Mantle cell lymphoma – relapse after first line treatment

Mantle cell lymphoma (MCL) remains a challenge for the modern oncology and hematology. It combines the unfavorable features of non-Hodgkin lymphomas: it is recurrent and incurable as indolent lymphomas and it grows rapidly as most aggressive lymphomas. In most cases the disease develops rapidly and is characterized by persistent relapses. The available treatment options do not offer satisfying results. So far, there is no therapeutic standard available neither in the first nor in the subsequent lines of treatment. The observed prolongation of survival is undoubtedly associated with the intensification of treatment, including the addition of the cytarabine, as well as with the first line treatment consolidation with autologous hematopoietic cell transplantation and the use of monoclonal antibodies. The standard for the second and subsequent lines of treatment has not been established and the treatment approach to patients with relapsed or refractory disease should be highly individualized. When deciding on the therapy in subsequent lines of treatment following should be considered: patient general and functional condition, age, presence of concomitant diseases, possibility of high intensity treatment tolerance, prior treatments and achieved responses to those therapies, as well as biologic features of the lymphoma. High hopes are raised by new molecularly targeted therapies both for the first and subsequent lines of treatment, which could change the prognosis for MCL patients

Mantle cell lymphoma: update on diagnosis and treatment

Chłoniak z komórek płaszcza (MCL) jest rzadką postacią nowotworu układu chłonnego wywodzącą się z dojrzałego obwodowego limfocyta B z patognomoniczną dla jej powstania translokacją (11,14)(q13;q32) powodującą nadekspresję cykliny D1 u większości chorych. Charakteryzuje się nawrotowym i często agresywnym przebiegiem klinicznym. W chwili rozpoznania choroba jest zwykle w stadium zaawansowanym, z zajęciem narządów pozawęzłowych i wymaga leczenia systemowego. Obecnie nie ma ustalonego standardu postępowania terapeutycznego, zarówno w pierwszej, jak i kolejnych liniach leczenia. W przypadkach zaawansowanej choroby powszechnie uznaje się potrzebę stosowania leczenia o maksymalnej możliwej intensywności dostosowanej do wieku, stanu wydolności ogólnej i narządowej, z konsolidacją chemioterapią w dużych dawkach, z napromienianiem całego ciała (TBI) lub bez niego i autologicznym przeszczepieniem macierzystych komórek krwiotwórczych (auto-HSCT) w pierwszej całkowitej lub częściowej remisji. Leczenie choroby nawrotowej ma raczej charakter paliatywny i nie prowadzi do wyleczenia, poza nielicznymi przypadkami zastosowania allotransplantacji (allo- HSCT), obarczonej jednak dużą śmiertelnością. Wiele grup badawczych stara się określić biologiczne markery, dzięki którym można byłoby dobierać właściwą terapię. Widoczne w ostatnich latach wydłużenie czasu przeżycia jest niewątpliwie związane z intensyfikacją leczenia oraz zastosowaniem przeciwciał monoklonalnych. Ogromną nadzieję budzą nowe generacje leków ukierunkowanych molekularnie, będące w trakcie badań klinicznych. Hematologia 2010; 1, 4: 330-341Mantle cell lymphoma (MCL) is a rare disease of lymphoid system arising from mature B lymphocytes with a typical translocation (11,14)(q13;q32) resulting in cyclin D1 overexpression in majority of patients. The disease is incurable and characterized by a multiple relapsing and aggressive course. At the time of diagnosis disease is usually in advanced stage with a frequent extranodal involvement in the majority of patients, and requires systemic treatment. Currently, no standard for first or second line treatment is available. The common first line treatment strategy in advanced disease is aggressive therapy tailored to the patient’s age and general health with a consolidation of high-dose chemotherapy, with or without total body irradiation (TBI) and autologous hematopoietic stem cell transplantation (auto-HSCT) in the first complete or partial remission. Treatment of relapse is essentially palliative except for limited cases of allotransplantation (allo-HSCT) burdened with high risk of treatment related mortality. Many research groups work on defining biomarkers that would prove useful in selecting appropriate therapy. Prolongation of survival seen in recent years is apparently related to more intensive therapy and use of monoclonal antibodies. New molecular targeted therapies currently arriving into clinical trials hold much of the promise for the future. Hematologia 2010; 1, 4: 330-34

