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    Maria Petti

    Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell... more
    Several studies have reported a higher prevalence of hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the general population. Treatment for NHL includes the use of chemotherapeutic agents such as cytotoxic drugs, corticosteroids, and rituximab, which can be immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV) when undergoing immunosuppressive therapy for haematological malignancies is a well-documented complication, data on HCV reactivation or liver function impairment after chemotherapy for NHL are controversial. From January 2006 to December 2009, 207 consecutive NHL patients treated with chemotherapy without rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV infection and baseline liver function tests were performed in all patients. The prevalence of HCV infection was 9.2%. This prevalence is higher than that observed in the general population in Italy (3%). Among the HCV-infected subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV-uninfected individuals. Although less frequent and less severe than in HBV-infected subjects, liver dysfunction can occur as a consequence of rituximab-containing regimens in HCV-infected patients with NHL. In the cases considered in this study, no patient treated with chemotherapy without rituximab developed hepatitis flares. The frequency and the severity of this complication vary in different reports. Therefore, we recommend the assessment of liver function and the screening of all patients with NHL for HCV infection before starting chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA serum levels during treatment.
    To determine whether patients with a HLA‐identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention‐to‐treat principles was performed within the framework of the EORTC‐GIMEMA... more
    To determine whether patients with a HLA‐identical sibling donor have a better outcome than patients without a donor, an analysis on the basis of intention‐to‐treat principles was performed within the framework of the EORTC‐GIMEMA randomized phase III AML 8A trial. Patients in complete remission (CR) received one intensive consolidation course. Patients with a histocompatible sibling donor were then allocated allogeneic bone marrow transplantation (alloBMT), the patients without a donor were randomized between autologous BMT (ABMT) and a second intensive consolidation (IC2). 831 patients <46 years old and alive >8 weeks from diagnosis were included. HLA typing was performed in 672 patients. AlloBMT was performed during CR1 in 180 (61%) out of 295 patients with a donor. Another 38 patients were allografted: five in resistant disease, 14 during relapse and 19 in CR2. ABMT was performed in 130 (34%) out of 377 patients without a donor in CR1, in six (2%) patients during relapse and in 38 (10%) patients during CR2. The disease‐free survival (DFS) from CR for patients with a donor was significantly longer than for patients without a donor (46% v 33% at 6 years; P = 0.01, RR 0.78, 95% confidence interval 0.63–0.96). The overall survival from diagnosis for patients with a donor was longer, but not statistically significant, than for patients without a donor (48% v 40% at 6 years; logrank P = 0.24). When patients were stratified according to prognostic risk groups, the same trend in favour of patients with a donor was seen for survival duration and the DFS remained significantly longer for this group of patients.
    Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP “AIDA” trial during the period July 1993 to February 1996. As a mandatory prerequisite for... more
    Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP “AIDA” trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15; 17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RARα fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all- trans retinoic acid (ATRA), 45 mg/m 2 /d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m 2 /d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of ...
    Background: FCR regimen has provided encouraging results in FL and Yttrium-90 Ibritumomab Tiuxetan (90Y-RIT) has been reported to be effective in patients with relapsed or refractory FL. Our study investigates the efficacy and safety of... more
    Background: FCR regimen has provided encouraging results in FL and Yttrium-90 Ibritumomab Tiuxetan (90Y-RIT) has been reported to be effective in patients with relapsed or refractory FL. Our study investigates the efficacy and safety of 90Y-RIT consolidation in relapsed FL patients, responding to second-line with FCR. Methods: At date reporting for this abstract we have recruited 10 patients median age 63 yrs (range 46–77). All enrolled patients were relapsed patients with histologically confirmed CD20-positive (grade 1 or 2) FL according to WHO classification. Major inclusion criteria were: age ≥ 18 years, WHO performance status of 0, 1 or 2, no prior therapy with Rituximab for 3 months and at the completion of FCR, patients achieving at least PR, with < 25% bone marrow involvement, with neutrophil count ≥ 1500/microlitre and platelet count ≥ 100000/microlitre. All patients at relapse received every 28 days FCR: F (25mg/m2×3 days), C (1gr/m2day1) and R (375mg/m2day4) for 4 cycle...
    Treatment of ET is still a matter of debate for the difficulty in deciding between platelet(plt)-lowering agents and a “wait and see” policy with anti-aggregating agents only: a main problem is to identify what patients are “at risk” to... more
    Treatment of ET is still a matter of debate for the difficulty in deciding between platelet(plt)-lowering agents and a “wait and see” policy with anti-aggregating agents only: a main problem is to identify what patients are “at risk” to develop severe thrombotic events during the course of the disease. Thus, we prospectively tested in ET patients at diagnosis with no clear indication to plt-lowering treatment a score system based on the following 5 variables: age, plt level, previous thrombotic events, smoking, dismetabolic diseases: the score was reassessed in each patient every 3 months during follow-up. From 04/92 to 03/98, 168 consecutive adult patients (57 males and 111 females, median age 59.5 yrs, range 20.5 – 84.8, median plt value 1,010 x 109/l, range 587 – 2,714) with ET according to PVSG criteria were diagnosed at our Institution. Among them, a plt-lowering treatment was started in 32 patients considered “symptomatic” for the presence at diagnosis or within 6 months befor...
    The AML8A protocol of the European Organization for Research on Treatment of Cancer (EORTC) and GIMEMA Cooperative Groups studied the value of allogeneic (allo-BMT) and autologous bone marrow transplantation (autoBMT) in adult acute... more
    The AML8A protocol of the European Organization for Research on Treatment of Cancer (EORTC) and GIMEMA Cooperative Groups studied the value of allogeneic (allo-BMT) and autologous bone marrow transplantation (autoBMT) in adult acute myelogenous leukemia (AML) when performed during first complete remission (CR). Following one or two courses of remission induction treatment, 66% of patients achieved a CR. Then 168 patients who had an HLA-identical sibling were assigned to alloBMT, while 254 were randomized for an autoBMT or for a second intensive consolidation course. Disease-free survival (DFS) of the intensive chemotherapy arm was 30% at 4 years, the DFS in the alloBMT and autoBMT arms were 55% and 48%, respectively. The two BMT arms gave significantly better results than the intensive chemotherapy arm (p = 0.03). The main reason for failure is relapse in both the autoBMT and the chemotherapy arms, while treatmentrelated mortality is higher in the alloBMT arm.
    The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short- lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha... more
    The advent of retinoic acid (RA) in the treatment of acute promyelocytic leukemia (APL) has led to a high frequency of short- lasting complete remissions (CR). We studied the response to RA by molecularly analyzing the RA receptor alpha (RAR alpha) locus, which has recently been shown to be rearranged in all APLs. Southern blot analysis demonstrated that the RAR alpha rearrangements persisted in the APL samples containing maturing myeloid cells 2 to 3 weeks after the start of RA treatment, but disappeared after 5 to 8 weeks, when the patients achieved CR. Our investigations provide clear evidence that CR occurs at molecular level and that there is reconstitution of an apparently normal, nonclonal hematopoiesis. Further, it shows that RA acts by triggering differentiation rather than by exerting a cytotoxic effect on the leukemic clone.
    1195 Poster Board I-217 The policy of the Rome Transplant Network (RTN), a metropolitan network of transplant Centers, for patients candidates to an allogeneic hematopoietic stem cell transplant (HSCT) and lacking an HLA identical sibling... more
    1195 Poster Board I-217 The policy of the Rome Transplant Network (RTN), a metropolitan network of transplant Centers, for patients candidates to an allogeneic hematopoietic stem cell transplant (HSCT) and lacking an HLA identical sibling is the contemporary search for one the HSC alternative sources such as Matched Unrelated Donor (MUD),Cord Blood Unit (CBU) or Haploidentical Related Donor (HRD). The main aim of the RTN policy is the identification of a suitable donor in order to perform transplant in adequate timing. The selection criteria for MUD consist of a 8/8 HLA loci matching tested at low resolution for class I HLA and at high resolution (HR) for class II; one difference in C Ag is considered acceptable in case of both I and II class HR identity.…
    Hematopoietic Stem Cell Transplantation (HSCT) is known to induce the inhibitory immune receptor NKG2A on NK cells of donor origin. This occurs in allogeneic recipients, in both the haploidentical and HLA-matched settings. To gain further... more
    Hematopoietic Stem Cell Transplantation (HSCT) is known to induce the inhibitory immune receptor NKG2A on NK cells of donor origin. This occurs in allogeneic recipients, in both the haploidentical and HLA-matched settings. To gain further insight, not only NKG2A, but also the activating receptors NKG2C and NKG2D were assessed by flow cytometry. Immunophenotyping was carried out not only on CD56(+) but also on CD8(+) lymphocytes from leukemia and lymphoma patients, receiving both HLA-matched (n = 7) and autologous (n = 5) HSCT grafts. Moreover, cognate NKG2 ligands (HLA-E, MICA, ULBP-1, ULBP-2 and ULBP-3) were assessed by immunohistochemistry in diagnostic biopsies from three autotransplanted patients, and at relapse in one case. All the NKG2 receptors were simultaneously up-regulated in all the allotransplanted patients on CD8(+) and/or CD56(+) cells between 30 and 90 days post-transplant, coinciding with, or following, allogeneic engraftment. Up-regulation was of lesser entity and ...
