Malignant Blood Cells Research Articles

An Intelligent Telediagnosis of Acute Lymphoblastic Leukemia using Histopathological Deep Learning

Leukemia, a global health challenge characterized by malignant blood cell proliferation, demands innovative diagnostic techniques due to its increasing incidence. Among leukemia types, Acute Lymphoblastic Leukemia (ALL) emerges as a particularly aggressive form affecting diverse age groups. This study proposes an advanced mechanized system utilizing Deep Neural Networks for detecting ALL blast cells in microscopic blood smear images. Achieving a remarkable accuracy of 97% using MobileNetV2, our system demonstrates high sensitivity and specificity in identifying multiple ALL sub-types. Furthermore, we introduce cutting-edge telediagnosis software facilitating real-time support for clinicians in promptly and accurately diagnosing various ALL subtypes from microscopic blood smear images. This research aims to enhance leukemia diagnosis efficiency, which is crucial for the timely intervention and managing this life-threatening condition.

Abstract LB076: Targeting an aging-related molecule overcomes resistance to anti-PD1 treatment of cancer

Abstract Purpose: Despite receiving great attention as a promising treatment, therapeutic efficacies induced by immune checkpoint inhibitors are low in clinical settings, and thus there are high expectations for the development of innovative diagnostic and therapeutic methods. We previously demonstrated that blocking FSTL1 overcomes anti-PD1 resistance in aged mice. In this study, we comprehensively analyzed and compared gene expressions in splenic T cells harvested from young and old mice receiving anti-FSTL1 or anti-PD1 therapy after tumor implantation using the GeneChip microarray in order to identify a key gene in the anti-PD1 resistance. In addition, we evaluated anti-tumor efficacy induced by blocking the identified molecule using aged tumor models and tumor metastasis models (3LL or Colon26), which are resistant to anti-PD1 therapy. Furthermore, to validate the clinical relevancy, we analyzed immune cells isolated from malignant tumor ascites and peripheral blood cells of gastric cancer patients by flow cytometry. Results: Using the GeneChip microarray data of splenic T cells, we identified α-synuclein (SNCA), which is a neuropathological molecule involved in Parkinson's disease and other synucleinopathies, as a gene that was significantly reduced by anti-FSTL1 therapy, but not anti-PD1 therapy, in splenic T cells of aged tumor models. SNCA+ cell subsets significantly increased not only in CD3+ T cells, but also CD11b+ myeloid cells and CD45- mesenchymal stromal/stem cells, within spleen, peripheral blood, and tumor tissues of aged mice and mouse tumor models, but rarely in those of young and naive mice. Increase of the subsets were also observed in malignant tumor ascites and peripheral blood of gastric cancer patients, but not those of healthy donors. Blocking SNCA with the specific mAb significantly induced potent CD8+ T cells with greater cytotoxicity in the in vitro CTL induction setting, and also significantly induced robust anti-tumor immunity in the in vivo therapeutic setting with anti-PD1-resistant tumor models. Combination of anti-SNCA therapy successfully elicited anti-PD1 therapeutic efficacy, providing significantly better prognosis in many tumor models, including severe tumor ascites models. Conclusions: These results suggest that SNCA is a type of immune inhibitory checkpoint molecules and an immunological determinant of anti-PD1 resistance, although the further study is needed to clarify the molecular functions in immune cells. Targeting this molecule may represent a promising strategy to overcome the anti-PD1 resistance and contribute to improved clinical outcomes in cancer treatment. Citation Format: Chie Kudo-Saito, Hiroshi Imazeki, Hirokazu Shoji, Narikazu Boku. Targeting an aging-related molecule overcomes resistance to anti-PD1 treatment of cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB076.

