented infection, regardless the ANC. Once administered, G-CSF was maintained in the following cycles. Nineteen patients required administration of G-CSF (5 micrograms/Kg B.W.), but for different reasons only 16 were treated (a mean of 10 +/- 3 doses/cycle). Comparing 48 cycles where G-CSF was not administered, with 50 where it was, in this last group we observed: 1) a ANC significantly higher at day 7 (p < 0.0001), day 14 (p < 0.0001) and day 21 (p = 0.0030); 2) a significantly lower (p = 0.0001) incidence of neutropenias (6 vs 29); 3) a trend (p = 0.1040) in favour of lower incidence of febrile neutropenias of infections (1 vs 6); 4) a significantly lower (p < 0.0001) incidence of cycle delays (1 vs 22) with a median of 8 days (1 to 20); and 5) a significantly higher (p < 0.0001) dose intensity (99.5% vs 87.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

The role of granulocyte colony-stimulating factor (filgrastim) in maintaining dose intensity during conventional-dose chemotherapy with ABVD in Hodgkin's disease.

BACKGROUND: The aim of the study was to evaluate the role and potential benefit of granulocyte colony-stimulating factor (G-CSF, Filgrastim), administered following cytotoxic chemotherapy with the ABVD regimen in Hodgkin's disease, in maintaining cycle schedule and dose intensity and in decreasing neutropenia and number of infections. PATIENTS AND METHODS: Twenty-two patients affected by high-risk Hodgkin's disease (14 localized and 8 diffuse), aged 15 to 69 years (median, 34), were given ABVD chemotherapy for a total of 6 courses (for the purpose of this study, each single course of chemotherapy was considered as two 15-day periods). No patient was given G-CSF after the first cycle. After each cycle, G-CSF was administered only for: 1)absolute neutrophil count < 1 x 10(9)/L between cycles; 2) delay in cycle schedule due to an absolute neutrophil count < 1 x 10(9)/L on the planned day of treatment; or 3) fever or a documented infection, regardless the absolute neutrophil count. Once administered, G-CSF was maintained in the subsequent cycles. RESULTS: Seventeen of 22 patients (77%) required the administration of G-CSF (5 micrograms/kg b.w.; a median of 5 doses/cycle); most of them (13/17) before the 5th dose of chemotherapy. The main reason for introducing G-CSF into therapy was neutropenia during the interval between courses (n = 4) or on the planned day of treatment (n = 11). Comparing 112 courses where G-CSF was not administered with 124 where it was, in the latter group we observed: 1) a significantly lower (P = 0.0002) incidence of cycle delays (0 vs 13), with a median delay of 7 days (5 to 11). The main reason for cycle delay was neutropenia (n = 13); 2) a greater dose intensity delivered to the patients while on G-CSF (100% vs 95.2 +/- 8.8%; P = 0.0001); 3) an absolute neutrophil count significantly higher at day 8 (P < 0.0001) and day 15 (P < 0.0001); 4) a significantly lower (P = 0.0003) incidence of neutropenia (2 vs. 17). No difference in the incidence of infections was observed between the two groups of cycles (P = 0.5889), but the duration and severity of the same were greater during chemotherapy without G-CSF, requiring antibiotic therapy and causing cycle delay. CONCLUSIONS: In conclusion, our data suggest the use of Filgrastim in Hodgkin's disease also during conventional-dose chemotherapy with ABVD. It is not required from the first dose of therapy, but as soon as neutropenia appears between cycles or on the planned day of treatment. Then, its use allows maintenance of the chemotherapy schedule and dose intensity. It also decreases frequency, duration and severity of neutropenia and its sequelae.

Adolescent↗
PubMed1993

Fludarabine: an active agent in the treatment of previously-treated and untreated low-grade non-Hodgkin's lymphoma.

