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G Capnist

Publications and source records attributed to G Capnist.

At least 19 recordsLinked to original sources

Long-term results of alpha interferon as initial therapy and splenectomy as consolidation therapy in patients with hairy cell leukemia. Final report from the Italian Cooperative Group for HCL.

PURPOSE: In 1987 the Italian Cooperative Group for the Study of hairy cell leukemia (HCL) started a prospective trial with the following three major aims: 1) to confirm the effectiveness of alpha-IFN as first-line treatment; 2) to assess the usefulness of splenectomy as consolidation treatment in patients achieving a satisfactory partial remission (PR) with alpha-IFN, and 3) to explore whether splenectomy in patients achieving complete remission (CR) with alpha-IFN can reduce the risk of relapse after discontinuation of the drug. PATIENTS AND METHODS: One-hundred seventy-seven patients with histologically-confirmed HCL were registered in the HCL88-A trial between December 1987 and January 1992. Inclusion criteria included no previous treatment and age less than 66 years. All patients received total doses of 3 MU of alpha-IFN daily for 12 months except for those who achieved early CR and would stop treatment after 6 or 9 months. Patients could be treated with different alpha-IFNs. At the time of the present analysis, 166 patients (93.8%) were fully evaluable. RESULTS: Treatment of HCL patients with alpha-IFN at the onset of the disease resulted in 28 CR (16.9%), 103 PR (62.0%), and 27 Minor Remissions (MR) (16.3%). Patients treated with different alpha-IFNs achieved similar results: the overall response rate (CR + PR + MR) was 92.7%, 97.2%, and 95.3% for patients treated with r-alpha-2a, r-alpha 2b, and alpha-N1, respectively. The presence of a leukemic phase and a poor performance status were associated with a statistically significant lower response rate. Patients who were randomly assigned and underwent splenectomy after achieving a PR had a better but not significant 4-year progression-free survival than cases randomized for observation (53% vs. 22%, p = 0.116). Overall, 5 patients died after study entry, with an actuarial 5-year survival rate of 96% for the entire group of 166 patients. After a mean follow-up time of 38 months, only one second malignancy has been recorded. CONCLUSIONS: Initial therapy with alpha-IFN, regardless of the type of alpha-IFN used, induces satisfactory responses in the majority of patients with HCL, but in most instances discontinuation of treatment results in recurrence of disease. In most cases alpha-IFN improves the performance status of patients and favors a satisfactory bone marrow recovery and thus could still play a role in the initial management of the disease. Although splenectomy following alpha-IFN could prolong the progression free survival, its use should be restricted to selected cases.

Adult↗

Impact of interferon at induction chemotherapy and maintenance treatment for multiple myeloma. Preliminary results of a multicenter study by the Italian non-Hodgkin's Lymphoma Cooperative Study Group (NHLCSG).

In 1990 the Italian Non-Hodgkin's Lymphoma Cooperative Study Group (NHLSG) started a multicenter study on the role of interferon (IFN) in multiple myeloma (MM). The schedule of treatment was based on the assumption that melphalan plus prednisone (MP) would be better for good-prognosis patients, whereas poor-prognosis patients would benefit from polychemotherapy. Accordingly, IFN was included randomly for the induction treatment of good-prognosis patients and randomly as maintenance of the response achieved in both groups. Up to now 78 patients of the 124 enrolled have completed the induction treatment and are evaluable for response and response duration. The overall response rate was 59%. Sixty-two percent of good-prognosis patients obtained objective response, 9/14 (64%) with MP and 9/15 (60%) with MP+IFN. Up to now, with a median follow-up of 9 months from the evaluation of response, no difference has been recorded between the maintenance and no maintenance groups on relapse rate, neither in good- nor in poor-prognosis patients.

Aged↗

Long term results of interferon treatment in hairy cell leukemia. Italian Cooperative Group of Hairy Cell Leukemia (ICGHCL).

