Long-term follow-up of idiopathic thrombocytopenic purpura in 310 patients.

BACKGROUND AND OBJECTIVES: Idiopathic thrombocytopenic purpura (ITP) induces thrombocytopenia by means of an autoimmune mechanism. Despite the available therapies a subset of patients develop chronic refractory severe thrombocytopenia (i.e. a platelet count consistently lower than 20 to 30x10(9)/L), and life-threatening bleeding can occasionally occur. It has been suggested that the risk of major bleeding is higher in elderly patients and in patients with bleeding at diagnosis. However, since clear data on the influence of clinical and/or laboratory parameters on outcome are lacking, some patients may be receiving unnecessary treatment. DESIGN AND METHODS: We made a retrospective analysis of a series of 310 patients with chronic ITP (108 males and 202 females), with a median age at diagnosis of 40 years (range 8-87 years). The median follow-up time was 121 months, (range 7-434 months). Therapy was most often started in the presence of hemorrhagic complications and/or a platelet count <30x10(9)/L either at diagnosis or during follow-up. RESULTS: Our findings confirmed that patients who were symptomatic at diagnosis were more likely to have bleeding during their follow-up. Moreover, all the patients who suffered major bleeding during their follow-up had median platelet counts of 10x10(9)/L (range 1-20) at that time. Only one patient, aged 43 years, died of hemorrhage following prolonged severe thrombocytopenia. Age >60 years was not associated with any significant differences in incidence of bleeding at diagnosis or during follow-up. INTERPRETATION AND CONCLUSIONS: We conclude that prospective studies are required to evaluate whether it may be reasonable to treat only symptomatic patients, independently of age.

Real-time quantification of different types of bcr-abl transcript in chronic myeloid leukemia.

BACKGROUND AND OBJECTIVES: The most common translocation in chronic myeloid leukemia (CML) t(9;22) (q34;q22) produces the BCR/ABL fusion gene. We set up and evaluated a rapid and reliable real-time reverse-transcription-polymerase chain reaction (RT-PCR) approach using TaqMan technology for detection and quantification of bcr-abl transcripts in CML patients at diagnosis and during therapy. DESIGN AND METHODS: A pair of primers and probe complementary to ABL exon 2 were designed, enabling detection of the most frequent bcr-abl transcripts, and also of the normal ABL-Ia transcript as an internal control. Conditions were established to amplify less than 1(-10) target molecules/reaction and detect one CML cell in 10(6) cells from healthy donors. To determine the utility of the assay, we quantified the bcr-abl/ABL-Ia ratio in 59 bone marrow samples (45 samples with evidence of different Ph+ chromosome percentages and 14 samples in complete cytogenetic remission) from 48 CML patients, 34 of them at diagnosis and 14 in clinical remission (CR). In 14 cases, this ratio was compared with results obtained by a competitive-quantitative RT-PCR/capillary electrophoresis method from contemporary specimens. RESULTS: By real-time RT-PCR, the median value of bcr-abl/ABL-Ia ratio at diagnosis was 15.334 (range 3.3-28.81) and fell to 0.9 (range 0.003-26.1) in CR. The median value of bcr-abl/ABL-Ia ratio at cytogenetic remission was 0.7 (range 0.003-2.83). The real-time bcr-abl/ABL-Ia ratios correlated with those obtained by competitive RT-PCR (p < 0.0001) and the percentage of Ph+ metaphases (p < 0.0001). The high sensitivity and specificity of the real-time RT-PCR procedure was confirmed in all 14 patients with minimal residual disease. INTERPRETATION AND CONCLUSIONS. We conclude that this real-time RT-PCR procedure is a reliable and sensitive method of monitoring CML patients after therapy, and that the bcr-abl/ABL-Ia ratio correlates strongly with cytogenetic analysis.

Testing Sokal's and the new prognostic score for chronic myeloid leukaemia treated with alpha-interferon. Italian Cooperative Study Group on Chronic Myeloid Leukaemia.