15 years Ludwig Boltzmann Institute for Hematology and Oncology (LBI HO): achievements and future perspectives

SummaryCancer stem cells, also known as leukemic stem cells (LSC) in the context of leukemias, are an emerging topic in translational oncology and hematology. The Ludwig Boltzmann Institute for Hematology and Oncology (LBI HO) was established in 2008 with the aim to translate LSC concepts into clinical practice. Major specific aims of the LBI HO are to identify LSC in various blood cell disorders and to improve anti-leukemic therapies by establishing LSC-targeting and LSC-eradicating approaches with the ultimate aim to translate these concepts into clinical practice. In addition, the LBI HO identified a number of diagnostic and prognostic LSC markers in various blood cell malignancies. Members of the LBI HO have also developed precision medicine tools and personalized medicine approaches around LSC in applied hematology. As a result, diagnosis, prognostication and therapy have improved in the past 10 years. Major disease models are myeloid leukemias and mast cell neoplasms. Finally, the LBI HO consortium launched several projects in the field of open innovation in science where patient-derived initiatives and their input supported the scientific community. Key aims for the future of the LBI HO are to develop LSC-related concepts and strategies further, with the long-term vision to cure more patients with hematologic malignancies.

Study of the immunomodulatory effect of lithium salt gamma-lactone of 2,3-dehydro-L-gulonic acid on healthy and malignant blood cells

Study of the immunomodulatory effect of lithium salt gamma-lactone of 2,3-dehydro-L-gulonic acid on healthy and malignant blood cells

Prediction of Time-to-First Treatment (TTFT) in Favorable-Risk Chronic Lymphocytic Leukemia (CLL) Patients Using a Novel Stratification through Transcriptome Risk Scoring

Background: CLL is the most prevalent adult leukemia with a highly heterogenous genetic landscape leading to extremely varied clinical outcomes. Previously, CLL patients with immunoglobulin heavy chain variable region ( IGHV) mutated status and presence of deletion 13q14 [del(13q)] were identified as favorable-risk with most patients remaining on lifetime observation. However, other intrinsic factors contributing to CLL disease progression and leading to treatment initiation remain unknown. Our goal was to identify patients at high-risk of progression with added predictive value (APV) beyond IGHV-status and presence of del(13q). Methods: Flow cytometry was used to sort CD19+CD5+ malignant cells in peripheral blood from CLL patients at Huntsman Cancer Institute at University of Utah and triple sequencing generated (tumor whole transcriptome and paired tumor-normal whole exome data). We used SPECTRA, a novel dimension reduction transcriptome approach, to derive a set of independent, intrinsic, quantitative transcriptome tumor variables from 249 CLL patients with quality-controlled transcriptome sequence data. From this set, 182 treatment-naïve (TN) patients with quality-controlled clinical variables were used as a discovery cohort set to derive a SPECTRA-based risk score for TTFT using multivariable Cox proportional hazards modeling. Event time was date of patient specimen acquisition to initiation of frontline therapy with patients censored at last follow-up or death. Gaussian mixture modeling (GMM) was performed to identify evidence for distinct risk groups within the quantitative risk score. GMM-risk groups, and further stratifications by IGHV mutational and del(13q) status, were used in hazard ratios (HR) and to illustrate differences in Kaplan-Meier time-to-event curves. An independent publicly available dataset of 548 TN CLL patients with clinical and transcriptome data for CD19+ enriched cells was used for replication. Results: SPECTRA produced 19 quantitative spectra variables to describe most of the expression variation across the 249 CLL patients. In multivariable Cox modeling for TTFT, 7 spectra were significant and retained in a final model, which GMM separated into a bi-modal distribution and defined high (N=83) and low-risk (N=99) groups (HR=5.7, 95% confidence interval [CI] 3.4-9.7). In a post-hoc model including IGHV mutational and del(13q) status, the spectra-risk score showed significant APV beyond both factors (p<0.001 for both). The discovery study timeframe was 6.3 years (y) and included 109 IGHV-mutated and 75 del(13q) patients. In the IGHV-mutated patients, median TTFT (mTTFT) was significantly shorter for spectra-high risk patients (3.1y) vs. spectra-low risk patients (median not reached [NR]; p<0.001). Similarly, in the del(13q) patients, mTTFT was significantly shorter in high-risk patients (3.3y) compared to median NR for spectra-low (p<0.001) ( Figure). Importantly, stratification of patients into low- and high-risk SPECTRA scores provided significant additional information for prediction of TTFT than IGHV mutational and del(13q) status ( Figure). For validation, we applied the same spectra-risk score to the independent data set containing 301 IGHV-mutated and 278 del(13q) CLL patients. In the replication set, the mTTFT in the IGHV-mutated patients who were spectra-high was 3.3y vs. 11.2y in spectra-low (p<0.001). Similarly, in the replication set of del(13q) patients, spectra-high-risk patients had a mTTFT of 2.7y vs. 10.7y for spectra-low (p<0.001). Conclusion: A transcriptome risk score utilizing novel SPECTRA variables identified a substantial subset of CLL patients with IGHV-mutated status and presence of del(13q) who have uncharacteristically short TTFT, but who would be classified as favorable risk under current best practice stratification. Future directions include validating our results with external patient cohorts from Mayo Clinic and investigating the genetic and transcriptomic profile of SPECTRA low- and high-risk cohorts to determine targetable pathways for treatment.

