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Introduction A meningeal solitary fibrous tumor (SFT), also called hemangiopericytoma, is a rare mesenchymal malignancy. Due to anatomic constrains, even after macroscopic complete surgery with curative intent, the local relapse risk is still relatively high, thus increasing the risk of dedifferentiation and metastatic spread. This study aims to better define the role of postoperative radiotherapy (RT) in meningeal SFTs. Patients and methods A retrospective study was performed across seven sarcoma centers. Clinical information was retrieved from all adult patients with meningeal primary localized SFT treated between 1990 and 2018 with surgery alone (S) compared to those that also received postoperative RT (S + RT). Differences in treatment characteristics between subgroups were tested using independent samplest-test for continuous variables and chi-square tests for proportions. Local control (LC) and overall survival (OS) rates were calculated as time from start of treatment until progression or death from any cause. LC and OS in groups receiving S or S + RT were compared using Kaplan-Meier survival curves. Results Among a total of 48 patients, 7 (15%) underwent S and 41 (85%) underwent S + RT. Median FU was 65 months. LC was significantly associated with treatment. LC after S at 60 months was 60% versus 90% after S + RT (p = 0.052). Furthermore, R1 resection status was significantly associated with worse LC (HR 4.08,p = 0.038). OS was predominantly associated with the mitotic count (HR 3.10,p = 0.011). Conclusion This retrospective study, investigating postoperative RT in primary localized meningeal SFT patients, suggests that combining RT to surgery in the management of this patient population may reduce the risk for local failures.

Daratumumab (DARA) is a human IgG-K monoclonal antibody (MoAb) targeting CD38 that is approved alone or in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for relapsed or refractory MM (RRMM) in patients previously exposed or double refractory to proteasome inhibitors (PI) and immunomodulatory drugs (IMiDs). However, there are limited data on its clinical activity and tolerability in real-world patients. Therefore, in the present study, we aim to determine the efficacy and toxicity profile of daratumumab in a real-life setting. In this study, we report the experience of the multiple myeloma GIMEMA Lazio Group in 62 relapsed/refractory MM patients treated with daratumumab as monotherapy who had previously received at least two treatment lines including a PI and an IMiDs or had been double refractory. Patients received DARA 16 mg/kg intravenously weekly for 8 weeks, every 2 weeks for 16 weeks, and every 4 weeks until disease progression or unacceptable toxicity. The overall response rate to daratumumab was 46%. Median progression-free survival (PFS) and overall survival reached 2.7 and 22.4 months, respectively. DARA was generally well tolerated; however, 2 patients interrupted their therapy due to adverse events. Present real-life experience confirms that DARA monotherapy is an effective strategy for heavily pre-treated and refractory patients with multiple myeloma, with a favorable safety profile.

This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8–20%), and constitutional (10–14%) and cardiovascular events (4–12%); peripheral neuropathy was limited (4–6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.

Summary Background Epidermolysis bullosa (EB) is caused by mutations in genes that encode proteins belonging to the epidermal–dermal junction assembly. Due to the extreme clinical/genetic heterogeneity of the disease, the current methods available for diagnosing EB involve immunohistochemistry of biopsy samples and transmission electron microscopy followed by single-candidate gene Sanger sequencing (SS), which are labour-intensive and expensive clinical pathways. Objectives According to the recently published recommendations for the diagnosis and treatment of EB, the assessment of the mutational landscape is now a fundamental step for developing a comprehensive diagnostic path. We aimed to develop a customized, cost-effective amplicon panel for the complete and accurate sequencing of all the pathogenic genes already identified in EB, and to minimize the processing time required for the execution of the test and to refine the analysis pipeline to achieve cost-effective results from the perspective of a routine laboratory set-up. Next-generation sequencing (NGS) via the parallel ultra-deep sequencing of many genes represents a proper method for reducing the processing time and costs of EB diagnostics. Materials and methods We developed an EB disease-comprehensive AmpliSeq panel to accomplish the NGS on an Ion Torrent Personal Genome Machine platform. The panel was performed on 10 patients with known genetic diagnoses and was then employed in eight family trios with unknown molecular footprints. Results The panel was successful in finding the causative mutations in all 10 patients with known mutations, fully confirming the SS data and providing proof of concept of the sensitivity, specificity and accuracy of this procedure. In addition to being consistent with the clinical diagnosis, it was also effective in the trios, identifying all of the variants, including ones that the SS missed or de novo mutations. Conclusions The NGS and AmpliSeq were shown to be an effective approach for the diagnosis of EB, resulting in a cost- and time-effective 72-h procedure.

