Katia Borgia Barbosa Pagnano

Background: There is little data regarding hepatitis B (HBV) and C (HCV) prevalence in chronic myeloid leukemia (CML) patients at diagnosis and hepatitis reactivation during tyrosine kinase inhibitors (TKI) treatment.

Erythropoiesis is increased in polycythemia vera (PV), with proliferation of erythroid precursors, and macrophages from erythroblastic islands play a key role in this process. Circulating monocytes were shown to perform some of the macrophage’s functions in normal conditions, but their participation during stress erythropoiesis, as in PV, is yet to be determined. In this study, we evaluated the monocytes from the blood of healthy donors or PV patients regarding their phenotype, involvement in the clearance of erythroid cells, and their expression of iron-related molecules. We showed that circulating monocytes from PV patients contained red blood cell-derived material, which correlated with a reduction in Sirp-ɑ expression, indicating that they play a role in erythroid cell clearance in PV. Both PV monocytes and PV erythroid cells seem to influence the increase in erythrophagocytosis. The enhanced expression of heme-oxygenase-1 and ferroportin post-phagocytosis suggests their capability for heme degradation and externalization of residual iron. Moreover, PV monocytes presented higher expression of CD169, CD163, and VCAM-1, which are involved with erythroid adhesion, and they influenced in vitro erythroid cell line differentiation, suggesting that they may interfere with erythropoiesis in PV. Our findings highlight the similarities between PV monocytes and macrophages of erythroblastic islands. These insights contribute to a deeper understanding of erythrophagocytosis and erythropoiesis in the disease, offering new perspectives for advances in the field.

Managing chronic myeloid leukemia during pregnancy presents significant challenges, with limited treatment options available depending on the stage of pregnancy. All existing tyrosine kinase inhibitors are considered teratogenic, especially during the first trimester and should be avoided. In this case report, we detail the successful, unplanned dichorionic diamniotic twin pregnancy of a patient with chronic-phase myeloid leukemia previously resistant to imatinib and dasatinib who was exposed to the allosteric tyrosine kinase inhibitor asciminib during the early weeks of gestation. Upon confirmation of the pregnancy, asciminib was discontinued, and the patient was treated with pegylated interferon. The patient developed preeclampsia, and the twins were delivered prematurely via cesarean section. No other abnormalities were observed in the newborns. During her pregnancy, the patient experienced a loss of the major molecular response; however, she regained it within two months of resuming asciminib after giving birth. To our knowledge, this case represents the first report of a twin pregnancy during asciminib treatment.

Summary: The Hodgkin lymphoma International Study for Individual Care (HoLISTIC) Consortium's A‐HIPI model, developed in 2022 for advanced‐stage classical Hodgkin lymphoma (cHL), predicts survival within 5 years amongst newly diagnosed patients. This study validates its performance in the Brazilian Hodgkin lymphoma registry. By 2022, the Brazilian HL registry included 1357 cHL patients, with a median 5‐year follow‐up. Probabilities for 5‐year progression‐free survival (PFS) and overall survival (OS) were calculated using A‐HIPI‐model equations. Discrimination (Harrell C‐statistic/Uno C‐statistic) and calibration measures assessed external validation and calibration. Lab values beyond the allowed range were excluded, mirroring the initial A‐HIPI analysis. A total of 694 advanced‐stage cHL patients met the original inclusion criteria (age 18–65 years, Stage IIB‐IV). Median age was 31 years; 46.3% were females. Stage distribution was IIB (33.1%), III (27.4%), IV (39.5%). Bulky disease in 32.6%. Five‐year PFS and OS were 68.4% and 86.0%, respectively. Harrell C‐statistics were 0.60 for PFS and 0.69 for OS, and Uno C‐statistics were 0.63 for PFS and 0.72 for OS. Calibration plots demonstrated well‐calibrated predictions with calibration slopes of 0.91 and 1.03 for 5‐year OS and PFS, respectively. Despite differing patient, clinical characteristics, and socioeconomic factors, the baseline prediction tool performed well in the Brazilian cohort, demonstrating adequate discrimination and calibration. This supports its reliability in diverse settings.

The introduction of all-trans retinoic acid combined with anthracyclines has significantly improved the outcomes for patients diagnosed with acute promyelocytic leukemia (APL), and this strategy remains the standard of care in countries in which arsenic trioxide is not affordable. However, data from national registries and real-world databases indicate that low- and middle-income countries (LMIC) still face disappointing results, mainly because of high induction mortality and suboptimal management of complications. The American Society of Hematology established the International Consortium on Acute Leukemias (ICAL) to address this challenge through international clinical networking. Here, we present the findings from the International Consortium on Acute Promyelocytic Leukemia study involving 806 patients with APL recruited from 2005 to 2020 in Brazil, Chile, Paraguay, Peru, and Uruguay. The induction mortality rate has notably decreased to 14.6% compared with the pre-ICAL rate of 32%. Multivariable logistic regression analysis revealed as factors associated with induction death: age of ≥40 years, Eastern Cooperative Oncology Group performance status score of 3, high-risk status based on the Programa Español de Tratamiento en Hematologia/Gruppo Italiano Malattie EMatologiche dell'Adulto classification, albumin level of ≤3.5 g/dL, bcr3 PML/RARA isoform, the interval between presenting symptoms to diagnosis exceeding 48 hours, and the occurrence of central nervous system and pulmonary bleeding. With a median follow-up of 53 months, the estimated 4-year overall survival rate is 81%, the 4-year disease-free survival rate is 80%, and the 4-year cumulative incidence of relapse rate is 15%. These results parallel those observed in studies conducted in high-income countries, highlighting the long-term effectiveness of developing clinical networks to improve clinical care and infrastructure in LMIC.

This study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07-4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01-3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease.