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Background: Despite advances made in targeted biomarker‐based therapy for acute myeloid leukemia (AML) treatment, remission is often short and followed by relapse and acquired resistance. Functional precision medicine (FPM) efforts have been shown to improve therapy selection guidance by incorporating comprehensive biological data to tailor individual treatment. However, effectively managing complex biological data, while also ensuring rapid conversion of actionable insights into clinical utility remains challenging. Methods: We have evaluated the clinical applicability of quadratic phenotypic optimization platform (QPOP), to predict clinical response to combination therapies in AML and reveal patient‐centric insights into combination therapy sensitivities. In this prospective study, 51 primary samples from newly diagnosed (ND) or refractory/relapsed (R/R) AML patients were evaluated by QPOP following ex vivo drug testing. Results: Individualized drug sensitivity reports were generated in 55/63 (87.3%) patient samples with a median turnaround time of 5 (4–10) days from sample collection to report generation. To evaluate clinical feasibility, QPOP‐predicted response was compared to clinical treatment outcomes and indicated concordant results with 83.3% sensitivity and 90.9% specificity and an overall 86.2% accuracy. Serial QPOP analysis in a FLT3‐mutant patient sample indicated decreased FLT3 inhibitor (FLT3i) sensitivity, which is concordant with increasing FLT3 allelic burden and drug resistance development. Forkhead box M1 (FOXM1)—AKT signaling was subsequently identified to contribute to resistance to FLT3i. Conclusion: Overall, this study demonstrates the feasibility of applying QPOP as a functional combinatorial precision medicine platform to predict therapeutic sensitivities in AML and provides the basis for prospective clinical trials evaluating ex vivo‐guided combination therapy. [ABSTRACT FROM AUTHOR]

Keywords: COVID-19; antibody-synthesising lymphocytes; full blood count; disease; severity; lymphocytes EN COVID-19 antibody-synthesising lymphocytes full blood count disease severity lymphocytes 33 36 4 07/01/20 20200701 NES 200701 Since emerging in China in December 2019, the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), has infected >3 million people worldwide (Johns Hopkins University and Medicine: Coronavirus Resource Center). The trends of the lymphocyte and lymphocyte subsets (Fig 1B,C) showed that while the lymphocyte count decreased gradually, the proportion of RE-Lymph and AS-Lymph progressively increased towards day 15-16. COVID-19, antibody-synthesising lymphocytes, full blood count, disease, severity, lymphocytes. [Extracted from the article]

Primary mediastinal large B‐cell lymphoma (PMBCL) is a distinct clinico‐pathological subtype of diffuse large B‐cell lymphoma with unclear prognostic factors and limited clinical data. Optimal treatment and role for radiotherapy is not fully defined. We performed a multicenter retrospective review of 124 patients with newly diagnosed PMBCL between 2001 and 2016. Treatment regimens were R‐CHOP (n = 41), R‐CHOP + RT (n = 37), and DA‐EPOCH‐R (n = 46). 6% (n = 3) in the DA‐EPOCH‐R group received RT. With a median follow up of 45 months, the overall 5‐year OS and PFS was 89.4% and 82.4%, respectively. The type of chemo‐radiotherapy regimen, B symptoms and Ann‐Arbor staging showed a significant association with OS on univariate analysis but only B symptoms remained prognostic (P = 0.012) after multivariate analysis. The chemo‐radiotherapy regimen, Japanese IPI and Ann‐Arbor stage was significantly associated with PFS in univariate analysis, but only chemo‐radiotherapy regimen remained significant (P = 0.02) after multivariate analysis. Patients who received R‐CHOP + RT or DA‐EPOCH‐R had better PFS than those receiving R‐CHOP alone, with 5‐year PFS of 90% vs 88.5% vs 56%, respectively (P = 0.02). In the subgroup analysis of patients with bulk (n = 71), R‐CHOP alone (n = 21) had inferior 5‐year PFS 56.6% compared to those who received R‐CHOP + RT (n = 23) 91.3% or DA‐EPOCH‐R (n = 27) 92.6% (P = 0.007). In contrast, in patients without bulk (n = 42), there was no impact of treatment regimen on PFS (P = 0.25). In conclusion, R‐CHOP + RT and DA‐EPOCH‐R provide excellent outcomes in patients with PMBCL. In patients with bulky disease, the use of DA‐EPOCH‐R may be preferable as it allows omission of RT without reduction in efficacy. [ABSTRACT FROM AUTHOR]

Inflammatory pseudotumours (IPT) are rare benign neoplasms of unknown aetiology. We present a case of hepatic IPT which was incidentally discovered in a patient with relapsed B-acute lymphoblastic leukaemia (B-ALL) undergoing pretransplant workup. After investigation to exclude an infective cause she underwent a reduced intensity conditioning stem cell transplant (SCT) successfully and currently remains well and in remission. On repeat liver MRI after SCT, the IPT was seen to be resolving. To the best of our knowledge this is the first report of an adult patient with hepatic IPT successfully undergoing SCT. The reduction in size of the IPT after SCT also suggests an inflammatory rather than an infective aetiology for IPT. [ABSTRACT FROM AUTHOR]

Key Clinical Message Cryptococcosis is a potentially fatal fungal infection caused mainly by Cryptocococcus neoformans ( CN) species and it rarely infects immunocompetent hosts. The outcomes are better only if the condition is suspected and diagnosed early and treatment is instituted. [ABSTRACT FROM AUTHOR]

Multiplemyeloma is the second most common hematologic malignancy in the world. Despite improvement in outcome, the disease is still incurable for most patients. However, not all myeloma are the same. With the same treatment, some patients can have very long survival whereas others can have very short survival. This suggests that there is underlying heterogeneity in myeloma. Studies over the years have revealed multiple layers of heterogeneity. First, clinical parameters such as age and tumor burden could significantly affect outcome. At the genetic level, there are also significant heterogeneity ranging for chromosome numbers, genetic translocations, and genetic mutations. At the clonal level, there appears to be significant clonal heterogeneity with multiple clones coexisting in the same patient. At the cell differentiation level, there appears to be a hierarchy of clonally related cells that have different clonogenic potential and sensitivity to therapies. These levels of complexities present challenges in terms of treatment and prognostication as well as monitoring of treatment. However, if we can clearly delineate and dissect this heterogeneity, we may also be presented with unique opportunities for precision and personalized treatment of myeloma. Some proof of concepts of such approaches has been demonstrated. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 72-year-old male with Philadelphia positive (Ph+) B-cell acute lymphoblastic leukemia (B-ALL). The patient was treated with Dasatinib and steroids. Neurologic examination showed subtle left-sided cerebellar signs and was started on Ponatinib. His symptoms improved and he has continued on Ponatinib.