Acute Myeloid Lymphoma Research Articles

Simultaneous merkel cell carcinoma and acute myeloid leukaemia: A diagnostic challenge.

Merkel cell carcinoma is a very aggressive primary skin tumour with a high risk of local recurrences and lymphatic and distant metastases. The frequent association between this carcinoma and other skin tumour and lymphoid malignancies, its similar cellular morphology with leukocytes, and limited infiltration in bone marrow constituted a challenging diagnosis. We report an unusual case of an 82-year-old male who simultaneously presented Merkel cell carcinoma and acute myeloid lymphoma. The diagnosis was established through flow cytometry, immunohistochemical studies and next generation sequencing (NGS) analysis. Flow cytometry allowed for the differentiation of the two cell populations in bone marrow aspirate, which was crucial to the diagnosis of Merkel cell carcinoma and acute myeloid leukaemia (AML), after confirmed by immunohistochemistry. AML could be classified based on NGS results. Following diagnosis, the patient received palliative care and died 50days later. immunophenotypic analysis by flow cytometry and Immunohistochemical study was crucial to establish the diagnosis of simultaneous affection of Merkel cell carcinoma and hematologic disorder.

Abstract 5714: Synergistic effect of the CDC7 inhibitor, monzosertib (AS-0141) with current therapies in AML models

Abstract Introduction: Cell division cycle 7 (CDC7) is a highly conserved serine-threonine kinase that plays an important role in the initiation of DNA replication and cell cycle progression. Aberrant expression of CDC7 have been reported to cause uncontrolled proliferation of many cancer types, suggesting that CDC7 inhibitors may provide a great potential for the development of novel therapy for cancers. Monzosertib (AS-0141) is a potent, selective, orally bioavailable small molecule inhibitor of CDC7, and is currently being evaluated in Phase I study for the treatment of solid tumors. In a preclinical cancer cell panel study, monzosertib showed strong antiproliferative activities against a variety of cancer types, and acute myeloid lymphoma (AML) cell lines were found to be the most sensitive to monzosertib. As a single agent, treatment with monzosertib accumulates DNA damage in cancer cells and induces cell death. In this study, we aimed to investigate the antitumor effects of monzosertib alone and in combination with other anticancer drugs in AML models. Method: Antiproliferative activity of monzosertib was examined against a panel of 35 human cancer cell lines of various cancer types. DNA metyltransferase (DNMT) inhibitors (azacitidine or decitabine) and BCL2 inhibitor (venetoclax) were evaluated for their synergistic/antagonistic effects in combination with monzosertib against human AML cell lines (THP-1, HL-60, MV4-11, MOLM-14, TF-1, U-937 and NOMO-1). The combination index (CI) was calculated using the Chou-Talalay method. Flow cytometry assay was used to analyze apoptosis. To evaluate the in vivo efficacy, tumor-bearing mice were treated with monzosertib alone or in combination with venetoclax. Results: The combination of monzosertib with azacitidine, decitabine, or venetoclax resulted in a significant synergistic antiproliferative effects against AML cell lines in vitro. The flow cytometry assay indicated that azacitidine combination induced apoptosis and increased cell death in THP-1 cells. In vivo, oral administration of monzosertib demonstrated robust in vivo antitumor efficacy in a MV4-11 tumor bearing xenograft mouse model, both as a single agent and in combination with venetoclax. Conclusions: Monzosertib, a selective CDC7 inhibitor, demonstrated strong antiproliferative activity against human AML cell lines, both as a single agent and in combination with standard therapies. Monzosertib exerts synergistic antitumor effect with venetoclax in a human AML xenograft mouse model. These results suggest that monzosertib has a potential to enhance the antitumor efficacy of standard of care agents for AML patients. Citation Format: Hiroko Endo, Hatsuo Furuichi, Akinori Arimura, Yu Nishioka, Masaaki Sawa. Synergistic effect of the CDC7 inhibitor, monzosertib (AS-0141) with current therapies in AML models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5714.

