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.

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.

Treatment of multiple myeloma: a randomized study of three different regimens.

The results of an Italian multicentric trial for treatment of symptomatic Multiple Myeloma (MM) are reported. One hundred and thirty-three previously untreated patients were singled out at random for three different chemotherapy schedules: Melphalan plus Prednisone (M.P.) X 6 monthly cycles; Vincristine plus Melphalan plus Cyclophosphamide plus Prednisone (VMCP) X 6 monthly cycles; Peptichemio, Cyclophosphamide, BCNU. Drugs in this latter schedule were administered sequentially, for a period of six months. Criteria for response, progression and relapse were those of the Southwestern Oncology Group. Fifteen patients in MP chemotherapy (35%) and 20 patients in VCMP chemotherapy (46%) achieved an objective response (decrease of at least 50% in the synthesis index of Monoclonal Component (M.C.], while only 3 out of the other 21 patients assigned to the third schedule responded to treatment. No significant differences were noted in the survival curves in either of the three treatment groups. The 38 responding patients did not receive maintenance therapy; no significant difference was found in remission duration between patients in MP and VCMP arms, with a median duration of 16 months for the whole group. No statistical difference was observed between survival and remission curves of patients with a 'response' (M. spike reduction greater than 75%) and those with 'improvement' (M. spike reduction between 75 and 50%). The authors conclude that the inclusion of Vintristine in a combination chemotherapy does not produce clear survival benefits; a longer induction period (12 cycles) could allow a better differentiation between MP and VMCP regimens.

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.

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.

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.

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.

Thrombotic thrombocytopenic purpura resistant to plasma-exchange: salvage treatment with high-dose IgG or vincristine. Italian Cooperative Group for TTP.

Even though plasma-exchange (PE), either alone or combined with cortisone or platelet anti-aggregating substances is the treatment of choice for TTP, 10-15% of patients is resistant to treatment. Since immunoglobulin (IgG) infusion was reported to cure the clinical symptoms of PE-resistant TTP, and vincristine (VCR) has been recently successful in treating TTP, we reviewed the results obtained with both drugs in 20 PE-resistant patients. Of 12 patients receiving IgG and 8 receiving VCR, 3 (25%) and 4 (50%), respectively, achieved complete remission. Even though no conclusions can be drawn from such results, if complete remission can be achieved in a however small number of PE-resistant patients, the use of these drugs is suggested as a salvage treatment for TTP.

[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.

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.

[Hodgkin's lymphoma and secondary leukemias]. / Linfoma di Hodgkin e leucemie secondarie.

The increase of survival in patients with Hodgkin's disease (HD) has made appear the problem of secondary neoplasms, included acute leukemias. The authors evaluate the incidence of acute leukemias in 205 HD with a follow-up more than 12 months (mean 92 months). With regard to these latter, 18 (8.7%) were treated with radiotherapy alone, 69 (33.6%) with chemotherapy alone and 118 (57.5%) with a combination of radiotherapy and chemotherapy. Chemotherapy consisted of 2-12 courses of MOPP alone or in combination with ABVD. The relative risk of acute leukemias is 96.7 (CI 95%: 44.2-183.6): nine cases against an expectancy of 0.093. The risk changes during five-years periods, but not significantly, and it not declines after ten years from the diagnosis. Only the alkylating chemotherapy seems to be important to favour the onset of acute leukemias. Among the patients who received a number of courses of MOPP less or equal than 6 (177), seven developed an acute leukemia (relative risk 85.3; CI 95%: 34.3-175.9); among those who received more than 6 (9), two developed an acute leukemia (relative risk 333.3; CI 95%: 40.3-1204.1). Neither the addition of radiotherapy nor the stage nor the splenectomy nor the histotype favour the onset of acute leukemia.

[Differentiating agents in myelodysplastic syndromes. Analysis of personal cases]. / Agenti differenzianti nelle mielodisplasie. Analisi della casistica personale.

