A population-based study of chronic myeloid leukemia patients treated with imatinib in first line.

Chronic myeloid leukemia (CML) treatment is based on company-sponsored and academic trials testing different tyrosine kinase inhibitors (TKIs) as first-line therapy. These studies included patients selected according to many inclusion-exclusion criteria, particularly age and comorbidities, with specific treatment obligations. In daily clinical practice (real-life), inclusion-exclusion criteria do not exist, and the treatment outcome does not only depend on the choice of first-line TKI but also on second- and third-line TKIs. To investigate in a real-life setting the response and the outcome on first-line imatinib, with switch to second generation TKIs in case of unsatisfying response or intolerance, we analyzed all newly diagnosed patients (N = 236), living in two Italian regions, registered in a prospective study according to population-based criteria and treated front-line with imatinib. A switch from imatinib to second-generation TKIs was reported in 14% of patients for side effects and in 24% for failure or suboptimal response, with an improvement of molecular response in 57% of them. The 5-year overall survival (OS) and leukemia-related survival (LRS) were 85% and 93%, respectively; the 4-year rates of MR3.0 and MR4.0 were 75% and 48%, respectively. Cardiovascular complications were reported in 4% of patients treated with imatinib alone and in 6% of patients receiving nilotinib as second-line. Older age (≥70 years) affected OS, but not LRS. These data provide an unbiased reference on the CML management and on the results of TKI treatment in real-life, according to ELN recommendations, using imatinib as first-line treatment and second-generation TKIs as second-line therapy. Am. J. Hematol. 92:82-87, 2017. © 2016 Wiley Periodicals, Inc.

Effects and outcome of a policy of intermittent imatinib treatment in elderly patients with chronic myeloid leukemia.

We report a study of an alternative treatment schedule of imatinib (IM) in chronic myeloid leukemia (CML). Seventy-six Philadelphia-positive (Ph+), BCR-ABL-positive patients aged 65 years or older who had been treated with IM for more than 2 years and who were in stable complete cytogenetic response (CCgR) and major molecular response (MMR) were enrolled in a single-arm study to test the effects of a policy of intermittent IM (INTERIM) therapy for 1 month on and 1 month off. With a minimum follow-up of 4 years, 13 patients (17%) lost CCgR and MMR and 14 (18%) lost MMR only. All these patients resumed continuous IM and all but one (lost to follow-up) regained CCgR and MMR. No patients progressed to accelerated or blastic phase or developed clonal chromosomal abnormalities in Ph+ cells or BCR-ABL mutations. In elderly Ph+ CML patients carefully selected for a stable CCgR (lasting >2 years), the policy of INTERIM treatment affected the markers of residual disease, but not the clinical outcomes (overall and progression-free survival). This trial was registered at www.clinicaltrials.gov as NCT 00858806.

Long term outcome of Ph+ CML patients achieving complete cytogenetic remission with interferon based therapy moving from interferon to imatinib era.

Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty-seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow-up, the BCR-ABL transcripts level was available in 96/101 living patients (95%) The BCR-ABL:ABL ratio was between 0.1 and 0.01% (MR(3.0) ) in 17%, and less than 0.01% (MR(4.0) ) in 81% of patients. No patient was completely molecular negative (MR(4.5) or MR(5.0) ). The OS at 10 and 20 years is 92 and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR(4.0) . Complete molecular response (MR(4.5) or MR(5.0) ) seems to be unnecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα.

Management of infection in PNH patients treated with eculizumab or other complement inhibitors: Unmet clinical needs.

This article presents the results of group discussion among an ad hoc constituted panel of experts aimed at identifying and addressing unmet clinical needs (UCNs) in the management of infectious risk associated with eculizumab or new terminal complement inhibitors (CIs) in paroxysmal nocturnal hemoglobinuria (PNH). With the Delphi technique, the most clinically relevant UCNs in PNH patients candidate to or on terminal CI were selected. They resulted to be: optimizing the infection prevention measures; developing non pharmacological infectious risk-mitigation strategies; improving the management of disease exacerbation during infectious complications. For each of these issues consensus opinions were provided and, when appropriate, proposals for advancement in clinical practice were addressed. The hope is that this comprehensive overview will serve to improve the practice of CIs therapy and inform the design and implementation of new studies in the field.

Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study.

OBJECTIVE: We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti-thyroid antibody-negative women from a mild-moderately iodine-deficient (ID) area. DESIGN: Observational cohort study. PATIENTS: The study included 168 women receiving prenatal preparations containing 150 µg of iodine from early pregnancy (150-I group); 105 women who had regularly used (>2 years) iodized salt prior to becoming pregnant (I-salt group); 160 women neither taking iodine supplements nor using iodized salt (no-I group). MEASUREMENTS: Maternal TSH, FT3 and FT4 were determined throughout gestation. RESULTS: Mean TSH concentrations were higher among the 150-I women than in the remaining two groups, and in a high proportion of them, TSH values were found to exceed the upper limit for gestational age. Conversely, the prevalence of low free-thyroxine levels in the 150-I women was similar to that observed in the I-salt women and markedly lower than that recorded for the no-I group. CONCLUSIONS: The regular use of iodine-containing supplements proved effective in reducing the risk of inappropriately low FT4 levels during pregnancy. The observed TSH increase in 150-I women may be because of a transient stunning effect on the thyroid gland, occurring as a result of the abrupt increase in daily iodine intake. Whilst the importance of gestational iodine supplementation is undisputed, we believe that in mild-moderately ID areas, women considering conception should be advised to take iodine supplementation for several months prior to pregnancy.

Molecular response and quality of life in chronic myeloid leukemia patients treated with intermittent TKIs: First interim analysis of OPTkIMA study.

BACKGROUND: Intermittent treatment with TKIs is an option for the great majority (70%-80%) of CML patients who do not achieve a stable deep molecular response and are not eligible for treatment discontinuation. For these patients, the only alternative is to assume TKI continuously, lifelong. METHODS: The Italian phase III multicentric randomized OPTkIMA study started in 2015, with the aim to evaluate if a progressive de-escalation of TKIs (imatinib, nilotinib, and dasatinib) is able to maintain the molecular response (MR3.0 ) and to improve Health Related Quality of Life (HRQoL). RESULTS: Up to December 2018, 166/185 (90%) elderly CML patients in stable MR3.0 /MR4.0 completed the first year of any TKI intermittent schedule 1 month ON and 1 month OFF. The first year probability of maintaining the MR3.0 was 81% and 23.5% of the patients who lost the molecular response regained the MR3.0 after resuming TKI continuously. Patients' HRQoL at baseline was better than that of matched peers from healthy population. Women was the only factor independently associated with worse baseline HRQoL (p > 0.0001). Overall, global HRQoL worsened at 6 (p < 0.001) but returned to the baseline value at 12 months and it was statistically significantly worse in women (p = 0.001). CONCLUSIONS: De-escalation of any TKI by 1 month ON/OFF schedule maintains the MR3.0 /MR4.0 in 81% of the patients during the first 12-24 months. No patients progressed to accelerated/blastic phase, all the patients (23.5%) losing MR3.0 regained the MR3.0 and none suffered from TKI withdrawn syndrome. The study firstly report on HRQoL in elderly CML patients moving from a continuous daily therapy to a de-escalated intermittent treatment.

Wound length and corticosteroid administration as risk factors for surgical-site complications following cesarean section.

