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Introduction: Alterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding. Methods: We examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated. Results: The chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping. Discussion: The identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements. [ABSTRACT FROM AUTHOR]

IntroductionAlterations of the NUP214 gene (9q34) are recurrent in acute leukemias. Rearrangements of chromosomal band 9q34 targeting this locus can be karyotypically distinct, for example t(6;9)(p22;q34)/DEK::NUP214, or cryptic, in which case no visible change of 9q34 is seen by chromosome banding.MethodsWe examined 9 cases of acute leukemia with NUP214 rearrangement by array Comparative Genomic Hybridization (aCGH), reverse-transcription polymerase chain reaction (RT-PCR), and cycle sequencing/Sanger sequencing to detect which fusion genes had been generated.ResultsThe chimeras DEK::NUP214, SET::NUP214, and NUP214::ABL1 were found, only the first of which can be readily detected by karyotyping.DiscussionThe identification of a specific NUP214 rearrangement is fundamental in the management of these patients, i.e., AMLs with DEK::NUP214 are classified as an adverse risk group and might be considered for allogenic transplant. Genome- and/or transcriptome-based next generation sequencing (NGS) techniques can be used to screen for these fusions, but we hereby present an alternative, step-wise procedure to detect these rearrangements.

The article focuses on differentiation syndrome in acute promyelocytic leukemia (APL) and the role of Auer rods in identifying maturing promyelocytes during treatment. Topics include the unique persistence of Auer rods during differentiation, the significance of ATRA-ATO therapy in inducing promyelocyte maturation, and the importance of distinguishing differentiation-related changes from poor treatment response.

In 1990 to 2005, a total of 138 hematopietic stem cell transplantations (HSCT) were made in patients with high risk group of acute myeloblastic leukemia (AML) (auto-HSCT in 20 patients, related allo-HSCT in 18, unrelated allo-HSCT in 20) and acute lymphoblastic leukemia (ALL) (auto-HSCT in 13 patients, related allo-HSCT in 24, unrelated allo-HSCT in 43). The patients' age was 2 to 55 years. Five-year relapse-free survival after auto-HSCT in the 1st-2nd remissions in AML was 40%; 8-year one was 30% in patients with ALL (including 3 patients with Ph+). In patients aged less than 21 years with acute leukemias, 5-year overall survival after related and unrelated donor allo-HSCT was 38 and 44%, respectively. Both allo-HSCT modes had the similar spectrum of complications in the early period (as long as 100 days). In patients with AML and ALL, 5-year overall survival depended on the stage of disease at the moment of allo-HSCT performance (52 and 5.9% in ALL and 62.5 and 27.3% in AML, remission and relapse, respectively). Auto- HSCT in ALL and AML is an effective method for remission consolidation and may be regarded as an alternative if the patient has no related or unrelated donor. The efficacy of allo-HSCT from a related or unrelated donor in acute leukemia depends on the stage of disease at the moment of its per- formance, which determines the likelihood of development of a relapse and different complications (toxic, infectious, graft rejection, etc).

Leukemic cells acquire complex and often multifactorial mechanisms of resistance to treatment, including various metabolic alterations. Although the use of metabolic modulators has been proposed for several decades, their use in clinical practice has not been established. Natural products, the so-called botanical drugs, are capable of regulating tumor metabolism, particularly in hematopoietic tumors, which could partly explain the biological activity attributed to them for a long time. This review addresses the most recent findings relating to metabolic reprogramming—Mainly in the glycolytic pathway and mitochondrial activity—Of leukemic cells and its role in the generation of resistance to conventional treatments, the modulation of the tumor microenvironment, and the evasion of immune response. In turn, it describes how the modulation of metabolism by plant-derived extracts can counteract resistance to chemotherapy in this tumor model and contribute to the activation of the antitumor immune system.