    An assessment of the lymphocyte sub-populations and cell mediated cytotoxicity was made in 12 adults with acute non-lymphoid leukemia after stopping chemotherapy. No significant differences were found between ANLL and controls, for... more
    An assessment of the lymphocyte sub-populations and cell mediated cytotoxicity was made in 12 adults with acute non-lymphoid leukemia after stopping chemotherapy. No significant differences were found between ANLL and controls, for absolute lymphocyte count, %SIg/+ cells, Fc gamma + cells and ERFC. The OKT4+/OKT8+ was reduced in ANLL. Leu-7+ cells were significantly higher in ANLL. Moreover it appears that in ANLL lymphocyte function is restored early after stopping chemotherapy.
    A short-term 51Cr-release assay was employed to investigate polymorphonuclear leukocyte (PMN) antibody-dependent (ADCC) and phytohemaglutinin-induced (PHA-ICC) cytotoxicity against chicken erythrocytes in 28 patients with myelodysplastic... more
    A short-term 51Cr-release assay was employed to investigate polymorphonuclear leukocyte (PMN) antibody-dependent (ADCC) and phytohemaglutinin-induced (PHA-ICC) cytotoxicity against chicken erythrocytes in 28 patients with myelodysplastic syndromes (MDS). MDS patients PMN-mediated ADCC and PHA-ICC were significantly reduced when compared to normal donors. When the patients were subdivided according to the revised FAB classification, a reduction in PHA-ICC from the RAEB group and a progressive impairment of ADCC from RA to RAEB-t patients was observed. These abnormalities may be ascribed to a reduced number of effector cells or to a metabolic impairment of their cytolytic capacity. These PMN functional deficiences may contribute to the increased susceptibility to infectious diseases, irrespective of the presence of granulocytopenia.
    Because of the lack of standard treatment in refractory and relapsed acute myelogenous leukemia (AML) several new drugs have been employed alone to evaluate their efficacy in this peculiar category of patient. Bisantrene, a new anthracene... more
    Because of the lack of standard treatment in refractory and relapsed acute myelogenous leukemia (AML) several new drugs have been employed alone to evaluate their efficacy in this peculiar category of patient. Bisantrene, a new anthracene bishydrazone derivative, has shown antileukemic effect in phase I and II clinical trials with acceptable extrahaematological toxicity. Seven patients (six males and one female, median age 41.8 years) received Bisantrene (250 mg/sqm/daily 1-7) as a single agent in relapsed or refractory leukemia. 5 out of 7 patients achieved complete remission, one attained partial remission and one was resistant. However, haematological toxicity was severe with prolonged myelosuppression. Hepatic toxicity was the main extrahaematological side effect and occurred in 3 of 7 patients, however all of them recovered within 40 days. No cardiovascular dysfunction occurred although all the patients had been heavily previously treated with anthracyclines. Our data confirm that Bisantrere is active in relapsed and refractory AML and suggest the need for larger clinical trials to better evaluate its efficacy.
