Tumoral Syndrome Research Articles

La leishmaniose viscérale infantile, une cause de syndrome d’hémophagocytose lympho-histiocytaire facilement curable

Infantile visceral leishmaniasis associated hemophagocytic lymphohistiocytosis (HLH) is a rare clinicopathological entity, difficult to diagnose and fatal if untreated. The diagnosis should be considered in young infants with fever and splenomegaly. We report two cases of HLH caused by visceral leishmaniasis. In the first case, a 3-month-old boy was admitted with fever and pancytopenia, leading to the diagnosis of HLH based on complete clinical and biological features including hemophagocytosis on bone marrow smears. Investigations for an underlying genetic, metabolic disease and an infectious trigger were negative. Primary or genetic hemophagocytic syndrome was suspected and immunosuppressive treatment (steroids and cyclosporin) was instituted. A second bone marrow examination performed 1 month later revealed leishmania. The boy was treated with liposomal amphotericin and recovered rapidly. In the second case, a 10-year-old child was hospitalized with fever, pancytopenia, and a tumoral syndrome. He had a history of recurrent infections. The bone marrow biopsy showed leishmania and treatment with liposomal amphotericin was delivered. After 3 days of treatment, the improvement was judged inadequate and the boy presented biological signs of HLH. He was treated with steroids. An underlying primary immunodeficiency (interleukin-12/interferon-γ axis disorder) was secondarily diagnosed.

Pan-FGFR Inhibition Leads to Blockade of FGF23 Signaling, Soft Tissue Mineralization, and Cardiovascular Dysfunction

The fibroblast growth factor receptors (FGFR) play a major role in angiogenesis and are desirable targets for the development of therapeutics. Groups of Wistar Han rats were dosed orally once daily for 4 days with a small molecule pan-FGFR inhibitor (5mg/kg) or once daily for 6 days with a small molecule MEK inhibitor (3mg/kg). Serum phosphorous and FGF23 levels increased in all rats during the course of the study. Histologically, rats dosed with either drug exhibited multifocal, multiorgan soft tissue mineralization. Expression levels of the sodium phosphate transporter Npt2a and the vitamin D-metabolizing enzymes Cyp24a1 and Cyp27b1 were modulated in kidneys of animals dosed with the pan-FGFR inhibitor. Both inhibitors decreased ERK phosphorylation in the kidneys and inhibited FGF23-induced ERK phosphorylation in vitro in a dose-dependent manner. A separate cardiovascular outcome study was performed to monitor hemodynamics and cardiac structure and function of telemetered rats dosed with either the pan-FGFR inhibitor or MEK inhibitor for 3 days. Both compounds increased blood pressure (~+ 17 mmHg), decreased heart rate (~-75 bpm), and modulated echocardiography parameters. Our data suggest that inhibition of FGFR signaling following administration of either pan-FGFR inhibitor or MEK inhibitor interferes with the FGF23 pathway, predisposing animals to hyperphosphatemia and a tumoral calcinosis-like syndrome in rodents.

Corticothérapie préalable au diagnostic de leucémie aiguë lymphoblastique (LAL) de l’enfant : effet délétère pour la prise en charge diagnostique et thérapeutique

The aim of this study was to show that steroid therapy taken before the diagnosis of acute lymphoblastic leukemia (ALL) can alter the management of the disease. We conducted a multicenter retrospective study on 11 children treated between 2005 and 2011, who received oral steroids ranging from 0.6 to 3.3mg/kg/day prednisolone equivalent for a duration of 2 to 15 days during the 2 months prior to diagnosis of ALL. Four children had febrile pancytopenia. Among them, 2 had severe infections and a noncontributive bone marrow aspiration. One of them presented a severe tumoral lysis syndrome and was hospitalized twice in the intensive care unit. Two teenagers had central nervous system involvement at diagnosis of T-ALL, 1 having associated cutaneous locations, the second one showing pulmonary and central nervous system (CNS) leukostasis with renal failure and disseminated intravascular coagulation. One child died of septic shock during the induction phase of steroid-resistant T-ALL. Four children had no complications during the induction phase. Steroid resistance occurred in 5 cases and steroid sensitivity could not be evaluated in 3 cases. Three allogeneic bone marrow transplants were performed: the first one because of early CNS relapse, the 2 others because of initial treatment resistance. Steroids can induce a delay in the management of ALL and seem to favor initial complications, and possibly increase diffuse locations as well as steroid resistance. Their prescription needs to be carefully managed, especially for uncharacteristic infectious symptoms. Then a complete blood count should be done.

