Endometrial polyp harboring a primary B-cell non-Hodgkin lymphoma: a useful in-office hysteroscopic approach.

A non-menopausal women underwent gynecological evaluation for spotting and menstrual irregularities. After first line gynecological assessments, the patient underwent office hysteroscopy. By using an in-office technique, two isthmic endometrial polyps and one cervical polyp were removed. One endometFial polyp was found to harbor a B-cell high-grade lymphoma just on the apex (found to be necrotic). The following staging examinatioIns and the pathological assessment of the endometrium, the uterus, the adnexa, and the lymphatic regional nodes did not find any localization of the lymphoma. No additional treatments were done. The patient is alive and disease-free at 18 months follow-up.

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: 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. PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.

A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group

The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years) with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky), were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5 percent) achieved complete remission and 4 (4.3 percent) partial remission. Three patients (3.2 percent) were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9 percent, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126). Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.

A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group.

The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years) with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky), were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5%) achieved complete remission and 4 (4.3%) partial remission. Three patients (3.2%) were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9%, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126). Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.

[Autologous peripheral stem cell transplantation in a patient with diffuse systemic sclerosis: our experience]. / Trapianto autologo di cellule staminali periferiche in un paziente con sclerosi sistemica diffusa: nostra esperienza.

The diffuse form of systemic sclerosis (SSc) can often lead to a rapidly progressive course with the involvement of the visceral organs which causes a severe prognosis. The 5-years cumulative mortality is between 30 and 60%, depending on the clinic form at the onset. Until now, no drug treatment has been proved to be efficacious against the progression of the disease or the regression of the fibrosis. Recently autologous peripheral blood stem cell (PBSC) transplantation has been found to be promising. We introduce the case of a patient, male, 56 years old, who came under our observation on February 2001, suffering from a SSc with a severe multisystem involvement of lungs, skin, heart and gastrointestinal tract, and a positive antibodies anti-Scl-70. The 8 months therapy, at first with iloprost and cyclophosphamide, then with bolus of cyclophosphamide, was ineffective, with a rapid worsening of the cutaneous and pulmonary involvement. Under the patient agreement we decided to carry out an autologous PBSC transplantation. On December 2001, we obtained the PBSC mobilization after the administration of cyclophosphamide and lenograstim and the PBSC recovery with two leucoaferesis procedures. On February 2002, we gave the conditioning therapy with: thiotepa, cyclophosphamide, fludarabine, rabbit antilymphocytic globulin; then we made the infusion of PBSC. The bone marrow recovery (GN >500 and PLT >20.000) arrived at the day + 10. For three months after the transplantation we made an antibacterial, antiviral and antifungin prophylaxis with valacocyclovir, co-trimoxazole and fluconazole. The one-year follow-up has shown an essentially good response with the improving of the skin involvement and of the subjective indicators of the disease, while the pulmonary involvement don't seen modified from the high dose therapy.

Very low toxicity and good quality of life in 48 elderly patients autotransplanted for hematological malignancies: a single center experience.

Between May 1994 and May 2000, we autotransplanted 48 consecutive patients, 21 females and 27 males aged over 60 years (range: 60-78, median: 63). Sixteen patients had multiple myeloma (MM), 14 high-grade non-Hodgkin's lymphoma (HGNHL), six low-grade non-Hodgkin's lymphoma (LGNHL), nine acute myeloid leukemia (AML), one chronic lymphocytic leukemia (CLL), one Hodgkin's disease (HD) and one breast cancer; the performance status (WHO) was 0-1. Seventeen patients were in 1st CR (35.4%) and one in 2nd CR (2.1%), 25 in PR (52.1%), while five patients had been transplanted with progressive disease (10.4%); seven patients with MM received a double transplant. Patients received high-dose therapy including melphalan alone (13) or associated with other drugs (26), busulfan-cyclophosphamide (three), BEAM (11) and TBI (two). All patients took a median of 11 (range: 8-25) days to reach neutrophils >500/microl, 13 (range: 9-83) days to reach platelets > 20,000/microl and 17 (range: 11-83) days to reach platelets > 50,000/microl. Hematological toxicity, hospital stay and supportive care did not differ from those of a cohort of younger patients. At present, 31 patients are alive (14 in CR, five in PR, five in PD and seven in relapse) and 16 died from PD at a median follow-up of 37 months (1-67). Only one patient died from transplant-related toxicity. Quality of life, evaluated using a QLQ-C30 questionnaire in 25 patients at day +90, was good. In our experience PBPC mobilization and transplantation is feasible in patients aged > or = 60 years and the toxicity of this procedure is acceptable, with an early transplant-related mortality of 1.8%; therefore patients with hematological malignancies potentially curable with high-dose therapy (HDT) should also be candidates for HDT.