Bezpośrednie i odległe wyniki leczenia guzów dołu podskroniowego i jego otoczenia z wykorzystaniem dostępu podskroniowego rozszerzonego

Background and purpose The aim of the study was to present our results of the surgical treatment of subtemporal fossa tumours and surrounding regions using the extended subtemporal approach. Material and methods Twenty-five patients (10 women, 15 men) with subtemporal fossa tumours were included in the study. The neurological and performance status of the patients were assessed before and after surgery as well as at the conclusion of treatment. The approximate volume of the operated tumour, its relation to large blood vessels and cranial nerves, as well as consistency and vascularisation were assessed. Results The symptom duration ranged from 2 to 80 months (mean: 14 months). In 44% of patients, headache was the predominant symptom. Less frequent symptoms were: paralysis of the abducent nerve and disturbances of the trigeminal nerve. Approximate volume of the tumours ranged from 13 to 169 cm3 (mean: 66 cm3). The most frequent histological diagnosis was meningioma (16%), followed by angiofibroma, neurinoma and adenocystic carcinoma (12%). Total or subtotal resection was achieved in 80% of patients. Conclusions The extended subtemporal approach allows for the removal of tumours of the subtemporal fossa and surrounding regions. This approach also allows one to remove tumours expanding in the regions surrounding the subtemporal fossa only. In such cases the subtemporal fossa constitutes the way of the surgical approach.Wstęp i cel pracy Celem niniejszej pracy jest przedstawienie własnych wyników leczenia operacyjnego guzów dołu podskroniowego i jego otoczenia z wykorzystaniem dostępu podskroniowego rozszerzonego. Materiał i metody Analizie poddano 25 przypadków guzów dołu podskroniowego, wśród których było 10 kobiet i 15 mężczyzn. Ocenie podlegał stan neurologiczny chorych przed rozpoczęciem leczenia, po operacji i po zakończeniu leczenia. Określano przybliżoną objętość operowanych guzów, ich stosunek do dużych naczyń i nerwów czaszkowych oraz konsystencję i stopień unaczynienia. Wyniki Długość wywiadu wahała się od 2 do 80 miesięcy i wynosiła średnio 14 miesięcy. W 44% przypadków wiodącym objawem był ból głowy. Rzadziej występowały niedowład lub porażenie nerwu odwodzącego oraz zaburzenia ze strony nerwu trójdzielnego. Przybliżona objętość usuniętych guzów wahała się od 13 do 169 cm3 i wynosiła średnio 66 cm3. Wśród usuniętych guzów najczęściej powtarzał się oponiak (16%). Rzadziej, bo w 12%, występowały naczyniakowłókniak, nerwiak i rak gruczołowo-torbielowaty. W 80% przypadków przeprowadzone resekcje były doszczętne lub z niewielkimi pozostałościami guzów. Wnioski Dostęp podskroniowy rozszerzony pozwala na usuwanie guzów dołu podskroniowego i graniczących z nim obszarów anatomicznych. Dostęp ten pozwala również na usuwanie guzów rozrastających się tylko w obszarach graniczących z dołem podskroniowym. W tych wypadkach dół podskroniowy stanowi drogę dostępu chirurgicznego

Nivolumab for relapsed/refractory classical Hodgkin lymphoma after brentuximab vedotin failure – Polish Lymphoma Research Group real-life experience

AimPolish centers analyzed retrospectively the real-life experience with nivolumab in relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) patients, after brentuximab vedotin (BV ) failure. BackgroundDespite the effective frontline treatment, for cHL patients relapsing after autologous stem cell transplantation, the only effective strategy remains the novel agents. Nivolumab, a checkpoint inhibitor, demonstrates the clinical benefit with an acceptable safety profile. Materials and methodsRetrospective analysis included 16 adult patients with R/R cHL after BV failure. All patients received single-agent nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity. ResultsAfter six cycles of nivolumab the overall response rate was 81% (complete remission rate of 56%, partial remission rate of 25%). The median PFS was not reached after a median follow-up of 19 months. Adverse events (AEs) of any grade occurred in 12 patients (75%), including grade 3 AEs observed in 5 patients (31%). There were no AEs of grade 4 or 5. After a median of 25 nivolumab doses, 62% of responding patients proceeded to allogeneic stem cell transplantation. ConclusionNivolumab monotherapy demonstrated a high efficacy and safety in R/R cHL patients after BV failure. More patients and longer follow-up may further establish the potential benefit

