Risk of histological transformation and therapy-related myelodysplasia/acute myeloid leukaemia in patients receiving radioimmunotherapy for follicular lymphoma.

Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT.

Accuracy of 18-F FDG PET/CT to detect bone marrow clearance in patients with peripheral T-cell lymphoma - tissue remains the issue.

Staging of peripheral T-cell non-Hodgkin lymphoma (PTCL) is determined by 18-F FDG PET scan and bone marrow biopsy. This study addressed the accuracy of PET at detecting bone marrow (BM) involvement at restaging in patients with known involvement pretreatment. We identified patients with biopsy proven BM PTCL at diagnosis and concomitant BM and PET at the end of therapy. Pre-treatment PET demonstrated 50% (8/16) had a false-negative PET scan of the BM. After induction, repeat biopsy revealed 62.5% (10/16) with BM involvement. Of these 10, two had a positive PET; eight were false negative by PET. Of the six patients with a negative posttherapy BM biopsy, four were PET negative and two false positive. The sensitivity of PET at end of treatment was 20% (2/10) with a specificity of 66.7% (4/6). PET/CT is not an accurate predictor of BM involvement in patients with known PTCL in the marrow.

The use of pembrolizumab for the treatment of metastatic uveal melanoma.

Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14-49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM.

Cremophor-induced lupus erythematosus-like reaction with taxol administration: a case report and review of the literature.

We report the first case of Cremophor EL-induced cutaneous lupus erythematosus-like reaction in a 40-year-old female undergoing treatment for breast cancer. There have been four reported cases of paclitaxel- and four cases of docetaxel-induced cutaneous lupus reactions in the published literature [Dasanu and Alexandrescu: South Med J 2008;101:1161-1162; Adachi and Horikawa: J Dermatol 2007;34:473-476; Lortholary et al: Presse Med 2007;36:1207-1208; Chen et al: J Rheumatol 2004;31:818-820]. Our patient developed findings of a cutaneous lupus-like reaction with administration of paclitaxel which was subsequently discontinued. She was re-challenged with albumin-bound paclitaxel which has no Cremophor EL compound in its formulation. This administration of albumin-bound paclitaxel did not induce further reaction. She did not develop a cutaneous lupus erythematosus-like reaction with three other subsequent administrations of albumin-bound paclitaxel. The diagnosis of lupus-like reaction in our patient was made based on the development of a malar butterfly rash sparing the nasolabial folds, the appearance of this rash in context of recently receiving treatments with paclitaxel, resolution of the rash after discontinuing the paclitaxel, and the presence of autoimmune antibodies in the patient's serum which resolved with discontinuation of the paclitaxel. This is the first case demonstrating that the cause of the cutaneous lupus erythematosus-like reaction is not likely due to the taxane component of paclitaxel but the chemical composition of Cremophor EL. If the chemotherapeutic agent was causing the reaction then the same reaction should be seen by albumin-bound paclitaxel. We propose that previously reported lupus reactions may actually be due to Cremophor EL, which consists of polyoxyethylated castor oil, and not the chemotherapeutic agent itself.