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The document discusses the use of chromosomal genomic array testing (CGAT) in adults with newly diagnosed acute lymphoblastic leukemia (ALL) to enhance risk stratification and inform treatment decisions. The study found recurrent chromosomal abnormalities in patients, including deletions and gains in specific genomic loci. While CGAT identified high-risk genetic signatures like IKZF1plus, there was no significant difference in overall survival between patients with IKZF1 alterations and those without. Additionally, ETV6 and ZCCHC7 deletions were associated with adverse prognostic outcomes in adults with ALL. The study suggests integrating CGAT into the initial workup of ALL patients but acknowledges the need for further prospective studies due to the limitations of the retrospective analysis. [Extracted from the article]

Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The alltrans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone. We conducted a three-institution retrospective study, aiming to evaluate the role of shortterm adjuvant chemotherapy in managing moderate DS for patients with low- or intermediate-risk APL initially treated with ATRA/ATO only protocols. We evaluated the difference in incidence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy. 57 low- or intermediate-risk APL patients were retrospectively identified and included for this study; 36 patients received ATRA/ATO only induction treatment, and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy. Similar proportions of patients experienced DS in both groups (66.7% vs. 81.0%, P = 0.246). The median duration of DS resolution in patients receiving ATRA/ATO only was 17 days (n = 23), and in patients receiving combination therapy was 8 days (n = 16) (P = 0.0001). The lengths of hospital stay in patients receiving ATRO/ATO only was 38 days (n = 7), and in patients receiving combination therapy was 14 days (n = 17) (P = 0.0007). In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and the length of hospital stay during APL induction treatment. [ABSTRACT FROM AUTHOR]

Central Nervous System Lymphoma (CNSL) can be primary (PCNSL) or secondarily metastatic from systemic lymphoma (SCNSL). Genomic testing of the resected CNS lymphoma showed PD-L1 and PD-L2 amplification and a high overall tumor mutational burden. CNS lymphomas have a significant rate of relapse after front-line methotrexate-based therapy and second-line treatment options are mainly based on small trials showing less than 50% durable remissions. [Extracted from the article]

Tosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission ( CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia ( AML) or high-risk myelodysplastic syndrome ( MDS). Thirty-four patients ≥60 years old (median age 70 years; range, 60-83) were randomized to receive tosedostat (120 mg on days 1-21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2/d) or decitabine (20 mg/m2/d) every 35 d. Twenty-nine patients (85%) had AML, including 15 (44%) with secondary AML/ MDS, and 5 (15%) had MDS-refractory anaemia with excess blasts type 2. The CR/ CR with incomplete count recovery ( CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3-internal tandem duplication mutations. Median follow-up was 11·2 months (range, 0·5-22·3), and median survival was 11·5 months (95% confidence interval, 5·2-16·7). Twenty-three patients (67·6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3-4 non-haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/ MDS, results in a CR/ CRi rate of >50%, and warrants further study in larger trials. [ABSTRACT FROM AUTHOR]

Outcomes for older adults with acute myeloid leukaemia ( AML) and myelodysplastic syndrome ( MDS) are generally poor, and new effective therapies are needed. We investigated oral clofarabine combined with low-dose cytarabine (LDAC) in patients aged 60 years and above with relapsed or refractory AML or high-risk MDS in a phase I/ II trial. A 3 + 3 dose escalation of oral clofarabine was followed by a phase II expansion with the aim of obtaining a complete response ( CR) rate ≥30%. We identified 20 mg/d for 5 d as the maximum tolerated dose ( MTD) of oral clofarabine. A total of 35 patients, with a median age of 72 years, were treated. Of 26 patients enrolled at the MTD, 4 had treatment-related grade 3-4 non-haematological toxicities, but none died within 28 d. The observed CR rate and median survival were 34% [95% confidence interval ( CI), 18-50%] and 6·8 months overall and 38% [95% CI, 19-57%] and 7·2 months at the MTD. The median disease-free survival was 7·4 months. Fifty-two percent (23/44) of cycles administered at the MTD were done without hospital admission. This combination of oral clofarabine and LDAC demonstrated efficacy with a CR rate of >30% and acceptable toxicity in older patients. [ABSTRACT FROM AUTHOR]

Combinations of agents may improve outcomes among elderly acute myeloid leukaemia ( AML) and high-risk myelodysplastic syndrome ( MDS) patients. We performed an adaptive phase I/II trial for newly-diagnosed AML or high-risk MDS patients aged ≥50 years using a Bayesian approach to determine whether 1 of 3 doses of bendamustine (45, 60, 75 mg/m2 days 1-3), together with idarubicin (12 mg/m2 days 1-2), might provide a complete response ( CR) rate ≥40% with <30% grade 3-4 non-haematological toxicity. We treated 39 patients (34 AML; five MDS with >10% marrow blasts; median age 73 years). None of the three bendamustine doses in combination with idarubicin met the required CR and toxicity rates; the 75 mg/m2 dose because of excess toxicity (two of three patients) and the 60 mg/m2 dose because of low efficacy ( CR rate 10/33), although no grade 3-4 non-haematological toxicity was seen at this dose. Median survival was 7·2 months. All patients began treatment as outpatients but hospitalization was required in 90% (35/39). Although we did not find a dose of bendamustine combined with idarubicin that would provide a CR rate of >40% with acceptable toxicity, bendamustine may have activity in AML/ MDS patients, suggesting its addition to other regimens may be warranted. [ABSTRACT FROM AUTHOR]

The incidence of acute myeloid leukemia (AML) is expected to increase in conjunction with our ageing population. Although it is proving to be a heterogeneous disease process, the only treatment with proven survival benefit for poor risk AML remains allogeneic hematopoietic cell transplant. Although this is presumed to be a curative strategy, many patients relapse after transplant, prompting us to examine various ways that we can improve outcomes. These efforts involve every step of AML diagnostics and therapy, including the intricate processes of conditioning, graft manipulation and immunomodulation. The hope is that improvement in these steps will ultimately improve survival and decrease relapse rates for AML patients after transplant. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 42-year-old man diagnosed with myeloid sarcoma (MS). Noted is the association of specific cytogenetic abnormalities with higher MS incidence. The potential role of neural cell adhesion molecule 1 expression in extramedullary disease pathogenesis of the patient is observed.

Acute myeloid leukemia (AML) is proving to be a heterogeneous disease process that is driven by various genetic mutations and aberrant protein expression. As our population ages, the incidence of AML is likely to increase, with approximately a third of adult cases categorized with normal cytogenetics. Advances in technology are now allowing us to explore the genetic expression and protein transcription patterns of AML, providing more information that must find its place in the prognosis and the therapeutic algorithm of this disease. As we learn more, we hope to further categorize patients with normal karyotype AML into discrete risk categories that will help in treatment decision making and further elucidate the necessity for hematopoietic cell transplantation. However, at this time, many of the identified mutations and expression patterns are still experimental, requiring further analysis to determine their exact role in AML. [ABSTRACT FROM AUTHOR]