Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial

IMPORTANCE High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. DESIGN, SETTING, AND PARTICIPANTS The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. INTERVENTIONS HSCT vs intravenous pulse cyclophosphamide. MAIN OUTCOMES AND MEASURES The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. RESULTS A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. CONCLUSIONS AND RELEVANCE Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN54371254.

Festskrift i anledning af Professor David Simonsens 70-aarige Fødselsdag

Nir Daṿid likhvod ha-rav he-ḥakham R. Daṿid Simonsen

Festschrift zum siebzigsten Geburtstage David Hoffmann's : gewidmet von Freunden und Schülern

hrsg. von Simon Eppenstein ...

Mittheilungen über die Michael David'sche Stiftung zu Hannover

von Max Landsberg

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

David Einhorn : Memorial Volume ; seclected sermons and addresses

ed. by Kaufmann Kohler. A biographical essay by Kaufmann Kohler. A memorial oration by Emil G. Hirsch

David Nieto : notícia biobibliográfica

Moses Bensabat Amzalak

Standpunkt und Leistung des R. David Kimchi als Grammatiker, mit Berücksichtigung seiner Vorgänger und Nachfolger : Dissertation

Breslau, Univ., Diss., 1866

Zur Erinnerung an David Graubart

[Verf.[[Elektronische Ressource]] : Arthur Zacharias Schwarz]

David Nassy of Surinam and his "Lettre politico-theologico-morale sur les juifs"

Sigmund Seeligmann

Leben und Wirken des am 25. December 1839 in Posen verstorbenen jüdischen Literaten David Caro : in besonderer Beziehung auf den Culturzustand der Juden des Grossherzogthums Posen während der letzten 50 Jahre

dargest. von N. Lippmann

David Bernhard Frankl : Prager Bürger und Kaufmann, Stadtrath, Inhaber des goldenen Verdienstkreuzes...

Biographische Skizze von W. [Mutmaßl. Verf.: Ludwig August u. Wilhelm Frankl]

Johann David Michaelis hebräische Grammatik nebst einem Anh. von gründlicher Erkenntniss derselben

Johann David Michaelis