Cutaneous B‐cell lymphomas: 2015 update on diagnosis, risk‐stratification, and management

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109952/1/ajh23863.pd

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS). Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data. Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86989/1/22139_ftp.pd

Challenges and opportunities for checkpoint blockade in T-cell lymphoproliferative disorders

Abstract The T-cell lymphoproliferative disorders are a heterogeneous group of non-Hodgkin’s lymphomas (NHL) for which current therapeutic strategies are inadequate, as most patients afflicted with these NHL will succumb to disease progression within 2 years of diagnosis. Appreciation of the genetic and immunologic landscape of these aggressive NHL, including PD-L1 (B7-H1, CD274) expression by malignant T cells and within the tumor microenvironment, provides a strong rationale for therapeutic targeting this immune checkpoint. While further studies are needed, the available data suggests that responses with PD-1 checkpoint blockade alone will unlikely approach those achieved in other lymphoproliferative disorders. Herein, we review the unique challenges posed by the T-cell lymphoproliferative disorders and discuss potential strategies to optimize checkpoint blockade in these T-cell derived malignancies.http://deepblue.lib.umich.edu/bitstream/2027.42/134748/1/40425_2016_Article_201.pd

Cutaneous B‐cell lymphomas: 2021 update on diagnosis, risk‐stratification, and management

Disease OverviewApproximately one‐fourth of primary cutaneous lymphomas are B‐cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL, LT).DiagnosisDiagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B‐cell lymphomas from systemic B‐cell lymphomas with secondary skin involvement.Risk‐StratificationDisease histopathology remains the most important prognostic determinant in primary cutaneous B‐cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5‐year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.Risk‐Adapted TherapyBoth PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single‐agent rituximab may be employed for patients with more widespread skin involvement, multi‐agent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162801/2/ajh25970.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162801/1/ajh25970_am.pd

The B7 Homologues and their Receptors in Hematologic Malignancies

The B7 homologues and their receptors regulate both peripheral tolerance and adaptive immunity. This field is rapidly evolving as new ligands and receptors are being identified. Much of the work supporting their role in the regulation of host anti‐tumor immunity has been derived from experimental models and clinical trials in solid malignancies. However, a growing body of evidence demonstrates that the B7‐H family has important immunologic and non‐immunologic functions in a variety of hematologic malignancies. Herein, we will review recent evidence that supports the therapeutic targeting of the B7 homologues in hematologic malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91338/1/ejh1766.pd

A retrospective comparative outcome analysis following systemic therapy in Mycosis fungoides and Sezary syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134845/1/ajh24564_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134845/2/ajh24564.pd

A single center phase II study of ixazomib in patients with relapsed or refractory cutaneous or peripheral T‐cell lymphomas

The transcription factor GATA‐3, highly expressed in many cutaneous T‐cell lymphoma (CTCL) and peripheral T‐cell lymphomas (PTCL), confers resistance to chemotherapy in a cell‐autonomous manner. As GATA‐3 is transcriptionally regulated by NF‐κB, we sought to determine the extent to which proteasomal inhibition impairs NF‐κB activation and GATA‐3 expression and cell viability in malignant T cells. Proteasome inhibition, NF‐κB activity, GATA‐3 expression, and cell viability were examined in patient‐derived cell lines and primary T‐cell lymphoma specimens ex vivo treated with the oral proteasome inhibitor ixazomib. Significant reductions in cell viability, NF‐κB activation, and GATA‐3 expression were observed preclinically in ixazomib‐treated cells. Therefore, an investigator‐initiated, single‐center, phase II study with this agent in patients with relapsed/refractory CTCL/PTCL was conducted. Concordant with our preclinical observations, a significant reduction in NF‐κB activation and GATA‐3 expression was observed in an exceptional responder following one month of treatment with ixazomib. While ixazomib had limited activity in this small and heterogeneous cohort of patients, inhibition of the NF‐κB/GATA‐3 axis in a single exceptional responder suggests that ixazomib may have utility in appropriately selected patients or in combination with other agents.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/1/ajh24895.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139920/2/ajh24895_am.pd

Relationship of blood monocytes with chronic lymphocytic leukemia aggressiveness and outcomes: a multi‐institutional study

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134120/1/ajh24376.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134120/2/ajh24376_am.pd

An Evaluation of Studies on the Potential Threats Contributing to the Decline of Eastern Migratory North American Monarch Butterflies (Danaus plexippus)

The migratory monarch butterflies (Danaus plexippus) of eastern North America have undergone large-scale declines, which may be attributable to a variety of underlying causes. The uncertainty about the primary cause of declines and whether individual threats are likely to increase in the future presents challenges for developing effective conservation management and policy initiatives that aim to improve population viability. This paper identifies five potential threats and classifies these threats according to the types of studies (observational, experimental, simulation/models) and their current impact and anticipated risk. Broadly, the threats can be classified into five categories: (1) change in suitable abiotic environmental conditions; (2) deforestation in the overwintering range; (3) exposure to contaminants including the bacteria Bacillus thuringiensis, herbicides, and insecticides; (4) loss of breeding habitat; and (5) predation, parasitism, and species-specific pathogens. The vast distribution of the monarch butterfly makes it likely that population declines are attributed to a suite of interacting factors that vary spatially and temporally in their contribution. Nonetheless, the published papers we reviewed suggest the decline in suitable environmental conditions in addition to overwintering (i.e., deforestation) and breeding habitat loss are the most likely threats to continue to affect the population viability of monarch butterflies