Leukemia Research Reports最新文献

Introduction

The prognosis of TP53 biallelic-mutated AML/MDS is severely poor. Azacitidine, venetoclax combination therapy (Aza/Ven) was shown to be effective and tolerable for AML patients who cannot receive standard chemotherapy and the efficacy even for adverse risk AML is expected.

Methods

We report 3 cases of TP53 biallelic-mutated AML/MDS, successfully bridged to allo-HSCT by Aza/Ven.

Results

Case 1 A 60-year-old male was diagnosed with MDS-MLD with complex karyotypes. TP53 p.V216G mutation (VAF 0.859) was detected by NGS. Because the disease progressed to MDS-EB1, one cycle of Aza/Ven was administered for disease control. No severe side effects happened during Aza/Ven. After allo-HSCT, CR was achieved and maintained for over 6 months. Case 2 A 57-year-old male was diagnosed as MDS-EB1 with complex karyotypes including -17. TP53 p.V216G mutation (VAF 0.733) and DNMT3A p.C497Y mutation were detected by NGS. After two cycles of Aza/Ven, myeloblasts in BM was decreased (9.4%→2.8%) without severe side effects. Although he received allo-HSCT, the disease relapsed. Case 3 A 62-year-old male was diagnosed with MDS-EB2. He has several complications including interstitial pneumonia. Although he received two cycles of Aza single therapy, the disease progressed. BM analysis revealed the complex karyotypes, including -17. TP53 p.R241 mutation (VAF 0.88) was detected by NGS. Thus, his treatment was switched to Aza/Ven. After two cycles of Aza/Ven, the disease did not progress, and no severe side effects were seen. He has just received allo-HSCT.

Conclusions

Aza/Ven could be an effective treatment option as a bridging therapy toward allo-HSCT even in TP53 biallelic-mutated AML/MDS cases.

AMeD syndrome is characterized by aplastic anemia, mental retardation, short stature, and microcephaly and is caused by digenic mutations in the aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 5 (ADH5) genes. We have successfully performed hematopoietic stem cell transplantation in two patients with AMeD syndrome and isochromosome 1q. AMeD syndrome with myelodysplastic syndrome or acute myeloblastic leukemia generally has a poor prognosis; however, early diagnosis may improve treatment response. Although the gain of 1q has been considered as a form of early clonal evolution in Fanconi anemia, it may be an equally important finding observed in AMeD syndrome.

Olaparib is (ADP‐ribose) polymerase inhibitor (PARPi), which stops the repair of single-stranded DNA breaks. This leads to the death of cancer cells with BRCA1/BRCA2 mutations or homologous recombination deficiency. Since being approved by the FDA in 2023 for treating castrate-resistant prostate cancer (CRPC), there have been some reports of myelodysplastic syndrome (MDS) and acute leukemia linked to PARP inhibitor use for ovarian, breast, pancreatic and breast cancers, there have been no reports of aplastic anemia after receiving PARPi therapy. This case report describes a 75-year-old man with BRCA2-positive metastatic castrate-resistant prostate cancer who developed aplastic anemia after taking olaparib.

Background

Chronic Myeloid Leukemia is characterized by the presence of the Philadelphia Chromosome (Ph) which contains the BCR::ABL1 fusion gene that occurs due to a reciprocal translocation between chromosomes 9 and 22. This accounts for up to 15 % of all adult leukemias [1]. Most patients treated with first line tyrosine kinase inhibitor (TKI) imatinib achieve durable response but may undergo relapse at some stage [2]. The most important mechanism that may confer imatinib resistance is point mutation within BCR::ABL kinase domain. Other generation ABL tyrosine kinase inhibitors such as dasatinib, nilotinib, bosutinib and ponatinib help to overcome imatinib resistance [3]. Sensitivity of the patient to each of the above TKIs depends upon the individual candidate mutation present. Thus, it is important to perform mutation analysis for effective therapeutic management of CML patients once they show imatinib resistance. We used direct sequencing to identify the different types of mutations responsible for resistance of imatinib treatment from north India.

Methods

In this study, the patient resistance for the imatinib were analyzed for BCR::ABL kinase domain mutation by direct sequencing and the detected mutations along with their percentage prevalence were reported.

Results

329 patients with CML-CP were analyzed for BCR::ABL kinase domain mutation. Total 66 (20.06 %) patients out of 329 had mutation in at least one of the domains of BCR::ABL conferring resistance to different generations of TKI. Mutations in BCR::ABL kinase domain was observed in different domain of BCR::ABL. ATP binding P-Loop (42.42 %), Direct binding site (36.36 %), C-Loop (10.60 %), A-Loop (6.06 %), SH2 contact (3.03 %), SH3 contact (1.51 %).

