International Journal of Hematology最新文献

Inotuzumab ozogamicin (InO), a CD22-directed antibody conjugated to calicheamicin, has demonstrated excellent efficacy in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). It has been used for patients with relapsed or refractory BCP-ALL as a bridge to allo-HCT. Children with Down syndrome (DS) have an increased risk of BCP-ALL and higher rates of relapse and toxicity, including treatment-related mortality. Although allo-HCT is potentially curative for relapsed or refractory ALL, post-transplant leukemic relapse rates and transplant-related mortality are dismal in patients with DS-ALL, which results in less frequent use of allo-HCT in this group than in the non-DS population. Therefore, novel and less toxic therapeutic strategies are required to improve outcomes. Here we report the case of a child with DS who was diagnosed with a second relapse of BCP-ALL and has maintained complete remission through regular single-agent InO therapy. Single-agent maintenance using InO can be a good option to avoid subsequent relapse in patients with relapsed or refractory BCP-ALL who cannot proceed to allo-HCT and require less-toxic treatments.

The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of chronic myeloid leukemia (CML), significantly improving patient prognosis. Asciminib, a novel specifically targeting the ABL myristoyl pocket inhibitor, has shown promise for CML patients unresponsive or intolerant to traditional TKIs. However, its use in hemodialysis patients remains underexplored. We present a case of a 71-year-old man with CML undergoing hemodialysis, successfully treated with asciminib. Initial treatment with bosutinib was effective but later failed, prompting a switch to asciminib. The patient achieved a major molecular response within 2 months without adverse effects. Pharmacokinetic analysis revealed significant drug clearance during hemodialysis, necessitating dosage adjustments. This case highlights the potential of asciminib in managing CML in hemodialysis patients, emphasizing the need for individualized treatment plans and close monitoring. Further studies are warranted to establish comprehensive guidelines for asciminib use in this unique patient population.

Although tyrosine kinase inhibitors (TKIs) have improved the prognosis of chronic myeloid leukemia (CML), some patients do not respond to TKIs. We evaluated 21 patients with CML treated with asciminib, which is effective in heavily pretreated patients. The median age was 63 years (range 25-82). Fourteen patients (67%) had been treated with at least three TKIs (range 2-5 prior lines). The switch to asciminib was due to intolerance in 14 patients (67%) and failure in seven patients (33%). The median duration of asciminib exposure was 237 days. With a median follow-up of 273 days, three patients (14%) discontinued asciminib due to failure and two (10%) due to intolerance. Among the 20 evaluable patients, the cumulative rates of molecular response with a two-log reduction, major molecular response, and four-log reduction were 80%, 60%, and 15%, respectively. The six-month event-free survival rate was 74.7%. The most frequent adverse events were liver dysfunction (29%), elevated amylase levels (14%), and renal dysfunction (10%). No patient experienced cardiovascular events. Six patients (29%) experienced cross-intolerance to asciminib, a rate similar to that for previous TKIs. Our study supports the efficacy and tolerability of asciminib in heavily pretreated CML patients in real-world settings.

Introduction: Prolonged activated partial thromboplastin time (aPTT) in plasma samples requires quick and accurate differential diagnosis. We developed two methods using clot waveform analysis (CWA) for plasma samples with prolonged aPTT, particularly for factor (F)VIII deficiency. One method estimates FVIII activity (FVIII:C) using CWA without measuring FVIII:C by template matching. The other utilizes CWA in the mixing test to quickly differentiate FVIII deficiency (FD), FVIII inhibitor (Inh), and lupus anticoagulant (LA).

Aim: To establish a more accurate system for differential diagnosis of aPTT prolongation, including FIX deficiency, by combining a CWA-based mixing test and template matching.

Methods: Samples with FD (n = 96), LA (n = 19), and Inh (n = 28) were incubated with normal plasma. FD, LA, and Inh were differentiated using a mixing test, followed by CWA-based template matching.

Results: In the mixing test, sensitivity for FD, Inh, and LA was 100%, 93%, and 100%, and specificity was 96%, 100%, and 100%. Samples with FIX inhibitor (> 0.6 BU/mL) were differentiated as the inhibitor sample. In template matching, almost all severe hemophilia A and B were judged as the respective severe types.

Conclusion: This novel CWA-based measurement system could aid in differential diagnosis of prolonged aPTT.