ST11 KPC-2-Producing Klebsiella pneumoniae Isolated from Patient with Acute Myelocytic Leukemia.

The emergence of the ST11-CRKP (ST11-CRKP) strain is expected to become a serious public health problem in China. As one of the most serious complications in patients with acute myeloid lymphoma, infections can cause systemic infection and life-threatening sepsis, seriously affecting the morbidity, mortality, and quality of life of patients. Thus, ST11-CRKP infections in patients with acute myeloid lymphoma are worthy of our attention. To investigate the occurrence and genetic characteristics of the ST11-CRKP from a patient with acute myeloid lymphoma. Species identification was determined by MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was conducted by VITEK 2 system with AST-N335 panel. Whole-genome sequencing was performed on the Illumina NovaSeq 6000 platform. Phylogenetic analyses were performed using Snippy based on the core-genome SNPs. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and Whole-genome analysis indicated blaKPC-2 genes were located on plasmids with a conserved genetic environment. Moreover, the eight ST11-CRKP strains carry a variety of antimicrobial resistance genes (ARGs) and virulence factors. The ability of biofilm formation of eight strains was verified by a crystal violet assay. Core genome single-nucleotide polymorphism (cgSNP) analysis suggesting a possible bacterial translocation event. We performed a comprehensive analysis of ST11-CRKP strains from a patient with acute myelocytic leukemia. Our study emphasized the need for continuous surveillance of ST11-CRKP in the clinic especially in the immunocompromised population.

Cancer in Ecuadorian subjects with Laron syndrome (ELS).

Meta-analyses from 2018-2022 have shown that obesity increases the risk of various cancers such as acute myeloid lymphoma, chronic myeloid lymphoma, diffuse beta cell lymphoma, Hodgkin's lymphoma, leukemia, multiple myeloma, non-Hodgkin's lymphoma, bladder, breast, cholangiocarcinoma, colorectal, ovarian, esophageal, kidney, liver, prostate, thyroid, and uterus. Contextually, obesity, and its comorbidities, is the largest, most lethal pandemics in the history of mankind; hence, identification of underlying mechanisms is needed to adequately address this global health threat. Herein, we present the metabolic and hormonal mechanisms linked to obesity that might etiologically contribute to neoplasia, including hyperinsulinemia and putative places in the insulin-signaling pathway. Excess insulin, acting as a growth factor, might contribute to tumorigenesis, while abundant ATP and GDP supply the additional energy needed for proliferation of rapidly dividing cells. Our observations in the Ecuadorian cohort of subjects with Laron syndrome (ELS) prove that obesity does not always associate with increased cancer risk. Indeed, despite excess body fat from birth to death, these individuals display a diminished incidence of cancer when compared to their age- and sex-matched relatives. Furthermore, in cell cultures exposed to potent oxidizing agents, addition of ELS serum induces less DNA damage as well as increased apoptosis. ELS individuals have absent growth hormone (GH) counter-regulatory effects in carbohydrate metabolism due to a defective GH receptor. The corresponding biochemical phenotype includes extremely low basal serum concentrations of insulin and insulin-like growth factor-I, lower basal glucose and triglyceride (TG) levels, and diminished glucose, TG, and insulin responses to orally administered glucose or to a mixed meal.

Detection of Blood Cancer Cells Using Microscopic Images

Abstract: Blood Cancer cells forming a tissue is called lymphoma. Thus, disease decreases the cells to fight against the infection or cancer blood cells. Blood cancer is also categorized in too many types. The two main categories of blood cancer are Acute Lymphocytic Lymphoma and Acute Myeloid Lymphoma. In this project proposes a approach that robotic detects and segments the nucleolus from white blood cells in the microscopic Blood images. Here in this project, we have used the two Machine learning algorithms that are k-means algorithm, Support vector machine algorithm. K-mean algorithm is use for segmentation and clustering. Support vector machine algorithm is used for classification. Keywords: k-means, Support vector machine, Lymphoma, Acute Lymphocytic Lymphoma, Machine Learning

