Research Spotlight

Hoang, J. T., R. Yang, Z. A. Shah, J. J. Spigel and J. E. Pippen (2018). “Clinico-radiologic features and management of hematological tumors in the breast: a case series.” Breast Cancer Sep 18. [Epub ahead of print].

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Hematological tumors arising in the breast are uncommon and require different treatment modalities dependent upon tumor type. Current treatment options include surgical excision, chemotherapy, and radiotherapy. Management of these breast malignancies are poorly outlined in the literature. The purpose of this case series is to report five cases consisting of extranodal marginal zone lymphoma, lymphoplasmacytic lymphoma, and extramedullary plasmacytoma occurring in the breast. The cases illustrate heterogeneous radiologic findings and varying management approaches to these tumors. The case series underscores the importance of having a wide differential at diagnosis and recognizes management of disease should be taken on an individual basis with consideration of prognosis and first-line treatment options.

Grayburn, P. A. and J. W. Choi (2018). “Changing the Tide of Left Atrial Inflow: Improved Pulmonary Vein Patterns Predict Smooth Sailing After Percutaneous Mitral Valve Repair.” JACC Cardiovasc Imaging Sep 6. [Epub ahead of print].

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Correspondence concerning Frank E. Corrigan, et al. Pulmonary Venous Waveforms Predict Rehospitalization and Mortality After Percutaneous Mitral Valve Repair. JACC: Cardiovascular Imaging, Available online 12 September 2018.

Flannery, B., J. R. Chung, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, M. Gaglani, K. Murthy, R. K. Zimmerman, M. P. Nowalk, M. L. Jackson, L. A. Jackson, M. A. Rolfes, S. Spencer and A. M. Fry (2018). “Influenza Vaccine Effectiveness in the United States during the 2016-2017 Season.” Clin Infect Dis Sep 11. [Epub ahead of print].

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Background: In recent influenza seasons, the effectiveness of inactivated influenza vaccines against circulating A(H3N2) virus has been lower than against A(H1N1)pdm09 and B viruses, even when circulating viruses remained antigenically similar to vaccine components. Methods: During the 2016-2017 influenza season, vaccine effectiveness (VE) across age groups and vaccine types was examined among outpatients with acute respiratory illness at 5 US sites using a test-negative design that compared the odds of vaccination among reverse transcription polymerase chain reaction-confirmed influenza positives and negatives. Results: Among 7083 enrollees, 1342 (19%) tested positive for influenza A(H3N2), 648 (9%) were positive for influenza B (including B/Yamagata, n = 577) and 5040(71%) were influenza negative. Vaccine effectiveness was 40% (95% confidence interval [CI], 32% to 46%) against any influenza virus, 33% (95%CI, 23% to 41%) against influenza A(H3N2) viruses and 53% (95%CI, 43% to 61%) against influenza B viruses. Conclusions: The 2016-2017 influenza vaccines provided moderate protection against any influenza among outpatients, but were less protective against influenza A(H3N2) viruses than B viruses. Approaches to improving effectiveness against A(H3N2) viruses are needed.

Fathi, A. T., H. P. Erba, J. E. Lancet, E. M. Stein, F. Ravandi, S. Faderl, R. B. Walter, A. S. Advani, D. J. DeAngelo, T. J. Kovacsovics, A. Jillella, D. Bixby, M. Y. Levy, M. M. O’Meara, P. A. Ho, J. Voellinger and A. S. Stein (2018). “A phase 1 trial of vadastuximab talirine combined with hypomethylating agents in patients with CD33-positive AML.” Blood 132(11): 1125-1133.