The aim of the study was to analyze the real cost of single or tandem high-dose chemotherapy (HDC) and peripheral blood progenitor cell autologous transplant (PBPCT) in patients with breast cancer. We analyzed the costs of 40 PBPCT performed in 20 patients. Tandem transplant was planned for each patient. Resources used and direct costs were identified for each patient. The study was carried out using the hospital perspective and monetary values were reported in 1999 Euro. The mean cost of whole procedure for single transplant was 20816.63 Euro, while the mean cost of tandem transplant was 38770.83 Euro. The cost distribution in the two groups was similar: the most expensive phase of procedure was the supportive phase post transplant (about 60% of total cost), with the categories of cost most represented being professional fees (about 28%) and pharmacy (about 35%). Awaiting more convincing trials of the clinical advantage of HDC in breast cancer, our analytical evaluation of transplant costs for different therapeutic options, single or tandem, permits identification of the most expensive categories in order to intervene for cost savings. Bone Marrow Transplantation (2001) 27, 1031–1035.

Of 17 patients with mild to moderate essential hypertension, 8 showed echocardiographic evidence of left ventricular hypertrophy. Cardiac and renal function evaluated by glomerular filtration rate (GFR) were studied in all patients before and after 20 weeks of quinapril treatment. Systolic pressure decreased from 174.7 +/- 16.7 to 131.7 +/- 7.7 mmHg (p.0001) and diastolic pressure decreased from 101.8 +/- 9.8 to 80 +/- 4.3 mmHg (p.0001). Left ventricular mass index decreased in the eight patients with left ventricular hypertrophy (p.01). Basal values of GFR were lower than normal in 41% of all patients; GFR increased significantly after 20 weeks of treatment (from 96.5 +/- 32.3 to 108.6 +/- 31.12 ml/min, p.01); it decreased in only one patient. Patients reported few adverse effects to quinapril, and no important clinical laboratory abnormality was observed. Quinapril not only lowered arterial pressure, but it had a distinct effect on regression of left ventricular hypertrophy and favorable effects on renal function.

Alpha-2a-interferon (IFN) has demonstrable activity in advance and refractory multiple myeloma (MM), because of the in vitro synergism between IFNs and cytotoxic agents we report the preliminary results of a therapeutic trial of 50 patients with MM. Twenty-eight patients were randomized to receive melphalan plus prednisone (MP) and 22 were randomized to receive IFN plus MP (IFN-MP). Criteria for response, progression and relapse were those of the Southwestern Oncology Group. 95% of the patients receiving IFN-MP responded to therapy as opposed to 68% of the patients receiving MP (P less than 0.05). Response was independent of M-component immunoglobulin class but in stage III it was higher in the IFN-MP group than in the MP group (P less than 0.05). The combination IFN-MP was well tolerated without unusual or unexpected toxic effects. The response duration time was longer in the IFN-MP group than in the MP group (P less than 0.025). The median survival was 80 weeks in the MP group and in the IFN-MP group the 93% of patients were still alive after 90 weeks (P less than 0.025). Our results show that the use of the IFN as an adjuvant to MP improves the percentage of responders, the response duration time and the median survival of untreated patients with MM.