Initial Results of the Phase I/II Panobidara Study of Panobinostat in Combination with Idarubicin and Cytarabine in Patients Aged 65 Years or Older with Newly Diagnosed Acute Myeloblastic Leukaemia (AML)

AbstractAbstract 1512 Introduction:Acute Myeloblastic Leukemia (AML) in elderly patients remains an unmet medical need with a long term survival rate inferior to 10% despite the use of novel drugs. Therefore, there is a need for new agents that could induce higher CR rates and, most importantly, that could prolong the relapse free survival (RFS) and the overall survival (OS) of these poor-prognosis patients. Agents targeting epigenetics such as the hypomethylating drug 5-Azacitidine, have emerged as a promising strategy for elderly patients with AML or MDS. A second group of drugs targeting the epigenome are deacetylase inhibitors. Panobinostat is a pan-deacetylase inhibitor, with clear in vitro activity in AML and which is synergistic with anthracyclines (Maiso et al. Leukemia 2009). Based on these data we designed a phase I/II trial of panobinostat in combination with idarubicine and cytarabine followed by panobinostat maintenance in newly diagnosed AML patients older than 65 years. Methods:The initial schema included one or two induction cycles with idarubicine (8 mg/m2 days 1–3) + cytarabine (100 mg/m2 days 1–7) followed by escalating doses of panobinostat three days per week, per 3 weeks starting at 20 mg. Patients achieving CR/CRi received a consolidation cycle with the same schema. Those patients remaining in CR/CRi started a maintenance phase with 40 mg oral panobinostat in monotherapy three days per week, for 3 weeks in 28-days cycles. This schedule was amended after the six first patients, to reduce the weeks of administration of panobinostat to two weeks in the cycles in combination and to every other week in the maintenance phase. Initially a dose-escalating phase I with the classical 3+3 schema was carried out to define the maximum tolerated dose (MTD) of panobinostat in this combination; and then a phase 2 expansion phase was started to determine the efficacy of this combination in terms of CR rate and RFS. Results:21 patients have been included after the amendment. Median age was 71 (range 66–83). Median % blasts was 40 (20–93). 35% of patients had AML with dysplastic features while adverse cytogenetics were present in 24%.Two out of 6 evaluable patients in the first cohort developed DLTs with panobinostat 20 mg (G3 hyperbilirrubinaemia in both, and one of them also G3 oedema), accordingly the dose of panobinostat was reduced to 10 mg. No DLTs were observed at this dose level, so 10 mg panobinostat was defined as the MTD in this combination. Treatment was well tolerated in the intensive cycles with the toxicity proper of standard induction chemotherapy. The most common non-hematologic toxicities (occurring in ≥20% of patients) included: fever (90%), infections (62%), mucositis (52%), diarrhoea (62%), constipation (43%), vomiting (57%), skin rash (38%), hepatotoxicity (38%) and hypokalaemia (24%). Grade 3/4 AEs were fever, infection, diarrhoea and hepatotoxicity in 2 patients each (10%) and hypokalaemia in 5 (24%). The median duration of the aplasia was 32 days (range 26–51). Regarding the maintenance phase with panobinostat monotherapy, the most frequent AEs were gastrointestinal: diarrhoea (62%), vomiting (62%) or abdominal pain (25%); as well as asthenia (50%. One of them being G3) and hyporexia (25%).In terms of efficacy, 11 patients (52%) achieved CR plus 2 more (10%) achieving CR with incomplete blood recovery (CRi) (overall 62%). There were 2 deaths in induction (10%), one due to a tumoral lysis syndrome before starting panobinostat and the other secondary to a respiratory infection. From the remaining 6 patients, 2 achieved partial response (10%) and 4 showed refractory disease (19%). With a median follow up of 6 months (range 2–14), among the 11 patients that achieved CR, 10 of them remain in CR and only 1 has progressed (in the 9th maintenance cycle). Both patients that achieved CRi have progressed in the 2nd and 6thmaintenance cycles. The median overall survival for the whole population is 13 months (2.3–23.6), and has not been reached for patients achieving CR. Conclusion:To the best of our knowledge, this is the first report of the use of a histone deacetylase inhibitor with chemotherapy in elderly AML patients. This combination was shown to be safe at the MTD. Although preliminary results are encouraging, particularly for the potential benefit of the maintenance phase, longer follow up is needed to evaluate if panobinostat maintenance is able to prolong RFS and subsequently OS in this poor prognostic population. Disclosures:Ocio:Novartis: Consultancy, Research Funding. Off Label Use: Panobinostat in newly diagnosed AML. Aliseda:Novartis: Employment. Winiger:Novartis: Employment. Hardikar:Novartis: Employment. Mateos:Novartis: Consultancy. San-Miguel:Novartis: Consultancy, Research Funding.