Analysis of eosinophil count as a predictor of Acute Lymphoblastic Leukemia (ALL)

Background: Acute lymphoblastic leukemia (ALL) is a malignancy of blood cells in many children. Predicting the severity of ALL is important for treatment. An easy and cheap marker is eosinophil count. This study aims to analyze eosinophil count as a predictor of ALL severity. Methods: Retrospective study using medical record data of 76 ALL patients from January 2020 to September 2021 was conducted at RSUP Dr. Wahidin Sudirohusodo Hospital. Patients are classified as ALL remission and relapses. Eosinophil Count based on routine blood test results using Sysmex XN-1000. Statistical Test using Kolmogorov-Smirnov test to assess data normality, Mann-Whitney test, eosinophil count diagnostic values analyzed with ROC curve to assess AUC and determination of cut-off value. The test results are significant if p<0.05. Results: The sample consisted of 59 ALL remissions and 17 ALL relapses. The mean eosinophil was found to be significantly lower in the relapse patient (0.19) than in the Remission patient (0.47) (p<0.05). Based on the ROC curve, the value AUC = 0.660 and significant (p<0.05). This shows that the cut-off value of eosinophil count can be used as a prognostic value for the status of ALL patients. ROC curve shows the sensitivity and specificity of the eosinophil count is 70.6% and 54.2% at a cut-off of 0.15. Conclusion: Eosinophil Count can be used as a prognostic value for the status of ALL patients with a cut-off value of 0.15. The eosinophil count was lower in the relapse patients than in the remission patients.

Circulating tumor cells in colorectal cancer - a review of detection methods and clinical relevance.

Colorectal cancer (CRC) is the third most common cancer; it is one of the leading malignancies contributing to cancer mortality. Colorectal cancer is the third most diagnosed cancer in men and the second in women worldwide. Diagnosis of CRC depends on several clinical features such as age, primary site, tumor-node-metastasis stage, genetic parameters and the presence or absence of metastasis. The latter is a phenomenon that is induced by the shedding of tumor cells in the blood circulation by the primary tumor. Such cells are known as circulating tumor cells (CTCs). The detection of CTCs is quite challenging due to their scarceness; thus it requires their enrichment and characterization. Studying the utility of CTCs in the diagnosis of CRC has been the aim of several studies; they demonstrated that ≥ 3 CTCs in 7.5 ml of blood is correlated with a worse prognosis and short progression-free and overall survival. Circulating tumor cells have also been monitored to study treatment response and predict future relapses. The present review aims to bring to light the different techniques used to detect and characterize these malignant cells in the peripheral blood of cancer patients as well as the clinical relevance of CTCs in CRC patients.

Cellular and Molecular Effects of Eribulin in Preclinical Models of Hematologic Neoplasms.

Despite the advances in understanding the biology of hematologic neoplasms which has resulted in the approval of new drugs, the therapeutic options are still scarce for relapsed/refractory patients. Eribulin is a unique microtubule inhibitor that is currently being used in the therapy for metastatic breast cancer and soft tissue tumors. Here, we uncover eribulin's cellular and molecular effects in a molecularly heterogeneous panel of hematologic neoplasms. Eribulin reduced cell viability and clonogenicity and promoted apoptosis and cell cycle arrest. The minimal effects of eribulin observed in the normal leukocytes suggested selectivity for malignant blood cells. In the molecular scenario, eribulin induces DNA damage and apoptosis markers. The ABCB1, ABCC1, p-AKT, p-NFκB, and NFκB levels were associated with responsiveness to eribulin in blood cancer cells, and a resistance eribulin-related target score was constructed. Combining eribulin with elacridar (a P-glycoprotein inhibitor), but not with PDTC (an NFkB inhibitor), increases eribulin-induced apoptosis in leukemia cells. In conclusion, our data indicate that eribulin leads to mitotic catastrophe and cell death in blood cancer cells. The expression and activation of MDR1, PI3K/AKT, and the NFκB-related targets may be biomarkers of the eribulin response, and the combined treatment of eribulin and elacridar may overcome drug resistance in these diseases.

Development of Consensus Guidelines for Hematology Fellow Competency in Peripheral Blood Smear Review Utilizing Nominal Group Technique

INTRODUCTION: Graduate medical education (GME) training in hematology in the United States is accredited by the Accreditation Council for Graduate Medical Education (ACGME). Trainees provide patient care that requires manual review and interpretation of peripheral blood smears (PBS). The ACGME milestones were developed with significant input from the American Society of Hematology (ASH) and mandate fellow competency in the interpretation of peripheral blood smears. However, there are currently no publications that define competency or propose consensus recommendations (CRs) for PBS review. The primary aim of this study was to establish CRs on PBS review with a focus at the GME level. METHODS: Nominal group technique (NGT) and constructivist grounded theory (CGT) were selected given the lack of existing published theory and consensus on the methodology of PBS review or other analogous visuospatial skills within GME. A convenience sample of hematologists with expertise in training and assessing fellows was recruited through the ASH Medical Educators Institute. Goal accrual was 5-10 hematologists. Participants were required to regularly review PBSs as part of their clinical practice and attend two 1-hour virtual focus group sessions. The facilitator guide for session 1 was developed a priori to prompt open discussion on PBS review. Dialogue was transcribed and organized into thematic concepts through inductive coding. Data from session 1 were analyzed using a mixed methods approach and were used to develop a facilitator guide for session 2. Draft CRs were created using CGT. Weak and strong consensus were pre-specified as 50 - 69%, and >70% agreement, respectively. CRs underwent iterative review which would continue for a pre-specified minimum of 2, but no more than 3 rounds. RESULTS: Eight academic hematologists (5 men, 3 women) enrolled in the focus group (Table 1). Duration of clinical practice ranged from 5 to 33 years. Clinical focus spanned classical and malignant hematologic conditions. Half had formally instructed trainees in course work on PBS morphology. All routinely worked with fellows. CRs were generated through CGT. Three rounds of review occurred. Participants provided a statement of agree vs. disagree and offered qualitative suggestions for each statement in which they disagreed. Response rates per round were 87.5%, 87.5%, and 100%. The most commonly identified themes included recognition of morphology suggestive of thrombotic microangiopathies and distinguishing between malignant vs. benign white blood cells (WBC), specifically as it pertains to acute leukemias. Strong consensus was reached on multiple aspects of PBS education, including curricular considerations, method of review, and morphology (Table 2). All agreed that trainees should learn PBS review through a systematic approach, although some agreed that this systematic approach is not always used in clinical practice. The group agreed that trainees should be educated through PBS review of patients under their clinical care as well as through formal slide "libraries". Many discussed the changing landscape of PBS education with the advent of digital microscopy, and formed strong consensus that trainees should understand the benefits and limitations of digital microscopy. Group discussion largely focused on disorders of WBCs and red blood cells (RBC) (43% and 48% of all coded statements respectively). Most discussion focused on disorders in which prompt recognition was imperative to avert significant patient morbidity or mortality. However, all agreed that trainees must also be competent in the identification of common conditions, regardless of the degree of clinical importance, including normal peripheral blood smear morphology. The group was unable to reach consensus on how to balance these competing philosophies. CONCLUSIONS: A formal theory of PBS education was systematically developed using CGT. Experts were able to form strong CRs on almost every aspect of PBS review at the GME level. FUTURE DIRECTIONS: We propose that these guidelines serve as a template for future research and curricular development for both PBS review and other visuospatial tasks in medical education. This framework can also be used by organizations, such as ACGME and ASH, when formally reviewing and codifying guidelines on PBS review. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Laser Micromachining of Bone as a Tool for Studying Bone Marrow Biology.

The bone marrow (BM) has traditionally been a difficult tissue to access because it is embedded deep within the bone matrix. It is home to the hematopoietic stem cells (HSCs) that give rise to all blood cells in the body. It is also the site of origin for malignant blood cells such as leukemia and multiple myeloma, as well as a frequent site of metastasis for many solid tumors including prostate and breast cancer. The following chapter describes how laser micromachining of bone can be used to improve both optical and physical access to the BM. For example, laser thinning of the overlying bone can improve optical access, enabling deeper imaging into the BM as well as enhancing optical resolution by reducing scattering and aberration. Laser micromachining can also be used to provide physical access into the BM by creating access ports for micropipette insertion and delivery of cells to precise locations in the BM, as well as for the extraction of BM cells and interstitial fluid, all under image guidance. This chapter provides a detailed protocol for installing a laser-micromachining capability for users with an existing multiphoton microscope. Additionally, we briefly outline how such a system improves the optical resolution during imaging as well as its potential useto study injury response.

A CNN Model for Early Leukemia Diagnosis

Blood cancer (leukemia) is one of the most serious diseases that affect blood-forming tissues. It usually involves white blood cells. The early detection of this severe disease helps doctors to provide efficient treatment. However, the discovery of this sickness at its first stages is often not easy due to similar morphological characteristics of malignant and healthy blood cells. Flow cytometry was the only used technique for early detection of leukemia, but it is very expensive and usually unavailable in hospitals. Deep learning is a machine learning technique that teaches computers to do what comes naturally to humans learn by examples. In the last few years, deep learning has achieved great successes to solve concrete problems. In particular, it has proven successful in medical imaging classification. In this work, we propose a Convolutional Neural Network (CNN) experiment for the classification of malignant white blood cells from normal ones using a dataset of microscopic images. The proposed approach leads to a balanced model that reaches a high level accuracy.

Enrichment-Free Single-Cell Detection and Morphogenomic Profiling of Myeloma Patient Samples to Delineate Circulating Rare Plasma Cell Clones.

Multiple myeloma is an incurable malignancy that initiates from a bone marrow resident clonal plasma cell and acquires successive mutational changes and genomic alterations, eventually resulting in tumor burden accumulation and end-organ damage. It has been recently recognized that myeloma secondary genomic events result in extensive sub-clonal heterogeneity both in localized bone marrow areas and circulating peripheral blood plasma cells. Rare genomic subclones, including myeloma initiating cells, could be the drivers of disease progression and recurrence. Additionally, evaluation of rare myeloma cells in blood for disease monitoring has numerous advantages over invasive bone marrow biopsies. To this end, an unbiased method for detecting rare cells and delineating their genomic makeup enables disease detection and monitoring in conditions with low abundant cancer cells. In this study, we applied an enrichment-free four-plex (CD138, CD56, CD45, DAPI) immunofluorescence assay and single-cell DNA sequencing for morphogenomic characterization of plasma cells to detect and delineate common and rare plasma cells and discriminate between normal and malignant plasma cells in paired blood and bone marrow aspirates from five patients with newly diagnosed myeloma (N = 4) and monoclonal gammopathy of undetermined significance (n = 1). Morphological analysis confirms CD138+CD56+ cells in the peripheral blood carry genomic alterations that are clonally identical to those in the bone marrow. A subset of altered CD138+CD56- cells are also found in the peripheral blood consistent with the known variability in CD56 expression as a marker of plasma cell malignancy. Bone marrow tumor clinical cytogenetics is highly correlated with the single-cell copy number alterations of the liquid biopsy rare cells. A subset of rare cells harbors genetic alterations not detected by standard clinical diagnostic methods of random localized bone marrow biopsies. This enrichment-free morphogenomic approach detects and characterizes rare cell populations derived from the liquid biopsies that are consistent with clinical diagnosis and have the potential to extend our understanding of subclonality at the single-cell level in this disease. Assay validation in larger patient cohorts has the potential to offer liquid biopsy for disease monitoring with similar or improved disease detection as traditional blind bone marrow biopsies.