    The occurrence of acute myeloid leukemia (AML) as a secondary tumor has been frequently reported in patients who received various chemotherapy regimens for hematologic malignancies wile the concomitant development of chronic... more
    The occurrence of acute myeloid leukemia (AML) as a secondary tumor has been frequently reported in patients who received various chemotherapy regimens for hematologic malignancies wile the concomitant development of chronic lymphoproliferative diseases (CLD) and AML in previously untreated patients is extremely rare. We report a case with an apparently spontaneous occurrence of AML and non Hodgkin low-grade lymphoma diagnosed by immunological, cytogenetical and molecular analyses. In particular genetic studies allowed to identify the coexistence of a clonal lymphoid population and a myeloid blast component characterized by inv(16) marker and CBFbeta-MYH11 gene fusion. Complete remission of AML and the CLD was obtained following high doses of hydroxyurea and two consolidation cycles of fludarabine plus intermediate dose cytarabine.
    Because of the reported high sensitivity of acute promyelocytic leukemia to daunorubicin, we treated 27 consecutive, newly diagnosed, acute promyelocytic leukemia (APL) patients with the new anthracycline idarubicin (IDA) as induction... more
    Because of the reported high sensitivity of acute promyelocytic leukemia to daunorubicin, we treated 27 consecutive, newly diagnosed, acute promyelocytic leukemia (APL) patients with the new anthracycline idarubicin (IDA) as induction therapy. IDA dosage ranged from 0.25 to 0.30 mg/kg/day and the drug was administered as single agent during a single induction course of 6 days. A total of 22/27 patients (81%) achieved complete remission, 4 (15%) died during induction and 1 patient was resistant to IDA. Extrahematological toxicity was acceptable. A total of 13/22 patients having achieved CR are still alive and in first CR after a median follow-up of 12 months. As for the treatment of the coagulopathy present in APL: 17/27 (63%) received tranexamic acid (6 g/daily) in continuous infusion for total of 7 d. None of the patients treated with tranexamic acid experienced thromboembolic complications. In conclusion, this multicentric pilot study confirms the antileukemic potency of IDA and the high sensitivity of APL to anthracycline derivatives.
    A multicentric prospective pilot study using three different schedules of high-dose Ara-C at dosage of 3 g/m2 every 12 hours during 3 h of infusion was undertaken by the Italian Cooperative Group GIMEMA in order: 1. to evaluate the safety... more
    A multicentric prospective pilot study using three different schedules of high-dose Ara-C at dosage of 3 g/m2 every 12 hours during 3 h of infusion was undertaken by the Italian Cooperative Group GIMEMA in order: 1. to evaluate the safety and efficacy of such treatment in previously untreated ANLL patients more than 50 years old; 2. to investigate whether the addition of a standard maintenance treatment after consolidation with 4 courses of DAT (Daunorubicin + Ara-C + 6-Thioguanine) could improve the duration of complete remission (CR) and the proportion of long-term survival. Overall 43/125 evaluable patients (34.4%) achieved CR. 32/125 died during the induction phase, the remaining 50 patients (40%) failed to achieve CR. As for the toxicity, the most significant toxicity of all schedules was hematologic. No substantial neurological or cardiac toxicity was observed. The multivariated analysis of several pretreatment characteristics revealed that age more than 60 yr, male sex and presence of infections at diagnosis were the most significant adverse factors for achievement of CR. The median duration of DFS for all responders was 9 months, with relapse-free survival at 4 yr estimated at 29%. The addition of maintenance treatment to consolidated patients had no advantages in respect to the control group, even though the statistical analysis revealed a p = 0.058. However, because of the small number of randomized patients, no conclusions can be drawn concerning the importance of maintenance treatment.
    Blastoschizomyces capitatus (formerly named Trichosporon capitatum or Geotrichum capitatum) is a rare cause of invasive fungal disease in immunocompromised hosts. We retrospectively studied epidemiologic, clinical, pathologic, and... more
    Blastoschizomyces capitatus (formerly named Trichosporon capitatum or Geotrichum capitatum) is a rare cause of invasive fungal disease in immunocompromised hosts. We retrospectively studied epidemiologic, clinical, pathologic, and microbiologic features of this infection during a 68-month period at the Division of Hematology of the University La Sapienza in Rome. Twenty patients with evidence of B. capitatus were identified: 12 were infected, four were possibly infected, and four had evidence of B. capitatus colonization but were not infected by this fungus. Pulmonary infiltrates were seen in seven infected patients; four of these patients eventually developed mycetomalike cavitations. Eight infected patients presented clinical and radiologic features of focal hepatitis compatible with hepatosplenic candidiasis. Of the 12 infected patients, two did not receive any antifungal treatment and died, five did not show any response to systemic antifungal therapy, and five received prolonged amphotericin B plus 5-fluorocytosine therapy. Of the last group, three patients achieved stable remission of their acute leukemia and were cured, and two improved but had an apparent relapse of B. capitatus infection after their acute leukemia recurred.
