Acta Haematologica最新文献

Introduction: The prevalence of preexisting obstructive coronary artery disease (CAD) and the occurrence of anginal chest pain as a presenting symptom in patients with light-chain (AL) and transthyretin (ATTR) cardiac amyloidosis (CA) are undetermined.

Methods: A single-center analysis of clinical, laboratory, imaging, and angiographic characteristics of CA cohort was performed.

Results: Included were 98 CA patients (43 AL, 47 wtATTR, 8 mutant ATTR). Eighteen patients (18%) had preexisting obstructive CAD at the time of CA diagnosis. These patients were older and had worse left ventricular ejection fraction, yet revealed similar cardiac biomarkers' levels. The 3-year survival rate was comparable between patients with versus without preexisting CAD (p = 0.974). Anginal chest pain was a presenting symptom of newly diagnosed CA in 24% of patients (n = 19) with no preexisting CAD, 53% (n = 10) of which had AL-CA. Two patients had an acute myocardial infarction. The prevalence of diabetes mellitus, dyslipidemia, hypertension, and smoking was similar among CA patients presenting with versus without chest pain. Of the newly diagnosed CA patients with no preexisting CAD who underwent symptoms evaluation (n = 37), 99mTc-Sestamibi myocardial perfusion scintigraphy demonstrated stress-induced perfusion defects in 45% (9/20) and normal study in 45% (9/20) of patients. Coronary evaluation revealed nonobstructive coronary artery lesions or normal coronaries in 75% of patients (18/24).

Conclusion: CA patients may initially present with anginal chest pain and myocardial perfusion defects which may reflect coronary microvascular ischemia. CA should be considered in the differential diagnosis of patients presenting with chest pain, nonobstructive CAD, and elevated cardiac biomarkers.

Background: Advances in novel therapies have improved outcomes for multiple myeloma (MM) patients and the use of allo-SCT has decreased. Current guidelines no longer support allo-SCT as consolidation therapy for newly diagnosed MM, even in high-risk cases.

Summary: Allo-SCT is now typically considered only within clinical trials for young, high-risk patients with relapsed or refractory MM (RRMM). It has not proven favorable despite its historical use. CAR T-cell therapy and bispecific antibodies have shown promise in treating triple- and penta-exposed/refractory MM, yet relapse remains common with poor survival rates. The efficacy of allo-SCT following BCMA-directed therapy and other new T-cell-directed therapies is unclear. Allo-SCT might be a viable option for eligible patients who relapse after these therapies, or where such options are unavailable. Advancements in reduced-intensity conditioning regimens have led to lower toxicity and transplant-related (TR) morbidity, lower graft-versus-host disease (GvHD), and TR mortality. Expanded use of alternative donors, like haploidentical donors, has yielded comparable outcomes. Better post-transplant GvHD regimens and maintenance strategies to prevent relapse have been developed.

Key messages: This review analyzes available literature to better understand the safety, efficacy, and current role of allo-SCT in managing MM. Newer regimens are needed as routine use of allo-SCT cannot be recommended.

Introduction: The study aimed to assess the safety, immunogenicity, and efficacy of long-term therapy with biosimilar of eculizumab (Elizaria®) in paroxysmal nocturnal hemoglobinuria (PNH) patients.

Methods: The study included 30 patients with PNH who had completed previous clinical trials. Of these, 25 patients continued receiving the biosimilar product, and 5 patients switched from the originator product Soliris. The maximum duration of follow-up was 104 weeks, during which the investigational product was administered 52 times at a standard dose.

Results: Throughout the study, the levels of lactate dehydrogenase, hemoglobin, reticulocytes, and PNH clone remained stable compared to baseline, regardless of the previous therapy (p > 0.05). There were no significant differences in the number of patients with chronic kidney disease at different visits, as well as in the number of patients who received donor red blood cell and platelet transfusions during the study (p > 0.05). There were 2 cases of adverse reactions reported in 2 patients (6.6%): elevated aspartate aminotransferase (3.3%) and alopecia (3.3%). Immunogenicity analysis showed no significant differences in the frequency of antidrug antibody detection compared to baseline (p > 0.05).

