Annika Rudat, Christian Wenning, Michael Schäfers, Fabian Wötzel, Jan-Henrik Mikesch, Stefanie Wiebe, Christoph Schliemann, Eva Wardelmann, Wolfgang E. Berdel, Linus Angenendt, Andrea Kerkhoff, Matthias Stelljes, and Torsten Kessler
Dear Editor, Multicentric Castleman’s disease (MCD) is a rare lymphoproliferative disorder characterized by hypercytokinemia, undulating signs of systemic inflammation, generalized lymphadenopathy, hepatosplenomegaly, and in severe cases vascular leak syndrome (VLS), organ failure, and death [1]. It is categorized into HHV8-positive MCD (HMCD), including HIV patients, and idiopathic MCD (iMCD). Therapeutic monoclonal antibodies are the mainstay of treatment. Whereas the antiCD20 antibody rituximab is preferentially advocated for HMCD [2, 3], the IL-6 disrupting antibodies tocilizumab and siltuximab are for iMCD [4]. We report the first case, to our knowledge, of a patient with severe iMCD responding with repeated long-lasting complete remissions (CR) to rituximab monotherapy and after failure a complete remission to allogeneic stem cell transplantation (alloSCT). In July 2008, a 25-year-oldmanwas admitted to our intensive care unit with fever of unknown origin, acute renal failure, and elevated cholestatic parameters following an episode of an inflammatory bowel disease known since 1998. Further findings included pancytopenia (leukocytes 2.03×10/l, hemoglobin 7.4 g/dl, platelets 125×10/l), generalized lymphadenopathy, hepatosplenomegaly, petechial exanthema, and VLS with anasarca, ascites, and pleural effusions. CRP was 25.7 mg/dl, creatinine 3.1 mg/dl, bilirubin 2.8 mg/dl, gammaGT 179 U/l, AP 219 U/l, haptoglobin 230 mg/dl, and LDH 330 U/l. Direct bilirubin was elevated without sonographic cholestasis. Symptoms and laboratory parameters undulated. MCD was histologically diagnosed (Fig. 1a). HIV and HHV8 serology and PCR were negative. Nevertheless, we treated the patient with 4 cycles of weekly rituximab (375 mg/m), known to induce remissions in HMCD [2, 5–7]. In January 2009, final examination established clinical, laboratory (Fig. 1b) and CT-graphic CR with residual splenomegaly of uncertain significance. In July 2010 (18months disease free), iMCD relapsed, again preceded by episodes of inflammatory bowel disease. Reexposition to 4 cycles of rituximab achieved a second CR. In July 2013 (21months disease free), another severe relapse occurred. Therapy was escalated to 6 cycles R-CHOP-21 resulting in another CR. Unfortunately, disease relapsed 1 month thereafter and, in March 2014, progressed further despite 2-cycle salvage therapywith R-Dexa-BEAM, supposed to induce remission before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). Given this desperate situation, it was not proceeded to HDT and ASCT, but a donor search for alloSCTwas initiated, while rituximab (375 mg/m) and tocilizumab (8 mg/kg) were given every 4 weeks. Diseaserelated symptoms vanished completely for 5 cycles of this combination until August 2014; however, there was no response on PET-CT. Progressing again, conditioning with fludarabine * Linus Angenendt angenendt@uni-muenster.de