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Introduction: NPM1‐mutated (NPM1mut) myeloid neoplasms (MNs) with <20% bone marrow (BM) blasts (NPM1mut MNs<20) are uncommon, and their classification remains inconsistent. Methods: The clinicopathologic features of 54 patients with NPM1mut MNs <20 were evaluated and compared with wild‐type NPM1 MNs <20 and NPM1mut MNs≥20, respectively. Results: NPM1mut MNs had similar features regardless of blast percentage, except for higher IDH2 (29% vs 7%, p =.023) and FLT3 (70% vs 11%, p <.001) frequency in patients with ≥20% BM blasts. Thirty‐three (61%) patients with NPM1mut MNs <20 received low‐intensity chemotherapy (LIC) and 12 (22%) received intensive chemotherapy (IC). Higher complete remission rates (75% vs 27%, p =.006) and median overall survival (mOS) (not reached vs 30.4 months, p =.06) were observed with IC compared to LIC. Young patients (age <60 years) did not reach mOS either when treated with LIC or IC. Stem cell transplant was associated with increased survival only in patients treated with LIC (HR, 0.24; p =.025). No differences in mOS were observed by BM blast strata (32.2 months, not reached and 46.9 months for <10%, 10%–19%, and ≥20% blasts, p =.700) regardless of treatment modality (LIC: p =.900; IC: p =.360). Twenty‐three patients (43%) with NPM1mut MNs <20 had marrow blast progression to ≥20%. Conclusions: Overall, NPM1mut MNs define a unique entity independent of BM blast percentage. NPM1 mutations define a unique leukemia entity regardless of bone marrow blast percentage. Patients with NPM1‐mutated myeloid neoplasms benefit from intensive chemotherapy approaches even in the setting of low bone marrow blast percentage. [ABSTRACT FROM AUTHOR]

Background: Allogeneic stem cell transplantation (SCT) remains the best consolidative modality in most patients with acute myeloid leukemia (AML). Along with factors directly pertaining to SCT, pretransplantation disease control, performance status, and prior treatment‐related complications are important factors that affect posttransplantation survival outcomes. Methods: The authors compared the survival outcomes of patients ≥60 years of age treated on the phase 2 clinical trial of venetoclax (Ven) added to cladribine (CLAD) and low dose cytarabine (LDAC) alternating with azacitidine (CLAD/LDAC/Ven arm) (NCT03586609) who underwent allogeneic SCT in first remission to a retrospective cohort of patients ≥60 years of age who underwent SCT after intensive chemotherapy. Intensive chemotherapy was defined as the use of cytarabine >1 g/m2 and anthracyclines during induction/consolidation. Results: Thirty‐five patients at median age of 68 years in the CLAD/LDAC/Ven arm were compared to 42 patients at a median age of 62 years in the intensive therapy arm. The 2‐year relapse‐free survival was superior with CLAD/LDAC/Ven versus intensive chemotherapy (88% vs. 65%; p =.03) whereas the 2‐year overall survival (OS) was comparable (84% vs. 70%; p =.14). On a competing event analysis, the 2‐year cumulative incidence of relapse (CIR) was significantly lower with CLAD/LDAC/Ven versus intensive chemotherapy (2.9% vs. 17.2%, Gray's p =.049) whereas nonrelapse mortality was comparable (16.2% vs. 17.1%; p =.486). Conclusion: In conclusion, treatment with CLAD/LDAC/Ven was associated with favorable outcomes in older patients who underwent subsequent allogeneic SCT. The OS was comparable to that with intensive chemotherapy followed by allogeneic SCT, but the CIR rate was significantly lower. Older patients (≥60 years of age) with acute myeloid leukemia who underwent allogeneic stem cell transplantation after low‐intensity therapy on the phase 2 trial of venetoclax added to cladribine and low dose cytarabine alternating with azacitidine had promising survival outcomes that were comparable to a retrospective cohort of patients who underwent allogeneic stem cell transplantation after intensive chemotherapy. [ABSTRACT FROM AUTHOR]

Therapy-related myeloid neoplasms following treatment with PARP inhibitors: new molecular insights. Keywords: PARP inhibitors; therapy related myeloid neoplasms; therapy-related acute myeloid leukaemia; therapy-related myelodysplastic syndrome EN PARP inhibitors therapy related myeloid neoplasms therapy-related acute myeloid leukaemia therapy-related myelodysplastic syndrome e25 e29 5 04/20/23 20230501 NES 230501 Therapy-related myeloid neoplasms represent 10%-20% of all newly diagnosed myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML).[1] These disorders are frequently associated with high-risk genetic features. Outcomes of patients with therapy-related myeloid neoplasms after treatment with poly(ADP-ribose) polymerase proteins inhibitors for solid tumours Therapy related myeloid neoplasms, PARP inhibitors, therapy-related myelodysplastic syndrome, therapy-related acute myeloid leukaemia. [Extracted from the article]

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. We applied automated sequential-iFISH coupled with single-cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD-B-ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD-B-ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD-B-ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)-negative childhood HHD-B-ALL patients: relapse-free survival beyond 5 years: 22.1% versus 87.9%, P < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-BALL patients. [ABSTRACT FROM AUTHOR]