Eighty nine of 104 patients with hairy cell leukemia (HCL), enrolled between 1985 and 1987 in a multicenter prospective study on human lymphoblastoid IFN alpha-n1, were evaluable for long-term follow-up. The induction treatment, 3 MU/mq daily for a median of 5.7 months, produced a response of 93%, complete+partial response (CR+PR) = 80%, minor (MR) = 13%. Neither prior splenectomy nor pre-treatment variables were associated with the rate of response to IFN. However maintenance treatment of 3 MU/mq weekly given randomly had a slightly significant effect on failure free survival (FFS). Of the 43 patients who relapsed, 31/36 (86%) obtained a new response with IFN. No differences in FFS were recorded between first and second response. At the third induction 7/11 patients were treated again with IFN, 4/7 obtaining some response, but the FFS was significantly worse. The overall survival is still 85%. We conclude that (1) IFN should be used as chronic uninterrupted treatment for HCL, (2) reduced dosage is sufficient to prolong the disease free status and (3) continuous lymphoblastoid IFN administration seems not to be associated with the development of resistance to retreatment.

Aged↗

Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Registry for hairy cell leukemia (HCL) has recorded 725 patients with HCL diagnosed over 25 years. We analysed this large series of patients with the aim of providing an evaluation of changes in clinical presentation, impact of initial therapy and modifications in prognostic factors over the period of two decades. Over time, a progressive down-staging of the disease at the onset, along with a reduction of patients with severe anemia and marked splenomegaly, has been observed. A second malignancy was found in 3.7% of patients, mostly detected several years after the onset of HCL. A striking improvement of survival rates has been observed, from 58.9% survival at five years for patients diagnosed before 1985 to 87.5% at five years for patients diagnosed after 1985 (p < 0.0001). Before 1985 hemoglobin alone provided prognostic information, whereas after 1985, clinical stage and the number of leukocytes correlated better with patient outcome. Survivals at 5 and 10 years were 34.4% and 29.6% respectively for untreated patients, 58.8% and 44.1% for patients receiving chemotherapy, steroids or other drugs, 64.1% and 56.1% for splenectomized patients and 88.9% (at 5 years) for alpha interferon (IFN)-treated patients (p < 0.0001). Our findings suggest that IFN has improved the prognosis of HCL, and that it must be considered a good initial treatment for patients with HCL.

Adult↗

Should alpha interferon be used as primary treatment for hairy cell leukemia? Italian Cooperative Group for Hairy Cell Leukemia.

To answer the question of whether interferon (IFN) should replace splenectomy, we reviewed the Italian HCL Registry: the records of 450 patients with hairy cell leukemia (HCL), seen from 1975 to 1988 were analysed. Of these, 321 were considered for the study: 231 had been splenectomized, 46 of them receiving subsequently IFN and 90 patients had IFN as initial therapy. Patients treated with splenectomy showed different survival according to Jansen and Hermans' staging system, which identified two risk groups: stage 1 and stages 2 and 3, p = 0.0329. On the contrary, patients treated with IFN did not show significantly different survival according to stage. By the comparison of stage 1 patients, either treated with splenectomy or with IFN, no statistical difference in survival was registered. Different survivals emerged for patients stage 2 + 3, which improved when treated with IFN, p = 0.0324. The median failure free survival (FFS) after splenectomy resulted in 89 months versus 33 months after IFN. In conclusion, splenectomy still remains the primary therapy for HCL patients stage 1. For high risk patients, stages 2 and 3, IFN should be adopted as first line therapy, improving substantially the survival. The short duration of response to IFN suggests a sequential combination of the two treatments for this group of patients, IFN reducing tumor mass quite safely and splenectomy assuring long lasting stable disease.

Humans↗

Splenic irradiation in chronic lymphocytic leukemia.

52 patients with CLL, presenting primarily with splenomegaly, stage II-IV according to the Rai stage system, were treated with a regime of low-dose splenic irradiation (SI) between January, 1979 and December 1987. The treatment modality consisted of 1 Gy, from 1 to 10 doses, given at weekly intervals. The median given dose was 700 cGy (100-1000). CHR occurred in 23/52 (44%), PR in 20/52 (38%) and no response (NR) in 9/52 (17%) of the patients. The median duration of remission was 9 months (range 3-24), 15 and 7 months for patients achieving CHR and PR, respectively. At relapse, 14 patients received a second course of SI by the same modalities: 2 of them obtained a second CHR, 9 a PR and 3 NR. The median duration of remission was 4 months. In conclusion, SI represents a suitable therapy for CLL patients presenting primarily with splenomegaly. The low rate of response and the short remission duration after the second treatment suggest that SI should be combined either with splenectomy or with other therapeutic approaches.

Adult↗

ProMACE-MOPP vs MACOP-B in high grade non-Hodgkin's lymphomas: a randomised study in a multicenter cooperative study group (NHLCSG).