BACKGROUND: Fludarabine (FLU) is a new antimetabolite chemotherapeutic agent with a promising therapeutic activity in the lymphoproliferative disorders. PATIENTS AND METHODS: We performed a phase II study with this drug in previously untreated and treated patients with resistant and/or relapsed low-grade non-Hodgkin's lymphoma (LG-NHL) to determine its response rate. Twenty-one patients were treated at a dosage of 25 mg/m2 per day for 5 consecutive days. RESULTS: Of the 21 patients, 3 achieved complete responses (CR) and 11 partial responses (PR). In addition, three patients obtained minor responses, and the remaining 4 showed no benefit from the treatment. An increased response rate was achieved in 8 untreated patients in which 3 CR and 3 PR were documented. Furthermore, 4 of the 5 patients showing a leukemic blood picture experienced significant reductions of lymphocyte count and 2 patients with macroglobulinemic lymphomas experienced significant reductions of the IgM monoclonal component from 7.8 and 5.9 g/100 mL to 1.0 and 1.1 g/100 mL, respectively. The toxicity on platelets was negligible. The major toxic effects observed were neutropenia (62%) and infections and/or febrile episodes (19%) that were fatal to only one patient. CONCLUSIONS: In consideration of its significant activity, the role of FLU needs to be further evaluated in the management of pretreated and untreated patients with LG-NHL.

Adult↗
PubMed1993

Fludarabine in patients with advanced and/or resistant B-chronic lymphocytic leukemia.

In this study, we evaluated the efficacy of fludarabine (FLU), an adenine nucleoside analogue, in 35 previously treated patients with advanced and progressed B-cell chronic lymphocytic leukemia (B-CLL) and in 6 at diagnosis. All patients were treated at a dose of 25 mg/m2 per day for 5 consecutive days (mean number of courses was 5, with a range from 4 to 6). The majority of patients experienced a beneficial effect on hematological parameters. In particular, a remarkable reduction of lymphocyte count together with an increase of neutrophils and platelets was observed. The overall response rate was 42% with 1 complete response and 16 partial responses. Ten patients achieved minor responses and the remaining 14 showed no benefit from treatment. An increased response rate was achieved in 6 untreated patients who showed an overall response rate of 67% (4/6). The major complications observed were neutropenia (66%) and febrile episodes (44%) that were generally infection-related and were fatal in 3 cases. Because we were dealing with patients whose disease was advanced and/or resistant to treatment, the overall results may be considered encouraging with acceptable toxic reactions not superior to those frequently observed with polychemotherapy.

Adult↗
PubMedDate not supplied

Magnetic resonance imaging and 67Ga scan versus computed tomography in the staging and in the monitoring of mediastinal malignant lymphoma: a prospective pilot study.

PURPOSE: To assess the potential value of magnetic resonance imaging (MRI) combined with 67Ga single-photon emission computed tomography (SPECT) versus computed tomography (CT) in the staging and in the monitoring of mediastinal malignant lymphoma. MATERIALS AND METHODS: Twenty-three patients, referred to our institute for the evaluation of lymphoma, underwent CT, 67Ga scan, and MRI between April 1993 and February 1996 at sequential intervals. The tests studied (MRI, 67Ga, and CT) were performed according to the following schedule: 1) before start of therapy; 2) after four courses of chemotherapy; and 3) 2, 6, 12, and 18 months after the end of treatment. RESULTS: All patients studied at the time of diagnosis had abnormal gallium accumulation in the mediastinum as well as pathologic CT and pathologic signal intensity at MRI. Six months after the end of treatment full consistency was found between the results of MRI and SPECT, whereas during treatment and 2 months after the end of therapy MRI and 67Ga scan were not in agreement in nine patients. In the 23 patients in follow-up, in CT there were nine false-positive and three false-negative findings; in SPECT three false negatives; in MRI one false positive and one false negative. CONCLUSION: MRI can give morphologic information similar to CT, even superior due to multiplanarity and with major precision in the distinction between fibrosis and active disease. MRI is thus an alternative to CT. The association with SPECT allows a great diagnostic accuracy in the positive and negative predictive value.

