Differences among young adults, adults and elderly chronic myeloid leukemia patients.

BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old) particularly for the frequency of splenomegaly (71%, 63% and 55%, P < 0.001), and the greater spleen size (median value: 4.5, 3.0 and 1.0 cm, P < 0.001). According to the EUTOS score, that is age-independent, high-risk patients were more frequent among YAs, than among adult and elderly patients (18%, 9% and 6%, P < 0.001). In tyrosine kinase inhibitors-treated patients, the rates of complete cytogenetic and major molecular response were lower in YAs, and the probability of transformation was higher (16%, 5% and 7%, P = 0.011). CONCLUSIONS: The characteristics of CML or the host response to leukemia differ with age. The knowledge of these differences and of their causes may help to refine the treatment and to improve the outcome. CLINICAL TRIAL NUMBERS: NCT00510926, NCT00514488, NCT00769327, NCT00481052.

Uterine myomas during pregnancy: a longitudinal sonographic study.

OBJECTIVE: To evaluate volumetric changes of uterine myomas (fibroids) during pregnancy. METHODS: This was an observational, longitudinal and prospective study of 38 consecutive Caucasian women with singleton pregnancies and a total of 42 uterine myomas, enrolled from a cohort of 1492 women who took part in our first-trimester Down syndrome screening program. Myoma volume was evaluated by ultrasound at 11-14, 20-22 and 32-34 weeks of gestation. RESULTS: Mean myoma volume increased significantly throughout pregnancy. Taking a volumetric change of > 10% between gestational periods to be an increase in size, 71.4% of uterine myomas increased in size between the first and second gestational periods, while this percentage was slightly lower (66.6%) between the second and third periods. Logistic regression analysis revealed that greater maternal age was correlated with a reduction/no change in overall myoma size and multiparity was correlated with a decrease/no change between the first and second trimesters, while a higher prepregnancy maternal body mass index (BMI) was correlated with a volumetric increase between the first and second trimesters and a decrease/no change between the second and third trimesters. CONCLUSIONS: Fibroids enlarge during pregnancy regardless of their initial size or local factors, and maternal age, prepregnancy BMI and parity are apparently correlated with these changes.

Liposomal amphotericin B in the treatment of visceral leishmaniasis in immunocompromised patients.

Leishmaniasis is a zoonosis caused by a protozoan of the Leishmania genus. First-line treatment for all forms is currently represented by the use of antimony derivatives, although toxic effects and the number of resistant strains in both immunocompromised and immunocompetent patients is increasing. Liposomal amphotericin B (L-AMB) is less toxic, more effective, and better tolerated, especially in human immunodeficiency virus-negative immunocompromised patients. We present 2 cases of transplanted patients affected by visceral leishmaniasis treated successfully with L-AMB.

A phase II trial of CHOP chemotherapy followed by yttrium 90 ibritumomab tiuxetan (Zevalin) for previously untreated elderly diffuse large B-cell lymphoma patients.

BACKGROUND: A prospective, single-arm, open-label, nonrandomized phase II combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus radioimmunotherapy trial was conducted to evaluate the efficacy and safety in untreated elderly diffuse large B-cell lymphoma (DLBCL) patients. PATIENTS AND METHODS: From February 2005 to April 2006, in our institute we treated 20 eligible elderly (age > or =60 years) patients with previously untreated DLBCL using a novel regimen consisting of six cycles of CHOP chemotherapy followed 6-10 weeks later by (90)Y ibritumomab tiuxetan. RESULTS: The overall response rate to the entire treatment regimen was 100%, including 95% complete remission (CR) and 5% partial remission. Four (80%) of the five patients who achieved less than a CR with CHOP improved their remission status after radioimmunotherapy. With a median follow-up of 15 months, the 2-year progression-free survival was estimated to be 75%, with a 2-year overall survival of 95%. The (90)Y ibritumomab tiuxetan toxicity included grade > or =3 hematologic toxicity in 12 of 20 patients; the most common grade > or =3 toxic effects were neutropenia (12 patients) and thrombocytopenia (7 patients). Transfusions of red blood cells and/or platelets were given to one patient. CONCLUSION: This study has established the feasibility, tolerability, and efficacy of this regimen for elderly patients with DLBCL.