Objectives: The objectives of this study were to assess the cutoff levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-alpha) for predicting acute leukemia with special attention to their correlation with blast counts in leukemia subtypes of acute lymphoblastic leukemia (ALL), acute myeloid leukemia, and mixed phenotypic acute leukemia. Methods: This observational cross-sectional case–control study was done from September 2018 to March 2020. A total of 35 newly diagnosed patients of acute leukemia were taken as cases and compared with 140 healthy controls. Complete phenotyping and blood film analysis was done for the cases. The serum levels of IL-6 and TNF-alpha levels were assessed and compared among cases and controls. The levels of IL-6 and TNF-alpha were correlated with blast counts of subtypes of acute leukemia. P < 0.05 was considered statistically significant. Results: Compared to controls, acute leukemia cases had significantly higher levels of IL-6 median interquartile range value (12.39 [8.056–136.894] vs. 8.27 [6.477–10.849]) and TNF-alpha (192.48 ± 633.01 vs. [20.63 ± 8.17]) with P < 0.05. TNF-alpha was found to be the better predictor of acute leukemias at cutoff of >24.906 with sensitivity of 71.43% as compared to IL-6 (Sn of 48.57%). Only TNF-alpha had a significant correlation with absolute blast count in ALL cases (r = 0.579, P = 0.0118). Conclusion: It can be concluded that an aberrant increased production of the pro-inflammatory cytokines IL-6 and TNF-alpha is shown in the acute leukemia patients as compared to the healthy controls. TNF-alpha is a better marker among both the cytokines for predicting acute leukemia with significant correlation with blast counts in ALL.

Simple Summary: Hematologic neoplasms comprise a heterogeneous group of diseases that interfere with normal blood production. Treating patients who fail available therapies for these diseases is an ongoing challenge. Thus, the search for new treatment options is urgent, and drug repositioning is emerging as an attractive strategy for finding new effective drugs. Eribulin is a drug that acts on microtubules, and it is used in solid tumors, and its safety is known. In the present study, we provide evidence of the effects of eribulin on hematologic cancers and identify the potential biomarkers of responsiveness. Our study indicates that eribulin is a candidate blood cancer drug for repositioning. 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. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 72-year-old male with severe pancytopenia. Topics include Trephine roll revealing multiple large cells with high nuclear-cytoplasmic ratio, pale blue-gray cytoplasm, open nuclear chromatin, and cytoplasmic blebs, and resembling megakaryoblasts; and characterized by an increase in primitive megakaryoblasts and myelofibrosis.

The study of circulating peptides in the blood offers significant opportunities for diagnosing, stratifying, and managing various diseases. With recent technological advances and the ongoing need to understand complex diseases such as acute leukemias (AL), peptidomic analysis of peripheral blood, especially serum and plasma, has become increasingly important for studying human biology and pathophysiology. Here, we provide insights and perspectives on technological developments and potential clinical applications using widely used peptidomic analysis methods. We discuss examples where peptidomics using serum or plasma has contributed to the understanding of AL. Specifically, we highlight the scarcity of peptidomic studies applied to AL and emphasize the importance of exploring this area, as the few published studies present promising results that can significantly contribute to precision medicine.

The article explores Acute myeloid leukemia (AML) with inv(16)(p13q22)/t(16;16) (p13;q22) has distinct clinicopathologic features, including myelomonocytic leukemic cells, abnormal bone marrow eosinophils, and a relatively favorable prognosis.1,2 Most cases are classified as AML M4 with abnormal eosinophils (M4Eo) in the French-AmericanBritish (FAB) classification.

Introduction: Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions. Methods: The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high‐throughput sequencing (HTS). Results: Acquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively. Conclusions: The GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway‐activating mutations may represent an extra option of targeted therapy with kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background: The High Complexity Oncology Unit (Unidade de Assistência de Alta Complexidade em Oncologia - UNACON/Acre) allowed the treatment of acute leukemias in Acre. Objective: To determine the clinical-epidemiological profile and hospital survival of acute leukemias treated at UNACON/Acre between 2007 and 2014. Method: This is a longitudinal, retrospective study of patients with acute leukemias between 06/15/2007 and 12/31/2014 whose medical records provided data for descriptive analysis of the variables, and subsequent analysis of 1-year and 2-year cumulative survival (Kaplan Meier method) and comparison of survival curves (log-rank test). Results: The survival for acute myeloid leukemia (AML) was 30 and 32% at 1 and 2 years, respectively, with a worse survival rate for males, white, age ≥20 years, leukometry <20,000 cells/mm3, lactic dehydrogenase ≥600 U/dl and subtype different from M3. For acute lymphoid leukemias (ALL), survival was 59 and 45% at 1 and 2 years, respectively. Female gender, age ≥20 years, and high leukometry had worse survival. For patients <20 years with ALL, better survival was observed in the age group of 2-9 years. Conclusion: This is the first epidemiological study of survival in Acre for acute leukemias with results consistent with the literature. However, new studies should be performed. [ABSTRACT FROM AUTHOR]

