LEUKEMIA & LYMPHOMA

Comprehensive review on learning models of leukemia detection based on morphological information
Ponnusamy U and Perumal V
Leukemia is a blood cancer caused by the abnormal multiplication of immature white blood cells and is the 11th most prevalent cancer worldwide. Early and accurate leukemia diagnosis is critically important because it directly influences treatment decisions and patient outcomes. Delayed or inaccurate diagnosis leads to disease progression, a higher risk of life-threatening infections, and poorer survival rates. Conventional detection techniques, including manual microscopic analysis and complete blood count tests, are time-consuming, less reliable, and require medical experts. Accurate and timely detection improves treatment outcomes and increases survival chances. Various artificial intelligence approaches have been implemented for leukemia detection and offer satisfactory results. This study presents a systematic review of artificial intelligence-based approaches used in leukemia diagnosis. It includes an analysis of image acquisition methods such as peripheral blood smear microscopy, flow cytometry, bone marrow biopsy imaging, and advanced imaging techniques. Preprocessing steps such as noise removal, artifact removal, and image enhancement methods that improve image contrast and quality are discussed. The review provides an overview of segmentation techniques, from conventional clustering algorithms to deep learning frameworks. It also examines machine learning and deep learning models used in leukemia classification, highlighting their merits and challenges while identifying existing issues and potential future directions.
Discordant cell-of-origin in refractory/relapsed LBCL at diagnosis and relapse
Riber Hansen EV, Dennis S, Brændstrup P, Eriksen JO, Everhøj AE, Litman T, Pedersen LM, Pedersen MØ and Gjerdrum LMR
Gene expression profiling (GEP)-based cell-of-origin (COO) classification is the gold standard for molecular subtyping of diffuse large B-cell lymphoma (DLBCL). However, the consistency of COO classification over time, particularly in relapsed or refractory (R/R) settings, remains insufficiently validated. In this longitudinal study, we assessed the stability and reproducibility of COO classification using the NanoString Lymph2Cx assay in paired primary and relapse samples from 84 patients with R/R LBCL. Of these, 90.2% were classified as either activated B-cell-like (ABC) or germinal center B-cell-like (GCB). COO inconsistencies were observed in 18 patients, with four patients showing a shift between ABC and GCB subtypes. While the Lymph2Cx assay demonstrates utility in COO determination, our findings raise important questions regarding the biological and clinical implications of COO shifts. Further investigation is needed to understand the mechanisms behind this instability and to refine the role of COO assessment in guiding therapeutic strategies for R/R LBCL.
First report of donor-derived active multiple myeloma from one AML patient after allogeneic stem cell transplantation
Liu N, Sun Y, Liu Y and Hu L
Autologous stem cell transplantation for the treatment of MGRS (monoclonal gammopathy of renal significance): experience from the University of Calgary
Cabello Modesto D, McCulloch S, Tay J and Jimenez Zepeda VH
Recipient polymorphism of the C-reactive protein (CRP) gene rs2794521 stratified disease-free survival, but did not influence maximum serum CRP levels during neutropenia after single-unit cord blood transplantation in adults
Konuma T, Hamatani-Asakura M, Kato S, Andoh S, Ichimura H, Kuroda J, Kondo K, Yokoyama K, Monna-Oiwa M, Nannya Y and Takahashi S
MRD contamination in peripheral blood autologous stem cell grafts: implications for relapse and prognosis in multiple myeloma
Lin J, He J, Cai Z and He D
A large number of clinical studies have shown that the detection of contamination with clonal plasma cells (CPCs) in peripheral blood autologous stem cell grafts by flow cytometry, next-generation sequencing (NGS), next-generation flow cytometry (NGF), and other methods can reflect the residual tumor burden of multiple myeloma (MM) patients before autologous stem cell transplantation (ASCT). Despite the disadvantages of single-time and unsustainable monitoring, the MRD detection of stem cell grafts remains a negative prognostic factor that reduces overall survival. However, it must be acknowledged that MRD contamination in stem cell grafts is not a primary contributor to disease relapse. In clinical practice, MRD in grafts can be incorporated as a robust additional risk factor within a comprehensive and dynamic evaluation framework. For high-risk patients who are MRD-positive for the grafts, early intervention strategies such as preemptive or intensive therapy, and maintenance therapy with different novel agents may improve clinical outcomes.
Treatment of older adults with peripheral T cell lymphoma (PTCL) amidst a changing therapeutic landscape: a 20-year single institution experience
Faisal MS, Anampa Guzman A, Attwood K, Torka P, Cortese M and Hernandez-Ilizaliturri F
Characteristics, patterns of care and outcomes of patients with T-cell lymphoma-associated hemophagocytic lymphohistiocytosis: a single-center retrospective analysis
Braun T, Keppel M, Dechow A, Pflug N, Liedgens P, Herling M, Heger JM and Eichenauer DA
Short-term costs associated with outpatient use of axicabtagene ciloleucel in second-line and above relapsed/refractory large B-cell lymphoma based on the zuma-24 clinical trial
Oluwole OO, Wade SW, Smith NJ, Spousta T, Kim J, Fang X, Best T, Ray M and Leslie L
Simultaneous auto-transplant and CD19 CAR T-cell 2nd line therapy followed by CD20 × CD3 bispecific antibody for refractory Burkitt lymphoma, a case report
Stegemann M, Macherndl-Spandl S, Mairhofer M, Kaltenbrunner S, Buxhofer-Ausch V, Clausen J, Petzer A and Schmitt CA
Interferon alpha in myeloproliferative neoplasms: evidence and practical considerations for clinical care
Metzger M and Mascarenhas J
Myeloproliferative neoplasms (MPNs) are a spectrum of clonal hematologic malignancies, characterized by an acquired somatic mutation in hematopoietic stem cells (HSC). Consequent constitutive activation of the JAK/STAT signaling pathway ultimately leads to HSC clonal expansion, a heightened inflammatory state, and aberrant trafficking of the malignant stem cells to sites of extramedullary hematopoiesis. While polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are distinct disease entities, each with their own diagnostic criteria, risk stratification, and molecular profiles, they share a common pathogenesis and exist on a spectrum, with overlapping clinical features, propensity for thrombohemorrhagic events, and risk for transformation to acute leukemia. Interferon alpha (IFN-α) has both anti-proliferative and immunomodulatory effects on MPN HSCs, and therefore is an effective treatment modality for PV, ET, and MF. In this review, we discuss the rationale for IFN-α use in MPNs, examine the evidence supporting its use, and convey practical considerations.
Real-world outcomes of patients with relapsed refractory multiple myeloma treated with commercial bispecific T-cell engager antibodies: a single center experience
Fogel L, Roney PC, Ahn J, Aleman A, Perez-Manon F, Arias-Orozco N, Monteleone G, Londono K, Builes K, Anand P, Parmar H, Phull P, Vesole D, Siegel DS, Ip A and Biran N
T-cell engagers (TCE) have altered the therapeutic landscape for relapsed/refractory multiple myeloma (MM). Yet, patients in the real-world may have been ineligible for pivotal studies and TCEs are not widely accessible. A single-center retrospective study of 79 patients treated with teclistamab, talquetamab, or elranatamab was conducted. Forty-six percent had high-risk cytogenetics, 42% had EMD, and 44% had prior BCMA-exposure. ORR was similar to trials, 64%. PFS and OS were 4.44 and 13.3 months, respectively - both substantially shorter than clinical trials. On univariate analysis, having Medicare supplemental, secondary insurance, or advantage plans was associated with improved OS, but this did not persist on multivariate. Income below the NJ median and lack of accompaniment trended toward inferior OS. Achieving less than a PR to the last line was associated with inferior PFS/OS. Prospective studies should evaluate earlier utilization of TCEs and increasing early access for patients with low income.
Beyond bone: the emerging role of osteoclasts in immune regulation, leukemia development and following myeloablative therapy
Kuek V, Kotecha RS and Cheung LC
Osteoclasts are important regulators of bone remodeling, with an established role in maintaining skeletal homeostasis. The emergence of osteoimmunology has identified osteoclasts as key players in the immune system. In particular, osteoclasts can initiate bi-directional crosstalk mechanisms with hematopoietic stem cells and various immune cells, such as T cells, B cells and NK cells, to influence hematopoiesis and inflammatory response. In recent years, emerging evidence suggests that osteoclasts can remodel the leukemia bone marrow niche, contributing to both leukemogenesis and leukemia-induced bone destruction. In addition, osteoclasts have been implicated as a major source of bone loss following myeloablative therapy for hematopoietic stem cell transplant. An understanding of the mechanisms by which osteoclasts contribute to leukemia-induced and post myeloablative therapy bone loss could pave way for development of new therapeutic approaches in the near future.
Pre- and post-transplant extramedullary involvement in adult patients with t(8;21)(q22;q22) acute myeloid leukemia: incidence, risk factors and outcomes
Li S, Chen G, Wang H, Guan W and Zhou W
The risk factors and prognostic impact of extramedullary involvement (EMI) before and after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in t(8;21)(q22;q22) acute myeloid leukemia (AML) remain inconclusive. We performed a multicenter retrospective study including 560 t(8;21) AML patients from 15 Chinese hematology centers. mutations were more frequently observed in patients with EMI at diagnosis. EMI at diagnosis was not an independent risk factor for overall survival (OS) after adjustment for mutations. The 3-year post-transplant OS rates between isolated extramedullary relapse (EMR) and bone marrow relapse after allo-HSCT were comparable. Chronic graft-versus-host disease (cGVHD) was associated with increased incidence of isolated EMR (HR = 2.33,  = 0.048). Pre- and post-transplant minimal residual disease (MRD), measured by transcript levels, showed no significant association with isolated EMR. In conclusion, EMI at diagnosis may not significantly impact survival in t(8;21) AML. For patients with cGVHD after allo-HSCT, EMR should be monitored.