Caesarean section on request: are there loco-regional factors influencing maternal choice? An Italian experience.

We aimed to evaluate regional differences in women's motivations and in obstetricians' attitudes re 'caesarean section on request' between obstetricians practicing in Southern and Northern Italy. An anonymous questionnaire was sent to 70 randomly selected specialists practicing in the Veneto region and Sicily. Demographic characteristics, percentage of caesarean section, increase of caesarean section on demand, maternal motivations and the role played by anxiety, relatives and instrumental examinations were analysed. Moreover, obstetricians' opinion and their behaviour in fulfilling, or not, the maternal request were evaluated. Among the emotional reasons, fear of pain was more frequently reported in Sicily (p = 0.045), and previous negative experiences and gestational anxiety in the Veneto region (p = 0.009; p = 0.001). As regards instrumental examinations influencing maternal request, a significant difference was found for ultrasonography (28% in Sicily vs 60% in Veneto, p = 0.002). The husband's role was more frequently reported in the Veneto region (p = 0.006). Obstetricians of both regions noticed a rising rate of caesarean section on maternal request. The reasons for this upward trend are complex, vary from one region to another and are influenced by local socio-cultural and healthcare background.

Cryotherapy in the prevention of oral mucositis in patients receiving low-dose methotrexate following myeloablative allogeneic stem cell transplantation: a prospective randomized study of the Gruppo Italiano Trapianto di Midollo Osseo nurses group.

Severe oral mucositis is a major cause of morbidity following allogeneic hematopoietic stem cell transplantation (AHSCT). Cryotherapy, that is, the application of ice chips on the mucosa of the oral cavity during the administration of antineoplastic agents, may reduce the incidence and severity of chemotherapy-related oral mucositis. In this multicenter randomized study, we addressed whether cryotherapy during MTX administration is effective in the prevention of severe oral mucositis in patients undergoing myeloablative AHSCT. One hundred and thirty patients undergoing myeloablative AHSCT and MTX-containing GVHD prophylaxis were enrolled and randomized to receive or not receive cryotherapy during MTX administration. The incidence of severe (grade 3-4) oral mucositis, the primary end point of the study, was comparable in patients receiving or not cryotherapy. Moreover, no difference was observed in the incidence of oral mucositis grade 2-4 and the duration of oral mucositis grade 3-4 or 2-4, or in the kinetics of mucositis over time. In univariate and multivariate analysis, severe oral mucositis correlated with TBI in the conditioning regimen and lack of folinic acid rescue following MTX administration. Thus, cryotherapy during MTX administration does not reduce severe oral mucositis in patients undergoing myeloablative allogeneic HSCT. Future studies will assess cryotherapy before allogeneic HSCT.

Mathematical model for preoperative identification of obstructed nasal subsites.

The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up.

Molecular remission after allogeneic or autologous transplantation of hematopoietic stem cells for multiple myeloma.

PURPOSE: To assess the clinical relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM), 50 patients were monitored while they were in complete clinical remission (CCR) after autologous or allogeneic stem-cell transplantation. PATIENTS AND METHODS: Stringent molecular monitoring using clonal markers based on rearranged immunoglobulin heavy-chain genes was performed in 44 of 50 MM patients in CCR. Molecular clinical remission (MCR) was defined as more than one consecutive negative polymerase chain reaction (PCR) test result. RESULTS: Twelve (27%) of 44 molecularly monitored patients achieved MCR; four of the 12 became PCR-positive, and one of these four relapsed. In comparison with patients who did not achieve MCR, patients who achieved MCR had a significantly lower relapse rate (41% v 16%; P <.05) and longer relapse-free survival (35 v 110 months; P <.005). Fourteen of 26 patients in CCR who had received allografts were evaluated on a molecular basis: seven (50%) of the 14 achieved MCR and did not relapse; one of the seven remaining patients relapsed. Thirty of 47 patients in CCR who received autografts were evaluated on a molecular basis: five (16%) of the 30 achieved MCR; two of these five became PCR-negative, and one of these two relapsed. Ten of the 25 remaining patients later relapsed. For these nonrandomized groups, the higher MCR rate after allograft procedures was statistically significant (P <.01; Fisher's exact test). CONCLUSION: MCR can be obtained in a relatively high proportion of MM patients who have achieved CCR after undergoing allograft procedures and in a smaller fraction of patients after undergoing autograft procedures. In approximately one fourth of MM patients who achieve CCR after transplantation, it may be possible to keep the disease burden constantly below the PCR threshold. Because MCR was associated with prolonged relapse-free survival, these patients could have a relatively favorable clinical outcome.