Tumoral Bing-Neel Syndrome presenting as a cerebellar mass

Waldenstrom’s macroglobulinemia (WM) is a low-grade alignant monoclonal proliferation of immunoglobulin M (IgM)roducing lymphocytes capable of exhibiting plasmacytoid or lasma cell differentiation [1]. According to the World Health Orgaization’s classification of neoplastic diseases of hematopoietic and ymphoid tissues, WM is classified as lymphoplasmacytic lymhoma. Clinical features of WM may include cytopenia, bleeding, ymphadenopathy, splenomegaly, and, most commonly, a hyperiscosity syndrome related to high serum levels of monoclonal IgM. entral nervous system (CNS) complications arise in approximately 5% of WM cases, usually as a result of the hyperviscosity syndrome r an immune-related neuropathy [1,2]. Rare cases of WM involvng direct CNS infiltration by malignant cells have been referred to s Bing-Neel Syndrome (BNS). To date, limited data exist regardng BNS. The authors describe a rare case of BNS presenting as a erebellar mass with associated brainstem infiltration and subacute eurologic deterioration.

Bendamustine for Mantle Cell Lymphoma: Retrospective Analysis of the Spanish Experience

Abstract 4942 INTRODUCTION.Patients with Mantle cell lymphoma (MCL) have an adverse outcome after relapse due to chemorefractory disease with conventional treatments. Bendamustine, a nitrogen mustard compound chemically related to the alkylating agents, has demonstrated high efficacy with a low toxicity profile in reported clinical trials. AIM.To analyze the Spanish experience in patients with relapsed/refractory MCL treated with Bendamustine. METHODS.Retrospective analysis of spanish experience in relapsed/refractory MCL treated with Bendamustine alone or in combination. This study has been approved by local ethical committees. RESULTS.Currently, there are 36 patients registered and 28 are available for this analysis. Patients’characteristics: 69% male, median age 65 years old (range 41–81), 87% ECOG≤ 1, 83% Ann Arbor stage IV, 37% high risk MIPI and 9% blastic variant. Previous regimens were CHOP or CHOP like ± R in 42.5%, HyperCVAD/MtxAraC ± R in 42.5%, R-CVP in 9% and other regimens in 6%. Median number of previous treatments were 2.6 (range 1–6), all patients had received prior Rituximab and 73% had chemosensitive disease to the last treatment. Bendamustine regimen was R-B (R-375mg/m2 D1, B-90 mg/m2 D1-2) in 78% patients, R-B with B-70 mg/m2 in 8%, B alone in 3%, R-B-Bortezomib in 3% and R-B plus consolidation (SCT, Y90Ibritumomab-tiuxetan) in 8%. Median number of cycles was 4.61 (range 1–7). G- CSF support was administered in 43% of cycles. Response: Overall response rate was 73%, with 43% CR & uCR and 30% PR. Survival: Median overall survival from diagnosis is 8,26 years (range: 1.6–11,6 years) without plateau. Median progression free survival (PFS) after Bendamustine treatment was 16 months (95% CI: 11.7–20.4), data that compares favourably with patients’ PFS to previous therapy (12 months, 95% CI: 6.5–17.5). Median PFS for patients who achieved CR/uCR is 32.6 months (95% CI: 19.9–45.4) versus 11 months in patients with PR (95% CI: 3.9–18.8). With a median follow-up for surviving patients of 12 months since Bendamustine treatment, the estimated OS at 3 years is 47% (+ SD 14%). Toxicity: No treatment related mortality has been described so far. Over 152 cycles, only 10 hospitalizations due to febrile neutropenia were reported. No one case of lysis tumoral syndrome has been reported. CONCLUSION.Bendamustine plus Rituximab is a good rescue treatment in non selected pretreated patients with mantle cell lymphoma. CR rate and duration of response seem to reproduce in current clinical practice the good data reported in previous clinical trials and compares favourably with other available treatments. Disclosures:No relevant conflicts of interest to declare.