Abbv-621 Is a Novel and Potent TRAIL Receptor Agonist Fusion Protein That Induces Apoptosis Alone and in Combination with Navitoclax and Venetoclax in Hematological Tumors

Cell death can be initiated through activation of the extrinsic and intrinsic apoptotic signaling pathways. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily of cytokines, preferentially triggers the extrinsic apoptotic pathway by binding as a trimer to two closely related cell surface death receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5). When these receptors undergo trimerization, it leads to the formation of the death-inducing signaling complex (DISC) to recruit and activate downstream caspases that ultimately leads to apoptotic cell death. Since TRAIL was found to induce apoptosis, several TRAIL receptor agonists have been developed for the treatment of cancer. ABBV-621 is a novel, second generation TRAIL receptor agonist that is currently being tested in Phase 1 clinical trials. It is an engineered fusion protein consisting as an IgG1-Fc linked to a single chain trimer of TRAIL subunits resulting in a total of six death receptor binding sites per molecule in order to maximize receptor clustering. ABBV-621 exhibited potent single agent activity in acute myeloid lymphoma (AML) and diffuse large B-cell lymphoma (DLBCL) cell lines following 24hrs treatment. This activity was rapid and mechanism-based since activation of downstream apoptotic signaling events (caspase activation, mitochondrial depolarization, phosphatidylserine exposure) were observed as early as 1 hour following the addition of ABBV-621, and cell death could be completely blocked with the pan caspase inhibitor z-VAD-FMK . In vivo, ABBV-621 demonstrated robust single agent anti-tumor activity in pre-clinical models of AML and DLBCL.The intrinsic apoptotic pathway is regulated by the BCL-2 protein family which controls the release of cytochrome c from the mitochondria resulting in the activation of downstream caspases. Because the two apoptotic pathways are linked, the intrinsic pathway can influence cell death mediated through the extrinsic pathway. The elevated expression of the anti-apoptotic proteins, BCL-2 and BCL-XL, can inhibit the activation of the intrinsic apoptotic pathway and enable resistance to anti-cancer therapeutics, including TRAIL. Venetoclax (ABT-199), a BCL-2 selective inhibitor, and navitoclax (ABT-263) a BCL-2/BCL-XL selective inhibitor, were tested in combination with ABBV-621 in a number of hematologic tumor cell lines in vitro and in vivo . The anti-tumor activity of ABBV-621 in combination with venetoclax or navitoclax exceeded that of either agent tested alone in pre-clinical and AML and DLBCL xenograft models.Collectively, these data highlight that targeting the extrinsic apoptosis signaling pathway with either ABBV-621 alone or in combination with venetoclax/navitoclax to harness the intrinsic apoptosis signaling pathway has potential therapeutic benefit in hematologic malignancies.Disclosures:All authors are employees of AbbVie. The design, study conduct, and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication. DisclosuresTahir:Abbvie: Employment, Equity Ownership. Smith:Abbvie: Employment, Equity Ownership. Solomon:Abbvie: Employment, Equity Ownership. Zhang:Abbvie: Employment, Equity Ownership. Xue:Abbvie: Employment, Equity Ownership. Xiao:Abbvie: Employment, Equity Ownership. Cheng:Abbvie: Employment, Equity Ownership. Buchanan:Abbvie: Employment, Equity Ownership. Morgan-Lappe:Abbvie: Employment, Equity Ownership. Phillips:Abbvie: Employment, Equity Ownership.

Lifetime occupational exposure proportion estimation methods: a sensitivity analysis in the general population.