OBJECTIVE: To evaluate the effect of some specific gestational factors and other known variables associated with poor wound healing in women who delivered by cesarean section. DESIGN: Observational, prospective study. SETTING: University Hospital of Messina. POPULATION: A total of 212 consecutive pregnant women at term delivering by elective cesarean section. METHODS: All data regarding demographic and gestational characteristics were collected at admission. The subcutaneous tissue depth was intra-operatively measured from the fascia to the skin surface, while the incision length was measured after skin closure. MAIN OUTCOME MEASURES: Onset of wound complications such as infection, seroma, hematoma, abscess or dehiscence > 1 cm. RESULTS: Body mass index (BMI) at term [odd ratio (OR) 1.2, 95%CI 1.03-1.38; p = 0.01], wound length (OR 1.03, 95%CI 1.01-1.05; p < 0.001) and corticosteroid administration (OR 3.4, 95%CI 1.5-7.9; p = 0.004) were found to be correlated with wound complications. The receiver operating characteristics curve analysis suggested a cut-off of 31.1 for the BMI at term and 166 mm for the wound length with an OR of 2.28 (95%CI 1.18-4.39; p = 0.013) and 4.3 (95%CI 2.2-8.6; p < 0.001), respectively. The multivariate logistic regression model, applied to these variables and to corticosteroid administration, showed an independent correlation (at term BMI > 31.1: OR 2.04, 1.01-4.13, p = 0.047; wound length > 166 mm: OR 4.89, 2.36-10.14, p < 0.001; corticosteroid administration: OR 3.11, 1.38-6.95, p = 0.006). CONCLUSIONS: To avoid wound complications obstetricians should be careful in the administration of steroids before surgery, in the skin incision length that should be kept as short as possible and in carefully observing gestational BMI.

Long-term follow-up of 386 consecutive patients with essential thrombocythemia: safety of cytoreductive therapy.

Cytotoxic agents like Hydroxyurea, Busulfan and Interferon-alpha are to date the most commonly used therapeutic approaches in Essential Thrombocythemia (ET). However, few data on the efficacy and safety of these agents in the long-term are currently available. We report a retrospective analysis of the long-term outcome of 386 consecutive ET patients, followed at single Institution for a median follow-up of 9.5 years (range, 3-28.5). Cytoreductive therapy was administered to 338 patients (88%), obtaining a response in 86% of cases. Forty-five patients (12%) experienced a thrombosis. Among baseline characteristics, only history of vascular events prior to ET diagnosis predicted a higher incidence of thrombosis. Evolution in acute leukemia/myelofibrosis occurred in 6 (1,5%) and 20 (5%) patients, and was significantly higher in patients receiving sequential cytotoxic agents. Overall survival was 38% at 19 years and was poorer for patients older than 60 years, with higher leukocytes count (>15 x 10(9)/L), hypertension and mellitus diabetes at ET diagnosis and for patients experiencing a thrombotic event during follow-up. Cytoreductive therapy was effective in decreasing platelet number with negligible toxicity; however, thrombocytosis control did not reduce the incidence of thrombosis and, for patients who received sequential therapies, the probability of disease evolution was higher and survival was poorer.

Prenatal identification of isolated bilateral radial dysplasia.

Radial aplasia or hypoplasia is characterized by complete or partial absence of the radius and/or radial ray structure occurring in 1:30,000 live births. It may be unilateral or bilateral of varying severity, and may be isolated or associated with other anomalies. We report an unusual case of isolated radial aplasia at 20 weeks' gestation with complete absence of the right radius and thumb associated with marked hypoplasia of the left radius. The intrauterine 2- and 3-dimensional findings, postnatal radiographic evaluation, and autopsy results are reported.

Emotional state and dreams in pregnant women.