From January '85 to April '87, 81 patients (pts) with diffuse intermediate and high-grade non-Hodgkin's lymphomas were treated with the ProMace/MOPP protocol in a large Italian Cooperative Study Group (NHLCSG). Criteria for entry into the study included: no prior therapy, stage III-IV or stage II with bulky disease and/or B-symptoms, age below 65. 79 pts were evaluable for response. Almost all pts received six courses of chemotherapy, plus radiotherapy on bulky disease. 53 pts (67%) achieved complete remission (CR), 7 (9%) partial remission (PR), 4 (5%) were considered stable disease (SD) and 15 (19%) progression disease (PD) with 5 of them died early during treatment. The actuarial overall survival (OS) and disease free survival (DFS) are respectively 54% at 61 mos and 62% at 41 mos. The median follow-up from the end of therapy is 56 mos (range 40-68). Until now 20 pts (38%) relapsed on a median time of 8 mos (range 2-21) from CR. These data allowed to us to consider this regimen as effective as the third generation protocols also taking into account the multicenter basis of this study. With the aim to evaluate the impact of the third generation regimen on the outcome of these pts, a randomized study has been performed comparing ProMACE-MOPP with the third generation regimens MACOP-B. Therefore, from 1988 up to now, 206 pts with similar clinical and histological characteristics, have been enrolled in the two arms. No differences in terms of CR and DFS have been registered between the two treatments, with roughly the same toxicity. An analysis of prognostic factors in the larger series of pts treated with ProMACE-MOPP in the first and in the second study (167 pts) was performed. On these basis it seems reasonable that our next step would be to candidate these poor prognosis pts to a new therapeutic strategy which included the use of ABMT and/or PBSC transplantation as first line.

Adult↗

Human lymphoblastoid interferon as initial therapy in hairy cell leukaemia: a multicentre study in non-splenectomized patients. Italian Cooperative Group for Hairy Cell Leukemia.

The Italian Cooperative Group for Hairy Cell Leukaemia (ICGHCL), between April 1985 and June 1987, conducted a multicentre study using human lymphoblastoid alpha-interferon as primary therapy as an alternative to splenectomy. Forty-eight evaluable patients with HCL entered the study, 38 of them had splenomegaly, in five patients the spleen was not palpable and five were unfit for surgery because of age and general condition. Daily dose of 3 MU s.c. alpha-IFN was given for 12 weeks, or until a satisfactory and stable response was obtained. Among these 48 patients the response rate after 3 months of therapy was 63%, with seven patients (15%) achieving complete remission and 23 (48%) partial remission; 13 (27%) patients had a minor response. In five patients no response was observed and they died within 2 months of treatment. Five other patients, after an initial response, presented a re-expansion of the disease. Actuarial survival at 30 months was 88.8% for the entire group of 48 patients and 92% for the 38 patients who would normally be treated by splenectomy. Thus, alpha-IFN as primary treatment in HCL offered a reasonable therapy for splenomegalic patients. The timing and validity of splenectomy still remains an open question.

Adult↗

A phase II study of idarubicin (4-demethoxydaunorubicin) in advanced myeloma.

Idarubicin (IDA) is an anthracycline analog which differs from the parent compound by the substitution of a C4 methoxyl group with an hydrogen atom in the aglycone moiety. This drug has shown greater potency and activity in experimental and human leukemias and lymphomas by intravenous and oral routes of administration together with less cardiotoxicity than doxorubicin (DX) and daunorubicin (DNR). We have treated 15 patients with advanced multiple myeloma (MM) refractory or relapsed to standard chemotherapy regimens. The treatment schedule consisted of idarubicin 40 mg/m2 orally on day 1 every 3 weeks for 6-8 months. We obtained 8/14 partial response, 4/14 minor response and 2 progressions. One patient was not evaluable for the response because of liver toxicity not related to IDA administration. The median duration of response was 8 months with a minimum of 2 and a maximum of 12 months. Hematologic toxicity occurred in about 20% of patients and no treatment was delayed. Cardiotoxicity, defined as impairement of left ventricular ejection fraction (LVEF), was observed in one case. The major systemic toxicity observed was nausea in 80% of patients and vomiting in 40%. Hair loss resulting was socially acceptable. These results indicate that IDA is useful as a single agent, easy to administer, not cross resistant with DX and recommended for a combination regimen.

Adult↗

Interferon alfa-2b and chlorambucil in the treatment of non-Hodgkin's lymphoma.

Twenty-two patients with non-Hodgkin's lymphoma (NHL) were treated with a combined regimen of interferon alfa-2b (Intron A; Schering-Plough) and chlorambucil to evaluate the response and efficacy in pre-treated or relapsed patients. Ten patients were classified as having follicular lymphoma and 12 diffuse lymphoma. The treatment schedule consisted of interferon alfa-2b 3 X 10(6) IU/m2 thrice-weekly and chlorambucil 10 mg daily for three weeks, with a week's rest between each cycle. Treatment continued for upto six cycles. We obtained two complete remissions (CR), 12 good partial remissions (GPR), seven no remissions (NR) and one stable disease. On histologic examination we observed a response in 8 of 10 patients with follicular lymphoma (2 CR and 6 GPR); three of five patients with diffuse mixed lymphoma, and three of seven patients with diffuse lymphoma showed GPR. The major toxicity consisted of fever and nausea and, in one case, lethargy. In one patient the treatment was stopped at the second cycle because of poor compliance. Hematologic toxicity was generally mild and occurred between the third and fourth cycle. We observed hepatic toxicity i.e. a transient increase of transaminase levels, in three patients. We consider this regimen to be effective in the treatment of relapsed or resistant NHL and no more toxic than single agent therapy. A randomized study to verify this therapeutic approach versus conventional therapy with chlorambucil alone in first-line treatment is recommended.

Aged↗

Treatment of 49 unrandomized patients with advanced Hodgkin's disease.

Forty-nine patients with previously untreated advanced Hodgkin's disease were treated in our Institution between 1973 and 1981. Treatment modalities of these patients were reviewed, and they were divided into 3 groups according to the treatment employed: 13 patients received MOPP only, 22 patients received MOPP plus involved field radiotherapy, and 14 received alternating MOPP/ABVD chemotherapy. The response rates for the 3 groups were respectively 38.5%, 63.6% and 78.6%. A longer follow-up is needed to assess a significant difference in survival curves. The advantages of adjuvant radiotherapy and alternating non-cross-resistant drugs in advanced Hodgkin's disease are discussed.

Adolescent↗

Treatment of acute lymphoblastic leukemia in adults.

Thirty-seven adult patients with acute lymphoblastic leukemia were treated with a protocol called HEAV'D including Adriamycin, Vincristine, L-Asparaginase, Cyclophosphamide and Dexamethasone. The complete remission rate was 70 per cent. The median duration of remission was more than 30 months. Patients with initial leukocyte count below 20 000/mmc experienced a longer remission (median not reached) than patients with a leukocyte count above 20 000/mmc (median 10 months).

Adolescent↗

The effect of thymic substances on T circulating cells of patients treated for Hodgkin's disease.

Forty-one patients with Hodgkin's disease staged as IA(4), IIA/B(4/6) IIIA/B(6/9) and IVA/B(3/9) who had had radiotherapy (subtotal nodal irradiation (STNI) or total nodal irradiation (TNI), or combined one (STNI/TNI plus chemotherapy MOPP or MOPP/ABVD) have been enrolled consequently and randomized to receive thymic hormone (17 patients) or pentapeptide treatment (14 patients) for 3-6 months at the end of the therapeutic regimens. In all patients severe immunodeficiency evaluated either as leukopenia (WBC less than 4000/mm3) or lymphocytopenia (lymphocytes less than 1500/mm3) or CD3 and CD2 cell reduction, or imbalance of helper/suppressor (H/S) ratio have been documented before starting thymic therapy. Different results by immunorestorative therapy have been registered according to the entity of immunodeficiency. In fact in the group of 15 patients with severe lymphopenia (lymphocytes less than 1000/mm3) either the thymic hormone or the synthetic drug produced a significant increase of all subsets examined: CD3-CD2-CD4-CD8 without or with minimal influence on H/S ratio, due to the increase of absolute lymphocytes count. In the remaining patients with mild or no lymphopenia the two drugs resulted ineffective on T cells. Comparing the overall group of patients who received thymic therapy with a control group of patients who did not, an advantage in terms of recruitment of T cell compartment has been observed in the former group when mean values are compared. According to the clinical impact of the immunotherapy with thymic substances on these patients, a significant decrease in incidence of herpes virus infection (HVI) has been observed in patients who had had thymic therapy compared with the incidence of HVI in the control group (18% versus 53.8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