International Journal of Hematology最新文献

Objective: G6PD deficiency is a potentially life-threatening condition in neonates presenting with hyperbilirubinemia. This study aims to identify clinical and laboratory predictors of G6PD deficiency in neonates presenting with hyperbilirubinemia.

Methods: This was a retrospective study of 227 term neonates admitted to Heyuan People's Hospital from January 2019 to October 2023. Hematological parameters and bilirubin were compared between those with G6PD deficiency and those with normal G6PD.

Results: Term neonates with G6PD deficiency had higher levels of total bilirubin, indirect bilirubin, mean corpuscular volume, mean corpuscular hemoglobin, immature reticulocyte fraction, high-fluorescence reticulocyte ratio, medium-fluorescence reticulocyte ratio, and content of reticulocytes than those with normal G6PD, but lower levels of red blood cells, hemoglobin, hematocrit, and low-fluorescence reticulocyte ratio. Medium-fluorescence ratios (OR = 1.291, P = 0.028) independently predicted G6PD deficiency in neonates. The optimal cut-off value for medium-fluorescence ratios was > 18.55%. The area under the curve for diagnosing G6PD deficiency was 0.924 (95% confidence interval: 0.886-0.962, P < 0.0001), with a sensitivity of 82.6% and specificity of 86.2%.

Conclusion: MFR emerged as a potentially valuable predictor for G6PD deficiency in neonates.

Post-transplant tyrosine kinase inhibitors (TKIs) show promise in preventing relapse after allogeneic hematopoietic cell transplantation (allo-HCT) for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). However, their real-world use and efficacy remain unclear. A comprehensive study across seven centers included Ph+ALL patients who underwent allo-HCT between 2002 and 2022. Post-transplant TKIs were administered in 28% of patients (49 of 173 transplanted in complete remission): 7% as prophylaxis during complete molecular remission (CMR), and 21% in response to measurable residual disease (MRD) positivity. Median first post-transplant TKI duration was 13.7 months for the prophylactic group and 4.0 months for the MRD-triggered group. Prophylactic TKIs appear particularly beneficial for patients not in CMR at allo-HCT, showing a trend towards higher 5-year relapse-free survival (RFS) compared to those not receiving prophylactic TKIs (100% vs. 73%; P = 0.11). Significant RFS differences were observed between the prophylactic, non-TKI, and MRD-triggered groups. However, patients with white blood cell counts <15000/µl at diagnosis and no additional chromosomal abnormalities-an MRD-triggered high efficacy cluster-demonstrated comparable 5-year RFS regardless of TKI strategy (100% vs. 85% vs. 80%; P = 0.87). This cluster highlights the potential effectiveness of MRD-triggered TKI administration in select low-risk patients, suggesting tailored TKI strategies based on risk factors.

This study discusses disseminated intravascular coagulation (DIC) associated with solid cancers and various vascular abnormalities, both of which generally exhibit chronic DIC patterns. Solid cancers are among the most significant underlying diseases that induce DIC. However, the severity, bleeding tendency, and progression of DIC vary considerably depending on the type and stage of the cancer, making generalization difficult. Moreover, during the process of creating these guidelines, it became apparent that despite solid cancers being a major underlying condition for DIC, there is a lack of high-quality research on DIC associated with solid cancers. Nevertheless, we developed recommendations for clinical questions (CQs) regarding the use of heparin and recombinant thrombomodulin. Additionally, statements concerning these five questions were provided. DIC associated with various vascular abnormalities, is characterized by hyperfibrinolytic activity and linked to underlying conditions such as aortic aneurysm, aortic dissection, vasculitis syndromes, and vascular malformations. These conditions must always be considered differential diagnoses when unexplained thrombocytopenia or bleeding tendencies are observed. Although no evidence was found to support the assignment of recommendation levels, three statements were made. However, traumatic vascular abnormalities have not been discussed in this context.

Sinusoidal obstruction syndrome (SOS), also known as hepatic veno-occlusive disease (VOD), is a life-threatening complication of hematopoietic stem cell transplantation. In severe cases, SOS/VOD progresses to multiple organ failure with a mortality rate higher than 80%. Early diagnosis and treatment based on severity assessment improve the prognosis of severe SOS/VOD, but conventional diagnostic criteria may be insufficient for an early diagnosis. We herein report a case of severe late-onset SOS/VOD that was histologically proven before clinical findings become evident. Although defibrotide therapy was started before the clinical diagnostic criteria were met, the disease progressed to multiple organ failure. This case suggests that some patients require earlier treatment before the appearance of clinical findings such as ascites and weight gain or hyperbilirubinemia, and supports the need to establish methods for predicting the onset and severity of SOS/VOD.