Identification of white blood cells for the diagnosis of acute myeloid leukemia

AbstractThe diagnosis of hematologic malignancies such as leukemia includes identifying malignant white blood cells. Manual microscopic analysis of white blood cells is time‐consuming and involves the assistance of medical specialists, and its accuracy may be affected by their abilities. Our objective is to develop an automated system that can identify 15 categories of white blood cells to assist medical practitioners in diagnosing acute myeloid leukemia. The proposed approach uses an ensemble model built with transfer learning‐based pre‐trained networks to categorize 15 kinds of white blood cells. An over‐sampling strategy is used to alleviate the problem of class imbalance, followed by data augmentation. For experimentation, a microscopic blood image dataset containing 18 365 cells images from 200 individuals representing 15 different forms of leukocytes is used. For cells with more than 400 images available, the suggested technique achieves an F1 score of more than 91%. Myeloblasts, which are frequent in myeloid leukemias and are detected in the peripheral blood, are recognized with an average precision of 95.74%. This work describes an image processing strategy that employs ensemble learning to assist in diagnosing acute myeloid leukemia by classifying 15 different types of leukocytes. Experiments show that our technique is both practical and effective. Extensive research supports the use of the leukocyte classifier in real‐world medical applications, such as assisting clinicians in diagnosing diseases and decreasing human resource requirements.

Clinical effects of a single dose of cannabinoids to patients with chronic lymphocytic leukemia

This phase II clinical trial investigates a one-time oromucosal dose of tetrahydrocannabinol/cannabidiol (THC/CBD) in 23 patients with indolent leukemic B cell lymphomas. Primary endpoint was a significant reduction in leukemic B cells. Grade 1 − 2 adverse events were seen in 91% of the patients; most common were dry mouth (78%), vertigo (70%), and somnolence (43%). After THC/CBD a significant reduction in leukemic B cells (median, 11%) occurred within two hours (p = .014), and remained for 6 h without induction of apoptosis or proliferation. Normal B cells and T cells were also reduced. CXCR4 expression increased on leukemic cells and T cells. All effects were gone by 24 h. Our results show that a single dose of THC/CBD affects a wide variety of leukocytes and only transiently reduce malignant cells in blood. Based on this study, THC/CBD shows no therapeutic potential for indolent B cell lymphomas (EudraCT trial no. 2014-005553-39).

Local asymptotic stability of a system of integro-differential equations describing clonal evolution of a self-renewing cell population under mutation.

In this paper we consider a system of non-linear integro-differential equations (IDEs) describing evolution of a clonally heterogeneous population of malignant white blood cells (leukemic cells) undergoing mutation and clonal selection. We prove existence and uniqueness of non-trivial steady states and study their asymptotic stability. The results are compared to those of the system without mutation. Existence of equilibria is proved by formulating the steady state problem as an eigenvalue problem and applying a version of the Krein-Rutmann theorem for Banach lattices. The stability at equilibrium is analysed using linearisation and the Weinstein-Aronszajn determinant which allows to conclude local asymptotic stability.

Early detection and manifestation of leukemia in the oral cavity of the child

Cancer is a chronic disease and is the third leading cause of death in children aged 1-14 years. About one third of cancer in child-ren is leukemia with an incidence of 9 cases per 100,000 population. Leukemia is a malignancy of blood cells originating from the bone marrow and can occur in children and adults. Early detection of oral lesions is very important for the prevention and treatment of complications that may arise during therapy, a better prognosis, lower morbidity and mortality for that disease. Oral manifestations of leukemia are gingival enlargement and spontaneous bleeding, oral ulceration, petechiae, hematoma and pale mucosa. Oral lesions occur in both acute and chronic forms of all types of leukemia and are more common in the acute stage. Dental care for patients with leukemia should be focused on preventing injury, local control of gingival bleeding by re-moving the biofilm, and prevention of oral infection. Oral hygiene by brushing teeth, use of fluoride, and a non-cariogenic diet should also be emphasized during treatment.

The Donor – Recipient Weight Ratio is a Reliable Marker for Cell Yield in Hematopoietic Stem Cell Donations

Bone marrow transplants remain an import source of hematopoietic stem cells for patients suffering from specific diseases like aplastic anemia, for pediatric patients with malignant and non-malignant blood cell disorders, and for situations in which graft-versus-host disease (GvHD) is a concern. Identifying the optimal donor to achieve a 3-5 x 108/kg of recipient weight TNC yield may be challenging. In an analysis of 687 consecutive donors, donor and procedure characteristics were related to TNC/kg of recipient weight using Spearman correlation coefficients as well as linear and multiple regression analysis. We found correlations between donor WBC (r = 0.17), donor platelet counts (r = 0.15), donor BMI (r = 0.10), and the percentage of donor estimated blood volume accessed for harvesting (r = -0.57) with TNC/kg of recipient weight. The strongest correlation existed between the donor-recipient weight ratio and the TNC/kg (r = 84). In a multivariate regression analysis, the donor-recipient weight ratio influenced the TNC/kg of recipient weight more significantly (adjusted R2 = 0.84) than all other related variables put together. The minimal donor-recipient weight ratio associated with a TNC/kg of at least 3x108/kg of recipient weight was 0.8 (mean 3.425; 95% CI 2.01, 5.8). Using this donor-recipient ratio provides national bone marrow donor registries with a practical and simple measure to assure optimal cell yield outcomes in hematopoietic stem cell donations.

Clinical Significance of Spatial Heterogeneity in Newly Diagnosed and Relapsed Multiple Myeloma

Clinical Significance of Spatial Heterogeneity in Newly Diagnosed and Relapsed Multiple Myeloma

Gold(I) Bis(1,2,3-triazol-5-ylidene) Complexes as Promising Selective Anticancer Compounds.

The synthesis and antiproliferative activity of Mes- and iPr-substituted gold(I) bis(1,2,3-triazol-5-ylidene) complexes in various cancer cell lines are reported, showing nanomolar IC50 values of 50 nM (lymphoma cells) and 500 nM (leukemia cells), respectively (Mes < iPr). The compounds exclusively induce apoptosis (50 nM to 5 μM) instead of necrosis in common malignant blood cells (leukemia cells) and do not affect non-malignant leucocytes. Remarkably, the complexes not only overcome resistances against the well-established cytostatic etoposide, cytarabine, daunorubicin, and cisplatin but also promote a synergistic effect of up to 182% when used with daunorubicin. The present results demonstrate that gold(I) bis(1,2,3-triazol-5-ylidene) complexes are highly promising and easily modifiable anticancer metallodrugs.

Precision Medicine in Hematology 2021: Definitions, Tools, Perspectives, and Open Questions.

During the past few years, our understanding of molecular mechanisms and cellular interactions relevant to malignant blood cell disorders has improved substantially. New insights include a detailed knowledge about disease-initiating exogenous factors, endogenous (genetic, somatic, epigenetic) elicitors or facilitators of disease evolution, and drug actions and interactions that underlie efficacy and adverse event profiles in defined cohorts of patients. As a result, precision medicine and personalized medicine are rapidly growing new disciplines that support the clinician in making the correct diagnosis, in predicting outcomes, and in optimally selecting patients for interventional therapies. In addition, precision medicine tools are greatly facilitating the development of new drugs, therapeutic approaches, and new multiparametric prognostic scoring models. However, although the emerging roles of precision medicine and personalized medicine in hematology and oncology are clearly visible, several questions remain. For example, it remains unknown how precision medicine tools can be implemented in healthcare systems and whether all possible approaches are also affordable. In addition, there is a need to define terminologies and to relate these to specific and context-related tools and strategies in basic and applied science. To discuss these issues, a working conference was organized in September 2019. The outcomes of this conference are summarized herein and include a proposal for definitions, terminologies, and applications of precision and personalized medicine concepts and tools in hematologic neoplasms. We also provide proposals aimed at reducing costs, thereby making these applications affordable in daily practice.