1111 Measurement of Hepatic Tissular Rso2 Using Near Infrared Spectroscopy as a Witness of Hepatic Tumor Regression

Background and aims: Near InfraRed Spectroscopy (NIRS) is a tool for evaluation of local blood flow and oxygen consumption (VO2) using measurement of regional oxygen saturation (rSO2). Purpose: To describe the feasibility and accuracy of the measurement of hepatic rSO2 (lirSO2) in an infant with tumoral syndrome in acute leukemia. Methods: A 7 weeks old girl was admitted with asthenia, bleeding, respiratory distress and hepatomegaly. Hemogram showed 117000 leucoblasts/mm3, Hb=7.1g/100 ml, 24000 platelets/ mm3. Blood gaz analysis showed : pH=7.37, HCO3- =18 mmol/l, PaCO2=31 mmHg and lactatemia=888 mg/l. Sonography showed a heterogeneous hepatomegaly. Diagnosis of acute monocytic leukemia (AML-M5) was made. Chemotherapy was started (ELAM 02 protocol). Infant was monitored using cardiac monitoring, continuous measurement of oxygen saturation (SpO2) and invasive blood pressure. CerSO2 and lirSO2 were measured using NIRS. rSO2 values were recorded every 6 seconds, hemoglobin and central venous SO2 (SvO2) in vena cava superior every 6 hours. Results: rSO2 measurement began 10 hours after the first chemotherapy (H0). SpO2 value was 96.4±2.0%, cerSO2 was 75.8±3.9% SvO2 values were stable around 70%, suggesting that there was no variation in systemic oxygen transport (TO2) lirSO2 value at H0 was 24.7±7.6% and raised up to 74.0±2.5% at H12. Conclusions: NIRS provides a non-invasive assessment of lirSO2 in acute hemopathies. The decrease in lirSO2 could be the witness of tissular hypoxia induced by myeloproliferation. Our data show an increase in lirSO2 under chemotherapy. NIRS could be helpful to evaluate the decrease in VO2 and the improvement of TO2 during chemotherapy.

Abdominal Actinomycosis

Abdominal Actinomycosis

Métastase ganglionnaire sus-claviculaire d’un carcinome thymique : présentation inaugurale inhabituelle d’une pathologie rare

Among the epithelial tumours of the thymus, thymic carcinomas are rare, involving more aggressive locoregional behaviour and a poor prognosis. More than one-third of cases present lymph node metastasis during an evaluation of the extension of a primitive mediastinal tumour of thymic origin. The authors report an unusual case in a 46-year-old woman presenting a metastatic form. The diagnosis of epidermoid thymic carcinoma was based on the histopathological examination of a right supraclavicular lymph node, associated with an anterior radiological mediastinal tumoral syndrome, raising the delicate problem of its diagnosis and treatment.

Granulocytic sarcoma of the rectum: Report of one case that presented with rectal bleeding

Granulocytic sarcoma is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. It may present in association with acute myeloid leukaemia, myelodysplastic syndrome and chronic myelogenous leukaemia. Granulocytic sarcoma may occur in any anatomical site but involvement of the gastrointestinal tract is rare, especially in the rectum. We report on the case of a 17 year old female who presented with rectal bleeding, abdominal pain and weight loss one mo prior to admission. Rectosigmoidoscopy revealed a rectal polypoid and ulcerated mass. The histological examination of the mass showed granulocytic sarcoma. Bone marrow examination was compatible with acute promyelocytic leukaemia (FAB type M3). This case report is a reminder of this peculiar sign of tumoral syndrome in acute myeloid leukaemia. We also discuss diagnostic methods and analyze the disease course.

Prise en charge de l’acromégalie évolutive au cours de la grossesse

Pregnancy in acromegalic patients is an infrequent event, due to perturbed gonadotroph function. On the other hand, pregnancy may cause an enlargement of the adenoma or an increase of growth hormone (GH) secretion. We report the case of a 26-year-old woman with a GH-secreting pituitary macroadenoma who was operated by transphenoidal approach. After surgery, she had a persistant acromegaly due to an intrasellar tumour. She was treated by lanreotide. After one year, the patient had married and became pregnant. Lanreotide was stopped when the diagnosis of pregnancy was established. The follow-up of this patient showed a progressive increase of IGF1 level during pregnancy without tumoral syndrome or visual troubles. No metabolic complication was detected. The patient went to term and gave birth to a healthy baby. In postpartum, the IGF1 level was normal, but the brain MRI revealed a 10mm intrasellar tumour. The pituitary adenoma was not significantly enlarged during pregnancy. Therefore, pregnancy doesn’t influence acromegaly in young women well controlled by medical treatment.