The Myelo-Dysplastic Syndromes are a heterogeneous group of diseases which includes patients with different prognosis. There is no agreement about the management and the therapeutic strategy must be based on many individual parameters, particularly the age of the patients and their performance status. The therapeutic options range from no cytotoxic therapy for low-risk patients up to more aggressive treatment for high-risk patients, with disappointing results except for the very few cases eligible for allogenic bone marrow transplantation. The leukaemic cell can be induced to differentiate, so losing its self-maintenance potential; different drugs such as Interferon, vitamin D3, retinoids and arabinosyl-cytosine (low doses) have shown a differentiating action on myeloid blasts in "vitro". We summarize the general strategy in the treatment of myelo-dysplastic syndromes based on literature data, and on our results about the efficacy and tolerance of a combination of the above mentioned differentiating drugs, in a group of 27 elderly patients affected by myelodysplastic syndrome with poor prognosis. We obtained 14 objective responses (52%), and the median overall survival of these patients have been compared with that of 25 patients with severe myelodysplastic syndrome treated with a conventional regimen. In the 27 patients receiving the differentiating combination the median survival was found to be 14.7 months, versus 8.4 months for the control group. The results obtained are encouraging about the tolerance and the efficacy of this combination in elderly patients with a poor MDS prognosis. Further randomized studies are necessary to establish whether this treatment can really improve the survival in this group of patients.

[The soluble IL-2 receptor in malignant hemopathies]. / Il recettore solubile dell'IL-2 nelle emopatie maligne.

The increase in the serum levels of the IL-2 receptors is due to its release both in vivo and in vitro from activated cells or neoplastic cells expressing it constitutively. The diagnostic, prognostic and physiopathologic significance of the sIL-2R was investigated by testing the serum of 271 haemopathic patients in various stages of the disease. In HCL the elevated sIL-2R level has a diagnostic value. In HD the sIL-2R level appears to be directly correlated with the extent of the disease and is equally important in the follow up of patients with HCL, NHL, HD, AL and MDS, where the serum level of the soluble receptor is usually associated with the biological and clinical activity of the disease. Unlike other B lymphoproliferations, patients with Multiple Myeloma on average show only slightly elevated levels of soluble receptor with no significant differences related to the stage or evolution. As for the chronic myeloproliferative disorders, we found only slightly elevated values in ET and PV, with frankly pathological values in CML during a blastic crisis or in the accelerated phase and in MFI during the clinically active phase of the disease.

[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.

Treatment of autoimmune thrombocytopenic purpura.

One hundred and two patients with newly diagnosed autoimmune thrombocytopenic purpura (ATP) were treated with prednisone (1.5-2 mg/kg/day for 4 weeks). A favourable response, lasting more then 12 months, was obtained in 22,5% of the cases. Different therapeutic strategies, such as immunosuppressive drugs, high dose immunoglobulins, splenectomy and others, were applied in unresponsive or relapsed patients. In our case study, splenectomy has proved the most satisfactory (87% of positive results) thus representing, in our opinion, the only effective therapy for resistant or relapsed case.

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.

Bone marrow cryopreservation: biological aspects.

Ten bone marrow suspensions have been cryopreserved by a Programmed Freezer Planer R 201. Total cellularity, viability, differential myelograms, cytochemical pattern and CFU-GM growth "in vitro", have been evaluated on the cellular suspensions both before and after 1 and 18 months of storage in liquid nitrogen. Total cellular recovery and viable cell recovery were satisfactory, cellular loss being due, almost entirely to death of the more mature cells. NASDA reaction did not vary after freezing, on the contrary peroxidase reaction and overall PAS reaction showed respectively a slight and an almost complete disappearance. LAP reaction was not valuable, after freezing, because of the more mature myeloid cell loss. CFU-GM recovery was satisfactory and clusters and colonies growth in methylcellulose appeared quite similar before and after 1 and 18 months of storage at very low temperature. Our cryopreservation technique cannot prevent some cellular loss or some qualitative cellular damage, but colonizing ability is almost completely preserved.