The aim of this study was to investigate the frequency of recall and the content of dreams during pregnancy, as well as their correlation with socio-demographic, obstetric and physician-patients relationship variables, emotional state and duration of labour. A questionnaire, designed to analyse background characteristics, was given to 290 women in the third trimester of gestation. The psychiatric analysis of anxiety and depression was performed using the Hamilton Rating Scale for Anxiety and the Montgomery-Asberg Depression Rating Scale, while dreams were divided into masochistic and pleasant according to Beck's criteria. Oneiric activity was found to be associated with age >or= 35 years, higher family income, higher educational level, and a "satisfactory" physician-patient relationship. Masochistic content was associated with age<35 years, quality of information and frequent thoughts of delivery. Concerning the emotional state, depression levels were higher in women reporting masochistic dreams, while no difference in anxiety levels was found. Labour duration was shorter in the dreamer group and in patients with masochistic dream content. These findings may indicate that, also in pregnancy, the number and the content of dreams are influenced by women's mood and that the evaluation of the oneiric activity might represent a useful tool for clinicians either to investigate the women's emotional state or to predict its repercussions on the course of labour.

Effects of antepartum electronic fetal monitoring on maternal emotional state.

BACKGROUND: To evaluate the emotional state of pregnant women undergoing computerised cardiotocography (cCTG). METHODS: A questionnaire including questions about socio-demographic background, personal obstetric history and physician-patient relationship was given to 204 pregnant women about to undergo cCTG. The Edinburgh Post-natal Depression Scale (EPDS) was used to assess patients' mood state before CTG, while the Spielberger State-Trait Anxiety Inventory (STAI) was used to evaluate anxiety levels before and after this examination. RESULTS: Mean STAI T-anxiety score did not differ before and after CTG (p=0.38), but higher levels of basal anxiety were found in women who had undergone only occasional prenatal controls (p=0.04), as well as smokers (p=0.01), and women preferring a vaginal delivery (p=0.01). The mean STAI S-anxiety score of 43.6+/-4.03 before the cardiotographic examination, increased to 45.2+/-5.4 after this test with a statistically significant difference (p=0.0001). This increase was found to be correlated with the presence of obstetric complications during the current pregnancy (p=0.036) and a lower number of fetal active movements (p=0.029). Based on the EPDS, 22 patients (14.1%) were found to be depressed, but this condition was not correlated with significant increases in anxiety levels. CONCLUSIONS: Anxiety levels in pregnant women who undergo routine CTG are increased, and this emotional reaction seems to be influenced by the perception of fetal movement during the examination, and is more evident in pregnancies affected by obstetric complications.

Endoglin, PlGF and sFlt-1 as markers for predicting pre-eclampsia.

OBJECTIVE: To evaluate the ability of endoglin, placental growth factor (PlGF) and the soluble form of vascular endothelial growth factor receptor (sFlt-1) measurements in gestational weeks 24-28 were used to predict pre-eclampsia. DESIGN: Observational, prospective study. Setting. Department of Gynecological, Obstetrical Sciences and Reproductive Medicine, University of Messina. Sample. Fifty-two pre-eclamptic and 52 healthy pregnant women. METHODS: A maternal serum sample was frozen and stored at 1-h 50-g glucose challenge test between 24 and 28 weeks' gestation. A second maternal serum sample was collected at admission for the onset of the disease in the pre-eclamptic group and at admission for delivery in the control group. Levels of endoglin, sFlt-1 and the PlGF were measured in the stored serum. Pre-eclamptic subjects were also divided into women with early-onset (<37 weeks) and women with late-onset pre-eclampsia (> or =37 weeks). RESULTS: Levels of endoglin, sFlt-1, and sFlt-1:PlGF ratio were found to be higher in the pre-eclamptic group in both trimesters. No differences were found between early- and late-onset pre-eclamptic. The Receiver Operating Characteristics curve, applied to the second trimester marker values, showed the best diagnostic profile for sFlt-1:PlGF (area under the curve, AUC=0.92) followed by endoglin (AUC=0.88), sFlt-1 (AUC=0.87) and PlGF (AUC=0.83). This finding was confirmed by Bayesian analysis which highlighted a specificity, a sensitivity, a diagnostic accuracy, a positive predictive value and a negative predictive value of 88.5% for sFlt-1:PlGF using a cut-off of 38.47. CONCLUSIONS: Endoglin, PlGF and sFlt-1 might be used as markers for predicting pre-eclampsia, but sFlt-1:PlGF seems to be more accurate.

