Medicine and Pharmacology

Abstract: Acute myeloid leukemia (AML) develops within a bone marrow environment that influences leukemic stem-cell behavior, residual disease, and response to therapy. This review examines evidence that the marrow microenvironment is not only a site of leukemic growth, but can actively shape AML initiation, maintenance, and treatment resistance. Clinical observations such as donor cell leukemia after allogeneic transplantation, together with experimental models in which stromal or osteolineage abnormalities induce myeloid disease, suggest that altered niches may contribute to leukemogenesis in selected settings. In established AML, vascular and endosteal compartments provide adhesive, chemokine, inflammatory, and metabolic signals that promote leukemic-cell retention, quiescence, survival, and chemotherapy tolerance. AML cells also remodel the surrounding marrow, suppressing normal hematopoiesis and generating stromal, endothelial, osteoblastic, adipocytic, and immune-cell programs that favor leukemic persistence. These interactions are especially relevant to drug resistance, including resistance to venetoclax-based therapy, where cytokine-mediated changes in apoptotic dependence, fatty-acid metabolism, mitochondrial adaptation, and stromal support may all contribute. Several therapeutic approaches have attempted to disrupt niche-mediated protection, including targeting CXCL12/CXCR4 signaling, adhesion pathways, inflammatory circuits, Hedgehog signaling, and metabolic dependencies. Although early-phase studies have shown activity in some AML subsets, randomized evidence remains limited and results have been inconsistent. We discuss how a better understanding of microenvironmental biology may help define when niche-directed therapy is most likely to complement conventional and molecularly targeted AML treatment.

Abstract: Background: Relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) remains a major therapeutic challenge, particularly in patients with peripheral T-cell lymphomas (PTCL), who frequently exhibit poor responses to salvage therapy and inferior survival outcomes. Achieving adequate disease control before autologous stem cell transplantation (ASCT) is a critical determinant of long-term survival. The bendamustine, gemcitabine, vinorelbine, and prednisolone (BEGEV) regimen has demonstrated high efficacy and favorable tolerability in relapsed/refractory classical Hodgkin lymphoma; however, data regarding its role in NHL are extremely limited. Methods: We conducted a retrospective, single-center analysis of patients with R/R NHL who received the BEGEV regimen as salvage therapy. Clinical characteristics, response rates, transplantation outcomes, progression-free survival (PFS), overall survival (OS), and safety data were evaluated. Treatment responses were assessed according to standard radiologic response criteria. Survival analyses were performed using the Kaplan–Meier method. Results: A total of 68 patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL) were included in the analysis. BEGEV was administered predominantly in later salvage settings. Among 56 evaluable patients, the overall response rate (ORR) was 73.2%, including a complete response (CR) rate of 51.8%. Following BEGEV therapy, 25 patients (36.8%) proceeded to autologous stem cell transplantation (ASCT), while 8 patients (11.8%) underwent allogeneic stem cell transplantation (allo-SCT). Median progression-free survival (PFS) and overall survival (OS) were 4 and 26 months, respectively. Patients proceeding to transplantation demonstrated significantly improved survival outcomes. Treatment-related toxicities were predominantly hematologic and generally manageable. Conclusion: BEGEV may represent an effective and feasible salvage regimen in patients with R/R NHL and could serve as a valuable bridge-to-transplant strategy, including selected PTCL patients. Given the paucity of data in this setting, our findings provide real-world evidence supporting further prospective investigation of BEGEV-based approaches in NHL.

Abstract: We report the first cases of asciminib-induced gynecomastia in two elderly patients treated for chronic myeloid leukemia, in the third-line setting for 6 months and in the second-line setting for 3 months, respectively. Both patients exhibited hormonal disturbances, with elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels; one had low serum total testosterone, while the other had elevated estradiol levels. Temporary discontinuation and dose reduction of asciminib alleviated symptoms. The pathophysiological mechanisms and management options for this adverse event are discussed.

Abstract: The treatment of chronic lymphocytic leukemia (CLL) has shifted from chemoimmuno-therapy to targeted therapy, resulting in improved outcomes and patient survival. The aim of this study was to evaluate the efficacy and safety of venetoclax-based regimens in patients with relapsed/refractory CLL, as well as their effectiveness in patients previously treated with ibrutinib. We retrospectively analyzed 98 patients with CLL who received venetoclax in the second or later lines of therapy in Slovakia between 2018 and 2024. The median age was 68 years, and treatment was administered either as monotherapy or in combination with rituximab. Response to treatment was assessed according to the iwCLL 2018 criteria and clinical practice. Survival outcomes were evaluated using Kaplan–Meier analysis. An overall response was achieved in the majority of patients, with 2% achieving complete remission, 65% incomplete complete remission and 32% partial remission. At a median follow-up of 34 months, median overall survival was not reached (mean 52.5 months), and median progression-free survival was 46 months. Patients previously treated with ibrutinib had significantly worse outcomes (p = 0.022). Adverse events were predominantly hematological (64%), with 19% being grade 3–4. Venetoclax-based regimens represent an effective and well-tolerated treatment optionfor relapsed/refractory CLL, including in patients previously treated with ibrutinib, with acceptable and manageable toxicity.

Abstract: Zinc is an essential micronutrient which is involved in many physiological processes in the human body including immune system regulation, cellular survival, neurologic function, and erythropoiesis. Therefore, a wide range of clinical manifestations can be associated with zinc deficiency, such as impaired immune function, dermatologic findings, and decreased growth. Another significant, yet often underrecognized, manifestation of zinc deficiency is anemia. This review discusses the pathophysiology leading to zinc deficiency-associated anemia, highlighting zinc’s role in erythropoiesis, heme biosynthesis, and red blood cell stability. It also outlines various populations which are more at risk for developing zinc deficiency-associated anemia as identifying these groups can aid clinicians to improve screening, especially in patients with unexplained or refractory anemia. Numerous trials in selected populations have demonstrated significant improvement in anemia following zinc supplementation. However, additional studies are critical in order to streamline screening guidelines and establish optimal zinc supplementation dosing. This review aims to increase awareness of zinc deficiency’s contribution to anemia in order to improve screening and clinical outcomes for patients.

Abstract: Background: Multiparameter flow cytometry is widely used in the diagnosis of acute leukemia, allowing rapid identification of leukemic cells based on their immunophenotype. The EuroFlow Acute Leukemia Orientation Tube (ALOT) was designed as a standardized screening tool to support early diagnostic orientation and guide further, more targeted testing. In this study, we assessed the diagnostic performance of the ALOT panel in pediatric patients with suspected acute leukemia. Methods: A total of 254 pediatric patients (0–18 years) with suspected acute leukemia were analyzed. Bone marrow samples were assessed using multiparameter flow cytometry with the EuroFlow ALOT panel, comprising eight markers (MPO, cyCD79a, CD34, CD19, CD3, cyCD3, CD7, and CD45). Final diagnoses were established using extended immunophenotypic panels and additional diagnostic methods when required. Diagnostic performance was assessed by calculating sensitivity, specificity, precision, accuracy, and negative predictive value. Results: Among 254 patients, 234 were diagnosed with hematologic disorders, while 20 had normal bone marrow findings. The ALOT panel correctly identified all pathological samples and did not misclassify any normal sample, resulting in 100% sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for discrimination between abnormal and normal samples. In terms of exact diagnostic orientation, ALOT correctly classified 244 of 254 cases (96.1%) using a single-tube approach. The remaining 10 cases (3.9%), including rare entities such as Burkitt leukemia, chronic myeloid leukemia, and transient myeloproliferative syndrome, required extended immunophenotypic evaluation. Importantly, these cases were not false-negative results, as all were correctly identified as abnormal. Conclusions: The EuroFlow ALOT panel is a reliable screening tool for rapid diagnostic orientation in pediatric acute leukemia. Its implementation facilitates targeted selection of extended immunophenotypic panels, improving the efficiency and cost-effectiveness of diagnostic workflows.

