Engraftment syndrome is a constellation of clinical manifestations that occur at the time of neutrophil recovery following hematopoietic stem cell transplantation. There are several risk factors, but the reports on some of them are rather conflicting. Additionally, not only the clinical manifestations but also the laboratory findings are nonspecific and may overlap with several conditions such as acute graft versus host disease, drug toxicity, radiation-induced damage and infectious disorders. Treatment of symptomatic and severe forms is similar to that of graft versus host disease. Hence, there is a need for: revision of the diagnostic criteria, establishment of scoring system to determine prognosis and to direct therapy as well as the addition new criteria to differentiate it from other similar conditions.
Introduction: Gut dysbiosis is an imbalance of the gut microbiome. The presence of dysbiosis can be a cause of systemic inflammation in the body or can be a contributing factor to it. Chronic systemic inflammation is a common feature of CLL, creating an environment in which CLL cells have a survival advantage. NF-κB and STAT3, master transcriptional regulators of pro-inflammatory markers, like IL-1 and IL-6, are reported to be involved in this process as are the Toll-like receptors (TLRs), key innate immunity receptors that are implicated in CLL pathophysiology. With increasing evidence for the role of dysbiosis in chronic inflammation, as well as the role of systemic inflammation in CLL, it seems relevant to prove the presence and the possible role of microbiome in the pathophysiology of CLL, to unravel the complex interaction between microbiome, nutrition and the host in patients with CLL. Our research investigate the hypothesis that dysbiosis i.e. the loss of "health-promoting" commensal gut microbes and/or the overgrowth of pathogenic bacteria distinguishes untreated patients with CLL versus aged-matched unaffected individuals. Methodology: Eight untreated CLL patients were with no history of gastrointestinal disorders, other malignancies and have not been on antibiotics for 4 weeks prior to samples collection. Two of them were not followed for logistical reasons. Six healthy volunteers matched for sex and age were also enrolled in the study. Stool samples from six patients and additional six matched healthy controls were collected and stored in a -40 freezer immediately until they were used for DNA isolation. Total genomic DNA was extracted using the Qiamp DNA stool mini kit and sequenced using Next Generation Sequencing and then analysis were done as per the manufacturer recommendations. Results: Our data indicates a reduced diversity and variability in bacterial phyla of gut microbiota in CLL patients as compare to healthy controls. Lower diversity with increase in certain bacterial types is a well-accepted sign of gut dysbiosis, which have been shown in many disorders such as; type-2 diabetes, obesity, and various autoimmune and neurological diseases. An increase in Proteobacteria numbers has been recognized as the signature of gut dysbiosis which we confirmed in our cohort of patients. Proteobacteria, Firmicutes and Bacteriodetes were also the most abundant bacterial phyla in CLL patients of our study which were reported previously in breast cancer patients. An elevated Firmicutes to Bacteroidetes ratio with altered gut microbiota in CLL patients compared with healthy subjects was also suggested in clinical studies involving obese individuals with insulin resistance. We have observed in CLL patients of this study relative increase in the numbers of Firmicutes and reduction in Bacteriodetes which is considered to be an inverted ratio as compared to healthy individuals which were also reported in ulcerative colitis, colonic and ileal crohn's disease as compared to healthy subjects. . Our finding of gut dysbiosis in this study is linked the association between CLL, inflammatory processes and dysbiosis. The microbiota may play a role in promoting malignancy through chronic inflammation, by disturbing the balance of cell proliferation, death and by initiating unwanted innate and adaptive immune responses. Conclusion: Restoring gut microbiota might open a new avenue for future researches as potential therapeutic intervention in CLL patients. Figure Disclosures No relevant conflicts of interest to declare.
All-trans retinoic acid (ATRA), a carboxylic acid form of vitamin A, was a revolutionary discovery in the treatment of acute promyelocytic leukemia (APL) that was found largely by chance in late 80s. The molecular hallmark of APL is the presence of a balanced reciprocal translocation resulting in the PML/RAR-a gene fusion, which represents the target of ATRA therapy. ATRA is considered to be a safe drug. Pseudotumor cerebri (PTC) is a rare neurological adverse event of ATRA that was mainly reported in pediatric population. It is characterized by neurologic and ocular signs and symptoms of increased intracranial pressure in the absence of any intracranial pathology or secondary causes of intracranial hypertension. Herein we report four cases of young female patients who were diagnosed with APL and experienced PTC with ATRA treatment. In three cases fluconazole was taken concurrently. Symptoms completely subsided with the temporary withdrawal of ATRA and discontinuation of fluconazole. PTC symptoms did not recur after reintroducing ATRA. In conclusion, we report a case series of young female patients that is suggestive of young age, female gender and concurrent use of fluconazole to be associated with increased risk of developing PTC with ATRA treatment. Fluconazole should not be used concurrently with ATRA. We also conclude that the drug could be safely reintroduced once the symptoms had resolved.
Multiple myeloma accounts for 10% of hematological malignancy and 1% of all cancer. It manifests with anemia, hypercalcemia, renal failure, and bone lesions, with the latter being the most common cause of morbidity. Over the last two decades, many advances were achieved in different aspects of the disease, including, but not limited to risk stratification and treatment approaches. With the approval of Chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma, the main effort in clinical trials is toward studying different CAR T-cell products in different combinations at different disease stages. Although more options are becoming available, more trials are needed to compare their efficacy and safety in the long-term, as well it is essential to consider side effects and quality of life, which will be more noticeable with patients’ lives long after the myeloma diagnosis. There continue to be several unmet needs for multiple myeloma patients, including extramedullary plasmacytoma, plasma cell leukemia, CNS myeloma, and high-risk/ultra-high-risk disease. These are extremely challenging and further randomized clinical trials are highly needed.
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