EJHaem最新文献

Background

Multiple myeloma (MM) is a genetically heterogeneous malignancy in which cytogenetic abnormalities critically influence prognosis. The prognostic significance of 17p gain/amplification (17p+), particularly relative to del(17p) and the high-risk 1q21 gain/amplification (1q21+), remains insufficiently defined.

Methods

We retrospectively analyzed 125 MM patients treated at a single center between 2015 and 2024. Cytogenetic profiles were assessed using fluorescence in situ hybridization (FISH). Kaplan–Meier curves and Cox proportional hazards models evaluated the impact of 17p+ on progression-free survival 1 (PFS1), time to next treatment (TTNT), and overall survival (OS).

Results

Compared with del(17p), 17p+ was associated with significantly longer PFS1 (HR 0.21, p < 0.01), TTNT (HR 0.18, p < 0.01), and OS (HR 0.25, p < 0.05). In patients receiving proteasome inhibitor–based therapy or not undergoing autologous stem cell transplantation, 17p+ remained favorable for PFS1 (HR 0.20, p < 0.05, HR 0.21, p < 0.01). Multivariate Cox models confirmed 17p+ as an independent protective factor for PFS1 (HR 0.08), TTNT (HR 0.07), and OS (HR 0.02) (all p < 0.001). Among patients with 1q21+, co-occurrence of 17p+ improved PFS1 (HR 0.47) and TTNT (HR 0.36) (p < 0.05), though no significant OS benefit was observed.

Conclusions

17p+ is associated with markedly improved clinical outcomes in MM and may partially mitigate the adverse prognostic impact of 1q21+. These findings highlight the relevance of 17p+ in cytogenetic risk stratification and personalized treatment strategies and support further validation in multicenter cohorts.

Trial Registration

The authors have confirmed clinical trial registration is not needed for this submission.

Background

IDH mutations are found in 15%–20% of acute myeloid leukemia (AML). Recent evidence suggests that IDH mutation subtypes may respond differently to intensive chemotherapy. We evaluated blast clearance patterns, remission outcomes, and overall survival (OS) in AML patients with IDH2 R140, IDH2 R172, and IDH1 R132 mutations to assess differences in treatment response.

Methods

We retrospectively reviewed AML patients diagnosed at Mayo Clinic, Rochester (2016–2023) with NGS data and treated with intensive chemotherapy (7+3 or CPX-351). Bone marrow blasts were assessed at diagnosis, mid-induction, and end-of-cycle; blast clearance was defined as < 5%. Composite remission (CRc) included CR/CRi per ELN 2022. IDH2 responders were classified as early (after Cycle 1) or late (≥ 2 cycles). Blast reduction was calculated as log₁₀ (diagnosis blasts/end-induction blasts) and normalized per day. OS was measured from diagnosis.

Results

Among 381 patients, 31 had IDH2 mutations (23 R140, 8 R172) and eight had IDH1 R132. Baseline blasts were similar. Mid-cycle blasts were lower in R140 versus R172 (4% vs. 10%), with higher clearance (68% vs. 38%). End-induction blasts were lower in R140 versus R172 (2% vs. 4%) with higher clearance (100% vs. 75%). IDH1 and IDH2 showed similar clearance patterns. Log₁₀ analyses showed deeper and faster blast reduction in R140 versus R172, with comparable kinetics between IDH1 and IDH2. OS did not differ across subtypes. Early CRc in IDH2-mutated patients was associated with numerically longer OS.

Conclusion

IDH2 R140 demonstrated faster blast clearance than R172, while remission and survival were similar across IDH subtypes.

Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.

Background

Aquagenic pruritus (AP) is a common and distressing symptom in myeloproliferative neoplasm (MPN) patients.

Methods

This study assessed cytoreductive therapy effectiveness using data from 489 patients in the OBENE Observatory (NCT02897297). AP severity was tracked regularly after diagnosis.

Results

Ruxolitinib and hydroxycarbamide reduced AP by 52.9% and 60.7%, respectively, but 61.4% still experienced persistent symptoms. Anagrelide and pegylated interferon were less effective and occasionally worsened AP. No correlation was found between full hematological response and symptom relief.

Conclusion

Despite treatment, AP remains prevalent, highlighting the need for targeted symptom management.

Trial registration: ClinicalTrials.gov identifier: NCT02897297

Background

Severe congenital neutropenia (SCN) is commonly treated with granulocyte colony-stimulating factor (G-CSF) to reduce neutropenia and the associated risk of infections. Pegfilgrastim, a long-acting form of G-CSF, provides the benefit of less frequent dosing; however, its application in SCN has not been extensively studied. This study aims to assess the long-term safety and effectiveness of transitioning SCN patients from standard G-CSF therapy to pegfilgrastim.

Methods

We followed eight patients with severe congenital neutropenia (five males, average age 17.8 years) who had been on G-CSF treatment for at least five years. They were switched to pegfilgrastim injections (3–6 mg every 7–14 days). Dosing was individualized to obtain an absolute neutrophil count (ANC) above 1000/µL in all patients. Over a five-year follow-up under treatment with pegfilgrastim, patients were evaluated for ANC levels, infection frequency, adverse effects, and quality of life using the Functional Assessment of Cancer Therapy-Neutropenia (FACT-N) questionnaire. In addition, yearly abdominal ultrasounds, bone density every two years, and genetic screening for RUNX1 and the G-CSF receptor mutations were performed.