Background: Panobinostat demonstrates activity against pediatric cancers in vitro. A phase I trial in children with refractory hematologic malignancies was conducted. Study design: The trial evaluated two schedules of oral panobinostat using 3 + 3 dose escalations in 28-day cycles. For children with leukemia, panobinostat was given once daily three days a week each week at 24, 30 and 34 mg/m2/day. For children with lymphoma, panobinostat was given once daily three days a week every other week at 16, 20 and 24 mg/m2/day. Cerebrospinal fluid (CSF) from Day 29 of the first cycle, when available, was evaluated for PK. The study was registered on clinicaltrials.gov (NCT01321346) Results: Twenty-two subjects enrolled with leukemia. Five enrolled at dose level 1, 6 at dose level 2, and 11 at dose level 3. There was one dose limiting toxicity (DLT) in the leukemia arm at dose level 3 (Grade 4 hypertriglyceridemia), but no maximum tolerated dose (MTD) was identified. No subjects required removal from protocol therapy for QTc prolongation. PK studies were available in 11 subjects with similar exposure in children as in adults. Four Day 29 CSF specimens were found to have panobinostat levels below the lower limit of quantification. Five subjects with lymphoma were enrolled and received study drug, and 4 were evaluable for DLT. A DLT was reported (Grade 3 enteritis) on the lymphoma arm. Conclusions: Panobinostat was tolerated in heavily pretreated pediatric subjects. Gastrointestinal effects were observed on this study. There were no cardiac findings. There were no responses. [ABSTRACT FROM AUTHOR]

Among fungal infection, mucormycosis is a rare but severe etiology in immunocompromised patients. Lung and sinus are the usual sites; the involvement of blood vessels is also described. The diagnosis is a real challenge, because blood tests (galactomannan, beta-D-glucan) are negative and the only diagnostic tool is usually the biopsy of the affected zone. Aortitis is rare and usually caused by bacterial infection, fungal etiology is unusual and only episodic cases are reported in literature. Medical therapy alone is usually not sufficient and debilitating surgical intervention is required. We report the case of a child affected by B precursor acute lymphoblastic leukemia, presenting a systemic fungal infection complicated by aortitis, probably due to Mucor. The patient developed fever and pneumonia during the Induction phase of chemotherapy. At the beginning, the infection was treated as bacterial and the diagnosis of Mucor infection was possible only after surgical intervention with histological analysis. Medical therapy (antifungal) was not sufficient alone to cure the infection and an urgent surgical intervention was required. This case underlines the challenge in the diagnosis of mucomycosis, that should be suspected in case of prolonged fever during aplasia, not responding to standard antibiotic and antifungal therapies. Mucor infection often require a combined intervention, both medical and surgical to cure the infection. [ABSTRACT FROM AUTHOR]

Objective: To study the immunophenotypic profile of 68 acute leukemia (Acute myeloid leukemia and acute lymphoblastic leukemia) cases at diagnosis. Materials & Methods: This is a cross-sectional, observational study carried out in department of Pathology, of a tertiary care center, Karad for a period of 2 years from June 2017 to May 2019. Diagnosis of Acute leukemia cases was based on peripheral blood smear examination, bone marrow aspiration, flowcytometry, cytogenetic and molecular studies. Results: Sixty eight cases of Acute leukemias were diagnosed in a period of 2 years, where 25 cases were of ALL & 43 cases were of AML. CD13, CD33 and cMPO were the most diagnostic and useful myeloid markers. CD14, CD64, CD11b, CD11c were useful monocytic markers. CD15 was most common maturation marker. B-ALL had an immunophenotype with CD34 +, TdT +, HLADR+, CD10+, CD19+, cCD79a +, co expression of CD10 andCD19 +, CD20 +. T-ALL expressed CD3+, cCD3+, CD5+, CD7+, CD2 dim to moderate +, tdt - to dim+, CD34-, HLADR. CD7 was the most common aberrant marker expressed in the present study. Conclusion: Our study concludes that immunophenotyping has become an important diagnostic tool in establishing the diagnosis of acute leukemias. It is very useful for detecting minimal residual disease and also reported to have prognostic significance. [ABSTRACT FROM AUTHOR]