    Purpose: Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor... more
    Purpose: Epigenetic changes play a role and cooperate with genetic alterations in the pathogenesis of myelodysplastic syndromes (MDS). We conducted a phase II multicenter study on the combination of the DNA-methyltransferase inhibitor 5-azacytidine (5-AZA) and the histone deacetylase inhibitor valproic acid (VPA) in patients with higher risk MDS. Experimental Design: We enrolled 62 patients with MDS (refractory anemia with excess blasts, 39 patients; refractory anemia with excess blasts in transformation, 19 patients; and chronic myelomanocytic leukemia (CMML), 4 patients) and an International Prognostic Scoring System (IPSS) rating of Intermediate-2 (42 patients) or high (20 patients). VPA was given to reach a plasma concentration of >50 μg/mL, then 5-AZA was added s.c. at 75 mg/m2 for 7 days in eight monthly cycles. Results: The median overall survival was 14.4 months. At a median follow-up of 12 months (range, 0.7-21.0), the disease progressed in 20 patients, with 21% cumulati...
    ... TRANSIENT SPONTANEOUS REMISSION IN A CASE OF ADULT ACUTE MYELOGENOUS LEUKAEMIA. Antonio Spadea,; Roberto Latagliata,; Elvira Martinelli,; Maria Concetta Petti. Article first published online: 12 MAR 2008. DOI:... more
    ... TRANSIENT SPONTANEOUS REMISSION IN A CASE OF ADULT ACUTE MYELOGENOUS LEUKAEMIA. Antonio Spadea,; Roberto Latagliata,; Elvira Martinelli,; Maria Concetta Petti. Article first published online: 12 MAR 2008. DOI: 10.1111/j.1365-2141.1990.tb07856.x. Issue. ...
    After the identification of discrete relapse-risk categories in patients with acute promyelocytic leukemia (APL) receiving all-trans retinoic and idarubicin (AIDA)–like therapies, the Gruppo Italiano Malattie Ematologiche dell'Adulto... more
    After the identification of discrete relapse-risk categories in patients with acute promyelocytic leukemia (APL) receiving all-trans retinoic and idarubicin (AIDA)–like therapies, the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) designed a protocol for newly diagnosed APL (AIDA-2000) in which postremission treatment was risk-adapted. Patients with low/intermediate risk received remission at 3 anthracycline-based consolidation courses, whereas high-risk patients received the same schedule as in the previous, non–risk-adapted AIDA-0493 trial including cytarabine. In addition, all patients in the AIDA-2000 received all-trans retinoic acid (ATRA) for 15 days during each consolidation. After induction, 600 of 636 (94.3%) and 420 of 445 (94.4%) patients achieved complete remission in the AIDA-0493 and AIDA-2000, respectively. The 6-year overall survival and cumulative incidence of relapse (CIR) rates were 78.1% versus 87.4% (P = .001) and 27.7% versus 10.7% (P < .0001...