As it has been shown that alpha-interferon (alphaIFN) treatment modifies the survival of chronic myeloid leukaemia (CML) patients in comparison with conventional chemotherapy, a new prognostic score was devised with the aim of providing a treatment-adapted risk evaluation. We have tested the new prognostic score (the Euro score) in an independent series of 272 patients less than 56 years old with previously untreated, chronic phase, Philadelphia (Ph)-positive CML who had been assigned prospectively to alphaIFN treatment between 1989 and 1991. The Sokal score system was used as a reference. The new Euro score predicted the response to alphaIFN as the Sokal score. The median survival of low-risk, intermediate-risk and high-risk patients was similar using the Euro score (105, 65 and 45 months) and Sokal score (105, 76 and 45 months) but, by multivariate analysis, the Euro was more potent than Sokal for predicting survival time. The new Euro score identified more low-risk cases (59% vs. 48%) and fewer high-risk cases (9% vs. 23%) than the Sokal score. The main differences between the Euro and Sokal scores concerned age (it is more important in the Euro than in Sokal), spleen size and the percentage of myeloblasts in peripheral blood (more important in Sokal than in Euro). We conclude that the new Euro score marks an improvement in the prognostic evaluation of CML treated with alphaIFN. By comparison with the Sokal score, the Euro was more potent and identified more low-risk patients but left only a small number of cases in the high-risk group.

Randomized trial of autologous filgrastim-primed bone marrow transplantation versus filgrastim-mobilized peripheral blood stem cell transplantation in lymphoma patients.

Although a large amount of data is available on the effects of filgrastim (granulocyte colony-stimulating factor [G-CSF]) on the mobilization of stem cells in the circulation, data concerning its effects on bone marrow (BM) harvesting is scarce and controversial. We have designed a randomized trial comparing filgrastim-mobilized peripheral blood stem cell (PBSC) transplantation with filgrastim-primed autologous bone marrow transplantation (ABMT). Fifty-five patients affected by non-Hodgkin's (n = 38) or Hodgkin's (n = 17) lymphoma, selected for autologous transplantation over a 12-month period in a single institution, were randomized 2:1 to undergo BM or PB harvest/collection after priming for 3 days with filgrastim, 16 microg/kg body weight daily subcutaneously. BM priming with G-CSF allowed the harvest of a significantly higher number of mononuclear cells (MNC) (0.53 x 10(8)/kg, range, 0.32 to 1.40), as compared with a historical control of unprimed BM harvests (0.43 x 10(8) MNC/kg, range, 0.15 to 0.72, P = .001). After high-dose ablative therapy, median time to neutrophil recovery above 0.5 x 10(9)/L was 12 days for BM and 11 days for PB (P = .219); median time to platelet recovery above 20 x 10(9)/L was 13 days for BM and 11 days for PB (P = .242). The same number of red blood cells, platelet transfusions, and posttransplant G-CSF doses were required in the two groups of patients. Less patients (50% v 70%) became febrile in the group transplanted with mobilized PB, but days of fever/patient and days on antibiotics were overlapping. The median time spent in the hospital after reinfusion was 16.5 and 15.5 days after primed BM and primed PB, respectively (P = .134). These data suggest that in patients with lymphoma submitted to autologous transplantation, the reinfusion of filgrastim-primed BM or filgrastim-mobilized PB leads to similar results, with an advantage of only 1 day in the neutrophil recovery and 1 day on the time spent in the hospital in favor of primed PB. Either option can be chosen on the basis of the availability of a surgery room or cell separator facilities and considering the patients' characteristics and wishes.

High bcl-2 expression in acute myeloid leukemia cells correlates with CD34 positivity and complete remission rate.

Flow cytometric expression of bcl-2 protein was analyzed in 90 newly diagnosed acute myeloblastic leukemia (AML) patients using an anti-bcl-2 monoclonal antibody by direct immunofluorescence technique and results were correlated with FAB cytotype, CD34 expression and clinical outcome. Bcl-2 was expressed in all AML cases with different intensity. The mean fluorescence index (MFI), expressed as the ratio of sample mean channel:control mean channel, ranged from 3.0 to 39.5 with a median value of 14. The MFI was significantly higher (P = 0.01) in M0 (20.9) and M1 (18.3) than in M2 (11.7), M3 (12.4), M4 (11.8) and M5 (9.5) cytotypes. In addition, bcl-2 MFI significantly correlated both with CD34 positivity (P = 0.001) and with CD34 MFI (P = 0.01), being CD34 antigen expressed in 65% of patients with a bcl-2 MFI >14, and only in 35% of AML cases with a bcl-2 MFI >14. When bcl-2 intensity expression was correlated with complete remission (CR) rate, a higher MFI was associated with a low CR rate after standard intensive chemotherapy. In particular, CR was achieved in 86% of patients with a bcl-2 MFI <14, but only in 57% of patients with a MFI >14 (P = 0.008). A further decrease of CR rate to 41% was observed in patients in whom a higher bcl-2 MFI was coupled with the presence of CD34 antigen on their blasts. By statistical analysis we also demonstrated that both bcl-2 high MFI (>14) and CD34 expression are independent prognostic factors for achieving CR in AML. These data raise the hypothesis that high values of bcl-2 may confer on myeloid blasts a higher resistance to standard chemotherapy. However, identification of patients with high expression of bcl-2 may be important for a different therapeutic approach.

Immunologic and clinical modifications following low-dose subcutaneous administration of rIL-2 in non-Hodgkin's lymphoma patients after autologous bone marrow transplantation.

In order to induce a therapeutic immunomodulatory activity, 11 patients with high-grade non-Hodgkin's lymphoma (HG-NHL) at a median of 42 days after autologous bone marrow transplantation (ABMT) received recombinant interleukin-2 (rIL-2) subcutaneously at a dose of 2 international megaunits (IMU)/m2 every other day for 2 weeks and then 3 IMU/m2 twice a week for 1 year. Immunological studies, including T and natural killer (NK) cell subset assessment, together with functional assay, such as NK and CD16-mediated cytotoxic activities, were performed before therapy, after 2 weeks and then monthly. Phenotypic analyses showed a significant and persistant (P = 0.001) increase in the proportion and absolute number of total lymphocytes and, particularly of both CD16 and CD56 NK cells, from pre-treatment values of 14 and 18% to 30 and 38% respectively, recorded after 6 months of therapy. No changes were observed in CD25 (p55)-positive cells, while a significant increase from 13 to 33% (after 6 months) was observed in CD122-positive cells. Furthermore, rIL-2 administration led to an enhancement of NK activity even at the lowest effector:target ratio and of CD16-mediated cytotoxic activity. Clinical tolerance was acceptable with moderate fever and fluid retention observed only at the onset of rIL-2 treatment. None of the patients have progressed with a median follow-up of 22 months (range 10-42 months) after starting therapy. In addition, two patients with a residual disease after ABMT, one in the liver and the second in the lymph nodes, obtained a complete response after 10 and 7 months of rIL-2 therapy, respectively. These preliminary data suggest that the infusion of low-dose rIL-2 s.c. after ABMT is safe and well tolerated and can selectively increase the NK cell number and function. Additional patients are needed in order to assess the impact of these immunological changes on relapse-free survival after ABMT for HG-NHL.

Cardiac injury as late toxicity of mediastinal radiation therapy for Hodgkin's disease patients.

BACKGROUND: During the last 20 years Hodgkin's disease (HD) has become one of the most curable neoplasms; in fact, more than 75-80% of patients are expected to achieve long-term relapse-free survival with appropriate therapy. However, overall survival has been affected by intercurrent or treatment-induced diseases such as the increased risk of cardiac toxicity in patients who received mediastinal irradiation. METHODS: The incidence of cardiac abnormalities after mediastinal radiotherapy was assessed in 102 consecutive HD patients who underwent this treatment from January 1970 to December 1980. Basal investigation procedures included electrocardiogram and echocardiography; myocardial perfusion scintigraphy with 201-thallium and coronary arteriography were performed in selected patients. RESULTS: Eleven patients (10.8%) presented cardiac abnormalities, which were asymptomatic in three cases. Eight cases of myocardial ischemia and 3 of constrictive pericarditis were observed. The incidence of late cardiotoxic effects was related to total mediastinal dose and to the irradiation technique. CONCLUSIONS: The increasing duration of follow-up shows that as mediastinal irradiation increases so does the risk of late cardiotoxic side effects. For this reason, a proper treatment strategy should reduce these risk factors through new combined modality protocols and routine evaluation of cardiologic follow-up.

Autologous bone marrow transplantation in late first complete remission improves outcome in acute myelogenous leukemia.

We evaluated the role of ABMT in late 1st CR AML adult patients using busulfan plus cyclophosphamide as preparative regimen. Fifty-one adult patients (mean age 36 years, range 15-59) with AML underwent ABMT in 1st CR. Three of them had a prior diagnosis of myelodysplastic syndrome; one patient had a secondary leukemia. The median interval between CR and ABMT was 8 months (range 4-20). Patients received busulfan, 4 mg/kg/day for 4 days plus cyclophosphamide 50 mg/kg/day for 4 days or 60 mg/kg/day for 2 days. No maintenance chemotherapy was administered after ABMT. Median days to reach 0.5 x 10(9)/I PMN and 20 x 10(9)/I platelets were 26 (range 12-250) and 74 (range 16-740), respectively. No transplant-related deaths were observed. Five-year actuarial overall survival rate is 76.9%; actuarial leukemia-free survival rate is 70.6%. Mean follow-up from ABMT is 35 months. Leukemia-free survival of this group was compared with that of 38 non-transplanted patients younger than 60 years, who maintained a CR longer than 8 months in the same period. This analysis shows a statistically significant difference in favor of ABMT patients. These results suggest that, even if performed late after 1st CR as post-remission intensification, ABMT can improve the outcome of AML patients.

High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin's lymphoma with partial response to front-line chemotherapy: a prospective randomized italian multicenter study.

PURPOSE: To evaluate, in a prospective multicentric study, the efficacy of a conventional salvage chemotherapy (dexamethasone, cisplatin, and cytarabine [DHAP]) versus high-dose chemotherapy (carmustine, etoposide, cytarabine, and cyclophosphamide [BEAC]) followed by autologous bone marrow transplantation (ABMT) in patients with aggressive non-Hodgkin's lymphoma (NHL) in clinical partial response (PR) after two thirds of a conventional front-line therapy. PATIENTS AND METHODS: From August 1988 to August 1991, 286 patients with aggressive NHL were randomized in seven Italian institutions to receive fluorouracil, methotrexate, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone (F-MACHOP) or methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B) as front-line therapy. Of the 286 patients enrolled onto the trial, 77 (27%) were considered in PR after two thirds of the front-line therapy, and 49 of 77 (64%) were randomized: 27 to receive DHAP chemotherapy and 22 to receive BEAC followed by ABMT. RESULTS: The response after second-line treatment was as follows: in the DHAP group, four patients (15%) achieved a complete remission (CR), 12 (44%) remained in stable PR, and 11 (41%) showed progressive disease; in the ABMT group, three patients (14%) obtained a CR, 18 (82%) obtained a stable PR, and one (4%) progressed, with an overall response (CR + stable PR) of 59% and 96% (P < .001) in the DHAP and ABMT groups, respectively. The overall survival was 59% versus 73% and the progression-free survival (PFS) was 52% versus 73% in the DHAP and ABMT groups, respectively (P, not significant). The toxicity was mild, particularly in the ABMT group, and no treatment-related deaths occurred in either group. CONCLUSION: Because of the small number of patients randomized, we were unable to determine whether ABMT or a standard salvage regimen (DHAP) is superior for PR patients. However, we confirmed that myeloablative treatment is a safe and well-tolerated procedure in this category of patients and this may enable us to evaluate its role as part of a front-line treatment in poor-risk NHL patients.

MACOP-B vs F-MACHOP regimen in the treatment of high-grade non-Hodgkin's lymphomas.