Introduction: Adipocytes produce a 16k Da protein known as leptin, which is associated with different acute leukemias. The purpose of the current study was to review the current body of evidence on leptin's role on acute leukemias. Methods: A thorough search of the literature was carried out utilizing databases like Scopus, PubMed, and Web of Science. "Adipokines," "Adipocytes," "Leptin," "acute leukemias," "acute myeloid leukemia," and "acute lymphoblastic leukemia" were the primary search terms. 36 of the 178 papers that were initially found, based on the inclusion and exclusion criteria were eligible to be assessed in this investigation. Results: The results of this study demonstrated that leptin serum levels rise in acute leukemia patients regardless of age or gender. Furthermore, compared to acute myeloid leukemia, leptin serum levels were greater in acute lymphoid leukemia. Leukemic cell proliferation is stimulated by leptin, both by itself and in conjunction with other cytokines. This may be the result of leukemic precursor cells' and progenitor cells' ability to resist apoptosis of their increased expression of certain receptors, which increases their reactivity to external stimuli. Leukemic hematopoiesis may also be indirectly impacted by leptin. However, Patients with acute leukemia should not use serum leptin levels as a diagnostic marker. Conclusion: Leptin's stimulatory effects on leukemia cells imply a possible function as a prognostic biomarker and therapeutic target. Elevated leptin levels are related with acute leukemia development, especially in the lymphoid subtype. [ABSTRACT FROM AUTHOR]

Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy. Also, many imaging studies may be hazardous during pregnancy. Management of these malignancies during pregnancy induces many treatment-related risks for mother and baby and should consider patient’s preferences for pregnancy continuation. In this article, hematologic malignancies diagnosed in pregnant patients including acute leukemias, chronic myeloid leukemia, lymphomas, multiple myeloma and myeloproliferative neoplasms, will be reviewed, including diagnostic and management strategies and their impact on the pregnant patient and the developing fetus.

It is considered that hypercholesterolemia is life-threatening and low cholesterol levels are a positive factor. However, taking into consideration the fact that cholesterol plays a key role in cell proliferation, it should be remembered that its low blood level may be linked to high cholesterol demands from neoplastic cells. The literature review analyzes the results of recent investigations of lipid metabolism in patients with hematologic cancers and their other types. All given investigations show a significant reduction in the serum levels of total cholesterol and high-density lipoproteins in patients with hematological disease at its onset. The data for other indicators of the lipid transport system are ambiguous. Such changes have been elucidated to be associated with the accumulation of cholesterol in the leukemia cells due to enhanced synthesis de novo, a more active absorption from circulation and blocked release of its surplus. If the disease runs a favorable course, lipid metabolic parameters become normalized and, in case of remission, correspond to those seen in healthy individuals. They continue to decline in patients with disease progression. This allows the consideration of cholesterol, its fractions, and apolipoproteins as biochemical prognostic markers in hematological cancer patients and as indicators for assessment of treatment results. In addition, there is evidence for the effect of chemotherapeutic agents on lipid metabolism. Recent attempts to elaborate new treatment strategies, by using the current knowledge on the role of lipid metabolism in cancers, are considered.

INTRODUCTION: In this study, it is aimed to emphasize the causes and importance of macrocytosis in paediatric practice. METHODS: in the paediatric hematology and oncology clinic, 1752 patients evaluated in 2017, patients with macrocytosis were examined retrospectively with clinical and laboratory findings. Patients with macrocytosis were compared with the frequency of severe hematologic diseases such as acute leukemia and bone marrow failure in patients with normocytic and microcytic mean corpusculer volume. RESULTS: Macrocytosis was detected in 72 out of 1752 patients (4.1%) in the study. Acute lymphoblastic leukemia in 11(15.2%), acute myeloid leukemia in 3(4.1%), Fanconi aplastic anemia in 7(9.7%), Diamond-Blackfan anemia in 2(2.7%), aplastic anemia in 1(1.3%), congenital diseritropoetic anemia in 1(1.3%), deficiency of vitamin B12 in 14(19.4%) were diagnosed. Down syndrome was presented in 33 cases (45.8%). The number of patients with acute leukemia diagnosis was 14(0.8%) in the group in which the mean corpusculer volume was either microcytic or normocytic. The incidence of acute leukemia and bone marrow failure was significantly higher in the group with macrocytosis compared between the two groups. CONCLUSION: Although vitamin B12 deficiency is considered firstly in patients who have undergone cytopenia and macrocytosis in our country, haematological malignancies, bone marrow failures, myelodysplasia and myeloproliferative diseases should be remembered especially in the individuals with Down syndrome at the same time.