To present a sensitivity analysis of the most widely used means of estimating lifetime occupational exposure proportion (LOEP) and their respective impacts on LOEP and population-attributable fraction (PAF) estimates. A French population-based sample with full job history (N = 10,010) was linked with four Matgéné job-exposure matrices: flour, cement, silica and benzene. LOEP and the 95% confidence interval were estimated using four methods: the maximum exposure probability during the career (Proba_max), two methods subdividing careers into job-periods (job-period_M1, job-period_M2) and one into job-years (job-year). To quantify differences between methods, percentages of variation were calculated for proportion values and PAF, and compared with published results for France using cross-sectional proportion multiplied by a factor. For each agent, LOEP estimated from the maximum probability during the career (Proba_max) was consistently lower than proportion taking account of job-periods or job-years. LOEP on Proba_max for flour, cement, silica and benzene were, respectively, 4.4% 95% CI (4.0-4.7), 4.3% (3.9-4.6), 6.1% (5.7-6.5) and 3.9% (3.6-4.2). Percentage of variation ranged from 0 to 55.8% according to the agent. The number of cancer cases varied by a twofold factor for exposure to silica and lung cancer and by a fourfold factor for exposure to benzene and acute myeloid lymphoma. The present study provides a description of several LOEP estimation methods based on exposure assessment over the entire career and describes their impact on PAF. For health monitoring purposes, we recommend to report a range of LOEP with low and high estimates obtained using job-periods (job-period_M1 and job-period_M2).

Human TERT promoter polymorphism rs2853669 is associated with cancers: an updated meta-analysis.

The polymorphism rs2853669 in the telomerase reverse transcriptase gene (TERT) promoter region is widely investigated for the risk of different cancers. However, previous results remained inconclusive. Thus, we performed this updated meta-analysis to comprehensively evaluate the association between rs2853669 and the susceptibility of human cancer. A systematic literature search via PubMed, EMBASE, Cochrane Library, and Web of Science databases was conducted that produced a total of 19 eligible studies containing 23,085 subjects. The relationship was calculated with the odds ratio (OR) and 95% confidence intervals (CIs). Statistical analyses were performed using the RevMan 5.4 software. The analysis indicated that rs2853669 is associated with an enhanced risk of overall cancer risk. From subgroup analysis, a significantly increased association in five genetic models (p < 0.05) was found among Asians, but no association was observed in Caucasians. Although we did not find any significant correlation between rs2853669 and breast cancer, an increased and statistically significant association was found for both lung cancer and acute myeloid leukemia. We did not find any association in other cancer types during stratified analysis. Our meta-analysis suggests that rs2853669 polymorphism in TERT gene is associated with an increased risk of overall cancer susceptibility, particularly in the Asian population. Moreover, rs2853669 is significantly associated with lung cancer and acute myeloid lymphoma. However, large-scale studies are needed to confirm our findings.

A Flow-Cytometric Analysis of Spectrum of Acute Myeloid Leukemia at Diagnosis

Background: Acute Myeloid Lymphoma is the clonal proliferation of non-lymphoid blasts comprising at least 20% of total nucleated cells either in bone marrow or peripheral blood. In the recent years, flow cytometry has emerged as a powerful diagnostic tool for AML due to its impact on treatment and prognosis.&#x0D; Aims &amp; Objectives:&#x0D; &#x0D; To analyse the flow cytometry findings in patients diagnosed as acute myeloid leukemias.&#x0D; To evaluate variations in flow cytometry expression in various subtypes of acute myeloid leukemia&#x0D; &#x0D; Materials &amp; Methods: Patients diagnosed as acute myeloid leukaemia on peripheral smears were subjected to flow cytometry analysis. This was a four-year study from July 2015 to June 2017 retrospectively and from July 2017 to June 2019 prospectively.&#x0D; Results: A total of 27 cases diagnosed as Acute Myeloid Leukemia (AML) were included in the study. Acute Promyelocytic Leukemia was observed to be the most common subtype. The most commonly expressed myeloid antigens were CD13 and CD33. There was an aberrant expression of CD7 and CD56 in 1 case each indicating adverse prognosis.&#x0D; Conclusion: Immunophenotyping of the myeloid cells by flow cytometry has revolutionised the diagnosis of acute myeloid leukemias. It aids in confirming the morphological diagnosis, and also helps in assigning specific lineage, accurate sub classification and adequate treatment in challenging cases. Aberrant expressions were observed in 3 cases of AML. Aberrant antigen expression is associated with a poor outcome. Flow cytometry results interpreted with morphology are not only complementary but also conclusive aiding in therapeutics and predicting prognosis.