Abstract: Classical Hodgkin lymphoma (cHL) remains one of the most curable hematologic malignancies, with long-term survival exceeding 80–90% in most contemporary series. However, a subset of patients experience primary refractory disease, relapse, treatment related toxicity, or late complications associated with conventional chemotherapy and radiotherapy. Over the last decade, major advances in frontline treatment have transformed the therapeutic landscape of cHL through the incorporation of targeted therapy and immune checkpoint inhibition into first-line regimens. Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, and programmed death-1 (PD-1) inhibitors such as nivolumab and pembrolizumab have significantly improved outcomes in advanced-stage disease and are increasingly being explored in limited-stage settings. The ECHELON-1 trial established BV-AVD as superior to ABVD in advanced-stage disease with improved progression-free survival and overall survival, while the SWOG S1826 study demonstrated superior progression-free survival and reduced toxicity with nivolumab-AVD compared with BV-AVD. These advances have shifted frontline treatment paradigms toward chemotherapy de-escalation, PET-adapted strategies, and immune-based treatment approaches. In parallel, the role of radiotherapy continues to evolve with efforts aimed at minimizing long-term toxicity without compromising cure rates. This review summarizes the biological rationale, pivotal clinical trials, evolving treatment strategies, and future directions in first-line treatment of cHL, with emphasis on evidence-based incorporation of novel agents and practical implications for modern clinical practice.

Abstract: The aim of this study was to organize and critically evaluate the tools to assess nutritional status in adults with acute myeloid leukemia (AML), with particular emphasis on screening instruments, biochemical and composite indices, body composition analysis and physical function. This paper is a narrative review. The literature search was performed in PubMed and Google Scholar and covered publications from 2015 to 2025. Eighteen original and review papers were included, predominantly involving adults with AML and, in selected cases, mixed populations if the results were applicable to patients treated according to AML-related regimens. The available evidence shows that nutritional impairment is common already at diagnosis and tends to worsen during remission-induction chemotherapy. PG-SGA and NRS-2002 are useful for identifying patients who require nutritional intervention, but they should not be interpreted separately from body composition and laboratory assessment. Body mass index alone appears insufficient, whereas albumin and albumin-based composite indices incorporating inflammatory burden, such as sCONUT, NRI, GNRI and CAR, show greater prognostic utility. In older adults and in patients evaluated before allo-HSCT, physical function often seems more closely related to outcomes than the MNA score itself. A multimodal approach combining nutritional screening, body composition assessment and evaluation of physical function appears to be the most justified clinical strategy. Future studies should focus on interventions integrating nutritional support with rehabilitation and prehabilitation.

Abstract: Background/Objectives: Treatment decisions for elderly patients with diffuse large B-cell lymphoma (DLBCL) often rely on subjective clinical impression rather than systematic frailty assessment. We evaluated whether a modified simplified frailty score (mSFS)—a binary adaptation of the Isaksen score—predicts treatment selection, toxicity, and survival. Methods: In this retrospective study of 117 patients aged ≥65 years with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or dose-attenuated R-CHOP (R-mini-CHOP) at MedStar Health community hospitals (2000–2025), the mSFS assigned one point each for age ≥80, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and ≥5 comorbidities; score ≥2 defined frailty. Results: Among 86 R-CHOP recipients, 17 (19.8%) were mSFS-frail; among 31 R-mini-CHOP recipients, 15 (48.4%) were mSFS-fit. In R-CHOP recipients, frailty independently predicted worse overall survival (adjusted hazard ratio [aHR] 7.67, 95% confidence interval [CI] 2.36–24.97), progression-free survival (aHR 2.90, 95% CI 1.18–7.13), grade ≥3 adverse events (adjusted odds ratio [aOR] 3.90, p = 0.035), and early discontinuation (aOR 4.41, p = 0.034). Frail R-CHOP patients had lower complete response rates (aOR 0.24, p = 0.038). Fit R-mini-CHOP patients had 88% lower odds of complete response versus fit R-CHOP patients (aOR 0.12, p = 0.003). Among R-mini-CHOP recipients, frailty was not significantly associated with outcomes. Conclusions: The mSFS revealed bidirectional discordance with oncologist-assessed frailty and independently predicted survival, toxicity, and response, supporting its integration into community oncology practice.

Abstract: Background/Objectives: Inflammatory and hematologic indices derived from routine blood tests have been increasingly investigated as prognostic biomarkers in multiple myeloma (MM). However, their clinical utility remains inconsistent, and data on novel composite indices, such as the mean corpuscular volume-to-lymphocyte ratio (MCVL) and the cumulative inflammatory index (IIC), are lacking in MM. Methods: We conducted a retrospective study including 122 patients with newly diagnosed MM. Hematologic and inflammatory indices were evaluated at baseline and after four cycles of induction therapy. Associations with progression-free survival (PFS) and overall survival (OS) were assessed using Kaplan–Meier analysis, Cox regression models, and receiver operating characteristic (ROC) curve analysis. Results: Baseline inflammatory biomarkers, including NLR, PLR, MLR, SII, as well as MCVL and IIC, were not significantly associated with PFS or OS. ROC analysis demonstrated poor discriminative ability for all evaluated markers at both baseline and post-induction timepoints (AUC values close to or below 0.50). In contrast, post-induction inflammatory indices, particularly PLR, MLR, AISI, and SIRI, were significantly associated with PFS in both univariable and multivariable Cox regression analyses. Neither baseline nor post-induction MCVL and IIC showed independent prognostic value. Conclusions: Baseline inflammatory and erythrocyte-derived indices, including the novel composite markers MCVL and IIC, have limited prognostic utility in MM. In contrast, dynamic changes in inflammatory biomarkers during treatment may provide more clinically relevant information regarding disease progression. These findings support the integration of longitudinal biomarker assessment into future risk stratification models in MM.

Abstract: The coagulation cascade depends on the active participation of several elements present in the blood as well as signals arising from the endothelial cells. A platelet plug is a temporary, fast-response seal formed by platelets at the site of a damaged blood vessel to initiate hemostasis. It acts as the first step in primary hemostasis, where platelets stick to exposed collagen, activate, and aggregate to create a plug that temporarily prevents blood loss. Among changes platelets undergo is the degranulation step. Platelet degranulation is the process where activated platelets release stored chemical mediators from their internal alpha and dense granules into the bloodstream to promote hemostasis and immune responses. Platelet degranulation results in the release of substances like ADP, serotonin, fibrinogen, and zinc. In the present work we provide evidence that the high local concentration of zinc is intended to target junctional adhesion molecule A (JAM-A) that remains inactive (inhibited cell-adhesion and cytoskeleton dynamics) when coagulation is not needed and platelets move through the blood stream as single units. Zinc-activated JAM-A leads the platelets to aggregate. Our experimentation includes work with platelets, and a synthetic biology small peptide to quench the effects of zinc. We suggest that further exploring this mechanism of zinc-activated JAM-A can be advantageous for better understanding hemostasis, its role in antithrombotic therapy, coagulation inhibition, or thrombosis prevention.

Abstract: Background: Pirtobrutinib has recently emerged as a promising first-line treatment option for chronic lymphocytic leukemia (CLL). Unlike currently established regimens, which are generally based on doublet combinations, pirtobrutinib can be administered as monotherapy. Because no head-to-head trials comparing pirtobrutinib with contemporary first-line combinations are currently available, indirect comparative evidence may help define its potential role. Methods: A non-anchored indirect comparison based on reconstructed individual patient data (IPD) was conducted using published Kaplan-Meier curves from randomized controlled trials evaluating first-line treatments for CLL. Progression-free survival (PFS) was the endpoint of interest. Reconstructed IPD were generated using WebPlotDigitizer and the IPDfromKM algorithm. Pirtobrutinib monotherapy was compared indirectly with acalabrutinib plus obinutuzumab, venetoclax plus obinutuzumab, and venetoclax plus ibrutinib. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using univariate Cox models. Results: The analysis included four randomized trials. Compared with pirtobrutinib monotherapy, HRs for PFS were 0.5544 (95%CI, 0.2696-1.1397) versus venetoclax plus obinutuzumab, 0.4583 (95%CI, 0.2066-1.0200) versus venetoclax plus ibrutinib, and 1.4453 (95%CI, 0.6684-3.1240) versus acalabrutinib plus obinutuzumab. Confidence intervals were wide and crossed unity in all comparisons, indicating substantial statistical uncertainty. Visual inspection of reconstructed Kaplan-Meier curves did not suggest inferior PFS for pirtobrutinib relative to established doublet regimens. Conclusions: This exploratory non-anchored analysis suggests that pirtobrutinib monotherapy may provide PFS outcomes broadly comparable to current first-line combination regimens for CLL. Given the methodological limitations inherent to indirect comparisons, prospective head-to-head studies are needed to clarify the optimal positioning of pirtobrutinib in treatment-naïve CLL.

Abstract: Background/Objectives: Search for the new drugs capable of suppressing the development of drug resistance in tumor cells is extremely important for clinical practice. Cell signaling pathway inhibitors that control cell proliferation and death can be used in the complex therapy of malignant tumors. Methods: Cell cycle assay by flow cytometry, In Vitro Cell Viability Assay Cells chemosensitivity was analyzed by direct cell counting after trypan blue staining using microscope. Results: In the present work, we have shown that the combined action of doxorubicin and XMU-MP-1, the inhibitor of the MST1/2 kinase in the Hippo signaling pathway, prevents the development of drug resistance in Namalwa cells and significantly slows it down in K562 cells. and restores the sensitivity of resistant K562 cells to doxorubicin. We have shown that the combined action of doxorubicin and XMU-MP-1, causes a significant decrease in cell division rate and leads to the death of hematological tumor cells the Burkitt's lymphoma Namalwa, and myeloma K562 cells compared to monotherapy. Cell cycle analysis has demonstrated that the combined action of XMU-MP-1 and doxorubicin results in a catastrophic disruption of the cell cycle, and a significant increase in the number of cells undergoing apoptosis containing fragmented DNA. Conclusions: Thus, XMU-MP-1 can potentially be used in combination with anthracy-clines for the treatment of hematological malignancies and, in particular, the drug-resistant forms of cancer.

Abstract: The complete blood count (CBC) is a diagnostic test to analyze abnormalities of blood cells. Currently, automated hematology analyzers and artificial intelligence technology are being used with automated blood analyzers to ensure accuracy and reliability. This study aimed to evaluate the performance of artificial intelligence (AI) based automated blood cell analyzer, Awalife AI-100Vet Multifunctional Morphological Analyzer, in dog and cat blood samples by comparison with the CBC manual method. In dogs, PCV, hemoglobin, RBC, MCH, WBC, % Neutrophil, %Lymphocyte, %Monocyte, %Eosinophil and %Reticulocyte were all significantly correlated. While in cats, PCV, Hemoglobin RBC, WBC, % Neutrophil, % Lymphocyte, and % Eosinophil were all also significantly correlated. AUC values obtained by the Awalife AI-100Vet analyzer for Hematology testing in dogs and cats were 0.72 and 0.92 respectively. These findings suggest that the Awalife AI-100Vet analyzer demonstrated good accuracy using dog blood for hematology testing as well as excellent accuracy when using cat blood. The AI-based automated blood analyzer has the potential to analyze hematological data and is close to the reference method. However, there are still differences in some parameters. Further optimization of the AI algorithm, which will involve increasing the accuracy of identifying unusual cell shapes, improving stability against various samples, such as stains, and achieving good results when working with unique pathologies, should be carried out.

Abstract: Background/Objectives: Obesity and inflammatory conditions, including steatotic liver disease are known to impact the hematopoietic niche and immune surveillance. Therefore, assessing the impact of steatotic liver disease on recipients of allogeneic stem cell transplantation (allo-HSCT) with bone marrow origin neoplasms is clinically relevant and an underexplored area of investigation. Methods: We evaluated steatotic liver disease prevalence in allo-HSCT recipients and report post-transplant outcomes in this cohort. Results: Of 306 allo-HSCT recipients from 2014 to 2020 at our center, 18 (5.8%) had steatotic liver disease detected on non-contrast CT imaging pre-transplant. With a minimum of 5 years follow-up for all, eight patients experienced post-transplant relapses (44%). Relapses (78%) followed by infections (55%) were the major contributors of mortality in this cohort. Pre-transplant transaminases were normal (AST median 28, ALT median 37) in all, while most patients (89%; 16/18) developed abnormal transaminases in the first-year post-transplantation without evidence of permanent liver injury. None experienced veno-occlusive disease of the liver. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 33% (6/18), with 55% (10/18) experiencing chronic graft-versus-host disease (cGVHD). Conclusions: Our study highlights that radiologically detected steatotic liver disease is not a contraindication to proceeding with allogeneic stem cell transplant, and its association with transaminitis, relapse, immune complications, and post-transplant metabolic health requires future mechanistic studies.

Abstract: Blood can clot into anomalous, fibrinolysis-resistant forms that arise from prothrombotic seeding areas, including damaged cellular debris and membrane-derived surfaces, giving rise to what we have termed fibrinaloid microclot complexes (colloquially: microclots).Their proteolytic resistance is due to the fact that they are amyloid in nature, and they can also entrap inhibitors of proteolysis. They consist of a variety of proteins besides the expected fibrin, and are highly enriched for other amyloidogenic proteins (in contrast to normal clots, whose proteome largely reflects the soluble plasma proteome). They also contain DNA in the form of neutrophil extracellular traps (NETs). Importantly, fibrinaloid microclot complexes are heterogeneous structures comprising multiple phenotypic forms, including those that nucleate and grow on cellular debris such as damaged membranes, microparticles, and immune-derived material. These debris-associated complexes act as catalytic scaffolds that recruit fibrin(ogen) and inflammatory molecules, thereby amplifying amyloidogenic transformation and prothrombotic activity. Fibrinaloid microclot complexes have been reported in a widening range of chronic inflammatory and thrombo-inflammatory diseases in which they have been sought, and are highly enriched for amyloidogenic proteins. Additionally, the thrombi extracted from ischaemic stroke also contain proteins in an amyloid form, implying that such macroclots can form via the accretion of microclots that already contain amyloid. We here show that these microclots exhibit a classical ‘apple-green’ birefringence when stained with the dye Congo red. The urgent task now is to find means of inhibiting the transition to amyloid forms during the clotting process.