Infectious complications after autologous peripheral blood progenitor cell transplantation followed by G-CSF.

Infectious complications after autologous peripheral blood progenitor cell transplantation (PBPCT) have been reported in a few studies including small patient numbers. The present study was performed to assess the incidence, types, outcome and factors affecting early and late infections in 150 patients aged 18 to 68 years (median 46.5) who underwent high-dose therapy, with G-CSF. Patients were kept in reverse isolation rooms and received antimicrobial chemoprophylaxis with oral quinolone and fluconazole. One hundred and fifteen patients (76.7%) developed fever (median 3 days, range 1-29); 20 patients (55.5%) had Gram-positive and 13 (36. 2%) Gram-negative bacterial infections. There were no fungal infections or infection-related deaths. Mucositis grade II-IV (P = 0. 0001; odds ratio 3.4) and >5 days on ANC <100/microl (P = 0.0001; odds ratio 2.3) correlated with development of infection. Only days with ANC <100/microl affected infection outcome (P = 0.0024) whereas the antibiotic regimen did not. After day +30 there were four cases of bacterial pneumonitis (2.7%), one case of fatal CMV pneumonia (0. 8%) and 20 of localized VZV infection (13.3%). Reduction of neutropenia duration with PBPCT and G-CSF is not enough to prevent early infectious complications since only a few days of severe neutropenia and mucositis are related to development of early infections. However, no infection-related deaths were seen. Although Gram-positive organisms were the major cause of bacteremia, a glycopeptide in the empirical antibiotic regimen did not affect infection outcome. In PBPCT recipients, early and late opportunistic infections were notably absent, which was at variance with what was seen with bone marrow recipients. Efforts should be made to prevent mucositis and neutropenia and identify new strategies of antibacterial prophylaxis.

VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group.

PURPOSE: The aim of this multicenter randomized study was to compare conventional therapy with conventional plus high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) as front-line treatment for poor-prognosis non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between October 1991 and June 1995, 124 patients, aged 15 to 60 years, with diffuse intermediate- to high-grade NHL (Working Formulation criteria), stages II bulky (> or = 10 cm), III, or IV were enrolled. Sixty-one patients were randomized to receive etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) for 12 weeks and cisplatin, cytarabine, and dexamethasone (DHAP) as a salvage regimen (arm A), and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT (Arm B). RESULTS: There was no significant difference in terms of complete remissions (CRS) in the two groups: 75% in arm A, and 73% in arm B. The median follow-up observation time was 42 months. The 6-year survival probability was 65% in both arms. There was no difference in disease-free survival (DFS) or progression-free survival (PFS) between the two groups. DFS was 60% and 80% (P = .1) and PFS was 48% and 60% (P = .4) for arms A and B, respectively. Procedure feasibility was the major problem. In arm B, 29% of enrolled patients did not undergo HDT and ABMT. A statistical improvement in terms of DFS (P = .008) and a favorable trend in terms of PFS (P = .08) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed. CONCLUSION: In this study, conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results. However, our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients.

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.

Factors affecting hemopoietic recovery after high-dose therapy and autologous peripheral blood progenitor cell transplantation: a single center experience.