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Treatment of acute myeloid leukemia (AML) among the elderly is challenging because of intolerance of intensive therapy and therapy-resistant biology. Hypomethylating agents (HMAs) are commonly used, with suboptimal outcomes. Vadastuximab talirine is a CD33-directed antibody conjugated to pyrrolobenzodiazepine (PBD) dimers. Preclinically, HMAs followed by vadastuximab talirine produced upregulated CD33 expression, increased DNA incorporation by PBD, and enhanced cytotoxicity. A combination cohort in a phase 1 study (NCT01902329) assessed safety, tolerability, and activity of vadastuximab talirine with HMAs. Those eligible had Eastern Cooperative Oncology Group status 0 to 1 and previously untreated CD33-positive AML, and declined intensive therapy. Vadastuximab talirine was administered intravenously at 10 mug/kg on last day of HMA (azacitidine or decitabine) infusion in 4-week cycles. Among 53 patients treated, the median age was 75 years. Patients had adverse (38%) or intermediate (62%) cytogenetic risk. Median treatment duration was 19.3 weeks. No dose-limiting toxicities were reported. The majority of adverse events were a result of myelosuppression, with some causing therapy delays. Thirty- and 60-day mortality rates were 2% and 8%, respectively. The composite remission rate (complete remission [CR] and CR with incomplete blood count recovery) was 70%. Fifty-one percent of remissions were minimal residual disease-negative by flow cytometry. Similarly high remission rates were observed in patients with secondary AML, aged at least 75 years, and with adverse cytogenetic risk. Median relapse-free survival and overall survival were 7.7 and 11.3 months, respectively. Compared with historical data for HMA monotherapy, the combination of vadastuximab talirine with HMAs produced a high remission rate, but was accompanied by increased hematologic toxicity.

Dubiel, R., L. Callender, C. Dunklin, C. Harper, M. Bennett, L. Kreber, R. Auchus and R. Diaz-Arrastia (2018). “Phase 2 Randomized, Placebo-Controlled Clinical Trial of Recombinant Human Growth Hormone (rhGH) During Rehabilitation From Traumatic Brain Injury.” Front Endocrinol (Lausanne) Sep 10(9): 520. eCollection 2018.

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Traumatic brain injury (TBI) is a major cause of death and disability, but there are currently no therapies with proven efficacy for optimizing regeneration of repair during rehabilitation. Using standard stimulation tests, as many as 40-50% of survivors of severe TBI have deficiency of one or more pituitary hormones. Of these, the somatotropic axis is the most commonly affected, with Growth Hormone (GH) deficiency affecting ~20% of persons with severe TBI. Treatment with recombinant human Growth Hormone (rhGH) is generally effective in reversing the effects of acquired GH deficiency, but there is no evidence documenting functional or neurocognitive improvement after GH replacement in TBI patients. As a consequence, screening for GH deficiency and GH replacement when deficiency is found is not routinely performed as part of the rehabilitation of TBI survivors. Given that most of the recovery after TBI occurs within the first 6-12 months after injury and IGF-1 and GH are part of a coordinated restorative neurotrophic system, we hypothesized that patients will optimally benefit from GH therapy during the window of maximal neuroregenerative activity. We performed a Phase IIa, randomized, double-blind, placebo-controlled feasibility trial of recombinant human Growth Hormone (rhGH), starting at discharge from an inpatient rehabilitation unit, with follow up at 6 and 12 months. Our primary hypothesis was that treatment with rhGH in the subacute period would result in improved functional outcomes 6 months after injury. Our secondary hypothesis proposed that treatment with rhGH would increase IGF-1 levels and be well tolerated. Sixty-three subjects were randomized, and 40 completed the trial. At baseline, there was no correlation between IGF-1 levels and peak GH levels after L-arginine stimulation. IGF-1 levels increased after rhGH treatment, but it took longer than 1 month for levels to be higher than for placebo-treated patients. rhGH therapy was well-tolerated. The rhGH group was no different from placebo in the Disability Rating Scale, Glasgow Outcome Scale-Extended, or neuropsychological function. However, a trend toward greater improvement from baseline in Functional Independence Measure (FIM) was noted in the rhGH treated group. Future studies should include longer treatment periods, faster titration of rhGH, and larger sample sizes.