Purpose: The objective of our study was to determine the maximum tolerable doses (MTDs) of both paclitaxel and cisplatin when given in a weekly schedule alone or simultaneously with G-CSF in advanced solid neoplasms. Patients and methods: Patients with advanced cancer either chemotherapy-naive or resistant to standard treatments received paclitaxel in a three-hour infusion followed by cisplatin, with or without the addition of r-HuG-CSF (5 μg/kg s.c. days three to five). The starting doses of CDDP and paclitaxel were 25 mg/m 2 /week and 45 mg/m 2 /week, respectively. During the first six courses the dosages of the two drugs were alternately escalated by 20% (CDDP = 5 mg/m 2 /week, and paclitaxel 10 mg/m 2 /week) at each step until the appearance of dose-limiting toxicity (DLT) in one-third or more of the patients enrolled in that cohort. Results: Fifty-five patients with cancer (16 lung, 16 breast, 11 ovarian, 7 head and neck, 1 renal, 1 esophageal, 1 cervical, 1 soft-tissue sarcoma, and 1 of unknown primary), 25 of whom were pretreated, were entered into the study. A total of 439 weekly courses were delivered. In chemotherapy-naive patients. the MTDs of cisplatin and paclitaxel were 30 mg/m 2 /week and 65 mg/m 2 /week, respectively. in the absence of G-CSF support, which increased to 40 mg/m 2 /week and 85 mg/m 2 /week, respectively, when G-CSF was given. There were no toxic deaths in this study. Neutropenia was the main dose-limiting toxicity (100/439 courses), but was seldom severe. Neurotoxicity was quite frequent (18 of 55 patients for the total of 88 courses) but never dose-limiting. It was more frequent and clinically relevant in cisplatin-pretreated patients. Overall 18 patients (eight ovarian, five breast, three lung, and two head and neck) achieved objective responses. Conclusions: The cisplatin-paclitaxel weekly administration seems a safe, practical and effective therapeutical approach in patients with advanced solid neoplasms. Large phase II trials are warranted to accurately define the efficacy of this schedule in cisplatin-paclitaxel sensitive tumors.

In ninety's breast cancer was first in Europe for the use of high-dose chemotherapy with autologous hematopoietic stem cell transplantation in solid tumors in adults. Some phase II trials of high-dose chemotherapy showed high response rates and prolonged progression free survival in selected metastastic breast cancer patients. Few large, powerful randomized phase III studies comparing this approach with conventional chemotherapy have been completed: some studies showed a better progression free survival in favor of high dose chemotherapy, but no statistically significant difference in overall survival was observed. Many variables inside high dose chemotherapy program need to be considered. The identification of subsets of breast cancer patients who can benefit from high-dose chemotherapy is essential: high-dose chemotherapy should be included in a global treatment strategy, evaluating the integration with innovative treatment modalities, with the aim of eradicating the minimal residual disease in breast cancer patients achieving complete response after high dose chemotherapy.

Primary cutaneous follicular lymphoma (PCFL) and nodal follicular lymphoma (NFL) are different entities, which, nevertheless, exhibit common features. The aim of this study was to compare the clinico-biological characteristics and the outcome of patients with PCFL and with limited stage NFL. A group of 22 consecutive patients with PCFL presenting with single or multiple cutaneous lesions was compared to a group of 21 patients with limited stage NFL. The median age was 56 and 55 years, respectively. The histologic features were compared, as well as treatment modalities and response. Treatment of PCFL consisted of restricted field radiotherapy (RT), chemotherapy (CHT) and combined modalities (CM) in 12, 5 and 5 cases, respectively. Among the 21 patients with NFL, RT was employed in 13, CHT in 7 and the CM in one patient. The response to treatment was: 17 complete responses, CR (12 RT, 2 CHT, 3 CM), 3 partial responses, PR (1 CHT, 2 CM) and 2 non-responses, NR (2 CHT) in the PCFL group, while in the NFL group 18 patients attained CR (13 RT, 4 CHT, 1 CM) and 3 PR (3 CHT). The relapse rate was 22.7 and 28.5% in PCFL and NFL, respectively (median follow up of 48 and 50 months). The estimated 4 years event free survival (EFS) in the PCFL and NFL patients were 68 and 70%, respectively, (P = 0.83). The estimated 4 years overall survival (OS) in the PCFL and NFL groups were 90% and 100% respectively, (P = 0.254). Among the 22 patients with PCFL, there was a higher incidence of large cells than in NFL, although the differences were not significant (P = 0.08). In conclusion, despite histologic (higher proportion of large cells) and biologic differences, cutaneous and limited stage NFL show similar responses to treatment, with similar relapse rates, EFS and OS.