We herein report a rare case of acute myeloid leukemia (AML) with t(11;12)(p15;q13) and NUP98::RARG, which seems to be involved in the development of AML. The morphological features were similar to those of classic acute promyelocytic leukemia (APL), but unlike classic APL, this leukemia was resistant to treatment with all-trans retinoic acid (ATRA). We decided to use standard chemotherapy for AML with monitoring of minimal residual disease (MRD) by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for NUP98::RARG mRNA. Although MRD disappeared after induction chemotherapy, it later reappeared, and hematological relapse occurred during subsequent chemotherapies. The patient received haploidentical hematopoietic stem cell transplantation while not in remission and achieved a second molecular remission. However, relapse occurred 4 months after transplantation. The specific mechanism of ATRA resistance in this unique case of AML remains unclear, and no standard treatment has been determined. This is the first case report of AML with NUP98::RARG rearrangement in Japan. Qualitative RT-PCR analysis for NUP98::RARG mRNA was helpful for the accurate diagnosis and evaluation of MRD to choose an adequate treatment for this type of AML.

Peripheral T cell lymphoma (PTCL) is an aggressive and highly heterogeneous lymphoma with a bleak prognosis, highlighting the urgent need for an effective biomarker to guide therapeutic strategies. Ovarian tumor domain-containing 7B (OTUD7B) has been shown to have a critical function in the progression of cancers. However, the prognostic significance of OTUD7B in PTCL remains unexplored. In this study, we demonstrated for the first time that PTCL patients with low expression of OTUD7B had shorter progression-free survival (PFS) and overall survival (OS). In addition, OTUD7B knockdown promoted chemoresistance to doxorubicin in PTCL cell lines, and led to increased translocation of p52 from the cytoplasm to the nucleus. Inhibition of non-canonical NF-κB partially restored the sensitivity of PTCL cells to doxorubicin. Remarkably, 5-azacytidine and cytarabine upregulated the expression of OTUD7B and exhibited a synergistic anti-lymphoma effect in PTCL. In summary, our study confirmed the prognostic role of OTUD7B in PTCL and the promising therapeutic potential of combining 5-azacytidine or cytarabine and doxorubicin for PTCL treatment.

DREAMM-11 (NCT03828292) was a Phase 1, open-label, dose-escalation study of belantamab mafodotin in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In Part 1, belantamab mafodotin monotherapy (2.5 or 3.4 mg/kg every 3 weeks) was tolerated and demonstrated clinical activity and a manageable safety profile. Part 2 investigated the tolerability, safety, clinical activity and pharmacokinetics of belantamab mafodotin (2.5 mg/kg on Day [D]1 of each 21-day cycle) plus bortezomib and dexamethasone (Arm A; N = 3) or belantamab mafodotin (2.5 mg/kg on D1 of the first 28-day cycle; 1.9 mg/kg on D1 of subsequent cycles) plus pomalidomide and dexamethasone (Arm B; N = 4) in Japanese patients with RRMM and ≥ 1 prior line of therapy. No dose-limiting toxicities were reported in Arm A; 1 (non-serious liver injury) was reported in Arm B. Safety profiles of each treatment combination were consistent with those of the individual agents and those in Western populations. An overall response was achieved by 3/3 (100%) patients in Arm A and 2/4 (50%) in Arm B. Pharmacokinetics were consistent between Japanese and Western populations. The clinical pharmacokinetics, safety, and efficacy data from this study can inform future use of belantamab mafodotin plus bortezomib/pomalidomide and dexamethasone in Japanese patients with RRMM.

Here, we investigated the clinical significance of NOTCH1 and FBXW7 alterations for adult T-cell leukemia/lymphoma (ATLL) treatment outcomes. NOTCH1 alterations were identified in 37 (14.4%) of 257 patients, of which 33 were single nucleotide variants/insertion-deletions in the PEST domain, and 7 were in the heterodimerization or LIN-12/Notch repeats domains. FBXW7 alterations were observed in nine ATLL patients (3.5%). For patients without allogeneic hematopoietic stem cell transplantation (HSCT), NOTCH1, but not FBXW7, alterations were significantly and independently associated with worse overall survival (median OS 0.5 years, 95% confidence interval [CI] 0.4-0.5 years for 27 patients with NOTCH1 alterations vs 1.8 years, 95% CI 1.3-2.2 years for 170 patients without). Also, for patients receiving mogamulizumab, but not allogeneic-HSCT, NOTCH1, but not FBXW7, alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab 0.4 years, 95% CI 0.3-0.5 years for 12 patients with NOTCH1 alterations vs 1.4 years, 95% CI 0.9-2.0 years for 87 without). In contrast, NOTCH1 alterations had no significant impact on survival of patients who did receive allogeneic-HSCT. Thus, mogamulizumab-containing treatment was unable to overcome treatment refractoriness of ATLL with NOTCH1 alterations. Therefore, patients with NOTCH1 alterations are recommended for allogeneic-HSCT.