A rare case of bone marrow infiltration by medulloblastoma in a child.

A seven-year-old boy was previously treated for the primarya posterior fossa tumour, medulloblastoma, with extensive central nervous system metastases including leptomeningeal and intrathecal spinal disease; methylation profiling confirmed a Group 4 tumour. At initial presentation a chemotherapy approach was preferred, due to both his young age and extent of disease; this achieved complete radiological and cytological remission prior to consolidation with high-dose chemotherapy and autologous stem cell rescue. He then experienced an asymptomatic localised posterior fossa relapse on surveillance imaging, treated with complete surgical resection, craniospinal irradiation and maintenance chemotherapy. This chemotherapy was interrupted due to poor count recovery following irradiation, and a bone marrow aspirate and trephine were performed which excluded metastatic medulloblastoma or secondary leukaemia. Alternative maintenance with temozolomide was well tolerated. Unfortunately, end-of-treatment MRI imaging of the neuro-axis revealed an asymptomatic new small enhancing intracranial lesion. An early repeat MRI was performed six weeks later which showed minor progression of the intracranial disease and no intrathecal metastases, but new low T1 signal in multiple vertebral bodies with sparing of T3 and T7 vertebrae (arrows; left image) compared with the imaging performed just six weeks previously. Full blood count revealed Hb 97 g/l, WCC 7.7 x109/l, neutrophils 5.4 x109/l and platelets 204 x109/l. In view of the radiological appearances, bone marrow aspirate and trephine were performed from the posterior iliac crest. Aspirate revealed heavy infiltration with clusters of non-haematopoietic cells, characterized by high nuclear:cytoplasmic ratio, open chromatin and agranular, pale basophilic cytoplasm with vacuolation (right upper image). Trephine immunohistochemistry demonstrated positive staining for synaptophysin, CD56, Neu-N (right lower image), retained INI1 and negative CD99 and desmin, confirming medulloblastoma. Spread of medulloblastoma to the bone marrow is a very rare event. In this case, despite an unremarkable full blood count, radiological changes in the spinal column correlated with easily identified disease in aspirate and trephine samples taken from the posterior iliac crest suggesting widespread marrow infiltration were confirmed by bone marrow examination. Early identification of extracranial metastasis afforded the family and clinicians the opportunity to make informed choices regarding ongoing management

Clonal hematopoiesis and therapy-related myeloid neoplasms following neuroblastoma treatment.

Therapy-related myeloid neoplasms (TMN) constitute one of the most challengingcomplications of cancer treatment.1 Whilst understanding of TMN pathogenesis remains fragmentary, genomic studies in adults have thus far refuted the notion that TMN simply result from cytotoxin-induced DNA damage.2–4 Analysis of the preclinical evolution of a limited number of adult TMN have retraced the majority of cases to clonal haematopoiesis (CH) that predates cytotoxic treatment and lacks the mutational footprint of genotoxic therapies.2–6 Balanced translocations, generally attributed to treatment with topoisomerase II inhibitors, are implicated in a minority of TMN.1 TMN is a leading cause of premature death in childhood cancer survivors, and affects 7-11% of children treated for high-risk neuroblastoma and sarcoma.7,8 However, the origin of pediatric TMN remains unclear. Targeted sequencing of known cancer genes detects CH in ~4% of children following cytotoxic treatment,6,9 whereas CH is vanishingly rare in young individuals in the general population.10,11 Moreover, to our knowledge, no cases of childhood TMN have been retraced to pretreatment CH. In light of these observations, we asked whether a broader driver landscape had eluded targeted CH screens in pediatric cancer patients and/or whether therapy-induced mutagenesis may be an under-recognised catalyst of CH and TMN in this patient group

Strateginen johtaminen Hatusen Liikenteen kehittäjänä

Hatusen Liikenne on Hämeenlinnan seudulla toimiva tilausajoyritys. Linja-autoala on tällä hetkellä isossa muutoksessa, koska EU:n palveluasetuksen siirtymäaika on umpeutumassa ja linja-liikenteen kilpailutus lisääntyy ja lähivuosina alan markkinat ennakoidaan jakautuvan uudella tavalla. Kuljetusala on myös toisaalta kustannuspaineiden alla, koska kulut ovat nousussa, mutta yleisen talouden takia saatavat asiakasmaksut ei nouse kulujen kanssa samaan tahtiin. Tämän kehittämistyön tarkoituksena oli luoda Hatusen Liikenteelle strategia ja seurantamittarit Balanced Scorecardin avulla. Tarkoituksena oli tutustua strategian työvälineisiin yrityksen kehittäjänä, erityisesti Balanced Scorecardiin. Kehittämistehtävän tavoitteena oli kehittää Hatusen Liikenteen strategista johtamista. Tavoitteena oli tätä kautta löytää Hatusen Liikenteen näkökulmasta sopivimmat kehittämisvälineet. Kehittämistehtävän teoreettinen viitekehys rakentui strategia-, johtaminen- ja Balanced Scorecardista koostuvasta kirjallisuudesta. Kehittämistehtävässä käytettiin konstruktiivista tutkimusta, koska kehittämistehtävän tarkoituksena oli luoda konkreettinen tuotos, eli strategia. Konstruktiivisessa tutkimuksessa käytettävät menetelmät voivat olla kirjavia, koska lähestymistapa ei sinänsä rajaa pois mitään menetelmää. Toteuttamalla tämän kehittämistehtävän avulla löydetyt mittarit, varmistetaan Hatusen Liikenteen menestyminen erittäin kilpailuilla markkinoilla. Strategian käytäntöön vienti on tärkeä asia yrityksessä ja mittariston kehittäminen luo järjestelmän, jonka avulla yritys pääsee haluttuihin tuloksiin.Hatusen Liikenne is a charter bus company in Hämeenlinna area at in Tavastia Proper region. The bus industry is undergoing great changes because of the European Union’s preferences of services. The transition time for the service regulation has now come to the end and it has been estimated that markets will be reorganized in the next few years. Additionally, the growth of expenses is a problem for the industry because of the current economic situation. The purpose of this thesis was creating a strategy and Balanced Scorecard for Hatusen Liikenne. The theoretical section explores the meaning of strategy, the phases of the strategy process, and the basis of the Balanced Scorecard. The sources of the theoretical part include literature and online material. A constructive research approach has been utilized in this thesis. The creation of new information, as required by the constructive research method, included gathering information, creating a new strategy, and utilizing the experiences. By implementing the development measures presented in this thesis, Hatusen Liikenne will more likely succeed in the very competitive markets. Implementing the strategy is very important for the company and with the Balanced Scorecard, the goals will be achieved

Surrogates of Quality of Life during Double Relapsed and/or Refractory Multiple Myeloma Therapy.

<p>^aAll Surrogates of Quality of Life were recorded from initiation of 1^st DRMM therapy until the end of follow up (or death)</p><p>^bAdverse events with no recorded grade are assumed to be grade 3 or 4.</p><p>Surrogates of Quality of Life during Double Relapsed and/or Refractory Multiple Myeloma Therapy.</p

Kaplan Meier curve showing overall survival, progression free survival and time to treatment failure.

<p>Kaplan Meier curve showing overall survival, progression free survival and time to treatment failure.</p