This study evaluated the effects of low-dose IL-2 plus G-CSF/EPO on post-PBSC transplantation (PBSCT) immune-hematopoietic reconstitution and NK activity in patients with breast (BrCa) and ovarian cancer (OvCa). To this end, two consecutive series of patients were prospectively assigned to distinct post-PBSCT cytokine regimens (from day +1 to day +12) which consisted of G-CSF (5 microg/kg/day) plus EPO (150 IU/kg/every other day) in 17 patients (13 BrCa and 4 OvCa) or G-CSF/EPO plus IL-2 (2 x 10(5) IU/m(2)/day) in 15 patients (10 BrCa and 5 OvCa). Hematopoietic recovery and post-transplantation clinical courses were comparable in G-CSF/EPO- and in G-CSF/EPO plus IL-2-treated patients, without significant side-effects attributable to IL-2 administration. In the early and late post-transplant period a significantly higher PMN count was observed in G-CSF/EPO plus IL-2-treated patients (P = 0.034 and P = 0.040 on day +20 and +100, respectively). No significant differences were found between the two groups of patients in the kinetics of most lymphocyte subsets except naive CD45RA(+) T cells which had a delayed recovery in G-CSF/EPO plus IL-2 patients (P = 0.021 on day +100). No significant difference was observed between NK activity in the two different groups, albeit a significantly higher NK count was observed in G-CSF/EPO plus IL-2 series on day +20 (P = 0.020). These results demonstrate that low-dose IL-2 can be safely administered in combination with G-CSF/EPO early after PBSCT and that it exerts favorable effects on post-PBSCT myeloid reconstitution, but not on immune recovery.

To evaluate the effect on survival of negative immunomagnetic purging in aggressive B-cell non-Hodgkin's lymphoma (NHL), 20 patients retrospectively staged according to the age-adjusted International Prognostic Index as high-intermediate (11 patients) or high-risk (9 patients) received autologous bone marrow transplantation (ABMT) in first complete remission (CR1). All patients received six to eight cycles of a F-MACHOP-like protocol as induction treatment and then underwent high-dose chemotherapy (HDC) with a CBV-like regimen. Negative purging included a panel of monoclonal antibodies against B-cell antigens and immunomagnetic beads. The data were compared to a historical control of 18 patients with the same characteristics treated in our institution who received unpurged bone marrow support. The median yield of mononuclear cells (MNC), colony-forming units-granulocyte/macrophage (CFU-GM), and CD34+ cells after purging were 52%, 49%, and 57%, respectively. The median B-cell depletion after negative selection was 1.8 logs. All patients obtained a complete engraftment with no significant differences between the purged and unpurged group. Two toxic deaths (one for each group) were observed and the main extrahematological toxicities were mucositis, vomiting, and diarrhea. The event-free survival (EFS) and overall survival (OS) at 3 years for the whole group of 38 patients were 73% (95% CI: 59-88%) and 81% (95% CI, 68-94%), respectively. The comparison between patients receiving purged marrow and patients receiving unmanipulated marrow indicated no significant survival differences between the two groups both for EFS 84% (95% CI: 67-100%) vs 61% (95%CI: 39-84%) ( P=0.12) and OS 84% (95% CI: 69-100%) vs 71% (95% CI: 50-93%) ( P=0.58). Our report shows that HDC followed by reinfusion of autologous bone marrow can produce long EFS and OS in high-intermediate and high-risk patients with B-cell NHL transplanted in CR1, but was not be able to demonstrate a significant clinical advantage using immunomagnetic purged marrow. However, the use of ex vivo negative purging combined with innovative treatment modalities (peripheral blood stem cell transplant, in vivo administration of monoclonal antibodies) needs to be explored.