    We evaluated the therapeutic efficacy of autologous bone marrow transplantation (ABMT) in 49 patients with acute leukemia, using ex-vivo-treated marrow with mafosfamide. This report summarizes data collected from 8 Italian centers,... more
    We evaluated the therapeutic efficacy of autologous bone marrow transplantation (ABMT) in 49 patients with acute leukemia, using ex-vivo-treated marrow with mafosfamide. This report summarizes data collected from 8 Italian centers, involving 27 cases with acute lymphoid leukemia (ALL) and 22 cases with acute nonlymphoid leukemia (ANLL). The analysis of the results shows that the disease-free survival of ALL and
    Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European... more
    Intensive consolidation therapy compared with standard consolidation and maintenance therapy for adults with acute myeloid leukaemia aged between 46 and 60 years: final results of the randomized phase III study (AML 8B) of the European Organization for Research and Treatment
    Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall.... more
    Neutropenic enterocolitis (NE) is a severe complication of intensive chemotherapy and is barely identifiable by clinical signs alone. Ultrasonography (US) supports the diagnosis of NE by showing pathologic thickening of the bowel wall. The aim of this study was to evaluate the prognostic value of the degree of mural thickening evaluated by US in patients with clinically suspected NE. Neutropenic patients with fever, diarrhea, and abdominal pain after intensive chemotherapy for hematologic malignancies were studied with abdominal US. We evaluated the degree of bowel wall thickening detected by US and its correlation with the duration of the clinical syndrome as well as NE-related mortality. Eighty-eight (6%) of 1,450 consecutive patients treated for leukemia had clinical signs of NE. In 44 (50%) of 88 patients, US revealed pathologic wall thickening (mean +/- SD, 10.2 +/- 2.9 mm; range, 6 to 18). The mean duration of symptoms was significantly longer in this group (7.9 days) than among patients without mural thickening (3.8 days, P <.0001), and the NE-related mortality rate was higher (29.5% v 0%, P <.001). Patients with bowel wall thickness of more than 10 mm had a significantly higher mortality rate (60%) than did those with bowel wall thickness < or = 10 mm (4.2%, P <.001). Symptomatic patients with sonographically detected bowel wall thickening have a poor prognosis compared with patients without this finding. In addition, mural thickness of more than 10 mm is associated with poorer outcome among patients with NE.
    The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single... more
    The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.
    From November, '85 to March, '87, 17 patients (12 males and 5 females, median 28 years) with resistant or relapsed ANLL received HiDAC (3 g/m2 c.i. 3 hs every 12 hs, day 1-4) + m-AMSA (100 mg/m2 i.v. day... more
    From November, '85 to March, '87, 17 patients (12 males and 5 females, median 28 years) with resistant or relapsed ANLL received HiDAC (3 g/m2 c.i. 3 hs every 12 hs, day 1-4) + m-AMSA (100 mg/m2 i.v. day 5-7) as salvage therapy: 8/17 patients (47.1%) achieved CR, 7/17 (41.1%) were resistant and 2/17 (11.8%) died during induction; 8/10 relapsed patients achieved a 2nd CR, while all 7 primary resistant patients failed to. Median period of PMN less than 0.5 x 10(9)/l was 28 days, median period of PLTS less than 30 x 10(9)/l was 25 days. All patients had infections during aplasia. Median CR duration was 6.6 months, while median survival of responders was 10.6 months. Two patients with severe induction-related complications relapsed after 2 and 5 months, respectively: 1 patient underwent BMT and relapsed after 21 months; 5 patients, 4 of whom had received a prior ABMT during 1st CR, underwent ABMT: 3 died from ABMT related toxicity and 2 relapsed after 8 and 18 months, respectively. We conclude that HiDAC + m-AMSA is highly effective in relapsed, but not in resistant patients with acceptable hematologic and extra-hematologic toxicity. The role and modalities of ABMT in prolonging a 2nd CR are at present controversial.
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    The prognostic value of 12 clinical and haematological parameters, recorded at diagnosis, in myelofibrosis with myeloid metaplasia (MMM) was retrospectively analysed in a consecutive series of 133 patients followed for a minimum of 60... more
    The prognostic value of 12 clinical and haematological parameters, recorded at diagnosis, in myelofibrosis with myeloid metaplasia (MMM) was retrospectively analysed in a consecutive series of 133 patients followed for a minimum of 60 months. Multivariate analysis showed that the following features were associated with a significantly shorter survival: (1) short period of time (less than 13 months) between first symptoms and diagnosis; (2) anaemia (haemoglobin less than 10 g/dl); (3) leucocyte count greater than 12 x 10(9)/l; (4) peripheral blood granulocyte precursors greater than 10%. Age, splenectomy and percentage of peripheral blood metamyelocytes were found significantly to affect survival only from univariate analysis, whereas sex, size of spleen, thrombocytopenia and thrombocytosis were of no prognostic significance. These data suggest that a more intensive chemotherapy might be useful for younger patients with bad prognostic factors at diagnosis.
    A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h,... more
    A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or doc...

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