A prospective randomized study on aggressive non-Hodgkin's lymphomas was conducted by investigators at several Italian institutions with the intent of comparing two third-generation conceptually different regimens: the regimen containing methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B), a short-term continuous twelve-week therapy, and F-MACHOP (5-fluorouracil, methotrexate with leucovorin rescue, cytarabine, cyclophosphamide, doxorubicin, vincristine, and prednisone), a monthly intensive cyclic treatment combining prednisone with six active non-cross-resistant cytotoxic drugs. The goals of this study were the response rate, relapse-free survival, and incidence of hematologic and nonhematologic toxicities. Two hundred-eighty-six patients included between 15 and 60 years fulfilled the criteria for entry to the study; 140 patients were treated with MACOP-B and 146 with F-MACHOP. The minimum follow-up was 24 months. Clinical characteristics of all patients were similar and known prognostic factors were equally distributed between the two groups. Complete remission (CR) was achieved by 61% and 67% of the patients treated with MACOP-B and F-MACHOP, respectively; 4% and 6% were primarily resistant, 2% and 5%, respectively, died of causes directly related to therapy. At 50 months, 74% of all CR patients were alive without disease and there were no significant differences in relapse-free survival between the two groups: 75% in the F-MACHOP group and 73% in the MACOP-B group at 50 months. There was a higher incidence of mucositis among patients treated with MACHOP-B than among those given F-MACHOP (11% vs 3.5%).(ABSTRACT TRUNCATED AT 250 WORDS)

CEP regimen (CCNU, etoposide, prednimustine) for relapsed/refractory Hodgkin's disease.

AIMS AND BACKGROUND: Although initial treatment of Hodgkin's disease induces a complete remission in most patients, approximately 50% of patients with advanced disease will not achieve a complete remission or will relapse following the first complete remission. PATIENTS AND METHODS: Twenty-three patients with relapsed/resistant Hodgkin's disease, observed between January 1991 and October 1993, underwent CEP combination chemotherapy (CCNU, etoposide, prednimustine). All patients had previously received MOPP and ABVD regimens, in combination at diagnosis or sequentially (at diagnosis and at the first relapse). RESULTS: Thirteen (56%) patients achieved complete responses and 4 (18%) had partial responses. Two partial responders obtained a complete remission after a successive autologous bone marrow transplantation. The complete remission was not influenced by the timing of MOPP and ABVD treatments, presence of extranodal involvement or presence of bulky disease, but was affected by the presence of a primary disease refractory to the first standard programs. All the complete responders but 2 were alive and relapse-free at a median follow-up of 15 months; no major toxic effects were recorded. CONCLUSIONS: These data suggest, as did those of other studies, that CEP is an effective regimen in patients with Hodgkin's disease in first or second relapse, also to reduce the tumor burden and to determine chemosensitivity before contingent bone marrow or peripheral blood stem cell support.

Splenectomy and the increasing risk of secondary acute leukemia in Hodgkin's disease.

PURPOSE: Following irradiation alone, secondary acute nonlymphocytic leukemia (ANLL) is uncommon; following chemotherapy alone, the risk is increased, but not as much as when combined modality treatments are used. Because ANLL seems more likely to occur in splenectomized patients, attention is focused on an unexpected association between splenectomy and the risk of secondary leukemia. PATIENTS AND METHODS: The risk of ANLL was assessed in 503 patients with Hodgkin's disease (HD) homogeneously treated with combined modality therapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP] plus radiotherapy). These patients were diagnosed from 1970 through 1984 and monitored until June 1991. RESULTS: ANLL was observed in one of 145 (0.69%) patients not splenectomized and in 21 of 358 (5.86%) splenectomized patients, demonstrating a significantly higher frequency of ANLL in the group of patients who underwent splenectomy. The group of patients who developed ANLL received a statistically greater number of MOPP courses than did the group not developing ANLL. ANLL was statistically more frequent in those patients who received more than four cycles of MOPP. Sex, symptoms, extent of radiotherapy, splenectomy, age, and number of MOPP courses were assessed for their impact on ANLL incidence by multivariate analysis. CONCLUSION: Cox's proportional hazards regression showed that splenectomy and, as previously described by others, the number of courses of MOPP are prognostic factors that increase the risk of secondary ANLL in HD patients treated with combined modality therapy. These data raise interesting questions regarding the possible role of the spleen in leukemia development.

Hodgkin's disease: summary of twenty years' experience.

