Progressive multifocal leukoencephalopathy in the context of newer therapies in hematology and review of new treatment strategies.

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system (CNS) caused by the reactivation of JC polyomavirus in the CNS. We present a case of a 54-year-old man with follicular lymphoma diagnosed with PML after being treated with anti-CD20 monoclonal antibody-based regimens for several years. Due to the lack of effective treatment choices for PML, the patient was treated with nivolumab, based on recent reports, but succumbed to his disease a few months after diagnosis. In this paper, we focus on reviewing the literature of PML cases correlated with newer agents used in hematology, possible factors affecting disease prognosis, as well as the available data on upcoming therapeutic options for patients with PML. Though newer promising treatments such as anti-PD1 monoclonal antibodies arise, a definitive treatment option is yet to be found. Vigilance, early detection, and prompt intervention play a crucial role in the prognosis of PML in patients with hematological malignancies.

Bone marrow ribonucleotide reductase mRNA levels and methylation status as prognostic factors in patients with myelodysplastic syndrome treated with 5-Azacytidine.

Ribonucleotide Reductase (RNR) is a two-subunit (RRM1, RRM2) enzyme, responsible for the conversion of ribonucleotides to deoxyribonucleotides required for DNA replication. To evaluate RNR as a biomarker of response to 5-azacytidine, we measured RNR mRNA levels by a quantitative real-time PCR in bone marrow samples of 98 patients with myelodysplastic syndrome (MDS) treated with 5-azacytidine with parallel quantification of the gene promoter's methylation. Patients with low RRM1 levels had a high RRM1 methylation status (p = 0.005) and a better response to treatment with 5-azacytidine (p = 0.019). A next-generation sequencing for genes of interest in MDS was also carried out in a subset of 61 samples. Splicing factor mutations were correlated with lower RRM1 mRNA levels (p = 0.044). Our results suggest that the expression of RNR is correlated with clinical outcomes, thus its expression could be used as a prognostic factor for response to 5-azacytidine and a possible therapeutic target in MDS.

A case report of Hodgkin lymphoma in a patient treated with ustekinumab for psoriasis.

RATIONALE: Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been case reports that raise concerns about its oncogenic potential. We are the first authors to report a case of Hodgkin lymphoma in a psoriatic patient receiving ustekinumab. PATIENT CONCERNS: A 22-year-old asymptomatic female patient presented to our department to investigate an enlarged cervical lymph node. Her past history was unremarkable, except for psoriasis since age 13. Two months before presentation the decision to administer Ustekinumab was taken and the patient had already received 3 doses. DIAGNOSES: During workup a Stage IV Hodgkin lymphoma was discovered. INTERVENTIONS: Ustekinumab administration was discontinued. The patient received treatment with the ABVD regimen. OUTCOMES: The patient's disease was refractory to the above-mentioned treatment. Therefore, a more aggressive regimen (BEACOPP escalated) was administered. LESSONS: Growing postmarketing surveillance data and case reports indicate that further research is warranted in order to elucidate a potential association between Ustekinumab and malignancy.

Post-Myelofibrosis Acute Myeloid Leukemia Effectively Treated with a Combination of Ruxolitinib and 5-Azacytidine.

BACKGROUND: Leukemic transformation is an unfavorable event emerging in a minority of patients with myelofibrosis (MF) and carrying a poor prognosis. Patients with post-MF acute myeloid leukemia (AML) may be treated with curative or noncurative intent, but there is no standard of care. The use of hypomethylating agents has been correlated with limited activity and low overall survival rates, while ruxolitinib has been proven to have modest antileukemic activity. CASE PRESENTATION: In this case study, we present the case of a 67-year-old female patient with post-polycythemia vera MF who developed AML and was successfully treated with a combination of 5-azacytidine and ruxolitinib, without any significant toxicity. SUMMARY: To our knowledge, this is the first report of a patient with post-MF AML achieving a complete remission with a combination of ruxolitinib and a hypomethylating agent. This combination is actively studied in phase I/II clinical trials and may be proven effective in this hard-to-treat group of patients.