Conscious sedation for transcatheter implantation of atrial septal occluders with two- and three-dimensional transoesophageal echocardiography guidance — a feasibility and safety study

Background: General anaesthesia may have negative impact on patient mortality and morbidity, as well as overall procedure costs, in atrial septal occluder (ASO) implantation. Aim: We sought to evaluate the safety, efficacy, and feasibility of conscious sedation for transcatheter implantation of ASOs. Methods: A total of 122 patients referred for transcatheter implantation of ASO were included. Mean patient age was 51 ± 15 years, and 43 (35%) patients were male. The initial dose of midazolam was 2 mg and fentanyl dose was 25 μg. Additional doses of midazolam and fentanyl were administered, if necessary. Patient responsiveness was assessed every 10 min, and the sedatives doses were titrated in order not to exceed grade 3 sedation in the Ramsey scale. Results: Atrial septal occluders were successfully implanted in the majority of patients (98.4%). In two (1.6%) cases the proce­dure failed because of too small patent foramen ovale (PFO) diameter (n = 1, 0.8%) or device instability (n = 1, 0.8%). The mean duration of procedure was 47.6 ± 28.4 min and was similar for ASD and PFO closure (p = 0.522). The overall mean dose of midazolam was 4.7 ± 2.2 mg (63.9 ± 32.5 μg/kg) and fentanyl was 30.0 ± 11.9 μg (0.43 ± 0.17 μg/kg). Median entrance dose of radiation at the patient plane was 25 (interquartile range: 16–57) mGy, and did not differ between ASD and PFO procedures (p = 0.614). The majority of patients were free of complications (91.0%). The following early complications were observed: transient ischaemic attack (n = 2, 1.6%), supraventricular arrhythmias (n = 4, 3.3%), left atrial thrombus formation (n = 1, 0.8%), symptomatic bradycardia (n = 1, 0.8%), and femoral venous bleeding (n = 5, 4.1%). After mean follow-up of 386 days residual shunt was observed in eight (6.6%) patients. Conclusions: Conscious sedation for transcatheter implantation of ASO is a feasible, safe, and efficient technique, allowing successful PFO and ASD closure in the majority of patients.Background: General anaesthesia may have negative impact on patient mortality and morbidity, as well as overall procedure costs, in atrial septal occluder (ASO) implantation. Aim: We sought to evaluate the safety, efficacy, and feasibility of conscious sedation for transcatheter implantation of ASOs. Methods: A total of 122 patients referred for transcatheter implantation of ASO were included. Mean patient age was 51 ± 15 years, and 43 (35%) patients were male. The initial dose of midazolam was 2 mg and fentanyl dose was 25 μg. Additional doses of midazolam and fentanyl were administered, if necessary. Patient responsiveness was assessed every 10 min, and the sedatives doses were titrated in order not to exceed grade 3 sedation in the Ramsey scale. Results: Atrial septal occluders were successfully implanted in the majority of patients (98.4%). In two (1.6%) cases the proce­dure failed because of too small patent foramen ovale (PFO) diameter (n = 1, 0.8%) or device instability (n = 1, 0.8%). The mean duration of procedure was 47.6 ± 28.4 min and was similar for ASD and PFO closure (p = 0.522). The overall mean dose of midazolam was 4.7 ± 2.2 mg (63.9 ± 32.5 μg/kg) and fentanyl was 30.0 ± 11.9 μg (0.43 ± 0.17 μg/kg). Median entrance dose of radiation at the patient plane was 25 (interquartile range: 16–57) mGy, and did not differ between ASD and PFO procedures (p = 0.614). The majority of patients were free of complications (91.0%). The following early complications were observed: transient ischaemic attack (n = 2, 1.6%), supraventricular arrhythmias (n = 4, 3.3%), left atrial thrombus formation (n = 1, 0.8%), symptomatic bradycardia (n = 1, 0.8%), and femoral venous bleeding (n = 5, 4.1%). After mean follow-up of 386 days residual shunt was observed in eight (6.6%) patients. Conclusions: Conscious sedation for transcatheter implantation of ASO is a feasible, safe, and efficient technique, allowing successful PFO and ASD closure in the majority of patients