Leukemia Research Reports最新文献

Introduction

Case report

Discussion

Conclusion

Background

Methods

Results

Conclusions

This case report explains an extraordinary presentation of chronic myeloid leukemia (CML) in a 39-year-old male with a T315I mutation, presenting with acute bilateral hearing loss and imbalance secondary to myeloid blast crisis. Neurological involvement was confirmed through MRI brain and cerebrospinal fluid analysis. Initial treatment with ponatinib and FLAG (fludarabine, cytarabine, G-CSF) regimen showed promise, but complications necessitated discontinuation. The patient's complex clinical trajectory, marked by complications and intolerance to tyrosine kinase inhibitors, highlights the intricate nature of CML blast crisis with T315I mutation management. Recognizing atypical presentations and early mutation analysis are pivotal for tailored treatment strategies.

Real-world data on treatment patterns and outcomes of patients with acute myeloid leukemia unfit for intensive chemotherapy are lacking before the advent of precision medicine in this setting.

Herein, we present the Italian sub-analysis of the CURRENT study in AML patients unfit for first line intensive chemotherapy, evaluating patients’ outcomes between 2015 and 2018.

Among 74 evaluable patients, 62 received systemic treatments (most used therapy was hypomethylating agents), while 12 best supportive care.

Key results include both efficacy and safety data, as well as HCRU and treatment patterns. In first-line therapy cohort median OS was 13.4 months vs. 2.7 months for BSC.

Introduction

Inflammatory bowel disease (IBD) is characterized by chronic inflammation within the digestive tract. In myelodysplastic syndrome (MDS) and aplastic anemia (AA), inflammation in the bone marrow is thought to be one of the causes. There are case reports of MDS or AA combined with IBD. Among these patients, there were several cases who improved hematopoietic function and IBD symptoms after treatment for MDS or AA. However, there are no summarized reports of cases of IBD combined with MDS or AA in Japan. We retrospectively reviewed the reports of IBD combined with MDS or AA in Japan.

Methods

We collected reports on cases of IBD combined with MDS or AA in Japan using Igaku Chuo Zasshi [Ichushi] and PubMed, and reviewed those cases.

Results

We collected 45 cases of IBD combined with MDS or AA. There were 28 and 19 cases of IBD combined with MDS and AA, respectively. Two cases progressed from AA to MDS. Seven cases occurred in the same period. In 21 cases, MDS or AA occurred prior to IBD. In 5 cases, hematopoietic stem cell transplantation restored both IBD and hematopoietic function.

Conclusions

We performed the first literature review of combined cases of IBD and MDS or AA in Japan. Considering the timing of onset and treatment response, there may be common pathologies in IBD and MDS or AA. However, we could not collect treatment details. We plan to construct a nationwide database of complicated cases and elucidate the pathophysiology of these cases.

Introduction

Inherited bone marrow failure syndrome (IBMFS) is characterized by a heterogeneous group of disorders with marked cytopenia in one hematopoietic cell lineage. Aldehyde Degradation Deficiency Syndrome (ADDS) is one of the newly discovered IBMFS, caused by a combined deficiency of ADH5 and ALDH2, which are important for the degradation of endogenously produced formaldehyde. Here, we utilized recent technological advances in data-independent proteomic analysis to establish a diagnostic testing for IBMFS, including ADDS.

Methods

We performed a multi-omics analysis of in-depth proteomic analysis, targeted capture DNA sequencing, and RNA sequencing among patients with IBMFS.

Results

In-depth non-targeted proteomic analysis was performed on 74 samples obtained from 60 patients with IBMFS and 14 healthy controls. We identified eight independent proteomic clusters (C1-C8), with ribosome pathway-related proteins specifically downregulated in C1 and C2, enriched for Diamond-Blackfan anemia and Schwachman-Diamond syndrome, respectively. In the 74 samples, four patients with ADDS showed significantly reduced ADH5 protein expression, whereas the remaining samples showed normal expression. To provide a large-scale rapid screening system in a practical clinical setting, targeted proteomic analysis was performed using a small panel, including ADH5 proteins, in a developmental cohort of 417 samples with hematological malignancies and healthy controls. ADH5 protein expression levels were significantly reduced in ADDS, and its sensitivity and specificity values were 100.0% and 97.5%, respectively.

Conclusions

We have performed the first integrated multi-omics analysis for IBMFS, and demonstrated that clinical applications of targeted proteomic assays would be useful in diagnosing for IBMFS, including ADDS.

Introduction

Allogeneic HSCT (aHSCT) is the only curative treatment, reserved for IPSS-R higher risk (HR, > 3.5) MDS. Molecular data have been integrated within the recently validated IPSS-Mol score system, in order to better predict clinical outcome. However, IPSS-Mol is not still used to guide clinical decisions. We aim to investigate IPSS-Mol significance in a cohort of MDS patients transplanted at our center.

Methods

We retrospectively analyzed a cohort of 74 MDS patients undergoing aHSCT between 2010-2022 at our center according to IPSS-R risk score. All patients received treosulfan-based conditioning regimens and PBSC as stem cell source from matched related/unrelated or haploidentical donors. NGS testing for somatic myeloid mutations was performed retrospectively on cryopreserved marrow cells at diagnosis and MDS risk score was then re-calculated according to IPSS-Mol.

Results

27 patients (36%) were lower risk (LR) at diagnosis and underwent aHSCT for disease progression. All the other patients were HR (IPSS-R > 3.5) and received aHSCT as upfront or consolidation treatment. At least one oncogenic mutation was found in 86.5% of cases by NGS testing. With IPSS-Mol 10 LR patients (37%) were re-stratified as HR (of note, 6/12 patients with intermediate IPSS-R ≤ 3.5), while 7 HR patients (15%) were re-stratified as LR.

Conclusions

aHSCT remains the only curative strategy in HR MDS. NGS testing and application of IPSS-Mol allow to better prognosticate MDS, mostly in patients with LR MDS and specifically in intermediate risk (≤3.5) group. This could help in guiding treatment and specifically optimizing the use of aHSCT in MDS.