The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome. Results of a multicenter prospective study.

BACKGROUND AND OBJECTIVES: The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor a (PDGFRalpha) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFRalpha tyrosine kinase. These cases with FIP1L1-PDGFRalpha rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. DESIGN AND METHODS: A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. RESULTS: Twenty-seven male patients carried the FIP1L1-PDGFRalpha rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15-60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. INTERPRETATION AND CONCLUSIONS: All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFRalpha rearrangement. For all patients with this rearrangement, chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses.

Midtrimester amniotic fluid leptin and insulin levels and subsequent gestational diabetes.

AIMS: To evaluate midtrimester amniotic fluid leptin levels in pregnancies subsequently complicated by gestational diabetes. METHODS: We studied 32 pregnant women with gestational diabetes and a control group of 43 normal pregnancies with an adequate gestational age fetus. All underwent a midtrimester amniocentesis: leptin and insulin were measured in the amniotic fluid. Data were compared with the Mann-Whitney U-test. RESULTS: Median leptin concentrations in the amniotic fluid of the gestational diabetes mellitus patients were significantly higher than in the control group (15.1 vs. 7.9 ng/ml) (p = 0.001); amniotic insulin concentrations were also higher in the gestational diabetes mellitus than in the control group (0.67 vs. 0.38 microU/ml) (p = 0.02). Furthermore, amniotic fluid leptin levels were directly correlated with amniotic insulin concentrations; instead, there was no correlation with maternal BMI and birth weight. CONCLUSION: Our data suggest that in pregnancies subsequently complicated by gestational diabetes, amniotic fluid leptin and insulin levels are higher in the early fetal period.

ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.

Resolution of a Pseudomonas aeruginosa outbreak in a hematology unit with the use of disposable sterile water filters.

We observed a significant increase of Pseudomonas aeruginosa bacteremias during 2002. Eighty-five microbiological samples were taken from different potential sources of infection. Twenty-nine out of 46 specimens obtained from water taps, shower heads and siphons tested positive for Pseudomonas aeruginosa. Weekly pharyngeal and rectal swabs in high risk patients, use of tap water after running the tap for at least 5 minutes and use of weekly disposable sterile filters in all taps and showers resulted in a significant decrease in Pseudomonas aeruginosa bacteremias. Moreover, we observed a significant reduction in Pseudomonas aeruginosa-positive surveillance cultures after implementation of these measures.

Cesarean section on demand: are there differences related to obstetricians' gender?

To assess possible differences related to the physicians' gender, in the motivations for a cesarean section on demand, an anonymous questionnaire was sent to 60 male and 60 female obstetricians. Maternal emotional motivations, role of relatives, influence of instrumental examinations and personal attitude towards fulfilling maternal choice were analysed. Among emotional motivations, a previous negative perinatal experience and the fear of childbirth were more frequently reported by males (96.6% vs. 46.6%, p = 0.001; 98.2% vs. 61.6%, p = 0.001), as was ultrasonography (48.2% vs. 15%, p < 0.001) among the instrumental examinations. On the contrary, no differences were evidenced for the role played by relatives and for the physician's attitude in fulfilling maternal choice.

C-reactive protein as an early predictor of gestational diabetes mellitus.

OBJECTIVE: To assess whether C-reactive protein at the beginning of the midtrimester is significantly increased in patients who subsequently develop gestational diabetes mellitus (GDM). STUDY DESIGN: A total of 72 subjects who underwent a Down screening program between the 14th and 16th weeks of gestation were studied: 32 developed GDM, and 40 were controls. The C-reactive protein serum levels were evaluated in all patients. RESULTS: There was a significant difference in body mass index (BMI) mean values between the GDM group (30.8 +/- 8.5) and control group (24.7 +/- 2.8), but in spite of this, no significant difference in C-reactive protein was found in the 2 groups. The median serum C-reactive protein values were 9.0 mg/dL (2.4-17, 5-95% CI) in the GDM group and 8.7 mg/dL (3.8-11.2, 5-95% CI) in the control group (p = 0.3). There was no correlation between C-reactive protein serum levels and BMI, birth weight or fasting insulin. CONCLUSION: C-reactive protein has no predictive value in GDM, and no positive correlation is found between BMI and this inflammation marker.

Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin's lymphoma: an Italian multicenter randomized trial.

PURPOSE: To evaluate the role of early intensification with high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) as front-line chemotherapy for patients with high-risk, histologically aggressive non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: We planned a multicenter, randomized trial to compare a conventional chemotherapy regimen of methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B; arm A) with an abbreviated regimen of MACOP-B (8 weeks) followed by HDT and ASCT (arm B) for intermediate-high-risk/high-risk patients (according to the age-adjusted International Prognostic Index). From September 1994 to April 1998, 150 patients with aggressive lymphoma were enrolled onto the trial. Seventy-five patients were randomly assigned to arm A and 75 patients were randomly assigned to arm B. In both arms, involved-field radiation therapy (36 Gy) was delivered to the site of bulky disease. RESULTS: The rate of complete response was 68% in arm A and 76% in arm B (P = not significant [NS]). Three toxic deaths (4%) occurred in arm B and one (1%) occurred in arm A (P = NS). In arm B, 30 patients (40%) did not undergo HDT and ASCT. According to the intention-to-treat analysis at a median follow-up of 24 months, 5-year overall survival probability in arms A and B was 65% and 64% (P =.95), 5-year progression-free survival was 49% and 61% (P =.21), and 5-year relapse-free survival was 65% and 77% (P =.22), respectively. CONCLUSION: Abbreviated chemotherapy followed by intensification with HDT-ASCT is not superior to conventional chemotherapy in patients with high-risk, aggressive NHL. Additional randomized trials will clarify whether HDT-ASCT as front-line therapy after a complete course of conventional chemotherapy improves survival in this group of patients.

Efficacy and safety of splenectomy in immune thrombocytopenic purpura: long-term results of 402 cases.

BACKGROUND AND OBJECTIVES: Immune thrombocytopenic purpura (ITP) is an acquired autoimmune disease characterized by platelet destruction. Glucocorticoids are the first-choice treatment, resulting in a complete (CR) or partial (PR) response in 70-80% of cases. In most cases, however, response is transient or glucocorticoid-dependent. For these and for selected patients with acute refractory ITP, splenectomy may produce a good response (CR+PR) in about 60-80% of cases. We report here the long-term outcome of a large cohort of ITP splenectomized patients. DESIGN AND METHODS: We retrospectively analyzed the data on 402 patients (137 males, 265 females) who underwent splenectomy for ITP between 1959 and 2002 in 22 different Hematology Centers. RESULTS: Seventy-nine of the 345 (23%) responsive patients relapsed, in most cases (80%) within 48 months from splenectomy. Sixty-eight out of these 79 patients (86%) were then treated with a good response in 46/68 (68%) cases. Fifty-four of the 57 patients refractory to splenectomy and were treated, after the surgery, with a good response in 27/54 (50%) cases. Infection and thrombosis did not significantly weigh upon the outcome of the patients. Only three patients died of hemorrhage during follow-up. By multivariate analysis, the number of therapies before (p<0.01) and higher peak post-splenectomy platelet count (p<0.00001) were predictive of a favorable response to splenectomy, whereas only higher post-splenectomy peak platelet count (p<0.001) was predictive of relapse. INTERPRETATION AND CONCLUSIONS: This study shows that splenectomy is a safe procedure and effective in approximately two thirds of patients with chronic ITP. Further studies are required to establish whether surgery-sparing treatments of chronic ITP, such as high-dose dexamethasone, anti-D and anti-CD20 immunoglobulins, have similar or even superior efficacy, risk and cost ratios compared to splenectomy.