In order to combine an active regimen with a simultaneous efficient mobilization of peripheral blood precursor cells (PBPC), we explored the combination of Docetaxel 75 mg/m2 and Epirubicin 120 mg/m2 with G-CSF 5 mcg/Kg/day s.c. to mobilize PBPC in breast cancer patients to support high-dose chemotherapy (HDC).Forty patients were enrolled: 27 high risk and 13 metastatic. The entire procedure, including chemotherapy and PBPC collection, was on an outpatient basis.The median day of starting apheresis was day +10 (range 10-12) and the average value of circulating CD34+ cells at peak was 175/microliter (range 33-403). The median yield of CD34+ cells per apheresis was 8.76 x 10(6)/Kg (range 1.83-27.87). None of the patients developed side effects which required hospitalization. All patients enrolled successively received HDC as consolidation treatment. High risk patients received one and metastatic patients two HDC with PBPC reinfusion. All patients obtained a complete engraftment. No significant differences between high-risk and metastatic patients were observed.Our study suggests that the combination of Docetaxel, Epirubicin, and G-CSF is feasible, safe and efficient outpatient mobilizing treatment for patients with breast cancer receiving HDC.

The present study describes the effects of losartan and the angiotensin-converting enzyme inhibitor enalapril on blood pressure, echocardiographically calculated left ventricular mass, renal function evaluated by glomerular filtration rate and quality of life. The renin-angiotensin-aldosterone system is of importance for cardiovascular growth. There is substantial experimental documentation in animals that the angiotensin II antagonist, losartan, decreases the cardiac hypertrophy response caused by elevated arterial pressure as well as intravascular volume overload. However, data in humans is scarce. This is a 3-year, randomised, double-blind study with parallel group design in 50 patients with essential hypertension. The results show that both drugs reduced blood pressure equally effectively, and also left ventricular mass (P < 0.001). After 3 years of treatment glomerular filtration rate significantly increased with losartan (P < 0.005). Serum uric acid fell modestly although significantly, dose-dependent in losartan patients compared with an increase in enalapril patients. A fall in serum potassium from the pre-study period was observed in all patients. There was no difference between treatments in terms of patient satisfaction on quality of life. Both drugs have relatively similar hormonal and haemodynamic effect, with an excellent tolerability profile; they appear to induce comparable blood pressure falls in hypertensive patients in particular, therapy based on specific Ang II blockade may offer advantages in high risk hypertensives if left ventricular hypertrophy is present. Both enalapril and losartan, in improving the renal function attenuating the intrarenal effects of angiotensin II, might be able to reverse the pathophysiology of essential hypertensive kidney disease, and should be first-choice drugs in the treatment of essential hypertension.

Hematopoietic growth factor (HGF) administration following autologous peripheral blood progenitor cell transplantation (APBPCT) is a current approach for shortening the duration of high-dose chemotherapy-induced transient peripheral pancytopenia. Several published clinical experiences and a retrospective study reported here show that recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) administration potentiates polymorphonuclear leukocyte (PMN) and white blood cell (WBC) recovery with some clinical benefits mainly related to the reduction of infectious complications during the shortened period of neutropenia. However, this therapeutic strategy does not produce any enhancement of platelet (PLT) recovery or potentiation of red cell production. Conversely, a recent phase I/II study carried out in our institution showed that the combined administration of rhG-CSF and recombinant human erythropoietin (rhEPO) is able to potentiate trilineage hematopoietic recovery with a reduction of PLT transfusions and to considerably simplify the clinical management of patients as compared to patients treated with APBPCT alone. The post-APBPCT administration of rhEPO with rhGM-CSF decreased the number of days with WBC < 1 x 10(9)/L but failed to produce any appreciable effect on PLT recovery. Both combined treatments significantly reduced the patients' hospital stay and allowed the abrogation of systemic antibiotic administration following APBPCT. A further group of patients were treated with the combined administration of rhEPO, rhG-CSF and rhGM-CSF; they did not show a faster hematopoietic recovery than rhG-CSF plus EPO treated patients and a consistent hyperthermia was observed in most patients as a prominent side effect. Future prospective randomized studies will clarify the efficacy of HGF administration following APBPCT. Moreover, further improvements in the hematopoietic support of transplanted patients may be obtained when stem cell factor, flt3/flk2 tyrosine kinase ligands or megakaryocyte growth and development factor will become clinically available.

We report a case of histiocytic necrotizing lymphadenitis (NHL) (Kikuchi-Fujimoto disease) in a 23-year-old patient with fever, lymphadenopathy and leukopenia. There were no other significant findings in laboratory data and all bacterial and viral researches were negative. Fever resolved spontaneously after one month, but lymphadenopathy and leukopenia persisted. The immunophenotype of bone marrow and peripheral blood cells showed an increase of B lymphocytes (CD20+, CD21+, CD22+) and activated (CD30+) and NK cells (CD16+, CD56+). This finding persisted after six months. The authors suggest that the clinical feature of NHL is sustained by an immunological substrate.

Twenty-five patients with Stage III ovarian cancer were entered into a trial with intraperitoneal combinations of carboplatin (400 mg/cqm) and recombinant interferon alfa (50 MU). All patients had received prior intravenous platinum-based chemotherapy and underwent 2nd look laparotomy at study entry. Our study indicates that this combination chemotherapy is safely administered by the intraperitoneal route. Myelotoxicity was frequent, but rarely of grade 3. No major local toxicity was recorded by accessing the peritoneal cavity with a temporary catheter. The response to treatment was promising in the group of patients with less then 2 cm residual disease at study entry (15 patients); in this group, all patients had no clinical evidence of disease at the completion of the therapy. In 2 cases reexploration was performed and pCR was recorded. Only one patient of this group relapsed during a mean follow-up of 21 months. Two pCRS were also recorded in the group of patients with more than 2 cm at 2nd look (9 patients), although relapse occurred after 9 and 15 months respectively. In the remaining patients of this group, persistence of disease was observed after intraperitoneal chemotherapy.

Human genomic DNA of patients originating from Southern Italy. We found a variant of the beta-globin gene polymorphism frameworks, i.e. non-random association of six single base variations, two of which constitute an AvaIl (IVS-2-16 C -G) and a BamHI (about 8 kb 3'(l) RFLPs (1). The framework variant is characterized by the presence [+ +] of both RFLPs and by C, C and T at codon 2, IVS-2-81 and IVS-2 -666, respectively, as in framework 1; by T at IVS-2-74, as in framework 2 and 3.

A novel 5.3-kb deletion of the alpha-globin gene cluster was observed in a family from Naples, Southern Italy. It removes the 5' end of the alpha 2-globin gene, causing an alpha (+)-thalassemia defect. Because of the presence of the residual 3' end of the alpha 2-globin gene, we indicated this new haplotype with the symbol (alpha)alpha 5.3. The 5' breakpoint, the first to be reported in the intergene region of the psi alpha 2- and psi alpha 1-globin genes, is located 822 bp upstream of the cap site of the psi alpha 1-gene and about 150 bp upstream of a 300-nt Alu family member. The 3' breakpoint is located in the IVS-1 nt 58 of the alpha 2-globin gene. The 5.3-kb deleted fragment shows particular characteristics: it contains four Alu sequences having long regions 80% complementary and the 5'-GGCC-3' short repeat at both ends. The sequences spanning across the breakpoints on the same strand and containing this repeat on their 3' and 5' ends, respectively, are 17 of 25 base complementary. These particular features led us to assume the formation of a multistem-loop due to the intrastrand interaction between the complementary regions as intermediate to the deletion. The unusual localization of the 5' breakpoint suggests that even the intergene region of the psi alpha 2- and psi alpha 1-globin genes may function as a deletion target.