Adolescent↗
PubMedDate not supplied

Alpha-interferon as maintenance drug after initial fludarabine therapy for patients with chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma.

BACKGROUND: Fludarabine monophosphate (FLU) is an adenine nucleoside analogue with promising therapeutic activity in lymphoproliferative disorders. In addition, the effectiveness of alpha-interferon (alpha-IFN) in low-grade non-Hodgkin's lymphoma (LG-NHL) and B-cell chronic lymphocytic leukemia (B-CLL) has been demonstrated in several clinical trials. METHODS: In a phase II study of 45 patients with B-CLL and 28 with LG-NHL, we used FLU as second and third-line chemotherapy. Dosages of 25 mg/m2 were given in 30-minute infusions for 5 consecutive days. Treatment was repeated every 28 days depending on patients' clinical status for a maximum of 6 cycles. Entrance in the human lymphoblastoid alpha-IFN maintenance portion of the study depended on response to initial FLU. Following randomization we administered alpha-IFN, or no therapy at all, to patients who obtained a complete or a partial response after FLU therapy. The alpha-IFN dose was 3 x 10(6) U three times per week until disease progression. RESULTS: Twenty-one B-CLL patients achieved major responses, as did 17 of those with LG-NHL. Twenty-four of the former group and 11 of the latter failed to respond or obtained only a minor response. The 38 patients who responded well and entered the second part of the trial showed significant prolongation of remission duration with maintenance alpha-IFN. CONCLUSIONS: In consideration of its significant activity, the role of FLU in the management of lymphoproliferative disorders needs to be evaluated further; at the same time, this preliminary analysis seems to indicate that maintenance alpha-IFN may extend remission duration in B-CLL and LG-NHL.

Adult↗
PubMedDate not supplied

The F-MACHOP regimen in the treatment of aggressive non-Hodgkin's lymphomas: a single center experience in 72 patients.

BACKGROUND: Since July 1991 we have employed the F-MACHOP regimen for the treatment of aggressive non-Hodgkin's lymphomas (NHL). The aim of the present study was to evaluate the response rate and the toxicity of this chemotherapy program. PATIENTS AND METHODS: Seventy-two consecutive patients entered the study and were treated with the F-MACHOP regimen for 6 planned courses, given every 21 days. G- or GM-CSF were administered whenever required. RESULTS: Sixty-six patients (92%) obtained a response: 38 (53%) a complete remission (CR) and 28 (39%) a partial remission (PR); 4 (6%) proved to be resistant and 2 (3%) died of chemotherapy-related toxicity. Fifty-seven patients with a good performance status were subsequently selected to undergo autologous stem cell transplantation (ASCT). During chemotherapy, grade III-IV neutropenia was observed in 59% of the patients; a significant drop in hemoglobin levels was detected, with blood transfusions being required in 21% of the cases; platelet counts were unaffected. The main extrahematological toxic events were: alopecia (100% of the patients), osteoarthromyalgias (58%), grade I-II neuropathy (53%) and grade I-II hepatic toxicity (43%). CONCLUSIONS: Our study confirms the efficacy of the F-MACHOP regimen in obtaining a high rate of response (CR + PR) in most aggressive NHL cases, with an acceptable toxicity and a low rate of toxic deaths. This regimen enables the majority of patients to be selected for ASCT as consolidation therapy without significant toxicity.

Adolescent↗
PubMedDate not supplied

Retrospective analysis of 23 cases with peripheral T-cell lymphoma, unspecified: clinical characteristics and outcome.