Conclusion: The study findings confirm the long-term efficacy and safety of biosimilar in patients with PNH.

Introduction: Treatment of patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) remains a significant clinical challenge. Many new strategies are changing the treatment landscape of r/r BCP-ALL in recent years. Blinatumomab has improved outcomes in r/r BCP-ALL, though high treatment costs and extended hospital stays are significant concerns. We considered that shortening the duration of blinatumomab administration during induction therapy might solve these problems.

Methods: We retrospectively analyzed 19 patients with r/r BCP-ALL treated with different durations of blinatumomab, where 10 patients received blinatumomab for 14 days (Bli 14D group) and 9 received it for a longer duration (LT group, 21-28 days).

Results: The overall response rate (ORR) was 63.2% (12/19) of patients in total, and the ORRs in 14D and LT groups were almost the same (60% and 66.6%, respectively). The median overall survival was not reached in either groups. The median event-free survival time was 4.1 months in LT group and not reached in D14 group. The most common adverse events were consistent with previous reports, including cytokine release syndrome, neurologic toxicity, and hematological toxicity.

Conclusion: A 14-day blinatumomab administration may be a promising and well-tolerated regimen in r/r BCP-ALL, offering the same ORR and survival rates.

Introduction: Thiamine-responsive megaloblastic anemia syndrome (TRMA) is a rare autosomal recessive disease with a homozygous or compound-heterozygous mutation in the SLC19A2 gene characterized by megaloblastic anemia, diabetes mellitus (DM), and sensorineural hearing loss with onset in childhood. Folic acid and vitamin B12 in serum are normal with dysplastic erythropoiesis in the bone marrow often mimicking myelodysplastic neoplasms (MDS) as a potential differential diagnosis. Thiamine substitution leads to normalization of anemia, without effects on hearing loss or DM.

Case presentation: We report about a 38-year-old male patient, presented with a 12-year history of anemia, insulin dependent DM, optic neuropathy, and a cataract since early childhood. The laboratory showed megaloblastic anemia. Other values were normal. The bone marrow smear showed dysplastic erythropoiesis with megaloblastic changes, and normal findings in cytogenetic and molecular genetic examinations. Next-generation sequencing-based diagnostics revealed a heterozygous missense variant in the SLC19A2 gene on the maternal allele and a 3.4 Mb inversion in the chromosomal region 1q24.2 with breaking points in FAM78B and SLC19A2 on the paternal allele. Treatment with oral thiamine 100 mg daily was initiated, and 12 weeks later hemoglobin levels and bone marrow morphology had normalized.

Conclusion: Late-onset TRMA should be considered in adult patients with indicative comorbidities and a typical phenotype, which may mimic features of MDS.

Introduction: The combination of venetoclax (VEN) and azacytidine (AZA) has demonstrated potential in achieving rapid and effective remissions in elderly patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation is a promising potential cure for high-risk AML, as VEN-based therapies have a worse prognosis in elderly patients. This study aimed to assess the efficacy of sequential haploidentical HSCT following two courses of VEN and AZA therapy in patients with AML aged 55 years and older.

Methods: We conducted a retrospective study on AML patients aged 55-70 years who received intensive chemotherapy or two courses of VEN/AZA therapy, followed by haploidentical allo-HSCT (haplo-HSCT) based on disease risk degree, measurable residual disease status, and patient's preference.

Results: Between January 2019 and December 2023, 141 newly diagnosed AML patients received initial treatment with intensive chemotherapy or VEN/AZA therapy. Among them, 64 patients received haplo-HSCT, while 77 did not. The 1-year overall survival (OS) and relapse-free survival (RFS) of patients who received haplo-HSCT were significantly higher than those who did not receive haplo-HSCT (p < 0.05). Among patients who received transplantation, there was no significant difference in 1-year OS and RFS between the VEN/AZA and intensive chemotherapy groups: 76.3% versus 69.3% (p = 0.367) for OS, and 74.5% versus 69.7% (p = 0.473) for RFS. High-risk ELN stratification and the presence of ≥4 gene mutations were associated with lower OS and RFS in both univariate and multivariate analyses.