Various methods have been investigated to concentrate hemopoietic stem cells before in vitro treatment and cryopreservation. Each procedure requires various degrees of cell manipulation; moreover, the extent of purification of the stem cell fraction depends on the further use of bone marrow. Fifty four bone marrows were treated with hydroxyethyl starch (HES) to isolate the mononuclear cell population. The manipulation with HES permitted to concentrate marrow stem cells in a small volume with removal of unwanted granulocytes, red blood cells and the donor isohemagglutinins in the major ABH incompatibility. We describe here a manual method which permits the transfusion of a very few number of red cells without depletion of progenitor cells and thus delay of engraftment.

In this report we describe the use of the immunomagnetic depletion of tumor cells from harvested bone marrow in two patients with acute lymphoblastic leukemia. The immunomagnetic procedure of purging involved one incubation of the marrow cells with a mixture of 4 monoclonal antibodies which bind to antigens of CD10 (ALB2), CD19 (HD37), CD20 (B1) and CD22 (HD39). Two incubations with magnetic beads (Dynabeads M-450) covered with antimouse antibodies followed by magnetic separation were performed. The bead/target B cell ratio was 50:1. After purging the recovery of mononuclear cells was 56% and 40%, while the recovery of CFU-GM was 45% and 38% respectively. Both patients engrafted rapidly without serious complications. One patient relapsed 4 months after transplant, the other remains in complete remission after 5 months. Our results confirm that the use of immunomagnetic beads is a simple, safe and reproducible technique to remove tumor cells before ABMT in patients with B malignancies using a broad mixture of MoAbs. However only a randomized trial using autologous marrow purged or not will clarify the effective clinical value of the procedure.

A prospective study was undertaken to determine the effectiveness of an empiric antibiotic treatment employing the combination of a beta-lactam and an aminoglycoside followed in non responders by vancomycin and amphotericin B after 48 and 96 hours respectively. We have evaluated 180 febrile episodes in 102 granulocytopenic leukemic patients. Febrile episodes (44%) were microbiologically documented; 29% were only clinically documented and 27% were possible. In the 180 evaluable episodes treated with a beta-lactam and an aminoglycoside the overall response rate was 61%. In non responders the addition of vancomycin increased the response rate to 83% and the subsequent addition of amphotericin B moved the total responders to 96%. Antibiotic related side effects were minimal. These data suggest the importance of an empiric strategy for treatment of bacterial infections arising in granulocytopenic patients. An early empiric antifungal therapy also appears necessary to control clinically undetected fungal invasion.

Five patients with high risk multiple myeloma not responsive to standard chemotherapy were treated by high-dose chemotherapy (Melphalan, Cyclophosphamide) (HDC) and total body irradiation (TBI) followed by autografting with blood stem cells. These cells were previously collected by leukaphereses from eight to twelve occasions during hematopoietic recovery following profound aplasia induced by each course of intensive chemotherapy (Vincristine, Adriamycin, Cyclosphosphamide, Prednisone) when the patient reached a neutrophil count of 1,000/microliters and a platelet count of 100,000/microliters. No patients had evidence of tumor plasmacells in leukaphereses products using cytology, immunocytochemistry and immunofluorescence. At this time the patient 5 is not evaluable because of the short follow-up. One died at day 30 from heart failure. All living patients achieved a complete remission which persisted at a follow-up of 300, 261 and 136 days. Autologous blood derived hematopoietic stem cells induced successful and sustained engraftment in all living patients. Our results indicate the feasibility of this therapeutic approach over allogenic or autologous bone marrow transplantation in selected patients with high tumour mass multiple myeloma.