Long Term Evolution of 328 Stage A0 B-CLL

Because at present time stages A0, i.e. stages A without peripheral tumoral syndrome, represent more than 50% of new diagnosed B-CLLs, we took back our 328 patients (pts) seen before 1998.Sex ratio-M/F is 1.41 similar to other pts. If a roughly “systematic” numeration leads to diagnosis of 90% of pts, 6% of our pts present B-symptoms. Median time between diagnosis and first pathologic numeration is 17 months and median value of LDT is 36 months with only 11% of pts with a LDT less than 12 months. Mean values of blood and medullary lymphocytosis are 19.5 G per l and 50% and among 222 BM biopsies, a diffuse dense pattern is seen in 8% of cases. Mean levels of hemoglobin and platelets are 141 g (5 pts with stage 3 Rai) and 243 G. Mean levels of seric LDH and β2-m are 0.96 N and 2.23 mg. Stage A“ according to the French definition represent only 19% of our pts while around 40% of our pts present at less one of our 5 clinical pejorative factors: 7 have a blood lymphocytosis >70 G; 70 a massive marrow involvement (>70% at myelogramm or diffuse pattern at BM); 25 a hemoglobin <120 g and 25 platelets <150 G, the 5th factor being the presence of a peripheral tumoral syndrome.At time of our first analysis (2006 July), the median follow-up time was more than 11 years and the median survival time was 9.7 years while 15- and 20-year survival rates were 33 and 20%. Median “corrected” survival time (without not-related deaths including those due to a solid tumor) was 15.4 years and the 20-year survival rate was 47% not statistically different from a matched control population. Only 3 pts developed a secondary MDS/AML while 15-year rates for occurrence of a Richter's syndrome and a solid tumor are 10% and 25%.If about 1/3 of our pts were treated at diagnosis, the 239 other ones were watched and only 20% of them needed a treatment. Median time of treatment is 65 months and the 5-and 10-year rates are 17 and 31% without aspect of plateau on actuarial curve. The 5-year rates of treatment are 17 and 31% among A′ and A″ pts (p=0.01) but our prognostic classification is more efficient with 13, 38 and 100% rates (p<10–6). Presence of LDH>1.25 N is also an indicator for treatment: 5-year rates are respectively 35 and 18% (p=0.04) and presence of β2-m >3 mg too: 35 and 18% (p=0.002). Combination of LDH and β2-m is more efficient: 5-year rates are 43 and 16% (p=0.0005) and this prognostic system is independent from our prognostic classification.Pts initially treated present a smaller “corrected” survival than watched pts: median are respectively 9 and 10.3 years and 15-year rates are 26 and 37% (p=0,006). Non related deaths represent more than half of all deaths and among them solid tumor represent 41% of causes before cardio-vascular causes and age (35 and 22%).We will actualize this study but 2 points are already clear. The “old” clinical prognostic factors remain very pertinent among these “good” B-CLL and need to be compared with “modern” prognostic factors. At least looking at treatment, primum non nocere.

Secretion of MMP-2 and MMP-9 induced by VEGF autocrine loop correlates with clinical features in childhood acute lymphoblastic leukemia

In children with acute lymphoblastic leukemia (ALL), leukemic cells express several members of the VEGF family and the three VEGF receptors which, via an autocrine loop are responsible for secretion of MMP-2/-9. MMP activity and the presence of elements of the autocrine loop are correlated with clinical and prognostic parameters as follows: i) high basal MMP-9 activity with tumoral syndrome, ii) MMP-2 activity with treatment failure, iii) VEGFR-1/-3 co-expression with high hemoglobin level and iv) expression of the VEGF-A 121 isoform and favorable response to treatment. These data implicate autocrine VEGF-induced secretion of MMP-2/-9 in the physiopathology of childhood ALL.

