Pretransplant Blinatumomab Improves Outcomes in B Cell Acute Lymphoblastic Leukemia Patients Who Undergo Allogeneic Hematopoietic Cell Transplantation.

BACKGROUND: Blinatumomab, a bispecific monoclonal antibody, effectively controls refractory B cell acute lymphoblastic leukemia (ALL) and promotes measurable residual disease (MRD) negativity. This study investigated the impact of pretransplant blinatumomab on allogeneic hematopoietic cell transplantation (HCT) outcomes in B cell ALL patients. METHODS: We analyzed the effect of pretransplant blinatumomab on transplant outcomes of 117 adults undergoing allogeneic HCT for B cell ALL at Princess Margaret Hospital, Toronto, between 2010 and 2021. Outcomes assessed included overall survival (OS), graft-versus-host disease and relapse-free survival (GRFS), cumulative incidences of relapse (CIR), and nonrelapse mortality (NRM). RESULTS: The median follow-up was 36 months. Thirty-one participants (26.5%) received blinatumomab. Blinatumomab group had higher proportions of individuals with high disease risk index, primary induction failure and was more likely to receive dual T cell depletion with antithymocyte globulin and post-transplant cyclophosphamide. Two-year OS, GRFS, NRM, and CIR in the blinatumomab and nonblinatumomab groups were, respectively: 65.4% versus 45.6% (P = .05), 42.2% versus 17.3% (P = .01), 3.2% versus 43.0% (P = .007) and 34.4% versus 14.4% (P = .02). Blinatumomab was associated with a lower incidence of day-100 grade 2 to 4 and grade 3 to 4 acute graft-versus-host disease (aGVHD): 27.5% versus 56.7% (P = .009), and 10.9% versus 34.7% (P = .04), respectively. Multivariate analysis confirmed the association between pretransplant blinatumomab and improved OS and NRM. CONCLUSIONS: Pretransplant blinatumomab is associated with improved OS and lower risk of NRM in B cell ALL patients undergoing allogeneic HCT, likely reflecting lower burden of treatment-related toxicity in this population. Larger prospective trials are warranted to validate our findings.

Incidence and risk factors for central nervous system relapse in patients with primary mediastinal large B-cell lymphoma in the rituximab era.

Central nervous system (CNS) involvement is rare in primary mediastinal large B-cell lymphoma (PMLBCL). We aimed to evaluate the incidence of CNS relapse as first treatment failure event and the effect of the induction chemotherapy regimen, central nervous system - international prognostic index (CNS-IPI) and other clinical and laboratory variables on the risk of CNS relapse in 564 PMLBCL patients treated with immunochemotherapy. Only 17 patients (3.0%) received CNS prophylaxis. During a 55-month median follow-up only 8 patients experienced CNS relapse as first event, always isolated. The 2-year cumulative incidence of CNS relapse (CI-CNSR) was 1.47% and remained unchanged thereafter. The CI-CNSR was not affected by the chemotherapy regimen (R-CHOP or R-da-EPOCH). None of the established International Prognostic Index factors for aggressive lymphomas predicted CNS relapse in PMLBCL. The 2-year CI-CNSR in patients with versus without kidney involvement was 13.3% versus 0.96% (p < 0.001); 14.3% versus 1.13% with versus without adrenal involvement (p < 0.001); and 10.2% versus 0.97% with versus without either kidney or adrenal involvement. CNS-IPI was also predictive (2-year CI-CNSR in high-risk vs. intermediate/low-risk: 10.37% vs. 0.84%, p < 0.001). However, this association may be driven mainly by kidney and/or adrenal involvement. In conclusion, in PMLBCL, CNS relapse is rare and appears to be strongly associated with kidney and/or adrenal involvement.

Current Clinical Applications and Future Perspectives of Immune Checkpoint Inhibitors in Non-Hodgkin Lymphoma.