Acute Bacterial Parotitis in Adult Hematologic Malignancy

Abstract Acute bacterial parotitis (ABP) is an uncommon condition in immunosuppressed adult cancer patients. Here, we report 2 cases of parotitis in immunocompromised patients; one with a diagnosis of extranodal marginal zone B-cell lymphoma and the other with acute myeloid lymphoma. Both patients were treated with antibiotics and local management with resolution of their parotitis. Per review of literature, this is the first article describing ABP in patients with bone marrow transplantation and hematologic malignancies. Moreover, this is also the first article reporting ABP due to Stenotrophomonas maltophilia, an opportunistic gram-negative rod bacterium.

BRAF inhibition in hairy cell leukemia with low-dose vemurafenib

AbstractThe activating mutation of the BRAF serine/threonine protein kinase (BRAF V600E) is the key driver mutation in hairy cell leukemia (HCL), suggesting opportunities for therapeutic targeting. We analyzed the course of 21 HCL patients treated with vemurafenib outside of trials with individual dosing regimens (240-1920 mg/d; median treatment duration, 90 days). Vemurafenib treatment improved blood counts in all patients, with platelets, neutrophils, and hemoglobin recovering within 28, 43, and 55 days (median), respectively. Complete remission was achieved in 40% (6/15 of evaluable patients) and median event-free survival was 17 months. Response rate and kinetics of response were independent of vemurafenib dosing. Retreatment with vemurafenib led to similar response patterns (n = 6). Pharmacodynamic analysis of BRAF V600E downstream targets showed that vemurafenib (480 mg/d) completely abrogated extracellular signal-regulated kinase phosphorylation of hairy cells in vivo. Typical side effects also occurred at low dosing regimens. We observed the development of acute myeloid lymphoma (AML) subtype M6 in 1 patient, and the course suggested disease acceleration triggered by vemurafenib. The phosphatidylinositol 3-kinase hotspot mutation (E545K) was identified in the AML clone, providing a potential novel mechanism for paradoxical BRAF activation. These data provide proof of dependence of HCL on active BRAF signaling. We provide evidence that antitumor and side effects are observed with 480 mg vemurafenib, suggesting that dosing regimens in BRAF-driven cancers could warrant reassessment in trials with implications for cost of cancer care.

Abstract 634: Novel antibody-drug conjugates targeting Axl show anti-tumor activity in solid cancer xenograft models