Carotid Chemodectomas: Long-Term Results of Subadventitial Resection with Deliberate External Carotid Resection

The aim of this study was to evaluate the short-term and long-term results of the subadventitial resection of carotid chemodectomas and to validate the importance of deliberate resection of the external carotid artery (ECA). From 1981 to 2006, 39 carotid chemodectomas of the carotid bifurcation or of the neighboring nerves were operated on in our department. There were 14 men and 22 women, with a mean age 44.4 +/- 5 (range 21-78) years. One of these operations was a redo surgery for local recurrence. One female patient presented with a bilateral tumor. Two tumors were secreting catecholamines. All these tumors affected the carotid body; 10 of them were also affecting the vagus nerve, and one among these last 10 affected the sympathetic nerve as well. In 11 cases, the tumor had spread into the subparotidal space and, in one case, into the skull. In two cases, the tumor had been revealed by hemispheric ischemia and in every case by tumoral syndrome. All the patients were followed up by clinical examination, duplex scan, or computed tomographic scan until the end of 2006. In 38 cases, complete resection was performed; an incomplete resection was performed in one case with cranial invasion. Under general anesthesia, and most of the time without pharmaceutical preparation, surgery consisted of a deliberate sacrifice of the ECA followed by subadventitial resection of the tumor. In one case, a previous embolization had been carried out to facilitate the cleavage, which in fact rendered it more complicated. In 22 cases, resection concerned the ECA; in seven cases, it concerned the common carotid artery and the internal carotid artery (ICA): in seven cases the superior laryngeal nerve, in nine cases the vagus nerve, in five cases the sympathetic nerve, and in four cases the jugular vein. In 13 cases, node clearing was associated. In 20 cases, an additional vascular procedure was performed: nine dilatations for spasm of the ICA, five autogenous vein grafts, two prosthetic bypasses, and one endarterectomy associated with a patch angioplasty. All patients were followed up until 2006. At 3 months, the observed complications were the sequelae of a homolateral hemispheric accident due to thrombosis of a vein graft, eight peripheral facial nerve palsies, 12 vocal palsies, seven Claude Bernard-Horner (CBH) syndromes, eight palatal paralyses, and 10 nociceptive pains. Some of these complications did persist: nine vocal cord paralyses that were successfully treated by speech therapy, three mild CBH syndromes, and nociceptive pains in 6% of the cases (15.4%), incapacitating in one case. With a follow-up of 115 +/- 27 (range 1-298) months, three local recurrences were recorded at 6 and 10 years. In two cases, local recurrence occurred when initial resection of the ECA had not been performed. Two patients presented with a contralateral lesion, at 12 and 16 years, respectively. At 40 months, one patient had to be reoperated on for an atheromatous stenosis. At 51 months, a female patient's death was not related to the operation. Subadventitial resection of carotid body tumors with deliberate resection of the ECA is a simple and efficient procedure. It is the preferential treatment for these slow-growing localized tumors.

Síndrome periódico asociado al receptor del factor de necrosis tumoral

Tumoral necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal dominantly inherited disease belonging to the hereditary periodic fever syndromes, which are the main subgroup among systemic autoinflammatory diseases. TRAPS is characterized by prolonged and recurrent inflammatory attacks associated with fever and an acute phase reaction. Articular, cutaneous, ocular and abdominal symptoms may also be present. We describe the case of a 4-year-old boy with recurrent inflammatory episodes, fever and cutaneous symptoms who was diagnosed with TRAPS. We review the clinical and laboratory findings, genetic diagnosis, and treatment approach in this disease.

Focal cortical resections for the treatment of extratemporal epilepsies in children

Children with lesion-related extratemporal epilepsies with suboptimal seizure control should be identified early and referred for presurgical evaluation before irreversible deterioration in cognitive or psychosocial functions ensues due to long-standing disabling seizures and chronic antiepileptic drug-related side effects. The success of epilepsy surgery depends upon the accurate preoperative localization of the epileptogenic zone and its complete resection. Children with medically refractory lesional epilepsies belong to different categories depending upon the degree of complexity involved in the presurgical evaluation to define their epileptogenic zone. While some patients, such as those with tumoral epilepsy syndrome, can be selected for surgery by simple noninvasive presurgical evaluation strategy, others with malformations of cortical development and those with multiple lesions often require complex and invasive means to define their epileptogenic zone. Recent advances in structural and functional imaging have obviated the need of invasive monitoring in the majority. These advances along with improvement in surgical techniques have made resective surgery safer and more effective. Prospective comprehensive follow-up studies are needed to evaluate the long-term seizure, cognitive, psychosocial, educational and occupational outcomes of surgically treated children with extratemporal epilepsies.