BACKGROUND: A retrospective analysis on HODGKIN'S DISEASE (HD) was finalized to see if changing the management and therapy during the years we improved the cure rate of lymphomas and reduced the incidence of side effects due to therapy. Up to twenty years' experience was based in two major therapeutic periods: the first included patients observed between 1970 and June 1980 and the second between July 1980 and December 1987. Significant differences between the two periods were the reduction of splenectomies as staging procedure, the reduction of radiation dose and extension and the sequential use of MOPP/ABVD instead of MOPP alone. METHODS: The analysis included all patients observed over the twenty years under study by looking to the differences concerning response to therapy, survival, relapse-free survival and major consequences due to therapy, namely death not directly related to lymphoma. 377 pts entered the first period and 193 the second one with a minimum follow-up of 4 years. RESULTS: Significant differences were recorded on CR rate, 80.9% vs 90.5%, respectively (p = 0.0024) and deaths in CR, 15.1% vs 2.6%, respectively (p = 0.000). The overall survival shows a probability of 60% and 83% at 11 years for the first and the second group, respectively (p = 0.000) being the probability of survival of 50% at 20 years for the first group of pts. The probability of being in remission is similarly of 79% and 78%, for the first and second group, respectively. The risk of death in remission accounting all causes not related to lymphoma shows a 17% probability vs 6% at 11 years (p = 0.006) for the first and second group, respectively, being 38% for the former group at 20 years. The most frequent single cause of death in remission was secondary leukemia which was recorded in 14 pts on the group of pts observed between 1970 and 1980, all splenectomized and treated by MOPP and extensive radiotherapy. CONCLUSIONS: The modifications of therapy of HD have produced improvements concerning the prognosis of pts; these improvements are due mainly to the reduction of late side effects such as acute leukemia and second solid tumor, and to the increase of remission rate and cure rate of the lymphoma.

"Very late" relapses in Hodgkin's disease patients: a rare but real phenomenon.

In the past several decades, scientific and therapeutic advances have transformed Hodgkin's disease from a uniformly fatal illness to one that can be treated with the expectation of long-term remission or cure in the majority of cases. Because patients now survive for long periods after treatment, various late complications are being identified. Among patients with such late complications, some have been reported to experience "very late" relapses (> 10 years). Here we document recurrences in three patients with Hodgkin's disease more than 10 years after remission.

Massive mediastinal involvement in stage I-II Hodgkin's disease: response to combined modality treatment.

Thirty-seven patients with stage I-II Hodgkin's disease and massive mediastinal involvement, observed between June 1981 and November 1989, underwent combined modality treatment. This treatment included: 3 cycles of mechlorethamine, vincristine, procarbazine, and prednisone followed by mantle-field irradiation, and subsequently by 3 additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Thirty-five (95%) patients achieved complete responses and only 2 (5%) had partial responses. All the complete responders are living and relapse-free at a median follow-up of 62 months; no major toxic reactions were recorded. These data suggest, as did those of other studies, that combined modality therapy is superior to either radiotherapy or chemotherapy alone for patients in stage I-II with bulky disease, especially in the mediastinum. In fact, in these particular patients, if adequately treated with a combination of chemotherapy and radiotherapy, the role of massive mediastinal involvement as a poor prognostic factor appears to be less significant.

Fifteen-year experience in Hodgkin's disease: role of combined modality treatment and splenectomy in the incidence of secondary acute leukemia.

BACKGROUND: Following irradiation alone, secondary acute leukemia is extremely uncommon; following chemotherapy alone, the risk is increased, but not as much as when continued maintenance chemotherapy or combined modality treatments are used. PATIENTS: The risk of secondary acute nonlymphocytic leukemia (ANLL) was assessed in 552 patients with Hodgkin's disease (HD), who were diagnosed at the Hematology Institute of Bologna from 1970 through 1984 and followed-up through July, 1990. Median follow-up time was 12 years. RESULTS: ANLL developed in 14 of 328 patients treated with the combined modality of extended-field radiotherapy (RT) plus chemotherapy (CT). All ANLL was observed in patients who had received the mechlorethamine-vincristine-procarbazione-prednisone (MOPP) regimen. No ANLL was documented among 115 patients treated with RT alone, nor among the 109 given CT alone. Leukemia, which developed 34-184 months after diagnosis of HD, was always preceded by a preleukemic phase and was fatal (after 1-12 months) to 13 patients. The karyotype of the leukemia cells was studied in 11 of the 14 patients and was always abnormal. CONCLUSIONS: A Cox's Linear Logistic Model that was performed did not demonstrate that the treatment categories, age, sex, and splenectomy were prognostic factors. Because all ANLL was observed in patients who were treated with extended-field RT plus MOPP and who had undergone splenectomies at diagnosis of HD, further research with larger numbers of patients and longer follow-up should be pursued. Thus with such additional data, clinicians could come to appreciate fully the statistical significance of our interesting observations.