The emerging role of immunotherapy in improving outcomes in Down syndrome - associated acute lymphoblastic leukemia: an insightful review
Mohammed Saleh MF, Nasiri A, Kotb A, Ahmed SO, Aljurf M and Hanbali A
Down syndrome-associated acute lymphoblastic leukemia (DS-ALL) is a biologically distinct subtype with high rates of treatment-related mortality and relapse. Genomic profiling reveals frequent CRLF2 rearrangements, JAK-STAT pathway mutations, and high-risk subtypes such as BCR::ABL1-like disease. Conventional chemotherapy achieves remission but is limited by toxicity in DS patients. Recent advances in immunotherapy, including blinatumomab, inotuzumab ozogamicin, and CD19-directed CAR T-cell therapy, have shown significant efficacy and favorable tolerability in pediatric and adult DS-ALL. Blinatumomab and inotuzumab enable minimal residual disease clearance and serve as chemotherapy-sparing or bridging strategies, while CAR T-cell therapy offers curative potential and may reduce transplant reliance. Emerging approaches incorporating early immunotherapy, MRD-guided treatment, and chemotherapy-free regimens may improve survival and quality of life. Prospective DS-specific trials are essential to optimize therapy and close the outcome gap in this high-risk population.
Early predictive factors of molecular relapse in chronic phase-chronic myeloid leukemia (CP-CML) patients after tyrosine kinase inhibitor (TKI) discontinuation
Laganà A, Scalzulli E, Carmosino I, Bisegna ML, Ielo C, Diverio D, Martelli M and Breccia M
Disparities in anatomic site and stage at diagnosis of mycosis fungoides: a population-based study
Nolasco B, Li N, Kabarriti R and Nadelmann ER
Effect of tyrosine kinase inhibitors on sperm parameter and pituitary gonadal axis in males with chronic myeloid leukemia: a prospective cohort study
Ganju N, Sharma M, Dhawan R, Oberoi G, Aggarwal M, Chaturvedi P, Mahapatra M and Seth T
As the survival of patients with Chronic Myeloid Leukemia (CML) on tyrosine kinase inhibitors (TKIs) is comparable to healthy counterparts, it is now being treated as a chronic disease. Hence, there is significant concern of the effect of TKI on fertility and pregnancy outcomes. While the teratogenic effects of TKIs are well established, data on their impact on male fertility remain limited. With a growing number of CML patients of reproductive age being diagnosed annually, understanding the effect of Imatinib on male fertility is crucial. To study the effect of Imatinib (TKI) on the Pituitary gonadal axis and sperm parameters in CML patients, as there is limited data in this area. A prospective cohort study (Oct 2018-Jan 2021) included 30 male CML-CP patients (18-60 years). Patients were excluded if they had known dysfunction of the pituitary-gonadal axis, structural abnormalities of the gonads, or a history of prior sterilizing treatments. After receiving imatinib treatment for 3 months, out of these 30 patients, sperm concentration declined in 22 (73.3%), though only 5 (22.7%) had oligospermia (<15 million/ml), and none had severe oligospermia (<5 million/ml). Among these 5 patients, 4 were aged ≤35 years, while 1 was older than 35 years. Progressive motility decreased in 11 patients, with 6 (54.5%) dropping below the reference range (<32%), potentially causing infertility. Vitality decreased in 13 patients. Out of these, in 10 patients, vitality dropped below the reference range (<58%). Normal sperm morphology declined in 16 patients, but in only 2 patients it fell below 4%. Post-Imatinib treatment, two patients had elevated FSH, while LH and testosterone levels remained normal in all. Although there was a mild decrease in mean values of post-imatinib samples, there was no statistically significant decrease in mean FSH (-value = 0.106), LH (-value = 0.080), or testosterone levels ( = 0.313). Mean sperm concentration reduced after imatinib treatment, though it was not significant (-value = 0.080). Mean progressive motility increased, but the change was not significant ( = 0.059). Mean sperm vitality increased, but it was not significant (-value = 0.264). Also, there was no significant correlation found between hormonal changes and sperm parameters. Imatinib therapy was associated with a decline in sperm concentration, progressive motility, vitality, and normal morphology in some patients; however, no statistically significant changes were observed in mean hormonal or semen parameters. Patients planning families should nonetheless be counselled regarding the potential impact of TKIs on sperm quality. While sperm cryopreservation is not routinely recommended, its role in selected patients warrants evaluation in larger and long-term studies.
Effective management of daratumumab-induced cytopenias with hematopoietic stem cell infusion in relapsed/refractory multiple myeloma: a case report
Slogrove O and Wight J
Rethinking response assessment in AL amyloidosis: the role of kidney function and absolute light chain levels
Shah CV
Pacritinib in patients with myelodysplastic/myeloproliferative neoplasms
Zargari M, Nayak N, Canonico M, Patel PC, Fedorov K, Walsh KJ, Kishtagari A, Mohan SR, Savona MR and Ball S