BACKGROUND AND OBJECTIVE: While the minimum number of CD34+ cells required for complete and long-lasting engraftment is quite well established, there is not general agreement about the optimal number of CD34+ per kg needed in order to obtain engraftment as rapidly as possible. In the present study we assess factors affecting hemopoietic recovery and the optimal peripheral blood progenitor cell (PBPC) number for rapid engraftment in patients treated with high-dose therapy. DESIGN AND METHODS: We enrolled 80 consecutive patients affected by hematologic and non-hematologic malignancies treated with a median of 10 chemotherapy courses (range 3-38). PBPC collection was performed after mobilization with high-dose chemotherapy and G-CSF 5 micrograms/kg/day. The circulating and harvested CD34+ cells were recognized in the cytofluorimetric CD45+/CD14- lymphocyte gate. After myeloablative therapy, PBPC infusion was followed by G-CSF 5 micrograms/kg/day from day +5 until WBC > or = 5.0 x 10(9)/L. Univariate and multivariate Cox analyses were performed to investigate factors affecting hemopoietic recovery. The Kaplan-Meier probabilities of hemopoietic reconstitution were compared by log-rank test to assess the optimal CD34+ cell number for rapid engraftment. RESULTS: We performed a median of two apheresis (range 1-4) per patient and we infused a median of 6.1 x 10(6) CD34+ cells/kg (range 0.5-30.5). Absolute neutrophil count (ANC) > 0.5 x 10(9)/L was reached after 11 days (range 8-15). The only factor affecting granulocyte recovery proved to be the CD34+ cell number; 5.0 to 7.8 x 10(6) CD34+ cells/kg allowed a significantly faster granulocyte recovery than < 2.5 x 10(6) CD34+ cells/kg (p = 0.0312). Platelet transfusion independence (> 20 x 10(9)/L) and 50 x 10(9)/L platelets were reached after 12 (range 8-24) and 15 days (range 9-40), respectively. The CD34+ cell number was also the only factor affecting platelet recovery; the number of 5.0 to 7.8 CD34+ cells/kg allowed a significantly faster platelet recovery than the lower dose, whereas a higher number did not. No late graft failures were observed. Patients receiving 5.0 to 7.8 x 10(9) CD34+ cells/kg had a significantly shorter duration of neutropenia, fewer platelet transfusions and less time spent in hospital than those receiving lower number did, whereas patients transplanted with a higher number had no advantage. INTERPRETATION AND CONCLUSIONS: When G-CSF is employed both for PBPC mobilization and after PBPC transplantation, the CD34+ cell number is the only factor that affects hemopoietic recovery. Moreover, > 5.0 x 10(6) CD34+ cells/kg is the optimal number for obtaining rapid platelet recovery and reducing the costs of HDT but there is no advantage exceeding the threshold of 7.8 x 10(6) CD34+ cells/kg.

[High prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma at the onset. Preliminary results of an Italian multicenter study]. / Elevata frequenza della infezione da virus dell'epatite C nei pazienti con linfoma non-Hodgkin all'esordio. Risultati preliminari di uno studio multicentrico italiano.

143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

Antiplatelet agents in thrombotic thrombocytopenic purpura (TTP). Results of a randomized multicenter trial by the Italian Cooperative Group for TTP.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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). INTERPRETATION AND CONCLUSIONS: 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.

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.

Thrombotic thrombocytopenic purpura and relapses: why do case series differ? The Italian Cooperative Group for TTP.

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.

Neocytoapheresis in the treatment of polycythemia vera.

In absence of thrombocytosis, periodic bloodlettings represent the elective therapy of polycythemia vera. In the present study we tested if neocytoapheresis, a method able to remove large quantities of younger, and then bigger red cells could represent an alternative therapeutic choice in these patients. We found that the employment of neocytoapheresis produced a remarkable delay in the time of procedures with a mean interval of 100 +/- 55 days. The mean value of hematocrit before neocytopheresis is resulted statistically different in comparison with the hematocrit after the procedure (p = 0.0001). The reticulocyte count is resulted higher in apheresis product in comparison with the blood control measured before procedure (p = 0.0001). In the same way, the mean corpuscular volume in the collection bags was higher than the volume measured before neocytoapheresis (p = 0.0095). We did not find any variation about the mean values of white blood cells and platelets before and after neocytoapheresis in the patients examined. These preliminary data seem to underline a better withdrawal of big size cells by this technique suggesting the efficacy of neocytoapheresis in the treatment of polycythemia vera.

Nitrite and Nitrate Plasma Levels, as Markers for Nitric Oxide Synthesis, in Thrombotic Thrombocytopenic Purpura (TTP).

The enhanced platelet aggregation and thrombosis occurring in TTP is probably due to an unbalance between agents insulting endothelial integrity and natural antithrombotic factors, such as NO. Using a sensitive and specific HPLC assay, we tested the hypothesis of NO involvement in TTP, comparing NO production, as the stable end-products nitrites and nitrates, in the plasma of 29 TTP patients and of 29 healthy subjects matched for sex and age. Average nitrate titer was 25.868 µM/L in the TTP group vs 24.234 µM/L in the control group (p = n.s.), while nitrite were undetectable in both groups. Moreover, nitrate titers did not correlate with hemoglobin value, platelet count, LDH values, or with Rose and Eldor's severity score. In conclusion, even though the enhanced platelet aggregation observed in TTP could be due to reduced natural antithrombotic substances, NO involvement in the pathogenesis of TTP appears unlikely.

Treatment of thrombotic thrombocytopenic purpura with high-dose immunoglobulins. Results in 17 patients. Italian Cooperative Group for TTP.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Intravenous prostacyclin (as epoprostenol) infusion in thrombotic thrombocytopenic purpura. Four case reports and review of the literature. Italian Cooperative Group for Thrombotic Thrombocytopenic Purpura.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vincristine sulfate for the treatment of thrombotic thrombocytopenic purpura refractory to plasma-exchange. The Italian Cooperative Group for TTP.

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.