Conclusions: AML patients over 55 years of age who received haplo-HSCT after two courses of VEN/AZA therapy had outcomes similar to those who received haplo-HSCT after intensive chemotherapy, suggesting that two courses of VEN/AZA therapy as a bridge to haplo-HSCT are feasible for patients over 55 years old.

Introduction: Ruxolitinib is approved for treatment of myelofibrosis. We evaluated ruxolitinib in patients with anemia (hemoglobin <10 g/dL) or thrombocytopenia (platelet count ≤100 × 109/L) at diagnosis.

Methods: This was a retrospective, secondary analysis of a Cardinal Health Oncology Provider Extended Network medical chart review of adults with myelofibrosis diagnosed between 2012 and 2016 who received first-line ruxolitinib.

Results: 176 patients received first-line ruxolitinib and were included in this analysis. At diagnosis, 120 patients had hemoglobin concentrations <10 g/dL and 59 had a platelet count ≤100 × 109/L. Most patients (95%) with thrombocytopenia also had anemia. Median time of observation after diagnosis was 21.4 months. Among patients with anemia or thrombocytopenia, ruxolitinib dose at end of study was ≥10 mg twice daily (bid) in 88.3% and 83.1%, respectively. Ruxolitinib treatment was ongoing in 76.1% of patients overall and was rarely discontinued for anemia or thrombocytopenia (n = 2 total, 1.1%). Per the treating physician, 79.7% of patients had improved symptoms and 62.7% improved spleen size.

Conclusion: Most patients with myelofibrosis and anemia or thrombocytopenia at diagnosis tolerated and maintained a ruxolitinib dose ≥10 mg bid for nearly 2 years, resulting in clinical benefit. This real-world evidence supports observations from prospective clinical trials of ruxolitinib in myelofibrosis.

Introduction: Treatment-free remission (TFR) has emerged as a new goal in the treatment of chronic myeloid leukemia (CML). TFR is considered a safe intervention because patients who experienced molecular relapse usually responded well to tyrosine kinase inhibitors resumption and regained molecular response quite efficiently. Nevertheless, there have been reports of occurrence of blast crisis during TFR.

Case presentation: We report a case of sudden lymphoid blast crisis in a CML patient who had been in TFR for 21 months without any prior molecular loss. Whole-exon sequencing identified a frameshift mutation of SETD2. In addition, we reviewed the current literature on cases of blast crisis in TFR. Only eleven cases of blast crisis have been reported among thousands of patients who discontinued tyrosine kinase inhibitor (TKI) therapy, including our patient. Of these cases, nine presented with lymphoid blast crisis. Additional gene mutations are frequently observed.

Conclusion: This case, along with others, emphasizes the necessity of implementing a long-term monitoring strategy following TKI discontinuation due to the potential for late onset of blast crisis. Systematic genetic studies in patients failing TFR should be properly carried out to further understand the mechanism and, eventually, to predict or prevent such adverse event in patients in TFR.

Introduction: Treatment for relapsed/refractory AL amyloidosis (AL) is an unmet need. The safety and efficacy of belantamab mafodotin (BLM) in multiple myeloma are known, whereas in AL data are limited.

Methods: We report a multi-center cohort of AL patients receiving BLM, and review all previous data on BLM therapy in AL.

Results: Twelve patients with a median of 3 (range 2-9) prior lines of therapy were included. The overall hematological response rate (ORR) was 75% (9/12), including 5 complete responses. Six of the 10 evaluable patients had organ responses. The median event-free survivals/overall survivals were 22.3 and 28.8 months, respectively. Grade 3 toxicities were mostly infections and keratopathy, occurring in 7/12 (58%). Hematological toxicities were rare. No grade 4/5 toxicities occurred. The review of the previous series reveals BLM provides an ORR of 60-83% with similar rates of corneal toxicity.

Conclusion: BLM, being an off-the-shelf therapy, with acceptable toxicity even in frail patients, may be a valuable option in AL, with a high ORR, and a signal for durable responses and high-quality organ responses.