Clinical Efficacy of Bortezomib Based Therapy in Plasma Cell Leukemias.

Introduction Plasma Cell Leukemia (PCL) is characterized by a high number of plasma cells in peripheral blood (>2 × 109/L) and more than 20% of circulating plasmocytes on differential count. Primary PCL or secondary form, after previous multiple myeloma (MM), represent the most aggressive forms of clonal gammapathy with very poor outcome from both conventional chemotherapy and autologous or allogeneic transplant. For this reasons new effective treatment approaches are required. The proteasome inhibitor Bortezomib has been shown to be effective in advanced MM with a rapid response but few reports have been published regarding its potential role on PCL. We report here the clinical results of a serie of PCL patients that received proteasome inhibitor, Bortezomib (Velcade®), as induction therapy.Patients and Clinical Results We describe 10 patients with PCL treated with Bortezomib. Median age was 58 y (30–70). 4 cases were primary, de novoPCL and 6 cases were secondary forms of relapsed or progressive MM. Patients with secondary PCL had received a median of 3 previous lines of therapy including autologous transplantation (5 cases). Bortezomib at standard dose iv: 1.3 mg/m2 days 1,4, 8,11 every 21 days were used alone in 2 patients and in combination with high dose of Dexamethasone +/− Adryamicin in the rest. 3 cases recived the BDD scheme (Bortezomib iv, Pegylated Doxorrubicin iv and oral Dexamethasone). 9 patients were evaluable for drug efficacy with 7 cases showing some grade of favourable response with the first cycle, including 3 cases of CR. 4 patients have died: 1 during first weeks and 3 for progression, 2–3 months after initial response. 3 cases received allogeneic transplant with related donor and reduced conditioning and are alive 12, 14 and 30 months postransplant. The median follow up since PCL diagnosis of 6 alive patients is 14 months (3–39 months). 3 patients received maintenance therapy that included low dose thalidomide. Grade 2 thrombopenia, neutropenia and gastrointestinal symptoms were the main secondary toxicity. No complicated tumoral lysis syndrome were observed.Conclusions and Comments Bortezomib has been shown to be effective by several mechanisms in patients with MM resistant to multiple previous treatments and as induction therapy alone or in combination with other drugs. The favourable responses observed in these cases of PCL; including de novo patients, and the biological ex vivo results in PCL cell lines, suggest the potential efficacy of this agent combined with dexamethasone and doxorubicin. Although more experience is necessary these data support future trials with Bortezomib combined with other drugs for example BDD scheme in the induction treatment of PCL. The role of allogeneic intensification therapy has also to be investigated in young patients after control of PCL with this approach. For maintenance of response, the role of this drug or other new drugs as thalidomide or lenalidomide has to be investigated.

Squamous cell carcinoma of the nail apparatus: clinicopathological study of 35 cases

Subungual squamous cell carcinoma (SCC) is rare. Its diagnosis is often missed or delayed because the clinical presentation is often atypical and can mimic other conditions such as verruca vulgaris, onychomycosis, trauma-induced nail dystrophy or exostosis. To define the different clinical presentations and the main pathological features and to evaluate the most appropriate surgical management of subungual SCC. A retrospective review of all the cases of subungual SCC seen in our institution over a 5-year period. Thirty-five cases were selected. The spectrum of the clinical features encountered was extremely large including leuconychia, subungual hyperkeratosis, trachonychia, subungual tumoral syndrome, longitudinal erythronychia and melanonychia. Most cases (31 of 35) were invasive. Relapse rate after surgical treatment was low after wide surgical excision (5%) of the nail apparatus or amputation of the digit. However, limited surgical excision led to more frequent relapses (56%). Nail apparatus SCC is often misdiagnosed. Most cases are invasive at the time of diagnosis. Wide surgical excision bears a lower risk of relapse. Micrographic surgery should be considered for a better control in cases treated with limited surgical excision.

An International Multicentric Trial with Fludarabine Plus Cyclosphosphamide in B-Cell Chronic Lymphocytic Leukemia (CLL) “Up Front”: Second Interim Analysis.