MACOP-B vs F-MACHOP in the treatment of high-grade non-Hodgkin's lymphomas.

From September 1988 two hundred-sixty-seven (267) untreated patients (pts) with stage II to IV high grade non Hodgkin's lymphoma (NHL) have been enrolled in a multicenter, randomized, still ongoing study, comparing two third-generation combination chemotherapy regimens, MACOP-B versus F-MACHOP. At the present time, 177 pts have completed the treatment program and are evaluable, with a median follow-up of 13 months. Clinical, histologic and laboratory characteristics are equally distributed in both groups. Among the 92 pts treated with MACOP-B, 58 (63%) achieved a complete remission (CR), 17 complete responders have relapsed (29%), and 21 have died (23%), including 3 treatment-related deaths. Among the 85 pts who received F-MACHOP, 65 (76%) achieved a CR, 9 complete responders have relapsed (14%), and 11 pts have died (13%), including 3 treatment related deaths. 30 months-projected survival is 64% for MACOP-B treated pts compared to 84% for F-MACHOP treated pts; 30 months-projected relapse- free survival is 80% and 84%, respectively. F-MACHOP seems to be superior in immunoblastic lymphoma (overall survival, OS, 82% vs. 54%) and in Burkitt-type lymphoblastic lymphoma (OS 100% vs, 42%). The degree of hematological and non-hematological toxicity was similar in both regimens. More reliable conclusions will be drawn after a longer follow-up.

Stage I high-grade non-Hodgkin's lymphomas: a retrospective analysis.

BACKGROUND: The treatment strategy for stage I non-Hodgkin's lymphomas (NHL) is far from being clearly established. METHODS: Thirty-seven patients (pts) with clinical stage I high-grade NHL treated between 1983 and 1989 have been retrospectively reviewed. Nineteen pts were treated by radiotherapy (RT) alone; 14 pts received chemotherapy (CT) followed by adjuvant RT, 3 pts CT alone and 1 pt underwent surgery alone. All pts with bulky disease were submitted to combined therapy. RESULTS: Estimated 7-yr overall survival (OS) was 82%, while freedom from relapse (FFR) was 73%. No differences in OS and FFR were recorded with regard to the type of treatment, site of the tumor, sex or histology. CONCLUSIONS: Our conclusion is that stage I NHL, even with unfavourable histology, may be successfully treated with RT only; however, CT before RT may be recommended in pts with a higher risk of relapse, i.e. the presence of bulky mass.

Ticlopidine lowers plasma fibrinogen in patients with polycythaemia rubra vera and additional thrombotic risk factors. A double-blind controlled study.

Thirty-seven patients affected by polycythaemia rubra vera (PRV) and with at least one additional thrombotic risk factor (overt vascular disease, diabetes mellitus, treated hypertension, smoking habit, plasma hyperviscosity, hyperfibrinogenemia) were enrolled in a double-blind randomized placebo-controlled study, and 18 were given ticlopidine 250 mg, b.i.d., for 60 days. All the patients had previously been submitted to cytoreduction, and PRV was under control in all cases at the start of the study. During the study, the haematological parameters were controlled every 15 days, and venesection was performed if haematocrit was greater than 46%. Whole blood viscosity, at low and high shear rates, plasma viscosity, and fibrinogen were measured on days 0 and 60. In the ticlopidine group, we recorded a significant 13.14% reduction of the mean fibrinogen level after treatment (390 +/- 63 vs. 449 +/- 97 mg/dl, p less than 0.01). All the other haemorheological parameters were not significantly modified by ticlopidine treatment, nor were there significant modifications recorded in the placebo group. Our study shows that ticlopidine may reduce a probable thrombotic risk factor (hyperfibrinogenemia) in PRV patients.