Cancer cells escape immune recognition by exploiting the programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) immune checkpoint axis. Immune checkpoint inhibitors that target PD-1/PD-L1 unleash the properties of effector T cells that are licensed to kill cancer cells. Immune checkpoint blockade has dramatically changed the treatment landscape of many cancers. Following the cancer paradigm, preliminary results of clinical trials in lymphoma have demonstrated that immune checkpoint inhibitors induce remarkable responses in specific subtypes, most notably classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma, while in other subtypes, the results vary considerably, from promising to disappointing. Lymphomas that respond to immune checkpoint inhibitors tend to exhibit tumor cells that reside in a T-cell-rich immune microenvironment and display constitutive transcriptional upregulation of genes that facilitate innate immune resistance, such as structural variations of the PD-L1 locus, collectively referred to as T-cell-inflamed lymphomas, while those lacking such characteristics are referred to as noninflamed lymphomas. This distinction is not necessarily a sine qua non of response to immune checkpoint inhibitors, but rather a framework to move the field forward with a more rational approach. In this article, we provide insights on our current understanding of the biological mechanisms of immune checkpoint evasion in specific subtypes of B-cell and T-cell non-Hodgkin lymphomas and summarize the clinical experience of using inhibitors that target immune checkpoints in these subtypes. We also discuss the phenomenon of hyperprogression in T-cell lymphomas, related to the use of such inhibitors when T cells themselves are the target cells, and consider future approaches to refine clinical trials with immune checkpoint inhibitors in non-Hodgkin lymphomas.

Acute Lymphoblastic Leukemia Presenting with Liver Infiltration and Severe Lactic Acidosis.

BACKGROUND Type-B lactic acidosis is a rare complication of solid tumors and hematological malignancies. It occurs secondary to Warburg effect, when glucose metabolism in cancer cells switches from the oxidative pathway to the glycolytic pathway. Malignant lactic acidosis is a life-threatening condition if not promptly diagnosed and treated urgently. CASE REPORT We report the case of a 58-year-old male patient who presented with severe chest pain, dyspnea, systemic symptoms, leukopenia, normocytic anemia, and severe lactic acidosis. He was admitted with a possible diagnosis of acute pericarditis and lactic acidosis. Sodium bicarbonate replacement did not improve the lactic acidosis. Liver biopsy was performed because of persistently elevated alkaline phosphatase and gamma-glutamyl transferase; the biopsy showed atypical lymphoblasts and bone marrow biopsy confirmed the diagnosis of precursor B acute lymphoblastic leukemia. Lactic acidosis normalized after initiation of chemotherapy. CONCLUSIONS Cancer, particularly hematological malignancy, should be considered as an etiology and differential diagnosis of type-B lactic acidosis. Prompt recognition and urgent initiation of specific therapy to control the underlying malignancy are critical to manage this serious metabolic complication.

Determination of phthalates in Jordanian bottled water using GC-MS and HPLC-UV: environmental study.

A simple, accurate and reliable method was presented and validated for the simultaneous monitoring of six phthalates at trace level concentrations in seven different brands of commercial bottled mineral water from Jordan. Liquid-liquid extraction with a mixture of methylene chloride-petroleum ether (20:80, v/v) was used for isolation and enrichment of the phthalates and sample cleanup. This was followed by gas chromatography-mass spectrometry (GC-MS) for identification and high-performance liquid chromatography (HPLC) with ultraviolet detection for quantification. The linear range of the GC-MS calibration curve was 0.3-1.2 µg/L with a mean correlation coefficient (R(2)) of 0.9920 ± 0.0063, the detection limit was < 0.1 µg/L and the percentage recovery was >90%. For HPLC, the linear range was 0.5-10 mg/L with R(2) = 0.9985 ± 0.0012 and an average detection limit of 0.20 ± 0.15 µg/L. The results indicated that the Jordanian bottled water was contaminated with dibutyl-, di-2-ethylhexyl- and di-n-octyl-phthalate, with total phthalate concentrations between 8.1 and 19.8 µg/L. Increasing the storage temperature of the bottled water increased the content of leached phthalates in the water (total concentration of 23-29.2 µg/L).