Polycythemia vera (PV) is a myeloproliferative neoplasm that is associated with an elevated risk of thrombosis. Treatment strategies are based on thrombosis risk classification. Phlebotomy is a commonly recommended treatment for all patients with PV, regardless of their risk classification, and reduces the incidence of thrombosis by lowering hematocrit levels. However, patients with PV frequently present with iron deficiency at diagnosis due to increased erythropoiesis, which repeated phlebotomy can exacerbate. This can produce symptoms that diminish quality of life, such as fatigue, lethargy, and impaired concentration. Recently, hepcidin mimetics have been developed to suppress iron utilization in erythropoiesis. Among them, rusfertide has been shown to control hematocrit levels without requiring phlebotomy. Further studies are needed to identify new treatment strategies for PV that also consider iron deficiency.

In patients with hemophilia A with inhibitor (PwHA-I), emicizumab drastically reduces bleeding events. However, few studies have investigated the behavior and effects of factor X (FX) in patients who require intensive treatment with factor VIII-bypassing agents (BPA) and emicizumab. A 59-year-old man with HA-I receiving emicizumab prophylaxis was admitted to our hospital because of acute gangrenous cholecystitis. He received percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy along with repeated administration of recombinant activated factor VII (rFVIIa). On day 10, a large hematoma developed around the residual gallbladder. Rotational thromboelastometry (ROTEM) suggested poor effect of rFVIIa and reduced activity of emicizumab. Considering that this could be due to consumption of FX, plasma-derived FVIIa/FX agent (pdFVIIa/X) was administered, and ROTEM parameters recovered considerably. The patient was discharged on day 19 uneventfully. Plasma assays revealed that FX antigen level (FX:Ag) was 107.5% at baseline but then decreased. Administration of pdFVIIa/FX restored FX:Ag (pre/post 47.2%/125.5%). ROTEM and thrombin generation assay with in vitro addition of anti-emicizumab antibody suggested that low FX:Ag was responsible for attenuating the effect of emicizumab, and pdFVIIa/FX administration restored coagulation potentials. In PwHA-I receiving intensive treatment with rFVIIa under emicizumab prophylaxis, FX consumption might attenuate the effect of emicizumab.

Objective: This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia.

Methods: In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2).

Results: In phase 1, MTD was not reached and RED was 120 mg/day. In phase 2, the CR rate was 50.0% after induction (90% confidence interval [CI] 40.4, 59.6); however, the lower confidence limit did not exceed the pre-defined 55% benchmark. Composite CR (CRc) rates were high following induction (86.6%, 95% CI [77.3, 93.1]), consolidation, and maintenance therapy (87.8%, 95% CI [78.7, 94.0], each). The probability of OS was 86.6% at 12 months. No new safety findings were reported.

Conclusion: In this interim analysis, gilteritinib 120 mg/day in combination with chemotherapy was well tolerated, with similar CRc rates to previous studies.

Ganciclovir and foscarnet are two representative anti-cytomegalovirus (CMV) agents. A previous regional study revealed a lower risk of chronic graft-versus-host disease (GVHD) in patients who received pre-emptive foscarnet. We conducted a retrospective nationwide study to confirm the results. A total of 8890 patients aged 16 or older with hematological malignancies who received foscarnet (n = 1555) or ganciclovir (n = 7335) during their first hematopoietic stem cell transplantation (HSCT) were included. The risks of chronic GVHD (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.13-1.40; P < 0.001) and extensive chronic GVHD (HR, 1.16; 95% CI, 1.01-1.33; P = 0.033) were higher with ganciclovir. Among male patients with a female donor, the incidence of extensive chronic GVHD 3 years after HSCT was clearly lower with foscarnet (13%; 95% CI, 9-16%) than with ganciclovir (27%; 95% CI, 25-29%; P < 0.001). In male patients who received HSCT from female donors, foscarnet recipients showed significantly lower incidence of extensive chronic GVHD than ganciclovir recipients, regardless of donor source or previous acute GVHD. While caution is necessary, these results indicate that foscarnet affects alloimmunization and might reduce the incidence of chronic GVHD.