A phase II study of alpha-interferon and oral arabinosyl cytosine (YNK01) in chronic myeloid leukemia.

YNK01 (Starasid) is a prodrug that is adsorbed in the gut and is transformed in the liver in arabinosyl cytosine (AC). Low-dose AC (LDAC) is useful for the treatment of Philadelphia positive (Ph+) chronic myeloid leukemia (CML), especially in combination with alpha-interferon (alphaIFN). The use of YNK01 can avoid the daily s.c. injection of conventional AC. To assess the safety and the efficacy of alphaIFN and YNK01, we enrolled 86 consecutive previously untreated chronic phase Ph+ CML patients in a phase II study of alphaIFN (Intron-A) 5 MIU/m(2) daily and YNK01 600 mg daily 14 days a month. The 6-month complete hematologic response and the 12-month major cytogenetic response rates were 78 and 28%, respectively. In a prior study of alphaIFN and conventional LDAC, they were 62 and 22%, respectively. However, the compliance to the treatment was poor, with 25% of cases discontinuing the treatment within the first year. This was not because of the severity of the side effects but because of the frequency, duration and repetition of the side effects, for an overall frequency of 13.17 adverse events, mostly grade 1 and 2, per patient per year. Therefore, the study of this effective combination is being pursued, testing lower doses of alphaIFN and YNK01.

Hysterectomy: benefits of clinical performance indicators in the evaluation of healthcare facilities.

PURPOSE: The aim of our study was to verify, by applying clinical performance indicators, the quality of healthcare given to hysterectomy patients and the benefits on their adoption in healthcare facilities. METHODS: The different surgical approaches and indications for surgery were evaluated in 534 patients analysing postoperative short-term complications and triggered clinical performance indicators (CPIs). RESULTS: Surgery was performed by the abdominal (80.9%) and vaginal route (19.1%). Postoperative complication rate was 13.5% and CPIs were triggered 108 times overall: 42 in benign conditions (10.3%) and 30 in malignancy (23.4%) (p = 0.001). In patients operated on for benign conditions the different approaches, abdominal or vaginal, showed differences in postoperative period (p = 0.4). In 10.9% of malignant and in 2.9% of benign conditions hospital stay was triggered (p = 0.001). Vaginal surgery showed a shorter average stay than laparotomy (p = 0.001). CONCLUSION: The use of CPIs may determine a refinement of clinical performance with positive effects on health, patient satisfaction, postoperative morbidity hospitalisation and healthcare cost savings.

Upper body venous thrombosis associated with ovarian stimulation: case report and review of the literature.

Thromboembolic events are a serious complication of assisted conception treatment. Thrombosis may be either arterial or venous but the latter is far more common. This phenomenon is more frequent in the lower limb, but several cases of upper extremity thrombosis have been described in the literature. Although the aetiology of these thromboembolic disorders is not fully understood, the mechanism is thought to be due to a hypercoagulable state associated with haemostasis and thrombophilia. Predisposing factors seem to be hyperoestrogenism, ovarian hyperstimulation syndrome, a hereditary hypercoagulable state and multifoetal pregnancy. We report a case of superior sagittal sinus thrombosis that developed in a patient following successful assisted conception in the absence of evident risk factors. In the current literature, the site of thrombosis, possible predisposing factors, oestrogen levels, number of foetuses, maternal and foetal outcomes, and management of thrombosis were analysed.

Managing chronic myeloid leukaemia in the elderly with intermittent imatinib treatment.

The aim of this study was to investigate the effects of a non-standard, intermittent imatinib treatment in elderly patients with Philadelphia-positive chronic myeloid leukaemia and to answer the question on which dose should be used once a stable optimal response has been achieved. Seventy-six patients aged ⩾65 years in optimal and stable response with ⩾2 years of standard imatinib treatment were enrolled in a study testing a regimen of intermittent imatinib (INTERIM; 1-month on and 1-month off). With a minimum follow-up of 6 years, 16/76 patients (21%) have lost complete cytogenetic response (CCyR) and major molecular response (MMR), and 16 patients (21%) have lost MMR only. All these patients were given imatinib again, the same dose, on the standard schedule and achieved again CCyR and MMR or an even deeper molecular response. The probability of remaining on INTERIM at 6 years was 48% (95% confidence interval 35-59%). Nine patients died in remission. No progressions were recorded. Side effects of continuous treatment were reduced by 50%. In optimal and stable responders, a policy of intermittent imatinib treatment is feasible, is successful in about 50% of patients and is safe, as all the patients who relapsed could be brought back to optimal response.

Circadian variations of rectal cell proliferation in patients affected by advanced colorectal cancer.

The circadian rhythm of the rectal cell proliferation was studied in five patients affected by advanced colon cancer. Biopsies were taken from apparently normal mucosa at 10 cm from the anal verge, every 6 h in a 24-h period. Fragments were incubated for 1 h in a culture medium containing bromodeoxyuridine (BrdUrd). As compared with the mean 24 h values, the percentage of BrdUrd-labelled cells in the crypts (Labelling Index, LI) was lower in the specimens collected at 10.00 PM (P = 0.02) The LI in such biopsies was also lower than the LI observed at the baseline time, 10.00 AM (P = 0.001) The results suggest that the rectal cell proliferation in patients with advanced colon cancer fluctuates during the day. The study of the rhythmicity of the intestinal cells may be useful to modulate the infusion of antiproliferative agents to prevent damage of the normal colorectal mucosa.

Incidence and prognostic relevance of CD34 expression in acute myeloblastic leukemia: analysis of 141 cases.

In 141 adult patients with diagnosis of acute myeloid leukemia the overall expression and intensity of expression of CD34 antigen on leukemic cells was investigated. Myeloid blasts were tested by applying direct immunofluorescence staining using anti-CD34 fluorescein monoclonal antibody in flow cytometry. CD34 antigen was found in 73 out of 141 (51%) cases and in particular in M0, M1 and M4 French-American-British (FAB) cytotypes, while M3 and M5 cases were rarely positive. In patients whose blasts expressed CD34 antigen a significantly lower rate of complete remission (CR) was observed as opposed to CD34 negative cases (61% vs 88%) (P = 0.001). Furthermore, a negative correlation between high intensity of CD34 expression, measured as a mean fluorescence index (MFI), and CR rate was observed. In particular, patients with a higher CD34 fluorescence intensity (MFI > 23), showed a further reduction in CR rate (48%). Also, these patients had a significantly lower overall survival (P = 0.03) as compared to patients with no expression of CD34 and patients with CD34 MFI < 23. In conclusion, these findings confirm that CD34 expression is frequently associated with "immature" FAB cytotypes (M0, M1 and M4) and with a reduced probability to achieve CR. Furthermore, a high CD34 intensity of expression should be considered as a reliable poor prognostic factor.

Interferon-alpha in the treatment of chronic myeloid leukemia. A summary and an update of the Italian studies.

Six-hundred patients were recruited between 1986 and 1991 for studies of the treatment of Ph positive chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha). The median survival of the patients who were assigned to treatment with IFN-alpha was 6 years or longer than 6 years, and was more than the survival of the patients who were assigned to conventional chemotherapy. Survival prolongation was significantly related with the achievement of a cytogenetic response. IFN-alpha treatment was not harmful for subsequent allogeneic or autologous bone marrow transplantation.

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-alpha-based therapy.