Results

Pegfilgrastim significantly improved ANC levels compared to prior G-CSF treatment (p = 0.008). Quality of life (QoL) significantly improved in six patients (p = 0.016). Varying maintenance dosages were required based on the therapeutic response. Bone pain was common, leading to discontinuation in one patient. Two patients developed hip osteopenia, and one showed progressive splenomegaly. Hospitalization rates and infection frequency remained unchanged. Oral ulcers were decreased overall.

Conclusion

Pegfilgrastim can be used as an alternative to daily G-CSF in SCN, providing stable ANC and QoL improvements with individualized dosing. Larger studies are warranted to evaluate its long-term safety and efficacy.

Clinical trial registration

This trial is registered at https://irct.behdasht.gov.ir/ in Iranian Registry of Clinical Trials (IRCT) # IRCT20150125020786N3.

DDX3X::MLLT10¸ which arises from t(X;10)(p11.4;p12.31), is infrequently observed in adult acute myeloid leukaemia (AML). The clinical and pathological characteristics are also not well characterised, detailed in only two cases published to date. This third case reports the fusion gene in a 27-year-old female with acute myelomonocytic leukaemia (AMML) with refractoriness to multiple lines of chemotherapy. Collectively, these cases highlight the genomic heterogeneity of this rare entity, as well as significant unmet clinical needs due to the poor prognosis and chemoresistance observed. These findings may inform future iterations of AML classification and prognostication in adults.

Background

Multiple myeloma (MM) is primarily a disease of the elderly; data on young patients are limited.

Aim

To evaluate the clinical characteristics and outcomes of MM patients aged $�\le$ 40 years.

Methods

We retrospectively analyzed newly diagnosed MM patients aged ≤ 40 years between 2013 and 2021.

Results

Of 1980 patients screened, 110 (5.5%) were ≤ 40 years (median age 36). Hypercalcemia, renal dysfunction, anemia, and bone lesions (CRAB) were seen in 11.9%, 17.3%, 42.7%, and 92.6% of patients, respectively. More than one-third had International Staging System (ISS) Stage III, 20.8% had HR cytogenetics and 21.6% had light chain disease (LCD). Macrofocal multiple myeloma (MFMM) seen in 31% of patients. Bortezomib–cyclophosphamide–dexamethasone (VCd) and bortezomib–lenalidomide–dexamethasone (VRd) were the common induction regimens. 26.8% received autologous stem cell transplantation (ASCT). At a median follow-up of 44.2 months, the median progression free survival (mPFS) was 45.9 months. 1-, 3-, and 5-year PFS rates were 84.9%, 62.2%, and 38.6% respectively. A 3-year PFS was 83.9% with proteasome inhibitor (PI) and 78.7% with immunomodulatory drug (IMiD) as maintenance therapy. A 5-year PFS was superior with ASCT (58.5%) versus without (27.8%). Poor PFS was associated with anemia, renal dysfunction, poor performance status, high risk cytogenetics, VCd (vs. VRd), poor response to induction chemotherapy, no maintenance therapy and no ASCT.

Conclusion

Young MM patients had encouraging survival outcomes despite resource limitations and limited access to novel agents.

Trial Registration

The authors have confirmed clinical trial registration is not needed for this submission.

Introduction

Specific granule deficiency type II (SGD2) is a rare heterogeneous congenital disease characterized by early-onset life-threatening infections. SGD2 is caused by autosomal recessive mutations in the SMARCD2 gene.

Methods

Prenatal screening in our patient revealed a novel homozygous nonsense mutation in SMARCD2 (c.208C>T, p.Gln70*).

Results

Postnatally, she suffered from infections, pneumonia, cholestasis, mucocutaneous bleeding, and dysmorphic features, including clubfoot. Hematological findings included neutropenia, monocytosis, myelodysplasia, and thrombocytopenia. In contrast to previous cases, this patient presented with dysplasia of all myeloid lineages, including hypogranular neutrophils, pseudo Pelger–Huët, macrothrombocytes, bilobular monocytes, and dysplastic erythroblasts. Due to the severity of her condition, she passed away after 1.5 months.

Conclusion

This report illustrates the role of SMARCD2 in hematopoiesis and provides an overview of all previously described SGD2 patients.

Trial Registration

The authors have confirmed clinical trial registration is not needed for this submission.

Background

The cumulative incidence and risk of cytomegalovirus (CMV) reactivation in patients with relapsed/refractory multiple myeloma (RRMM) receiving elranatamab remain unclear.

Methods

We retrospectively analyzed RRMM patients treated with elranatamab to assess cumulative incidence and risk factors for CMV reactivation.

Results

Among 32 patients, the 6-month cumulative incidence of CMV reactivation was 37.3%. High CMV immunoglobulin G (IgG) titers were significantly associated with CMV reactivation (57.9% vs. 9.1%, p = 0.012), while prophylactic immunoglobulin reduced CMV reactivation risk within high CMV IgG group.

Conclusion

Baseline CMV IgG titers may help guide risk-adapted monitoring and prevention strategies during elranatamab therapy.