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AbstractCytokine release syndrome (CRS) occurs frequently after haplo-identical allogeneic stem cell transplantation (alloSCT) with post-transplant cyclophosphamide (PTCy), increasing nonrelapse mortality (NRM) and decreasing survival. Data on CRS in HLA-matched alloSCT are limited and effects of specific HLA-mismatches on CRS development unknown. We hypothesized that in HLA-matched alloSCT increasing degrees of HLA-mismatching influence CRS incidence, NRM and survival. Retrospective analysis of 126 HLA-matched PTCy-alloSCT patients showed that higher degrees of HLA-mismatching significantly increased CRS incidence (26%, 75% and 90% CRS with 12/12, 10/10 and 9/10 matched donors, respectively). Maximum temperature during CRS increased with higher HLA-mismatch. Specific associations between HLA-mismatches and CRS could be determined. Grade 2 CRS and CRS-induced grade 3 fever were associated with significantly increased NRM (p < 0.001 and p = 0.003, respectively) and inferior survival (p < 0.001 and p = 0.005, respectively). NRM was mainly caused by disease conditions that may be considered CRS-induced inflammatory responses (encephalopathy, cryptogenic organizing pneumonia and multi-organ failure). [ABSTRACT FROM AUTHOR]

We present the case of a 50-year-old patient with folliculotropic mycosis fungoides (FMF) unresponsive to retinoids and the chemotherapeutic regimens CHOP, gemcitabine, and brentuximab-vedotin. During immunosuppressive therapy, the patient developed extensive progressive molluscum contagiosum. The mollusca did not respond to topical imiquimod but showed a swift complete response to interferon-alpha 2a (IFNa). Recently, the patient started with alemtuzumab as induction therapy for an allogenic stem cell transplantation and simultaneously continued IFNa therapy. [ABSTRACT FROM AUTHOR]

Primary cutaneous follicle center lymphoma (PCFCL) is characterized by lesions on the trunk and head-and-neck region consisting of centrocytes and admixed centroblasts. In general, PCFCL has an indolent behaviour with a 5-year disease-specific survival of 95%. Local radiotherapy results in a complete remission in 99% of the patients, however, cutaneous relapses are frequent (30%) and 10% of the patients develop progressive disease with extracutaneous dissemination or large-cell transformation. As it is difficult to identify these patients, the aim of this study was to identify 'clues' in clinical presentation, histopathology, immune phenotype, and genetic profile of PCFCL patients at time of diagnosis that may help to identify patients at risk for disease progression. In total, 15 patients with progressive PCFCL and 15 patients with indolent PCFCL (without disease progression and a follow-up duration of at least 5 years) were selected from the Dutch Registry of Cutaneous Lymphoma. Clinical presentation and histopathology were reviewed and immune phenotyping and molecular analysis, including targeted next-generation sequencing (NGS) with a 200 B-cell lymphoma-related gene panel, were performed. At diagnosis, all patients presented with classic PCFCL lesions on the trunk or head-and-neck region. Histology showed a characteristic predominance of centrocytes with admixed centroblasts. The median follow-up duration was 65 (range, 30 to 193) months with a progression-free survival of 26 (range, 4 to 147) months, during which five patients died of progressive PCFCL and one patient died of cardiac disease. In patients with progressive disease, IgM was significantly more often expressed compared with patients with indolent disease (53% vs. 7%; p=0.005). Targeted NGS demonstrated one or multiple PCFCL-like mutations in TNFRSF14, IRF8, CREBBP, EP300, EZH2, SETD2, SOCS1, STAT6 in 6 of 11 (55%) patients with indolent disease and in 9 of 12 (75%) patients with progressive disease. In 7 of 9 of these patients with progressive disease, however, additional non-PCFCL-like alterations were detected that were absent in patients with indolent disease, including MYC rearrangements in two patients and ERBB4, ZEB2, ARID1A, and ITBKB mutations in four patients as well as MYD88, CD79B, PIM1, and TBL1XR1 mutations in one of these patients. In three patients with progressive disease but without a PCFCL-like profile, we detected mutations in MYD88, PIM1, and TBL1XR1 in one patient, a MYD88 non-L265P mutation amongst others in one patient, and mutations in BRAF and CIITA in one patient, of which CIITA was also detected in one of the indolent patients. In conclusion, expression of IgM at diagnosis might represent a clue for a progressive disease course in PCFCL and may warrant additional genetic analysis and closer clinical follow-up of these patients. As this observation was made on a limited number of patients, these results need validation in an independent cohort. [ABSTRACT FROM AUTHOR]

Summary: The development of resistance to chemotherapy is a major obstacle for lasting effective treatment of cancer. Here, we demonstrate that endogenous mesenchymal stem cells (MSCs) become activated during treatment with platinum analogs and secrete factors that protect tumor cells against a range of chemotherapeutics. Through a metabolomics approach, we identified two distinct platinum-induced polyunsaturated fatty acids (PIFAs), 12-oxo-5,8,10-heptadecatrienoic acid (KHT) and hexadeca-4,7,10,13-tetraenoic acid (16:4(n-3)), that in minute quantities induce resistance to a broad spectrum of chemotherapeutic agents. Interestingly, blocking central enzymes involved in the production of these PIFAs (cyclooxygenase-1 and thromboxane synthase) prevents MSC-induced resistance. Our findings show that MSCs are potent mediators of resistance to chemotherapy and reveal targets to enhance chemotherapy efficacy in patients. [Copyright &y& Elsevier]