BACKGROUND AND OBJECTIVE: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of post-thymic malignancies relatively uncommon in the Western world and their prognosis and therapeutic approach are still not well defined. The aim of this study was to retrospectively analyze the clinical, hematological and histological features at diagnosis, the relevance of the International Prognostic Index and the outcome of a group of 23 patients affected by peripheral T-cell lymphoma, unspecified (PTCL-U), according to the Revised European-American Classification of Lymphoid Neoplasms (REAL), observed between September 1985 and April 1995 at our Institution. METHODS: Patients were separated into different prognostic groups according to Ann Arbor stage, cell size and International Prognostic Index. All patients had been treated with multiagent combination chemotherapy, mainly CHOP (9 cases) and F-MACHOP (9 cases), and were evaluable for response. The treatment was intensified with allogeneic bone marrow transplantation (BMT) in 1 patient and with autologous BMT in 4 patients. RESULTS: Median age was 55 (range 18-77) years and 70% of the patients were males. Four patients were in stage II (17%), 5 in stage III (22%) and 14 in stage IV (61%). Patient risk was classified according to the International Prognostic Index as follows: 8 cases (35%) low risk, 2 cases (9%) low-intermediate, 8 cases (35%) high-intermediate, 5 cases (21%) high. Median follow-up time was 20 months (range 2-132). Median progression-free survival (PFS) and overall survival (OS) for all the patients studied were 10 and 34 months, respectively. Stage IV was associated with a poorer response rate and a shorter PFS (median 6 months) and OS (median 32 months). No statistical correlation was found between cell size and overall response (complete + partial remission), PFS (p = 0.38) or OS (p = 0.59), although a better trend was observed for the large cell group. A less favorable outcome was observed in patients in the high-intermediate + high risk groups, where median PFS and OS were 7 and 24 months, respectively, than in patients in the low + low-intermediate risk groups. No difference in response or outcome was detected between patients treated with the CHOP and the F-MACHOP regimens, while all 5 patients given high-dose chemotherapy and BMT are alive and in CR. INTERPRETATION AND CONCLUSIONS: Our experience shows that PTCL-U are rare lymphomas frequently having an aggressive presentation. The response to conventional polychemotherapeutic regimens like CHOP or F-MACHOP is generally poor, especially in those cases with advanced stage and a high-intermediate or high International Prognostic Index. The observation that all five patients who were treated with bone marrow transplantation are alive and in complete remission suggests using this strategy, particularly in young patients with a poor International Prognostic Index.

Adolescent↗
PubMedDate not supplied

Hepatitis C virus infection among cryoglobulinemic and non-cryoglobulinemic B-cell non-Hodgkin's lymphomas.

BACKGROUND AND OBJECTIVE: Since hepatitis C virus (HCV) infection has been associated with different histotypes of B-cell non-Hodgkin's lymphoma (NHL), with or without concomitant production of cryoglobulins (cryolg), we have investigated the prevalence of the infection among NHL with the aim of defining its relationship with the histotype and with the production of cryolg. METHODS: Four-hundred and seventy unselected, consecutive patients with a diagnosis of B-cell NHL were investigated. Anti-HCV antibodies (Ab) and cryolg were sought in all while HCV RNA and rheumatoid factor were detected on HCV-Ab positive samples. RESULTS: Overall, the prevalence of HCV infection was 8.9% (42/470). It was 95.4% (#21) among the 22 patients with, and 4.6% (#21) among the 448 without production of cryoIg. The most common histotype among the HCV-positive, cryoIg-producing cases, was the immunocytoma (16/21, 76%). Among the HCV-positive, non cryoIg-producing cases, the marginal zone and the follicle center lymphomas were the commonest. INTERPRETATION AND CONCLUSIONS: Close association between HCV infection and cryoIg production, already described in mixed cryoglobulinemia, is confirmed also among B-cell NHL. Nevertheless, 50% of HCV-related lymphomas are non-cryoIg producers. Low-grade lymphomas (in particular the immunocytoma) are the most frequent HCV-related lymphomas. Since new therapeutic strategies might be necessary if the virus is detected, screening for cryoIg and for HCV-Ab among B-cell NHL at diagnosis is mandatory.

Cohort Studies↗