Rapidly progressive diffuse systemic sclerosis (dSSc) is a life-threatening condition characterized by increased mortality with few effective therapies, typically only helpful in stabilizing disease. Autologous hematopoietic stem cell transplantation (AHSCT) is the only treatment that has demonstrated improved survival. Despite promising results from three randomized controlled trials (RCTs), best practice use of AHSCT in the real-world setting is not well established. The primary objective of this thesis was to summarize the clinical efficacy, limitations and utilization of AHSCT in the management of rapidly progressive dSSc. Specifically, we conducted (1) a systematic review to describe the efficacy of AHSCT in dSSc as well as practice variation in patient selection and treatment regimens; and (2) a multicenter retrospective cohort study to compare outcomes for subjects who received AHSCT in France compared to those who received conventional care in Canada. There was important variability in the criteria for patient selection and treatment protocols. While AHSCT is associated with improved overall survival, skin fibrosis and lung function, further studies are needed to understand its potential for expanded eligibility and effects on other disease manifestations.

Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients ≤ 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (MCL; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients ≤ 65 years but produced worse PFS in HL patients when compared with BEAM.

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Introduktion Autolog stamcellstransplantation är idag en vanlig behandling vid myelom och högmaligna lymfom hos patienter <65 år utan omfattande komorbiditet. Behandlingen delas upp i fem faser: induktionsbehandling, stamcellsmobilisering, stamcellsskörd, konditionering med högdoscytostatika och stamcellsåtergivning/transplantation. Initialt behandlades alla patienter som genomgick autolog stamcellstransplantation inom slutenvården under den sista behandlingsfasen, det vill säga i samband med konditionering och stamcellsåtergivning. Sedan 1990-talet har man dock på många håll i världen övergått till poliklinisk vårdform för denna patientgrupp. Detta innebär att patienten genomgår stamcellstransplantationen inom slutenvården men efter detta behandlas som öppenvårdspatient med fasta återbesök på sin hemklinik under posttransplantfasen. Poliklinisk vårdform har visat sig vara en säker, uppskattad och kostnadseffektiv vårdform som inte medför större risker för patienten och som inte ökar mortalitet och/eller morbiditet i samband autolog stamcellstransplantation. Syfte Syftet med denna studie är att undersöka om det föreligger skillnad i grad av cytostatikarelaterat fördröjt illamående och kräkningar mellan patienter som vårdats polikliniskt jämfört med patienter som vårdats inneliggande på vårdavdelning efter autolog stamcellstransplantation. Metod Studiepopulationen utgörs av 91 patienter varav 33 vårdades polikliniskt och 58 vårdades inom slutenvården efter autolog stamcellstransplantation. Patienterna fyllde i en illamåendedagbok i samband med behandlingen varpå dessa analyserades utifrån variabler gällande cytostatikarelaterat fördröjt illamående och kräkningar. Resultat Resultatet visar att de polikliniserade patienterna mår generellt bättre än de icke- polikliniserade patienterna vad gäller cytostatikarelaterat fördröjt illamående och kräkningar. Sammanfattning Föreliggande studie indikerar ett positivt samband mellan poliklinisk vårdform och lägre incidens av cytostatikarelaterat fördröjt illamående och kräkningar hos patienter som genomgår autolog stamcellstransplantation. / Introduction Treatment for myeloma and lymphoma today typically involves autologous stem cell transplantation for patients <65 years without coexisting comorbidity. The treatment consists of five stages: induction treatment, stem cell mobilisation, stem cell harvest, conditioning with high dose chemotherapy and stem cell rescue (transplantation). Historically all patients treated with autologous stem cell transplantation received treatment as inpatients but this practice has since the 1990ies, due to for instance financial reasons, gradually shifted into an outpatient approach to this line of care. Thus, for the patient the outpatient approach entails myeloablative conditioning and stem cell transplantation as inpatient followed by post transplant care as outpatient part of the home clinic’s outpatient program. Outpatient care following autologous stem cell transplantation has proven to be a safe, highly appreciated and cost effective method of care without any adverse effects on behalf of the patients with regards to clinical outcome, mortality and/or comorbidity. Objectives The aim of this study is to ascertain whether or not there is a difference in degree of chemotherapy-induced delayed nausea and vomiting between an outpatient population and an inpatient population following autologous stem cell transplantation. Methods A total of 91 patients, 33 of whom were included in an outpatient program while remaining 58 were treated as regular inpatients, participated in the study. Patients each day filled out a diary with regards to nausea and emesis during the entire treatment phase. Submitted data was then analysed concerning parameters related to chemotherapy-induced delayed nausea and vomiting. Results The result shows that the outpatient population suffers less in general than the inpatient population in terms of chemotherapy-induced delayed nausea and vomiting. Conclusion To conclude, this study suggests a positive correlation between outpatient care following autologous stem cell transplantation and a lower incidence of chemotherapy-induced delayed nausea and vomiting.

Background: Ewing sarcoma is one of the most frequent soft-tissue tumors in pediatric patients. The current treatment protocols recommend stem cell apheresis (SCA) after completion of the second course of induction therapy with vincristine, ifosfamide, doxorubicine, and etoposide (VIDE). The feasibility of SCA and graft compositions in adult patients with Ewing sarcoma have not been previously analyzed. Methods and Materials: The authors analyzed 29 stem cell collections of 19 adult patients (9 male, 10 female) at a median age of 27 (range 19–53) years mobilized after VIDE (n = 17), cyclophosphamide/topotecan (n = 1) or vincristine, dactinomycin and ifosfamide (n = 1) chemotherapy. All patients were mobilized with filgrastim 5 μg/kg twice daily from day +7 of chemotherapy. The collections were performed if CD34+ cell count in peripheral blood was >10/μL. The target yields were ≥4106 CD34+ cells/kg body weight. Results: Median CD34+ cells/μL in peripheral blood before SCA were 45.8 (range 6.7–614.4)/μL. The median cumulative yields were 10.6 (range 1.5–38.8) CD34+ cells/kg body weight and ≥2106 in all but two patients (89%). CD34, CD3, and CD56 yields in collections after the third VIDE and after later courses did not differ. Four patients underwent high-dose therapy with autologous transplantation, and all were engrafted. Discussion: Stem cell mobilization is feasible in most Ewing sarcoma patients. Additionally, the present study's data suggest that it is safe to postpone stem cell collection to a later VIDE chemotherapy cycle if medically indicated

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.

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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.