Leukemia Research Reports最新文献

Introduction

Germline DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features of DDX41-mutated MNs remain unclear.

Methods

Here, we enrolled a total of 346 patients with DDX41 pathogenic/likely pathogenic (P/LP) germline variants and/or somatic mutations from 9,082 MN patients, together with 525 first-degree relatives of DDX41-mutated and wild-type (WT) patients. We performed a comprehensive characterization of DDX41-mutated MNs.

Results

P/LP DDX41 germline variants explained ∼80% of known germline predisposition to MNs in adults. These risk variants were 10-fold more enriched in Japanese MN cases (n=4,461) compared to a Japanese general population (n=20,238). This enrichment of DDX41 risk alleles was much more prominent in male than female (20.7 vs. 5.0). P/LP DDX41 variants conferred a large risk of developing MNs, which was negligible until 40 years old but rapidly increased to 49% by 90 years of age. DDX41-mutated MDS patients rapidly progressed to AML, which was, however, confined to those having truncating variants. Co-mutation patterns at diagnosis and at progression to AML were substantially different between DDX41-mutated and -WT cases, where none of the co-mutations affected clinical outcomes. Even TP53 mutations made no exceptions and their dismal effect, including multi-hit allelic status, on survival was almost completely mitigated by the presence of DDX41 mutations. Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System (IPSS-R/M).

Conclusions

Our findings establish that DDX41-mutated MDS defines a unique subtype of MNs that is distinct from other MNs.

Introduction

There is uncertainty about how choice of therapy in myelodysplasia (MDS), low-blast count AML (LB-AML) or chronic myelomonocytic leukaemia (CMML) is made by patients, physicians and carers when >1 treatment type is available. This study's primary objective is to compare patients’ treatment preference using the patient ‘treatment preference in myelodysplasia questionnaire’ (pTPMQ). Secondary objectives include evaluation of preference by carers (cTPMQ), and clinicians (mTPMQ).

Methods

This phase 3b, open-label, multi-centre study (NCT05883956), with sites in Australia and New Zealand, will compare preference between oral decitabine/cedazuridine (Treatment A) and SC AZA (Treatment B). The study design includes 28 days of screening, four continuous 28-day cycles of study treatment, and a follow-up period with two 28-day cycles of continued therapy. Patients (N=42) will be randomised to two balanced treatment sequences: ABBA or BAAB (Figure 1). Patients will express a preference twice in the study, first after completing Cycle 2, then after completing Cycle 4. This will be assessed via the pTPMQ. Clinician and carer preference will also be assessed.

Results

Trial to be activated in Australia and New Zealand, with first patient recruited in December 2023. We will report the primary and secondary objectives. Exploratory objectives including treatment discontinuation rates, quality of life and safety of SC AZA and oral decitabine/cedazuridine will also be reported.

Conclusions

This study aims to address an evidence gap in the comparison of patients’, carers’ and clinician's preference between an oral and a parenteral treatment, preference strength, and the reasons for it.

Introduction

Myelodysplastic syndrome (MDS) represents a group of malignant clonal hematological disorders characterized by dysplasia in one or more hematopoietic lineages in the bone marrow, leading to cytopenias and an increased risk of developing acute myeloid leukemia. The only treatment option that has shown benefit in PFS and OS for high-risk MDS is 5-azacitidine (5-AZA).

Methods

The aim of this study was to determine the impact of 5-AZA on the treatment outcome of patients with high-risk MDS from January 1, 2013, to December 31, 2021, at the Clinical Hospital Merkur in Zagreb, Croatia. Retrospective analysis was performed on data from patients with high-risk MDS. The study included 38 patients (M:F=25:13), at time of study conclusion, 34 patients died. Laboratory data and overall survival of the patients were analyzed. Data were analyzed using the Kaplan-Meier method, Log-rank test, and Mann-Whitney U test.

Results

A longer overall survival was observed in patients treated with more than 12 cycles of 5-AZA. The median survival of the group receiving more than 12 cycles of 5-AZA was 24 months, while the median survival of patients receiving less than 12 cycles was 11 months (p=0.023). Higher creatinine levels at diagnosis and lower LDH levels before the first cycle were observed in the group of surviving patients.

Conclusions

The results of this study highlight the efficacy of 5-AZA in the first-line treatment of high-risk MDS patients, with a statistically significant difference in overall survival observed in group of HR MDS patients receiving at least 12 cycles of 5-AZA.

Posterior reversible encephalopathy syndrome (PRES) has rarely been described in myeloma, but chemotherapy is a known risk factor. We report 3 patients with myeloma who developed PRES, and analyzed them with 13 published cases, mostly women. The most frequent causative agents were proteasome inhibitors and autologous stem cell transplantation. Risk factors were frequently associated: hypertension, infection or renal failure. Symptoms included headache, blurred vision, altered mental status, seizures. Most patients experienced rapid clinical recovery, without relapse even after resuming treatment. Although rare, we must remain vigilant about PRES in myeloma patients. Stricter control of blood pressure could limit its occurrence.