Summary: The presence of a serum monoclonal component has been associated with poor outcomes in some lymphomas. However, data in follicular lymphoma (FL) are scarce. We studied 311 FL patients diagnosed at a single institution, for whom information on serum immunofixation electrophoresis (sIFE) at diagnosis was available. Baseline characteristics and outcomes were compared between patients with a positive (+sIFE) and a negative sIFE (−sIFE). sIFE was positive in 82 patients (26%). Baseline features were comparable between both groups, except for an older age and higher proportion of elevated β2‐microglobulin levels in the +sIFE group. With a median follow‐up of 4.6 years, a +sIFE was associated with a higher risk of early relapse (POD24, 27% vs. 15%, P = 0·02), shorter progression‐free survival (PFS; 42% vs. 52% at 5 years, P = 0·008), and shorter overall survival (OS; 59% vs. 77% at 10 years, P = 0·046). In patients >60 years, a +sIFE was an independent predictor of OS [hazard ratio (HR) = 2·4, 95% confidence interval (CI): 1·2–5·0; P = 0·02]. Approximately one quarter of patients with FL has a +sIFE at diagnosis, which is a predictor of poor outcome. These findings encourage further investigation of its relationship with B‐cell biology and the tumour microenvironment. [ABSTRACT FROM AUTHOR]

This is the first study analyzing the interval between frontline treatment and the second relapse (PFS2) in follicular lymphoma. The PFS2 was <2 years in 41 patients (46%), 2-5 years in 29 patients (33%), and >5 years in 19 patients (21%). Although not statistically significant, the CR rate after frontline and second-line treatments was higher for patients with a PFS2 > 5 years (95 and 84% for first- and second-line treatment), compared with those with a PFS2 2-5 years and <2 years. [Extracted from the article]

Summary: In the European LeukemiaNet favourable risk category, allogeneic haematopoietic stem cell transplantation (alloSCT) is not indicated in first complete remission for patients with acute myeloid leukaemia (AML) with NPM1 mutations (ELNfav NPM1 AML), although a proportion of these patients will relapse. Given the prognostic importance of measurable residual disease (MRD), CETLAM‐12 considered a pre‐emptive intervention in patients with molecular failure (MF). We analyzed 110 ELNfav NPM1 AML patients achieving complete remission (CR) after induction chemotherapy. Two‐year cumulative incidence of relapse (CIR), overall survival (OS) and leukaemia‐free survival (LFS) were 17%, 81·5% and 82%, respectively. Forty‐six patients required additional therapy for MF (n = 33) or haematological relapse (HemR; n = 13), resulting in a molecular LFS (molLFS) and a cumulative incidence of MF at two years of 61% and 38% respectively. Two‐year OS for these 46 patients was 66%, with a different outcome between patients with MF (86%) and HemR (42%) (P = 0·002). Quantitative NPM1 detection at different timepoints was predictive of molLFS; an MRD ratio (NPM1mut/ABL1 × 100) cut‐off of 0·05 after first consolidation identified two cohorts with a two‐year molLFS of 77% and 40% for patients below and above 0·05, respectively. In conclusion, MRD‐based pre‐emptive intervention resulted in a favourable outcome for ELNfav NPM1 AML patients. [ABSTRACT FROM AUTHOR]

The article presents several case studies related to early T-cell precursor lymphoblastic leukaemia. It discussed the conditions of patients including a 31-year-old man, presented with a mediastinal mass and white blood cell (WBC) count, without central nervous system (CNS) involvement; a 34-year-old man who presented with pancytopenia; and a 39-year-old man, presented with a mediastinal mass and presence of 0.6 percent leukaemic cells.

The article present a case study of a 54-year-old black man from Guinea-Bissau presented with a 3-month history of progressive nodular skin lesions. It mentions a skin biopsy showed a lymphoid infiltrate in the dermis with epidermotropism in some areas; and also mentions the patient treatment started with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) plus zidovudine and interferon, but unfortunately died after the second cycle due to a bacterial pneumonia.

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery. Multivariable analysis-derived hazard ratios (HR), including 1.8 for European LeukemiaNet (ELN) adverse karyotype, 4.7 for KMT2Ar, 1.7 for TP53 MUT , 2.6 for KRAS MUT , and 2.1 for IDH2 WT were applied to develop an HR-weighted risk model: low, intermediate, and high; respective median survival censored for allogeneic stem cell transplant (ASCT) (3-year survival) were "not reached" (67%), 19.1 (33%), and 7.1 months (0%). In patients achieving CR/CRi, adverse karyotype, KMT2Ar, KRAS MUT , IDH2 WT predicted inferior survival, allowing for a complementary response-stratified risk model. The model was externally validated and was shown to be superior to the ELN 2024 risk model (AIC 179 vs. 195 and AUC 0.77 vs. 0.69). Survival was inferior with failure to achieve CR/CRi or not receiving ASCT; 3-year survival for high-risk with or without ASCT was 42% versus 0% (p < 0.01); intermediate 72% versus 43% (p = 0.06); and low-risk 88% versus 78% (p = 0.53). The Mayo genetic risk models offer pre-treatment and response-based prognostic tools for ND-AML treated with Ven-HMA. The current study underscores the prognostically indispensable role of achieving CR/CRi and ASCT., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)