Blood Research最新文献

This case report describes the clinical course of a 78-year-old patient diagnosed with polycythemia vera (PV), who presented with pronounced acrocyanosis of the hands in 2021. The patient was treated with hydroxyurea (oncocarbide), and nailfold capillaroscopy revealed an "abnormal pattern" characterized by pronounced architectural disarray and capillary tortuosity, which is uncommon in patients with myeloproliferative neoplasms (MPNs). In 2023, owing to suboptimal symptom management and hematological side effects, the treatment was switched to ruxolitinib, which led to significant clinical improvements by 2024, including near-complete resolution of acrocyanosis and substantial improvement in capillaroscopic abnormalities, with only residual capillary tortuosity noted. This case emphasizes the need for individualized therapeutic interventions for PV, and underscores the potential role of ruxolitinib in ameliorating microvascular dysfunction.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies.

Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed.

Results: The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) grades II-IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III-IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05).

Conclusions: These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients without human leukocyte antigen-matched donors.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common prophylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.

Method: The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from January 2019 to February 2023.

Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II-IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II-IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038).

Conclusion: Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II-IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: Despite advances in the treatment of adult acute lymphoblastic leukemia (ALL), relapse remains the most significant challenge in improving prognosis. Measurable residual disease (MRD) assessment can predict bone marrow relapse based on MRD positivity. As access to innovative therapies remains limited because of the high cost, chemotherapy is the widely utilized treatment option. The efficacy of a combination of bortezomib and Hyper-CVAD has been reported in patients with multiple myeloma; however, its efficacy has not yet been confirmed in patients with ALL.

Methods: This prospective cohort study involved patients with ALL who presented with MRD-positive results or relapse and received treatment with a combination of bortezomib and Hyper-CVAD at two reference centers in Mexico City.

Results: Of the 20 patients with positive MRD included in this study, 60% (n = 12) exhibited MRD negative results after combination treatment, 30% (n = 6) persisted positive MRD results, and 10% (n = 2) passed away. Of the 23 patients with bone marrow relapse, 43.5% (n = 10) achieved a second complete remission (2CR), 34.8% (n = 6) exhibited refractory status, and 21.7% (n = 5) passed away. To achieve a 2CR, 20% (n = 2) patients required less than four cycles of treatment, 50% (n = 5) required four cycles (two A and B cycles each), and 30% (n = 3) required six cycles.

Conclusion: The combination of bortezomib and Hyper-CVAD treatment exhibited better results in achieving MRD negative results, indicating its potential as a promising first-line treatment strategy for ALL.

Purpose: This network meta-analysis aimed to evaluate the relative efficacy of systemic treatments in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL), focusing on key genetic mutations, specifically the 17p deletion and TP53 mutations.

Methods: We conducted a systematic literature review to identify all publicly available randomized controlled trials (RCTs) using PubMed, EMBASE, the Cochrane database, and meeting abstracts published through December 2023. A Bayesian network meta-analysis was performed to estimate the hazard ratios (HRs) for progression-free survival (PFS) with 95% confidence intervals (CIs) and to determine the ranking of the included regimens.

Results: Twelve trials involving 4,437 patients and 13 treatment options were included in the meta-analysis. Venetoclax plus rituximab and zanubrutinib emerged as the most effective treatments for the overall R/R CLL population, showing the lowest PFS HR (HR 0.62, 95% CI 0.32-1.20 and HR 0.65, 95% CI 0.49-0.86, respectively) versus ibrutinib, and were ranked as the best agent (surface under the cumulative ranking curve [SUCRA] value of both 90%, respectively) among the included drugs. In the 17p deletion/TP53 mutation subgroup, zanubrutinib demonstrated the most favorable efficacy (HR 0.52, 95% CI 0.31-0.88 versus ibrutinib) with the highest SUCRA value (97%). In patients without these mutations, venetoclax plus rituximab was the most effective (HR 0.49, 95% CI 0.26-0.94 versus ibrutinib) with a SUCRA value of 94%.

Conclusion: Our findings highlight the superior efficacy of venetoclax plus rituximab and zanubrutinib for treating R/R CLL and confirm that the role of each regimen may vary depending on the clinically significant mutations.

Background: Acute myeloid leukemia (AML) is a heterogeneous malignancy that responds to various therapies. The sensitivity of leukemia cells to chemotherapy is affected by the DNA damage response (DDR). In this study, we examined the association between RAD51 rs1801320, XRCC3 rs861539, NBS1 rs1805794, MRE11 rs569143, and RAD50 rs2299014 variants of the homologous recombination repair (HRR) pathway and AML outcomes.

Material and methods: PCR-RFLP was applied for the genotyping of 67 newly diagnosed cases. We performed Sanger sequencing to confirm the results of RFLP genotyping. Outcomes and organ toxicities were collected and χ² testing was performed for association analysis.

Results: RAD50 variant allele carriers were protected from renal and hepatic toxicities (p = 0.024 and p = 0.045, respectively), and were associated with resistant disease (p = 0.001). RAD51 variant alleles were protected from liver toxicity (p = 0.031) and correlated with disease resistance (p = 0.012).

Conclusion: RAD50 rs2299014 and RAD51 rs1801320 polymorphisms may be useful for drug adjustment in AML.

Purpose: This study investigated the occurrence of subsequent malignancies (SM) in adult patients with severe aplastic anemia (SAA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to address the lack of large-scale, long-term data on this complication.

Methods: A retrospective cohort analysis of 376 adult patients with SAA who underwent allo-HSCT between 2002 and 2021 at a single center was conducted. The incidence, risk factors, and survival impact of SM were also examined.

Results: During the follow-up period, 31 cases of SM (8.2%) were identified. Approximately one-third (32.3%) of SM cases were hematologic malignancies, including post-transplant lymphoproliferative disorder (16.1%), myelodysplastic neoplasm (6.5%), and acute myeloid leukemia (3.2%). Solid tumors accounted for 67.7% of cases, with thyroid cancer being the most prevalent (25.8%). The 15-year cumulative incidence of SM was 11.2%, and the hazard ratio for overall survival according to the development of SM was 16.25 (p < 0.001). High-dose total body irradiation (TBI), anti-thymocyte globulin (ATG), and moderate-to-severe chronic graft-versus-host disease (GVHD) were identified as significant risk factors for subsequent malignancy. Post-transplant SAA patients exhibited a 3.54-fold higher observed cancer incidence than the expected incidence calculated from the age-, sex-, and calendar year-matched general population.

Conclusion: SM is a significant long-term complication in patients with posttransplant SAA and has a substantial survival impact. Patients receiving high-dose TBI or ATG, and those with moderate-to-severe chronic GVHD, require vigilant long-term monitoring.