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ABSTRACT: Among all the patients treated by the Italian Cooperative Group for TTP, we retrospectively reviewed the results obtained using vincristine (VCR) in 8 TTP patients (4 men and 4 women, average age: 39.25 years, range: 23–48) who did not respond to combined apheretic and pharmacologic treatment. All patients, after failing to respond to treatment, were started on VCR at the dose of 2 mg, i.v., once a week. Despite this treatment, 4 patients (50%) died 1, 7, 12 and 25 days after the first VCR dose, respectively. The other 4 patients who received VCR achieved complete remission 24, 30, 40 and 50 days from the beginning of the treatment. Total doses of VCR ranged from 2 to 6 mg in the deceased group, and from 6 to 14 mg in the cured patients. In our experience, VCR is a promising agent to treat TTP patients resistant to conventional plasma-exchange and pharmacologic therapy.
European Journal Of Haematology 04/2009; 52(4):222 - 226. · 2.61 Impact Factor
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A Olivieri,
G Santini,
C Patti,
T Chisesi,
C De Souza,
A Rubagotti,
S Aversa, A Billio,
A Porcellini,
M Candela, [......],
M Brunori,
S Nati,
M Spriano,
R Vimercati,
G Marino,
A Contu,
L Tedeschi,
I Majolino,
M Crugnola,
M R Sertoli
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ABSTRACT: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL.
Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B).
According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement.
Aggressive NHL patients do not benefit from upfront HDS/HDT.
Annals of Oncology 01/2006; 16(12):1941-8. · 6.43 Impact Factor
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ABSTRACT: We examined the retrospective case series of the Italian Cooperative Group to determine the incidence of relapses in TTP patients. Of 60 patients who have crossed the 10-year threshold from the first episode, only 9 (15%) relapsed during that period, a figure far lower than that reported recently. Such difference is hardly explainable on the basis of our current knowledge of the biological behaviour of TTP. Furthermore, we unsuccessfully analyzed the treatment performed in each of our relapsed patients, in search of some element that could retrospectively predict the subsequent relapse.
American Journal of Hematology 08/1996; 52(3):215-6. · 4.67 Impact Factor
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ABSTRACT: Among all the patients treated by the Italian Cooperative Group for TTP, we retrospectively reviewed the results obtained using vincristine (VCR) in 8 TTP patients (4 men and 4 women, average age: 39.25 years, range: 23-48) who did not respond to combined apheretic and pharmacologic treatment. All patients, after failing to respond to treatment, were started on VCR at the dose of 2 mg, i.v., once a week. Despite this treatment, 4 patients (50%) died 1, 7, 12 and 25 days after the first VCR dose, respectively. The other 4 patients who received VCR achieved complete remission 24, 30, 40 and 50 days from the beginning of the treatment. Total doses of VCR ranged from 2 to 6 mg in the decreased group, and from 6 to 14 mg in the cured patients. In our experience, VCR is a promising agent to treat TTP patients resistant to conventional plasma-exchange and pharmacologic therapy.
European Journal Of Haematology 05/1994; 52(4):222-6. · 2.61 Impact Factor
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ABSTRACT: The enhanced platelet aggregation which is observed in TTP, was suggested to be due to an imbalance between unknown agents insulting endothelial wall and defense factors, such as prostacyclin (PGI2). Several reports suggested an aberration of PGI2 activity as a critical step in the pathogenesis of TTP. Therefore, PGI2 was proposed as an alternative treatment for TTP patients.
We report the results obtained with increasing doses (from 2 ng/Kg/min to 10 ng/Kg/min in 5 days) of PGI2-as epoprostenol-in 4 TTP patients from the retrospective series of the Italian Cooperative Group who were considered resistant to conventional plasma-exchange (PE)-based treatments.
Despite PGI2 infusion, 2 patients died, while the extant 2 achieved stable complete remission. Notably, the only patient whose PE was administered with adequate frequency and for an adequate period of time, and thus the only unquestionably PE-resistant patient, was also resistant to PGI2 infusion. Major side-effects were few and observed at the highest doses.
In our experience and from the analysis of the literature, which, as far as we know, includes only 23 patients treated with PGI2-like substances, the role of PGI2 in the treatment of TTP appears to be modest. Maybe the identification of subgroups of TTP patients exhibiting some defects in PGI2 metabolism, together with the use of more manageable PGI2 analogs, such as iloprost, could revive interest in these molecules in the future.
Haematologica 79(5):429-37. · 6.42 Impact Factor
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ABSTRACT: Antiplatelet agents are often included in plasma exchange-based regimens for thrombotic thrombocytopenic purpura (TTP) patients; however, the opportuneness of their use in TTP is still controversial. The italian Cooperative Group for TTP carried out a randomized trial to investigate their actual effectiveness, both in acute TTP and as maintenance treatment.
Seventy-two TTP patients were randomized to receive plasma exchange and steroids with (group B) or without (group A) aspirin and dipyridamole. Treatment efficacy was evaluated after 15 days and salvage treatments were also considered for non-responders. Upon disease remission, the patients already treated with antiplatelet agents received ticlopidine for one year.
Regarding the treatment of acute phase TTP, similar overall response rates were observed in the two groups (91.4% in group B vs. 75.6% in group A), but lower mortality rates were observed at 15 days in the patients treated with antiplatelet agents; as a matter of fact, 5 patients from arm A died in the first 15 days (13.5%) versus only one in arm B (2.8%). These figures, while not statistically significant, seem to suggest that antiplatelet agents might be useful in preventing deaths in acute TTP; moreover, bleeding did not worsen in antiplatelet agent-treated patients. As for the role of maintenance treatment, our results support the efficacy and safety of one-year ticlopidine therapy since the current relapse rate is significantly higher in non-treated patients; as a matter of fact, 6 patients (21.4%) in the non-ticlopidine group and only 2 (6.25%) in the ticlopidine group relapsed (P = .0182 in favor of maintenance treatment).
Our results suggest the usefulness of antiplatelet agents in the treatment of acute phase TTP patients. Moreover, one-year ticlopidine maintenance therapy appears to be beneficial in preventing TTP relapses; however, only the completion of an adequate follow-up for all patients will definitively confirm this observation.
Haematologica 82(4):429-35. · 6.42 Impact Factor
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ABSTRACT: The experimental observation that plasma from TTP patients sometimes exhibits a protein which can cause platelet agglutination, and that such agglutination can be inhibited in vitro by the use of IgG led some authors to treat plasma exchange-resistant TTP patients with high-dose IgG (HDIgG).
We report the results obtained with HDIgG treatment in 17 patients retrospectively examined by the Italian Cooperative Group for the study of TTP: 6 males and 11 females, mean age was 31.7 years for the women (range: 20-65) and 44.6 for the men (range: 26-66). In all cases HDIgG administration was combined with other treatment modalities.
Of the 17 patients, 7 died from disease progression (41.1%), 2 achieved partial remission (11.7%) and the remaining 8 achieved complete remission (47%). Of the 10 cases (58.8%) with a positive response, only in 4 did the addition of HDIgG seem to produce significant improvement. All efforts made to characterize the subgroup of patients who responded to HDIgG and compare them with the non responders failed.
Although our results do not unquestionably demonstrate the role of HDIgG in the treatment of TTP, they suggest a possible role for HDIgG in the treatment of those rare plasma exchange-resistant TTP cases.
Haematologica 80(4):325-31. · 6.42 Impact Factor