Abstract Axl is a receptor tyrosine kinase of the TAM family, which is structurally characterized by the presence of two extracellular immunoglobulin-like domains and two fibronectin type III domains, a single-pass transmembrane region and an intracellular tyrosine kinase domain. Axl is aberrantly expressed and activated in both solid and hematological malignancies and has been associated with poor clinical prognosis in a number of cancers, including non-small cell lung cancer, breast cancer, pancreatic cancer and acute myeloid lymphoma. Functionally, Axl has been implicated in multiple pathological processes, such as tumor cell motility, adherence and migration, epithelial-to-mesenchymal transition, metastasis, angiogenesis and resistance to tyrosine kinase inhibitors. With the aim to target Axl expressing cancers, a panel of Axl-specific antibody-drug conjugates (ADC) was generated. First, high affinity human Axl antibodies were generated in HuMAb mice. Binding studies using Axl mutants, in which specific human Axl domains had been replaced with their murine analogs, demonstrated that the Axl antibody panel consisted of antibodies against different Axl extracellular domains. Second, the Axl antibodies were conjugated with the microtubule disrupting agent monomethyl auristatin E (MMAE) using the protease cleavable valine citrulline linker. Axl ADCs showed cytotoxic activity in vitro, which was dependent on target expression and on conjugation with cytotoxic payload. The anti-tumor activity of Axl ADCs was confirmed in vivo. Axl ADCs induced tumor regression in cell line derived xenograft models for lung cancer and epidermoid carcinoma. Anti-tumor activity was especially efficient in the lung cancer xenograft model, in which inhibition of tumor growth was observed upon treatment with a single dose of 0.5 mg/kg Axl ADC. In the same model, 1 mg/kg Axl ADC was sufficient to induce complete tumor regression. Importantly, Axl ADCs also showed efficient anti-tumor activity in patient-derived xenograft (PDX) models that showed heterogeneous target expression. In summary, Axl is a novel target for antibody-mediated delivery of cytotoxic agents into tumor cells. The promising results obtained in preclinical tumor models support further development of Axl-specific ADCs. Citation Format: Esther C.W. Breij, Sandra Verploegen, Andreas Lingnau, Edward N. van den Brink, Maarten Janmaat, Mischa Houtkamp, Wim K. Bleeker, David Satijn, Paul W.H.I. Parren. Novel antibody-drug conjugates targeting Axl show anti-tumor activity in solid cancer xenograft models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 634. doi:10.1158/1538-7445.AM2015-634

Relapsing polymyositis in chronic graft versus host disease

Chronic graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation, which contributes to the morbidity and mortality of transplant patients. A polymyositis pattern of injury is a rare manifestation of chronic GVHD in skeletal muscle after hematopoietic stem cell transplantation. We report a 54-year-old man with acute myeloid lymphoma who underwent an allogeneic bone marrow transplantation and subsequently developed acute gastrointestinal GVHD 2months post-transplantation and polymyositis 14months post-transplantation. Upon tapering of steroids, the patient experienced a relapse of polymyositis. The literature on polymyositis in chronic GVHD is briefly reviewed.

Radioimmunotherapy with α-particle-emitting radionuclides.

α-particle-emitting radionuclides are highly cytotoxic and are thus promising candidates for use in targeted radioimmunotherapy of cancer. Due to their high linear energy transfer (LET) combined with a short path length in tissue, α-particles cause severe DNA double-strand breaks that are repaired inaccurately and finally trigger cell death. For radioimmunotherapy, α-emitters such as (225)Ac, (211)At, (212)Bi/(212)Pb, (213)Bi and (227)Th are coupled to antibodies via appropriate chelating agents. The α-emitter immunoconjugates preferably target proteins that are overexpressed or exclusively expressed on cancer cells. Application of α-emitter immunoconjugates seems particularly promising in treatment of disseminated cancer cells and small tumor cell clusters that are released during the resection of a primary tumor. α-emitter immunoconjugates have been successfully administered in numerous experimental studies for therapy of ovarian, colon, gastric, blood, breast and bladder cancer. Initial clinical trials evaluating α-emitter immunoconjugates in terms of toxicity and therapeutic efficacy have also shown positive results in patients with melanoma, ovarian cancer, acute myeloid lymphoma and glioma. The present problems in terms of availability of therapeutically effiective α-emitters will presumably be solved by use of alternative production routes and installation of additional production facilities in the near future. Therefore, clinical establishment of targeted α-emitter radioimmunotherapy as one part of a multimodal concept for therapy of cancer is a promising, middle-term concept.

