High Level of CD8+PD-1+ Cells in Patients with Chronic Myeloid Leukemia Who Experienced Loss of MMR after Imatinib Discontinuation.

Treatment-free remission (TFR) is achieved in approximately half of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors. The mechanisms responsible for TFR maintenance remain elusive. This study aimed to identify immune markers responsible for the control of residual CML cells early in the TFR (at 3 months), which may be the key to achieving long-term TFR and relapse-free survival (RFS) after discontinuation of imatinib. Our study included 63 CML patients after imatinib discontinuation, in whom comprehensive analysis of changes in the immune system was performed by flow cytometry, and changes in the BCR::ABL1 transcript levels were assessed by RQ-PCR and ddPCR. We demonstrated a significant increase in the percentage of CD8+PD-1+ cells in patients losing TFR. The level of CD8+PD-1+ cells is inversely related to the duration of treatment and incidence of deep molecular response (DMR) before discontinuation. Analysis of the ROC curve showed that the percentage of CD8+PD-1+ cells may be a significant factor in early molecular recurrence. Interestingly, at 3 months of TFR, patients with the e13a2 transcript had a significantly higher proportion of the PD-1-expressing immune cells compared to patients with the e14a2. Our results suggest the important involvement of CD8+PD-1+ cells in the success of TFR and may help in identifying a group of patients who could successfully discontinue imatinib.

Severe hypereosinophilic syndrome successfully treated with a monoclonal antibody against interleukin 5 receptor α - benralizumab.

Hypereosinophilic syndrome (HES) is a group of a rare diseases characterized by marked eosinophilia in blood or tissue and eosinophil-related clinical manifestations. Benralizumab is a humanized, monoclonal antibody against interleukin 5 (IL-5) receptor α, which is expressed on human eosinophils. Here, we present the case of a patient with severe HES in whom treatment with benralizumab, an anti-IL-5 receptor monoclonal antibody, was initiated 6 months ago. Prior to benralizumab administration, the patient was treated with glucocorticoids (GS) and mepolizumab. However, instead of the applied treatment and normal level of peripheral eosinophils the patient presented with fluctuating lower respiratory tract symptoms and recurrent exacerbations of HES. Treatment with benralizumab (30 mg s.c. every 4-6 weeks) was started, resulting in significant improvement of respiratory signs and symptoms, normalization of eosinophil count and significant reduction of the methylprednisolone dose (after 5 doses of benralizumab administration). No substantial side effects have been noted during treatment and 6-month follow-up. We argue that in the severe and relapsing course of HES, rescue treatment with benralizumab should be taken into account, particularly in cases of relative inefficacy of GS and mepolizumab.

Role of rituximab in the first-line therapy of high-risk diffuse large B-cell lymphoma: a retrospective analysis by the Polish Lymphoma Research Group.

INTRODUCTION: R-CHOP immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is a standard first-line treatment for diffuse large B-cell lymphoma (DLBCL). None of the randomized trials have proved a statistically significant overall survival (OS) benefit in high-risk subgroups according to the International Prognostic Index (IPI). OBJECTIVES: We retrospectively investigated the role of adding rituximab to anthracycline-based chemotherapy in patients with high-risk DLBCL according to the IPI. PATIENTS AND METHODS: A total of 371 patients with high-risk DLBCL treated at 15 Polish hematology centers were retrospectively analyzed in 2 distinct age groups: older than 60 years and 60 years old or younger. Response rates, OS, and progression-free survival (PFS) were compared and analyzed. RESULTS: The overall response rate (ORR) of high-risk DLBCL patients significantly improved in rituximabtreated patients compared with patients treated without rituximab (76.7% vs 95.6%; P <0.05). The R-CHOP immunochemotherapy prolonged survival in both older and younger subgroups. The 5-year projected OS and PFS in younger patients treated with rituximab vs chemotherapy alone were 42% vs 38% and 46% vs 27%, respectively (P <0.05), while the 5-year projected OS and PFS in older patients treated with rituximab vs chemotherapy alone were 82% vs 52% and 67% vs 45%, respectively (P <0.05). CONCLUSIONS: With all the limitations of a retrospective analysis, the superiority of adding rituximab to CHOP combination chemotherapy has been clearly demonstrated regarding ORR, OS, and PFS in both age subgroups of patients with high-risk DLBCL.