Abstract: Sickle cell disease (SCD) is one of the most common inherited blood disorders worldwide. Clinical manifestations are variable, but include hyposplenism, renal impairment, cardiovascular disease, respiratory complications, and cerebrovascular disease. Frequent painful vaso-occlusive crises, hospitalisations, and other physical and psychological ramifications can have profound effects, including children missing school time resulting in impaired academic performance and adults missing work leading to employment loss. This review examines the possible risks and benefits of exercise in the SCD population. Regular exercise plays an important role in improving physical and mental health, but fears around the potential consequences of exercise for the SCD population are present in children, their families, schools, and other organisations. This can result in children not taking part in as much regular exercise as their peers and being excluded from group activities. Studies have suggested that healthcare professionals are often not discussing possible benefits of physical exercise with patients, likely as there are no guidelines regarding a safe level of activity. An acute increase in inflammation secondary to exercise could increase the risk of vaso-occlusive crises, but regular physical activity is known to play an important role in disrupting chronic inflammation across a wide range of pro-inflammatory diseases. Indeed, studies have demonstrated positive responses to exercise in the SCD population, from improvements in skeletal muscle microvasculature to performance in cardiovascular tests. It is important that recommendations are developed regarding types of exercise and the ideal amount of exercise for maximum benefit with minimum risk in SCD individuals.

Abstract: Objectives: Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults, and consolidation with autologous hematopoietic stem cell transplantation (HSCT) in AML patients represents an alternative therapeutic option in the absence of related or unrelated donors, in the elderly or in patients with good or standard risk. In this retrospective analysis, the data were evaluated from a total of 47 AML patients who underwent autologous hematopoietic stem cell transplantation between November 2012 and March 2023 at the Bone Marrow Transplantation Unit of Medicalpark Izmir Hospital. The present study also investigates the factors affecting overall survival (OS) and pro-gression-free survival (PFS). Methods: This study is a retrospective evaluation of the data obtained from 47 patients with AML who underwent an autologous HSCT. Results: 24 patients were female, and 23 patients were male. The median age at diagnosis was 39 years (range: 18-68 y). The mean OS from diagnosis to the last follow-up or death was 26 months (4-116 months), and the PFS was 20 months (3-69 months). An assessment of the factors that influenced OS and PFS showed no significant association of NPM positivity, gender, risk group, response to first-line chemotherapy, transplantation at CR (Complete remission) 1 or CR2, LDH (lactade dehidrogenase) , CD34 count, and the day of neutrophil engraftment with OS or PFS. In patients with FLT3(fms benzeri tirozin kinaz 3) positivity, OS was significantly shorter (p < 0.05), while PFS was not significantly different (p=0.21). Conclusions: Consolidation with auto-HSCT in AML patients can be preferred in subjects with good or intermediate 1 risk category according to ELN (European leukemia net )criteria, or in subjects with intermediate 2 or poor-risk category who have no related or unrelated donor.

Abstract: Physiotherapy is an evidence-based healthcare occupation aiming to collaborate in the diagnosis, prevention and treatment of myriad of diseases and clinical scenarios throughout all stages of human life. Its development has been accelerated over the last two decades. The scope of physiotherapy is continuously evolving. However, the accumulated evidence in the context of rare diseases is scarce. Remarkably, the opportunity for improvement and potential benefit for complex diseases with low prevalence is also very high, both as an isolated approach or within multidisciplinary specialized units. Systemic light-chain (AL) amyloidosis is a rare, chronic, complex, heterogeneous, incurable, and challenging disease, which may involve different organs and systems, including the heart, kidney, liver, peripheral nerves, lung, muscle, skin, and others. Heart is the most frequently involved organ leading to failure and arrhythmias. Peripheral neuropathy is a relatively frequent symptom. Renal, respiratory, and hepatic failure may also occur. The aim of this narrative review is summarizing, updating, and critically underlining potential new avenues of development on the role of physiotherapy in systemic light-chain (AL) amyloidosis, compared with its application on multiple myeloma, a closely related but not so rare entity.

Abstract: Therapy for chronic lymphocytic leukemia (CLL) has evolved dramatically with the introduction of targeted agents, particularly Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitors (BCL2is). This review summarizes contemporary frontline and relapsed/refractory treatment strategies, with an emphasis on molecular risk stratification, combination and triplet regimens, measurable residual disease (MRD)–guided therapy, and time-limited approaches. We further examine how genomic complexity, prior therapies, and sociodemographic factors influence disease progression, treatment resistance, and clinical outcomes.