B/T mixed phenotype acute leukemia (MPAL) is a rare aggressive leukemia. Three cases of B/T MPAL were identified with comprehensive immunophenotypic, cytogenetic, and molecular studies. T-lineage predominant B/T MPAL shares a genetic signature with T-ALL whereas B/T lineage co-dominant B/T MPAL lacks such a T-ALL signature. All three patients were treated with lineage-matched-ALL therapy and alive at the last follow-up. Our study is the first to demonstrate molecular heterogeneity within B/T MPAL in a context of an immunophenotype of T-lineage versus B-lineage predominance. The implication of such a phenotype-genotype association on diagnostic classification is briefly discussed.

Acute myeloid leukemia (AML) patients undergoing induction chemotherapy receive transfusion support to manage severe cytopenias and associated sequelae. Jehovah's Witness (JW) patients typically decline transfusion of most or all blood products. This can lead to exclusion of JW patients from otherwise life-saving treatments due to safety concerns. We present two cases demonstrating the successful induction of JW patients without the need for red cell or platelet transfusion support; the first, an older AML patient induced with azacitidine & venetoclax; the second, a patient with acute promyelocytic leukemia induced using arsenic trioxide and all-trans retinoic acid. Both patients required modifications to the induction regimens to accommodate their wishes. These cases support growing evidence that selected JW patients with AML can be successfully treated using appropriate accommodations.

In the context of chronic lymphocytic leukemia (CLL), Hyperviscosity Syndrome (HVS) typically arises from hyperleukocytosis, although it infrequently stems from IgM hyperparaproteinemia. We present a distinctive case of HVS induced by IgM hyperparaproteinemia in a patient experiencing relapsed CLL, marked by bulky disease and cytopenias upon progression. The patient exhibited new symptoms, including headache, dizziness, and confusion. Laboratory analysis revealed an elevated total protein level, and serum electrophoresis identified an elevated M spike at 4 g/dL with IgM on immunofixation. Suspecting HVS, prompt plasmapheresis was initiated, resulting in symptom resolution within two days.

A comprehensive literature review suggests that CLL patients with an elevated IgM level often face a poor prognosis, though HVS symptoms are not commonly observed. Our case underscores the significance of swiftly identifying HVS when IgM hyperparaproteinemia is detected in CLL patients. Notably, our patient not only achieved successful treatment for the acute presentation but also initiated second-line therapy for relapsed disease. In conclusion, effective management and stabilization of CLL patients with IgM-associated HVS are attainable, emphasizing the crucial role of prompt recognition.

This case report discusses a 95-year-old man diagnosed with two types of lymphomas. He was hospitalized for erysipelas in September 2018. The lymph node revealed high-grade B-cell lymphoma with Myc and Bcl-2 rearrangement. Bone marrow biopsy revealed hairy cell leukemia, a rare type of indolent B-cell lymphoma. We found that the bone marrow and left inguinal lymph node were non-homologous. There are no known reports of super-aged patients with two types of lymphoma simultaneously. The toxicity of R-CHOP in elderly people limited its usage, so we first chose rituximab. However, this approach was not successful. We then considered the Bruton tyrosine kinase (BTK) inhibitor, but its use was limited due to high blood pressure. Finally, we administered venetoclax, which the patient took for 2 years. The results of the routine blood examination were close to normal and no enlarged superficial or abdominal lymph nodes were observed.This is the oldest reported patient with two types of malignant lymphatic diseases. Additionally, this rare case suggests that targeted therapy can be more effective and safe for super-aged individuals. To summarize, a 95-year-old man diagnosed with two types of lymphomas, high-grade B-cell lymphoma and hairy cell leukemia, was successfully treated with venetoclax after other treatments failed. This case suggests that targeted therapy can be effective and safe for super-aged patients with multiple malignant lymphatic system diseases.

Orbital plasmacytoma is rare and has only been reported in the context of the initial diagnosis of multiple myeloma. Moreover, isolated orbital plasmacytoma without any signs of multiple myeloma is extremely rare.

We report the case of a 59-year-old female patient diagnosed with IgA Kappa multiple myeloma. It was stage I ISS (International Staging System) and stage I R-ISS (Revised ISS). According to the Tunisian national protocol, the patient was included in the standard-risk group and was eligible for four cycles of CTD (Cyclophosphamide, Thalidomide, Dexamethasone) followed by autologous stem cell transplantation. Taking into account the partial response after the CTD cycles, the patient has benefited from two VTD cycles (Bortezomib, Thalidomide, Dexamethasone). Thus, complete remission was obtained. The patient refused autologous stem cell transplantation. Therefore, maintenance treatment based on Thalidomide only was started and received over a twelve-month period.

Five months after the end of maintenance treatment, she reported frontal headaches that were resistant to symptomatic treatment, with ptosis in the right eye in physical examination. Brain MRI revealed the presence of a right cranio-orbital tissue mass with intra-orbital and extra-axial cerebral components. The mass measured 32/36 mm on axial sections and 47 mm in height. The patient underwent a complete resection of the cranio-orbital mass with cranioplasty. The histopathological examination of the mass with Immunohistochemistry staining confirmed the diagnosis of orbital plasmocytoma.

An update of the multiple myeloma assessment did not reveal any biological, cytological or radiological signs in favor of multiple myeloma. Therefore the diagnosis of isolated orbital plasmacytoma without signs of multiple myeloma was made.

Post-operative brain MRI showed complete disappearance of the right cranio-orbital tissue lesion. There was only a persistent meningeal enhancement of the dura mater at the surgical site, suggestive of post-operative changes. The patient was then referred for cranio-orbital radiotherapy.