Conclusion

Total 20.06 % patients (66/329) show mutation in at least one of the structural motifs of BCR-ABL kinase domain, which further confer the resistance to a particular generation of TKI.

Bartonelloses are diseases caused by Bartonella sp., transmitted to humans by blood sucking arthropod vectors. Clinical presentations include bacillary angiomatosis, cat scratch disease and atypical forms. We performed a review of cases of bartonelloses and hematological malignancies published in HIV-negative patients. Terms used were Bartonella or Bacillary Angiomatosis and Leukemia, Lymphoma, Multiple Myeloma, or Cancer. Fifteen cases met our criteria. Clinical presentations included bacillary angiomatosis, chronic fever, chronic lymphadenopathy, osteomyelitis, neuroretinitis, chronic anemia and hepatosplenic peliosis. Fourteen patients were asymptomatic after antibiotic therapy, and one died before antibiotic treatment. Clinicians should be suspicious of Bartonella sp. infections in immunocompromised patients.

Background

Acute lymphoblastic leukemia represents 20% of acute leukemias in adults. Currently, there is limited data in Chile regarding the clinical, cytogenetic, and prognostic characteristics of this condition.

Methods

This is a retrospective, observational, and descriptive study of 67 patients treated for acute lymphoblastic leukemia at the Arturo Lopez Perez Foundation between 2018 and 2021. The main objective is to evaluate epidemiological and clinical characteristics, as well as identifying factors associated with improved overall survival and/or progression-free survival.

Results

88% of the cases were B-lineage, mainly the common B phenotype. Cytogenetic analysis was performed in less than 50% of the patients, with lower yield than expected according to the literature. Molecular testing was performed in 86.5% of the patients, with the most frequent alteration being BCR-ABL. No study was performed to search for Ph-like abnormalities. The rate of complete response after induction was 83.3%, the majority of patients having negative minimal residual disease. Only 12% of the patients received consolidation with allogenic bone marrow transplant. At 2 years, the overall survival was 69% and the progression-free survival was 59%.

Conclusion

The results in terms of overall survival and progression-free survival are similar to those reported in the literature. Important diagnostic gaps prevent adequate prognostic characterization. Allogeneic consolidation transplantation was performed in a lower percentage than expected, highlighting the national deficit in access to this treatment.

Noonan syndrome is a genetic disorder frequently caused by PTPN11 mutations. Patients with Noonan syndrome are characterized by facial dysmorphism, short stature and congenital heart defects and they have a reported predisposition to malignancies such as leukemia, and solid and central nervous system tumors. Here, we report a case of a 14-year-old boy with Noonan syndrome treated for T-cell acute lymphoblastic leukemia who presented with 2 concomitant abnormalities: cerebral abscess and high grade glioblastoma. This exceptional association exhibits to a poorer prognosis and may sometimes delay the diagnosis and therefore the therapeutic intervention.

Chimeric antigen receptor (CAR) T-cells have unveiled a promising therapeutic horizon for relapsed/refractory multiple myeloma (R/R MM). Nevertheless, immune impairment induced by cellular therapies, previous treatments and MM itself could promote infectious events. COVID-19 could evolve into a life-threating infection in R/R MM patients who often have suboptimal responses to SARS-CoV-2 vaccines. Here, we describe a case of severe and long-lasting COVID-19 pneumonia after CAR T-cell therapy for R/R MM requiring a complex clinical management. Long-term infectious complications in MM patients undergoing CAR T-cells should be taken into consideration as they could counteract the efficacy of this new treatment.

Intravascular large B cell lymphoma (IVLBCL) is exceedingly rare and difficult to diagnose. We describe a case of IVLBCL in a 56-year-old male which was identified after recurrent strokes. Right partial nephrectomy was then performed which demonstrated renal oncocytoma and IVLBCL. Chemotherapy was initiated with standard R-Hyper-CVAD which included intrathecal methotrexate and cytarabine. R-CHOP is largely considered the treatment of choice in IVLBCL, however low doses of chemotherapy in this regimen do not cross the blood brain barrier like in R-Hyper-CVAD. The patient achieved complete remission after completion of treatment and has remained in remission for 5 years after diagnosis.

A 63-year-old woman presented with plaques covering 60 % body-surface-area and leonine facies. Blood work showed no diagnostic aberrancies. Skin biopsy contained a malignant CD4+/CD56+ mononuclear cell population concerning for blastic plasmacytoid dendritic cell neoplasm. A later bone marrow biopsy confirmed AML with KMT2A::MLLT10 fusion detected by next-generation sequencing (NGS). This patient's LC preceded blood and marrow based symptoms of AML. NGS of the initial skin biopsy should be considered as part of diagnostic guidelines in cases with LC in the differential as this may have led to earlier diagnosis in this case and future cases.