1.Progressive Multifocal Leukoencephalopathy after Ibrutinib Therapy for Chronic Lymphocytic Leukemia.
Mathias LUTZ ; Arik B SCHULZE ; Elisabeth REBBER ; Stefanie WIEBE ; Tarek ZOUBI ; Oliver M GRAUER ; Torsten KESSLER ; Andrea KERKHOFF ; Georg LENZ ; Wolfgang E BERDEL
Cancer Research and Treatment 2017;49(2):548-552
Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.
Antibodies, Monoclonal
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Immune System
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Immunocompromised Host
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JC Virus
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Leukemia, Lymphocytic, Chronic, B-Cell*
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Leukoencephalopathy, Progressive Multifocal*
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Protein-Tyrosine Kinases
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Rituximab
2.Testicular expression of survivin and human telomerase reverse transcriptase (hTERT) associated with spermatogenic function in infertile patients.
Steffen WEIKERT ; Frank CHRISTOPH ; Wolfgang SCHULZE ; Hans KRAUSE ; Carsten KEMPKENSTEFFEN ; Martin SCHOSTAK ; Kurt MILLER ; Mark SCHRADER
Asian Journal of Andrology 2006;8(1):95-100
AIMTo characterize the coexpression of survivin, an inhibitor of apoptosis (IAF), and human telomerase reverse transcriptase (hTERT) in human testes with varying spermatogenic function.
METHODSTranscript levels of survivin mRNA and hTERT mRNA were determined in normal testes (n=11) and testes with defective spermatogenesis (n=28) using real-time reverse-transcription polymerase chain reaction (RT-PCR). The histological work-up was performed according to a modified Johnsen score.
RESULTSExpressions of both survivin and hTERT were highest at median levels of 96.8 and 709 in normal spermatogenesis and dropped to 53.3 and 534 in testes with postmeiotic spermatogenic arrest (n=10). In severe spermatogenic failure (n=18), survivin expression was lacking in most specimens (n=16), whereas at least low levels of testicular hTERT expression were largely detectable with a normalized expression of 73 in premeiotic spermatogenic arrest (n=7) and 45 in patients with Sertoli cell-only syndrome (SCOS) (n=3). Both survivin and hTERT expressions increased with a progressing Johnsen score (P for trend=0.001).
CONCLUSIONAlthough both survivin and hTERT are correlated with spermatogenic function, they show different expression patterns in testes of infertile patients. These findings substantiate results from studies in the rodent testis suggesting a predominant expression of survivin in meiotically dividing germ cells.
Biopsy ; DNA-Binding Proteins ; biosynthesis ; Gene Expression ; physiology ; Humans ; Infertility, Male ; metabolism ; Inhibitor of Apoptosis Proteins ; Male ; Microtubule-Associated Proteins ; biosynthesis ; Neoplasm Proteins ; biosynthesis ; Spermatogenesis ; physiology ; Telomerase ; biosynthesis ; Testis ; metabolism