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Twenty years after landmark publications, there is a consensus that the somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is an important cornerstone for accurate risk stratification and therapeutic decision-making in patients with chronic lymphocytic leukemia (CLL). The IGHV SHM status has traditionally been determined by conventional Sanger sequencing. However, NGS has heralded a new era in medical diagnostics and immunogenetic analysis is following this trend. There is indeed a growing demand for shifting practice and using NGS for IGHV gene SHM assessment, although it is debatable whether it is always justifiable, at least taking into account financial considerations for laboratories with limited resources. Nevertheless, as this analysis impacts on treatment decisions, standardization of both technical aspects, and data interpretation becomes essential. Also, the need for establishing new recommendations and providing dedicated education and training on NGS-based immunogenetics is greater than ever before. Here we address potential and challenges of NGS-based immunogenetics in CLL. We are convinced that this perspective helps the hematological community to better understand the pros and cons of this new technological development for CLL patient management.

A patient on a regimen of idelalisib and corticosteroids for a relapse of follicular lymphoma presented to our emergency ward with a fever of unknown origin. Despite the initiation of broad-spectrum antibiotics and fluids, the patient’s clinical condition deteriorated. Eventually, a diagnosis of disseminated cryptococcosis was established and immunophenotyping revealed complete absence of circulating B and CD4+-T lymphocytes, and a markedly diminished CD8+-T lymphocyte count. In this case, treatment with idelalisib and corticosteroids likely resulted in profound lymphopenia and the first reported instance of disseminated cryptococcosis under this regimen. After the withdrawal of idelalisib and steroids and initiation of antifungal therapy, lymphocyte counts partially recovered. After clinical improvement, the patient could be discharged from the hospital. This case highlights that the combination of idelalisib and corticosteroids can cause significant immunocompromise and opportunistic infections. Additionally, we illustrate the rate of lymphocyte reconstitution after withdrawal from idelalisib and corticosteroids.

The aim of our qualitative study was to investigate the understanding of patients with intermittent claudication (IC) regarding the etiology and atherosclerotic nature of their disease. Patients were recruited from participants of the SUPER study, a randomized trial comparing angioplasty and supervised exercise therapy for alleviation of IC owing to an iliac artery obstruction. Patients were submitted to explorative, semistructured, in-depth interviews that were fully transcribed, coded, and categorized. We interviewed 19 patients. The majority of respondents (79%) recognized smoking as a major risk factor contributing to the etiology of IC. However, nearly one-half (47%) underestimated the effects of unhealthy dietary and exercise patterns. In contrast, a substantial number of respondents (42%) overestimated the contribution of genetics to the etiology of their disease. Most respondents (79%) were unaware of the fact that IC implies systemic atherosclerosis.This study shows that the patients' interpretation of the etiology and nature of IC was mostly incorrect. Therefore, we suggest that health care providers enhance counseling about etiologic factors and the systemic nature of IC to optimize outcomes of lifestyle adjustments.