We measured using a competitive quantitative polymerase chain reaction-capillary electrophoresis (PCR-CE)-based assay, the levels of bcr-abl transcripts in 44 patients with chronic myeloid leukemia (CML) after interferon-alpha (IFN-alpha) therapy, who achieved a major (10 patients, MCR group) or complete (34 patients, CCR group) cytogenetic response. All 34 CCR patients had molecular evidence of residual disease detected in bone marrow samples at the time of best karyotypic response. The median number of bcr-abl transcripts of 34 evaluable patients in the CCR group at the time of complete cytogenetic remission was 4/microg RNA (range 3-4600), while the median number of bcr-abl transcripts of 10 patients in the MCR group at the time of best cytogenetic response was 4490/microg RNA (range 600-23 900) (P = 0.000024). In nine CCR and five MCR patients we were able to quantify the amount of bcr-abl transcript both at diagnosis and after interferon therapy: no statistical difference (P = 0.18) was found between the two groups at diagnosis (median bcr-abl transcripts/microg RNA was 30 000 vs. 39 650, respectively). During IFN-alpha therapy, the two groups were evaluable at the time of major karyotypic conversion: at this point, there was a statistical difference of expression of bcr-abl transcript between the CCR group (17 patients) (median 2700; range 76-40 000) and the MCR group (10 patients) (median 4490; range 600-23 900), respectively (P = 0.046). No differences of bcr-abl amount of transcript were found in patients with CCR obtained either by IFN-alpha therapy alone (20 patients) vs. IFN-alpha plus ABMT (13 patients) (P = 0.47). We firstly demonstrated that although the CCR and MCR groups were clinically, cytogenetically and molecularly indistinguishable at diagnosis, the two groups could be recognized successfully during interferon therapy based on the level of bcr-abl transcript.

Is Hodgkin's disease a unique entity?

The theoretical bases of Hodgkin's disease (HD) have recently been revised in the light of new findings obtained by means of immunohistochemistry and molecular analysis. These findings have questioned the concept that HD is a unique entity and have made the borders between HD and non-Hodgkin's lymphomas unclear. The clinical relevance of nodular lymphocyte predominance HD (LP-HD), the distinction between T-cell rich B-cell lymphoma and diffuse LP-HD, and the relationships between HD and anaplastic large cell lymphoma are reviewed and discussed.

Bone marrow findings further support the hypothesis that essential mixed cryoglobulinemia type II is characterized by a monoclonal B-cell proliferation.

One-hundred-sixteen consecutive bone-marrow biopsies were taken from 76 patients with essential mixed cryoglobulinemia type II (type II cryo), whose median follow-up was 97 months. Fifty-four out of fifty-six subjects who underwent ELISA and RIBA tests for HCV, were found to be positive. At conventional light microscopic examination, 64/76 patients showed discrete lymphoid infiltrates consisting of small elements with plasmacytoid differentiation and with frequent paratrabecular location. Thirty-nine biopsies were studied by immunohistochemistry that revealed the B-cell nature of the infiltrates (CD20+, CD45RA+, CD79 alpha+, CD3-, CD45RO-), with demonstrable monotypic Ig light-chain restriction in 22 cases. It is worthy of note that the lymphoid elements usually appeared protected against apoptosis, because of the strong expression of the bcl-2 oncogene product, and provided with a very low proliferative capacity, the Ki-67 index being lower that 3%. The latter findings are in keeping with the indolent behaviour of the clonal lymphoid population observed in type II cryo and allow some speculation as to the need for environmental stimuli for its maintenance as well as further mutagenic events for its eventual transformation into an overt lymphoma.

Granulocytic sarcomas: clinical, diagnostic and therapeutical aspects.

Granulocytic sarcomas (GS) are extramedullary tumor masses of immature myeloid cells most frequently associated with acute myeloblastic leukemia. We report our diagnostic, clinic and therapeutic approaches in the treatment of 6 patients affected by GS who presented with different localizations and symptoms: mediastinal mass with chest pain, rectal tumor with bowel occlusion, bladder mass with acute kidney failure, quadriceps tumor with pain, vertebral localization with pain and bowel mass with pain, respectively. The correct diagnosis of GS by bone biopsy, the immunohistological evaluation of the tumor masses, the prompt use of active drugs in the first line therapy schedule as for acute myeloblastic leukemia are the parameters for the achievement of the long-term remission.

Anaplastic large cell lymphoma: update of findings.

The problem of anaplastic large cell lymphoma (ALCL) is extensively reviewed by depicting the clinical, pathological and biological characteristics of the four main varieties of ALCL: common, Hodgkin's like/Hodgkin-related, lympho-histiocytic, and giant-cell rich. Special emphasis is given to the differential diagnosis between ALCL Hodgkin like and Hodgkin's disease in the light of possible therapeutical differences.