Spinal Epidural Granulocytic Sarcoma in a Child Precedent to Clinical Manifestation of Acute Myeloid Lymphoma -Case Report-

A 13-year-old boy presented with an epidural thoracic granulocytic sarcoma manifesting as rapidly progressive paraplegia preceding clinical manifestation of acute myeloid leukemia (AML). Magnetic resonance imaging revealed a thoracic epidural tumor. He underwent emergent laminectomy and the tumor was totally resected. The initial histological diagnosis was malignant lymphoma. The correct diagnosis of epidural granulocytic sarcoma and AML was established based on cell-surface markers and a chromosomal study of the bone marrow cells. A combination of chemotherapy and bone marrow transfusion achieved complete remission of leukemia. No evidence of AML has emerged over the 18-month follow-up period. Granulocytic sarcoma should be considered in the differential diagnosis of an epidural mass in pediatric patients with or without acute leukemia. Immediate diagnosis and appropriate treatment are recommended to prevent leukemic transformation.

Zielgerichtete Radionuklidtherapie mit α-Emittern - Grundlagen, experimentelle und erste klinische Studien

α-particle emitting nuclides are highly cytotoxic and are thus promising candidates for use in targeted radionuclide therapy of cancer. Due to their high linear energy transfer (LET) combined with a short range in tissue, α-particles cause severe DNA-damages that are repaired inaccurately and finally trigger cell death. For targeted therapy, α-emitters like actinium-225, astatine-211, bismuth-213 and thorium-227 are coupled to antibodies or receptor ligands via appropriate chelators that bind to proteins that are overexpressed or exclusively expressed on tumour cells. Application of α-emitters seems particularly promising for targeted therapy of disseminated tumour cells and small tumour cell clusters that remain in the body following resection of the primary tumour. α-emitter conjugates have been successfully applied in numerous experimental studies for therapy of ovarian, colon, gastric and breast cancer. Initial clinical trials evaluating α-emitter antibody conjugates in terms of tolerance and therapeutic efficacy also have shown positive results in patients with melanoma, ovarian cancer, acute myeloid lymphoma (AML) and glioma. Therefore the aim could be clinical establishment of targeted α-emitter radionuclide therapy as one part of a multimodal concept for therapy of cancer.

Determinants of anemia in cancer patients receiving chemotherapy

9719 Background: Anemia is common in cancer patients. It affects their quality of life and puts them at risk of severe complications when treated with blood transfusions. Little is known about the determinants of anemia. Improvements in this regard could lead to better management. Methods: Data were available from cross-sectional study surveys conducted in five European countries (France, Italy, Germany, Spain and United Kingdom) in 1999, 2000, 2001 and 2003 using the same Case Report Forms (CRF). Details of one cycle out of all chemotherapy cycles were recorded retrospectively in 41,114 patients. Anemia was defined as a hemoglobin level < 12g/dL. Risk of anemia was investigated through the effects of gender, age, chemotherapy type, country, cycle number and year of treatment with logistic regression (with 95% confidence intervals (CI)). Eight different tumor types were considered: breast, Small Cell lung (SCL), Non Small Cell lung (NSCL), ovarian, Acute Myeloid Lymphoma (AML), Non Hodgkin Lymphoma (NHL), Hodgkin Disease (HD), Multiple Myeloma (MM). Results: Across all tumor types anemia was reported in 67% of the patients and in > 95% in AML patients. Incidence increased over time for breast cancer, SCL, NSCL, NHL and MM. It was decreasing for ovarian cancer. Age had no independent effect except for NHL with less anemia in patients > 40 years. Consistent differences across countries were observed. The UK (Odds Ratio (OR) = 0.44), Spain (0.47) and Italy (0.54) have less likely anemia compared to Germany (OR = 1 (referent)) and France (0.85). Apart from MM and NHL a clear risk tendency for anemia to increase with subsequent cycles is observed. No association between cisplatin and platinum-based regimens with anemia in first cycle was seen. Conclusions: Anemia affects the majority of cancer patients receiving chemotherapy, being more frequent in men and during subsequent chemotherapy cycles. Research is required to better understand the frequency differences noted across countries in Europe and to identify patients at high risk, particularly in the initial cycle, since prevention and/or treatment measures are readily available. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen