Toxicity of a Modified PEG-Asparaginase-Based SMILE Regimen Is Comparable to L-Asparaginase-Based SMILE in a Non-Asian Population.

INTRODUCTION: L-asparaginase-based chemotherapy regimens are effective for treating chemotherapy-resistant natural killer- (NK-) cell neoplasms. To treat these lymphoma subtypes in Asia, where NK/T-cell lymphomas are more prevalent, the NK-Cell Tumor Study Group developed the SMILE regimen, which includes a steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide. In the US however, the only commercially available form of asparaginase is the pegylated form (PEG-asparaginase) which has been incorporated into a modified SMILE (mSMILE). We sought to study the toxicity associated with replacing L-asparaginase with PEG-asparaginase in mSMILE. PATIENTS AND METHODS: We retrospectively identified all adult patients treated with the mSMILE chemotherapy regimen in our database at Moffitt Cancer Center (MCC) between December 1, 2009, and July 30, 2021. Patients were included if they were treated with mSMILE irrespective of their underlying diagnosis. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. The rate of toxicity in our mSMILE treatment group was numerically compared to data published in a metanalysis of the SMILE regimen's toxicity (Pokrovsky et al., 2019). RESULTS: A total of 21 patients were treated with mSMILE at MCC during the 12-year analysis window. Compared to patients receiving the L-asparaginase-based SMILE, patients receiving mSMILE experienced grade 3 or 4 leukopenia less often, with a toxicity rate of 62% (median with SMILE, 85% [95% CI, 74%-95%]); thrombocytopenia, however, was more common, with a toxicity rate of 57% (median with SMILE, 48% [95% CI, 40%-55%]). Other hematological, hepatic and coagulation related toxicities were also reported. CONCLUSION: In a non-Asian population, the mSMILE regimen with PEG-asparaginase is a safe alternative to the L-asparaginase-based SMILE regimen. There is a comparable risk of hematological toxicity, and no treatment-related mortality was seen in our population.

Graft-Versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplant: SARS-CoV-2 Vaccine as a Potential Trigger.

Allogeneic hematopoietic stem cell transplant (AHSCT) recipients are at a risk of developing immune-mediated tissue damage from activation of the donor's immunocompetent T cells by the recipient's normally expressed antigens, a phenomenon called graft-versus-host disease (GVHD). With the emergence of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), new vaccines have been developed to prevent morbidity and mortality, including the highly vulnerable hematologic malignancy patients after undergoing AHSCT. The early pathophysiologic events in GVHD include priming the donor T cells with molecules that are endogenous or pathogenic. In this case series, we present two cases of AHSCT recipients in which the SARS-CoV-2 vaccination series proceeded the development of GVHD manifesting with oral mucosal symptoms and derangement in the liver function tests. Our experience raises the question if any of the vaccine components serve as a molecular trigger for GVHD, making the current SARS-CoV-2 vaccines a risk factor for activating the immune system and developing GVHD.

Serum sickness reaction to obinutuzumab in a patient with chronic lymphocytic leukaemia.

Serum sickness (SS) is a known phenomenon; however, it is commonly missed due to vague symptoms, and is usually confounded by other aetiologies that present similarly. Obinutuzumab is a novel anti-CD20 antibody agent that has been approved for chronic lymphocytic leukaemia (CLL) treatment. At the time of approval, it was not linked to SS; however, this phenomenon has been recognised with other anti-CD20 agents like rituximab. SS remains a rare entity, but it is important to be recognised accurately and quickly in the appropriate circumstances, so that effective treatment with corticosteroids can be initiated to alleviate inflammatory symptoms. Here we present a patient with CLL who developed maculopapular rash, fever and polyarthritis and elevated inflammatory markers consistent with serum sickness triggered by obinutuzumab and was effectively treated with corticosteroids.