Introduction: Autologous stem cell transplantation (ASCT) is the standard treatment for younger patients with newly-diagnosed multiple myeloma (MM). However, due to restrictive exclusion criteria, more than half of eligible patients are usually excluded from transplant-studies. Methods: This retrospective monocentric analysis included 540 patients with MM who received an ASCT between 1996 and 2019. Results: Up to 2005, induction therapy consisted mainly of conventional chemotherapies, e.g. vincristine/doxorubicin/dexamethasone (VAD). In the following years, the triple-combinations based on bortezomib coupled with doxorubicin/dexamethasone (PAD), melphalan/prednisolone (VMP), cyclophposphamide/dexamethasone (VCD) or bendamustine/prednisolone (BPV) became the most popular treatment options. A progressive improvement in PFS was observed in patients treated with the two current induction therapies BPV (47 months) or VCD (54 months) compared to VAD (35 months, p<0.03), PAD (39 months, p<0.01 and VMP (36 months, p<0.01). However, there was no significant difference in median OS (VAD 78, PAD 74, VMP 72, BPV 80 months and VCD not reached). In our analysis, we also included 139 patients who do fulfill at least one of the exclusion criteria for most phase 3 transplant-studies (POEMS/amyloidosis/plasma cell leukemia, eGFR<40 mL/min, severe cardiac dysfunction or poor general condition). Outcome for these patients was not significantly inferior compared to patients who met the inclusion criteria for most of the transplant studies with PFS of 36 vs 41 months (p=0.78) and OS of 78 vs 79 months (p=0.34). Conclusions: Our real world data in unselected pts also stress the substantial value of ASCT during the first line treatment of younger MM pts.:Inhaltsverzeichnis Bibliographische Beschreibung …………………………………………………...………………..……….……………………......2 Inhaltsverzeichnis …………………………………………………………………………………………………………………...…........3 Abkürzungsverzeichnis ………………………………………………………………………………………………………………..…….4 1. Einführung …………………………………………………………………..…………………..…...................................7 1.1. Das multiple Myelom ………………………………………………….……………………………..………………………..7 1.2. Klinik und Diagnostik ……………………………………………………………………………..…………………………….7 1.3. Stadieneinteilung ……………………………………………………………….…………..…………………………………...8 1.4. Remissionsbeurteilung ……………………………………………………………………………………………………….10 1.5. Therapie …………………………………………………………………………………………….……………………………...12 1.5.1. Konventionelle Chemotherapie ……………………………………………………………………………………….…12 1.5.2. Neue Substanzen in der Myelomtherapie …………………………………………………………………………..13 1.5.2.1. Immunmodulatorische Substanzen ……………………………………………………………………………….……13 1.5.2.2. Proteasomen-Hemmer ……………………………………………………………………………………….………………13 1.5.2.3. HDAC Hemmer ……………………………………………………………………………………………………………………13 1.5.2.4. Monoklonale Antikörper …………………………………………………………………………………………………….14 1.5.2.5. BCMA basierte Therapien …………………………………………………………………………………………………..14 1.5.3. Autologe Stammzelltransplantation in der Ära der konventionellen Chemotherapie ………...15 1.5.4. Allogene Stammzelltransplantation …………………………………………………………………………………….15 1.5.5. Autologe Stammzelltransplantation in der Ära der neuen Substanzen ………………………………..16 1.6. Aufgabenstellung der Arbeit ……………………………………………………………………………………………….17 2. Publikation …………………………………………………………………………………………………………………….……18 3. Zusammenfassung der Arbeit ……………………………………………………………………………………………..33 Literatur …………………………………………………………………………………………………………………………………..…..…37 Tabellenverzeichnis …………………………………………………………………………………………………………………………49 Darstellung des eigenen Beitrags …………………………………………………………………………………………………….50 Selbständigkeitserrklärung ………………………………………………………………………………………………………………52 Lebenslauf ……………………………………………………………………………………………………………………………………….53 Verzeichnis der wissenschaftlichen Veröffentlichungen……………………………………………………………………54 Danksagung ……………………………………………………………………………………………………………………………………..56

Medulloblastoma is a common malignant brain tumor in childhood, but a rare disease amongst adults. The tendency to metastasize along cerebrospinal fluid pathways is well known. Extraneural metastases represent only a small number of recurrences and are associated with a poor outcome. Encouraging results of high-dose chemotherapy followed by autologous stem cell transplantation were reported previously in children with recurrent malignant brain tumors.

No description available.

L’objectif général de cette thèse a été de mettre en évidence la contribution de l’approche transcriptomique dans la physiopathologie et le traitement des hémopathies malignes. En particulier, comment la technologie des microarrays nous a aidée à étudier diverses problématiques en onco-hématologie.Dans la première partie, notre objectif était d’étudier les cellules Natural killer (Nk) chez les patients atteints de leucémie aiguë myéloïde (LAM). Nous avons comparé la signature transcriptomique des cellules Nk de patients LAM à celle des cellules Nk de sujet sains et suggéré que le facteur de transcription ETS-1 est un bon candidat capable de réguler les récepteurs activateurs NCR (natural cytotoxicity receptors) dont les gènes sont situés sur deux chromosomes différents, même si leur expression reste fortement cordonnée.Dans la seconde partie, nous nous sommes intéressés à la prédiction du sepsis en utilisant une approche transcriptomique dans le cadre de l’autogreffe de cellules souches hématopoïétiques (auto-CSH). En utilisant le même modèle, dans la troisième partie, nous avons mis en évidence l’effet du melphalan en tant que chimiothérapie de conditionnement sur les cellules mononuclées du sang périphérique et identifié un marqueur potentiel de rechute précoce chez les patients atteints de myélome dans le cas de l’auto-CSH. Enfin, dans la dernière partie, notre objectif a été d’analyser le profil d’expression génique des lymphomes B diffus à grandes cellules liés à l’infection par le VIH afin de vérifier ou pas l’existence des sous-types décrits chez les patients immunocompétents. / The aim of this research is to demonstrate transcriptomic approach contribution in the physiopathology and treatment of hematological malignancies. In particular, how microarrays technology is used to study several oncohematology difficulties; which remain deaths-related infection, as well as the failure to obtain remission and death related relapse. In the first part, our focus was to study natural killer cells (Nks) in patients affected with acute myeloid leukemia (AML). We compared transcriptomic AML-NKs signature with healthy donors-NKs signature and suggested that ETS-1 transcription factor is a good candidate able to regulate the natural cytotoxicity receptors (NCRs), whose coding genes, are located on two different chromosomes even if their expression remain strongly coordinated.Our second part, aimed to predict sepsis using a transcriptomic approach in the case of autologous stem cell transplantation (auto-HSCT). Using the same model, in the third part, we highlighted the melphalan high-dose chemotherapy effect on peripheral blood mononuclear cells and identified a potential good biomarker of early relapse in patients affected by myeloma in the case of auto-HSCT.Our final focus was to analyze gene expression profile of HIV-related large diffuse B-cell lymphoma type in order to verify the existence of subgroups described in immune-competent patients.