Introduction: On August 2002 an international multicentric trial on Fludarabine monophosphate (FAMP) plus Cyclophsphamyde (Cy) among previously untreated B-cell CLL, was activated. Our aim is to evaluate efficacy and toxicity of FAMP plus Cy in previously untreated B-cell CLL patients (pts). This is the second interim analysis after a fourth-year period.Material and Methods: Treatment consists in three consecutive days of oral FAMP 40 mg/m2 (n=84) or i.v. FAMP 25 mg/m2 (n=13) plus i.v. Cy 600 mg/m2 on day 1 or Cy 250 mg/m2 from day 1 to 3, every 28 days × 6 cycles. Responses were assessed according to the National Cancer Institute working group criteria after cycle 3 and again after cycle 6. Since August 2002 to March 2006, 109 CLL pts from Argentina (n=95), Perú (n=11) and Uruguay (n=3) were enrolled for this protocol; eighty-nine were evaluated for response and toxicity. Median age: 64 years old (range: 44–81); male = 47, female = 42; Binet staging: A=14, B=45, C=30; median beta-2 microglobuline = 4.00 mg/dL (range: 1.3–9.2); median LDH = 341 UI/L (range: 101–762); among patients with available data the CD 38 expression more than 10% was 38% (22 of 58 pts). Blood counts at inclusion: median values (range); Lymphocytes: 32 ×109/L (2,7–137), Hb: 120 g/L (50–164), platelets: 175×109/L (10–364). Renal and hepatic parameters within normal range limits. Cytogenetic by banding was available in 27 cases: no alterations (n=17), +12 (n=1), del (6), del (12) (n=1), lost Y (n=1).Results: At the time of this second interim analysis (March 2006), 56.2% (50 pts) had completed 6 cycles and 97.8% (87 pts) had undergone at least 3 cycles.Overall responses: 92% = 81 pts (CR: 39% = 35 pts; PR: 52% = 46 pts); treatment failure: 9% = 7 pts. Evaluation for toxicity: 89 episodes of haematological toxicity and 7 episodes of infection grade 3–4 were reported after 436 cycles. Thirteen pts died: seven due infectious complications because of prolonged hematologic toxicity; one due to tumoral lysis syndrome, one due hemoptysis associated with lung cancer and the remaining four due disease progression. At 24 months, estimated DFS was 70% (figure 1, SE 7.6%) and estimated Overall Survival was 76% (figure 2, SE 7.4%). The median survival was not achieved in responders (PR and CR).Conclusion: FAMP plus Cy combination as front-line treatment is effective in B-cell CLL. Haematologic toxicity is the most severe adverse events. The response rates to this therapy is quite similar to those reported for other multicentric trials and better than others GATLA protocols. [Display omitted] [Display omitted]

Análisis y protocolización de la utilización de rasburicasa en pacientes con neoplasias hematológicas

Objective To describe the use of rasburicase in adult patients with hematological neoplasias and to present a protocol for its administration jointly prepared by the hematology and the pharmacy departments based on the scientific evidence available. Method Retrospective study that reviews treatments with rasburicase administered in a tertiary 800-bed hospital from July 2002 to May 2004 to adult patients with hematological neoplasias. The following data were collected: demographic and clinical data, daily dose of rasburicase and length of treatment, plasma levels of creatinine, potassium, phosphate, calcium, LDH, uric acid and white blood cell count daily and until 48 hours after administering the last dose of rasburicase. Results Rasburicase was administered to a total of 18 adult patients (mean age of 57 years; range 27-84; 11 men and 7 women). Prior to treatment, 16 patient had high levels of LDH, 12 patients had a blood count over 50,000 white blood cells/mm 3, and 11 had serum levels of uric acid above 7 mg/dl. The dose of rasburicase administered was 0.2 mg/kg/day and the median length of treatment was 5 days (range 1-10). The levels of uric acid returned to normal values in all patients. Furthermore, an statistically significant decrease of creatinine levels was observed. The other biochemical parameters studied were duly controlled throughout the treatment. Conclusions A high variability is observed in the use of rasburicase in our patients. The hematology and pharmacy services have been working jointly to prepare a consensus-based protocol according to which, depending on the patient’s risk of developing TLS (tumoral lysis syndrome), standard prophylaxis is administered to low-risk patients (intravenous hydration, alopurinol and urine alcalinization) and rasburicase is administered initially for 1-3 days to patients with high risk of developing TLS.