The authors examine the main clinical, cytologic and nosographic aspects of conditions and syndromes associated with SBH on the basis of the literature data (about 40 cases) and 23 personal ones. It is necessary to distinguish between three nosological conditions of SBH: hereditary disease, hereditary asymptomatic, acquired per se asymptomatic. From the clinical viewpoint less a half of all SBH cases are hereditary and present a syndrome based on splenomegaly, periodic hemorrhagic diathesis (due to variable thrombocytopenia), not rarely associated with hepatomegaly and lung or nervous system changes (often eyes are involved). There is also a second SBH hereditary form, vary rare and clinically different from the former, determined by deficiency of plasma-lecitin-cholesterol acyltransferase. The peculiar features of SBH are discussed by means of optical, cytochemical, electron microscopical investigations which point out the polymorphous aspect of these "famished" macrophages. The material stored by SBH is heterogeneous and the enzymatic defect of the most frequent form still remains obscure. The presence of SBH in different haemopathies has an analogous significance as Gaucher's cells found outside Gaucher's disease. It is impossible today to deny the existence of two well-identified SBHS.

Traumatic blindness is a well recognized entity with a guarded prognosis. Previous studies have variously reported the incidence of concomitant optic canal fractures and response to surgical therapy. With the advent of CT scanning, a new technique for study of these severely injured patients has become available. Over a period of 20 months, optic foramen fractures were demonstrated in 10 such patients using finely collimated, high-resolution CT scans. Fractures were easily classified by location, relation to the optic nerve assessed, and associated facial injuries imaged. The technique is easy, rapid, and superior to polytomography in this setting. Possible implications for therapy are discussed.

10 patients recovering from acute myocardial infarction with stable symptomatology, underwent 3 subsequent ergometric trials: the first, basic, the second, after one month of practice on an ergometer bicycle and the third, with a longer period of training, after acute administration of nifedipine. The purpose of the study was to establish whether the administration of a drug such as nifedipine, acting principally on the after load, could further improve the working abilities of ischemic cardiopaths, already trained for muscular work. The results demonstrated that proper training can significantly increase the duration of muscular exercise, while the acute administration of 20 mg of nifedipine was not able to improve, to a greater degree, the working ability of patients who were already trained. The result was interpreted as being due to the inability of the trained organism to further increase the peripheral oxygen-saving mechanisms.

Contains fulltext : 118008.pdf (Publisher’s version ) (Open Access) Ankyloblepharon, ectodermal defects, cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder caused by mutations in the p63 gene, essential for embryonic development of stratified epithelia. The most severe cutaneous manifestation of this disorder is the long-lasting skin fragility associated with severe skin erosions after birth. Using a knock-in mouse model for AEC syndrome, we found that skin fragility was associated with microscopic blistering between the basal and suprabasal compartments of the epidermis and reduced desmosomal contacts. Expression of desmosomal cadherins and desmoplakin was strongly reduced in AEC mutant keratinocytes and in newborn epidermis. A similar impairment in desmosome gene expression was observed in human keratinocytes isolated from AEC patients, in p63-depleted keratinocytes and in p63 null embryonic skin, indicating that p63 mutations causative of AEC syndrome have a dominant-negative effect on the wild-type p63 protein. Among the desmosomal components, desmocollin 3, desmoplakin and desmoglein 1 were the most significantly reduced by mutant p63 both at the RNA and protein levels. Chromatin immunoprecipitation experiments and transactivation assays revealed that p63 controls these genes at the transcriptional level. Consistent with reduced desmosome function, AEC mutant and p63-deficient keratinocytes had an impaired ability to withstand mechanical stress, which was alleviated by epidermal growth factor receptor inhibitors known to stabilize desmosomes. Our study reveals that p63 is a crucial regulator of a subset of desmosomal genes and that this function is impaired in AEC syndrome. Reduced mechanical strength resulting from p63 mutations can be alleviated pharmacologically by increasing desmosome adhesion with possible therapeutic implications.