Paraneoplastic pemphigus in a patient with Chronic Lymphocytic Leukemia (CLL)

Abstracts patients <60 years (1.27; p¼0.027). Higher SIR was shown for secondary leukemia, melanoma and head and neck cancers, while a lower SIR was found for lung, digestive tract, and bladder cancers. The development of OC was associated with shorter survival: 16.2 years for patients with OC vs. 22.9 years for patients without OC (p¼0.035). Factors that independently predicted development of OC were advanced age, male gender and lower platelet count. Conclusions: We confirmed in a large cohort of LTS patients with CLL that the overall incidence of OC is increased as compared to the general population. An increased risk of OC may persist indefinitely in patients with CLL, independently from their treatment status. In these patients the presence of OC represents an independent predictor of shorter survival. Keywords: CLL, survival, other cancers.

308 Paraneoplastic pemphigus in a patient with Chronic Lymphocytic Leukemia (CLL) Adan Rios, MD,1 Andres Quesada, MD,1 Bradley Bowden, MD,1 Brian Dihn, PharmD,2 Maren Chan, MD3 1

UT Medical School of Houston; 2Memorial Herman Hospital; 3Aurora

Diagnostics

Paraneoplastic pemphigus (PNP) is a rare, often fatal, mucocutaneous blistering disease, associated with three neoplasms: non Hodgkin’s lymphoma, chronic lymphocytic leukemia (CLL), and Castleman’s disease. Antigenic targets are desmoplakins, intracellular proteins anchoring intermediate filaments to desmosomal plaques and important in epidermal cell adhesion processes. Clinical findings include a painful erosive mucositis and polymorphous skin eruption in the setting of neoplastic disease. We report a case of PNP successfully treated with pulsing doses of steroids, mycophenolate and rituximab-bendamustine with complete negativization of epidermalproteins auto-immune antibodies. Case Report: A 67-year-old patient with CLL treated with FCR (fludarabine, cyclophosphamide, and rituximab), relapsed and started on ibrutinib, a B cell receptor tyrosine kinase inhibitor. After six months he developed stomatitis and skin lesions which progressed despite treatment and been off ibrutinib for at last five weeks. A biopsy of the vermillion of the lower lip revealed the diagnosis of PNP. He was started on bendamustine rituximab for his CLL. In addition he received weekly rituximab with pulsing doses of steroids (100mg of dexamethasone once day for two days) and 2g daily of mycophenolate for one month. Mycophenolate was discontinued due to neutropenia and fever. Atovaquone was given for prophylaxis of P. jiroveci together with famvir and diflucan. Due to another recent episode of neutropenic fever course five of treatment consisted of only one day of bendamustine instead of two and only one day of dexamethasone at a reduced dose of 50mg. He has received nutritional support and anabolic steroids. His stomatitis and skin lesions have significantly improved, with concurrent weight gain and normalization of his peripheral blood count and differential. This table shows the negativization of autoimmune antibodies with treatment:

Specimen date

ME titer

Skin titer

DSG-3

12-19-14

1:5120

1:1280

205/370*

1-26-15 2-9-15

1:2560 1:1280

1:320 1:160

81 79

2-24-15 3-30-15

1:320 1:160

1:80 1:40

57 12

5-1-15 6-12-15

1:40 negative

1:20 negative

8 0

*test repeated due to value >100 units/mL serum ME-monkey esophagus, DSG-desmoglein,

Conclusion: PNP is a serious uncommon life threatening complication of hematological malignancies. It requires treatment of the primary tumor together with added vigorous immunosuppressive therapy. Monitoring of antibodies against epidermal proteins can assist in its management. The administration of steroids in pulsing doses appears to be better tolerated than daily doses particularly when other immunosuppressive agents are added to the treatment of PNP.

309 dPI3-K inhibition elicits anti-leukemic effects through the induction of Bim-dependent apoptosis Matthew J. Carter,1 Robert J. Oldham,1 Kerry L. Cox,1 Stuart J. Blakemore,1 Graham K. Packham,1 Christophe Quéva,2 Mark S. Cragg1 1

Cancer Sciences Unit, University of Southampton, Southampton,

UK; 2Department of Biology, Gilead Sciences, Foster City, CA, USA

Context: Primary and secondary lymphoid organs represent key survival niches for neoplastic cells in Chronic Lymphocytic Leukemia (CLL). Within these sites microenvironment-derived prosurvival stimuli both maintain neoplastic populations and drive their therapeutic resistance. Many of these pro-survival effects are elicited through activation of the PI3-K/Akt pathway. Consequently, delta isoform selective PI3-K inhibitors (dPI3-Ki) have provided encouraging therapeutic responses in clinical trials. Whilst the therapeutic potential of these agents is unquestionable, the exact therapeutic mechanism remains largely unknown. Disruption of stromal cell-mediated support, immunomodulation through Treg inhibition, and cell death all represent potential in vivo mechanisms. However, conclusive proof from clinical trials and in vivo animal models has been lacking. Objective: To ascertain the relative importance of intrinsic apoptosis toward in vivo dPI3-Ki therapeutic responses in a murine model of CLL. Materials and Methods: EmTcl1-Tg animals were utilized as an in vivo model of CLL and were crossed onto apoptosis deficient strains, including the Bim-/- background, and analysed for therapeutic responses to dPI3-Ki. Results: dPI3-Ki imparted significant therapeutic responses in Em-Tcl1-Tg leukemia-bearing animals. Equivalent responses were seen in immunodeficient SCID mice indicating T cell responses were not required, implicating a tumor-cell intrinsic mechanism. In vitro dPI3-Ki disrupted microenvironment-derived pro-survival stimuli

Clinical Lymphoma, Myeloma & Leukemia September 2015

- S27