Objectives: To demonstrate the importance of regional efforts to register features and report frequency of hematology diseases in the context of incomplete national registries. Methods: Frequencies and salient characteristics of hematologic diseases in Northeast Mexico were documented in a reference center at a tertiary care university hospital during the decade 2005-2015. Disease categories were grouped by age, sex and diagnosis. Age group distribution followed WHO guidelines in years as children (0-17), adults (18-64) and elders (+65). Results: 2406 patients were included: 1239 (51.5%) were females and 1167 (48.5%) males; F:M ratio was 1.06:1; median age was 35 years (0-95). The frequency by age group included adults, 1370 cases (56.9%), children, 695 cases (28.9%), and elderly, 341 (14.2%). Most frequent diagnoses were acute lymphoblastic leukemia (ALL) 18.2% (n = 438), anemia 15.9% (n = 383), non-Hodgkin’s lymphoma (NHL) 15.7% (n = 378), immune thrombocytopenic purpura (ITP) 9.8% (n = 235) and Hodgkin’s lymphoma (HL) 6.5% (n = 156). Median age for the whole cohort was 35 years; for children, was 6 years, for adults 40 and for the elderly 73. Results for ALL, anemia and ITP were comparable to high-income countries; NHL, HL and chronic myeloid leukemia presented a decade earlier. Discussion: Complete, opportune reliable information on the number of cases, age and sex distribution with the potential to influence strategies for timely diagnosis and treatment options for important hematologic diseases can be accrued by regional centers. Conclusion: Information on hematology diseases derived of regional registries in low-middle income countries is a reasonable alternative to complement and update national registries. [ABSTRACT FROM AUTHOR]

Haplo-identical transplants (Haplo-Tx) are an important alternative for patients with hematological malignancies who lack a HLA-identical donor. Seventy-one T-replete Haplo-Tx were performed in 70 high-risk patients at our center; 22/70 (31%) patients with refractory/relapsed leukemia received sequential salvage therapy (SeqTh) with high-dose chemotherapy followed by Haplo-Tx during the chemotherapy-induced neutropenia. Graft-versus-host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (days + 3 and + 4) with tacrolimus and mycophenolic acid. After a median follow-up of 29.2 months, 3-year overall survival (OS) and event-free survival (EFS) were 43.8 and 40.2%, while 3-year cumulative incidences (CIs) of non-relapse mortality (NRM) and relapse (RI) were 27 and 33%. Day 100 and day 400 CI of grade III-IV acute and moderate-severe chronic GVHD were 11 and 15%. Three-year RI was significantly lower in patients in complete remission (CR) versus those not in CR at the time of transplant (21.5 vs. 48%, p = 0.009) and in patients who received PBSC as compared to BM (22 vs. 45%, p = 0.009). In patients treated with SeqTh, 3-year OS was 19%, while 3-year RI and NRM were 52 and 28% at a median follow-up of 50 months. Overall, Haplo-Tx was feasible in heavily pretreated high-risk patients without a suitable HLA-identical donor. [ABSTRACT FROM AUTHOR]

Introduction: in this study, it is aimed to emphasize the causes and importance of macrocytosis in paediatric practice. Methods: in the paediatric hematology and oncology clinic, 1752 patients evaluated in 2017, patients with macrocytosis were examined retrospectively with clinical and laboratory findings. Patients with macrocytosis were compared with the frequency of severe hematologic diseases such as acute leukemia and bone marrow failure in patients with normocytic and microcytic mean corpusculer volume. Results: macrocytosis was detected in 72 out of 1752 patients (4.1%) in the study. Acute lymphoblastic leukemia in 11(15.2%), acute myeloid leukemia in 3(4.1%), Fanconi aplastic anemia in 7(9.7%), Diamond- Blackfan anemia in 2(2.7%), aplastic anemia in 1(1.3%), congenital diseritropoetic anemia in 1(1.3%), deficiency of vitamin B12 in 14(19.4%) were diagnosed. Down syndrome was presented in 33 cases (45.8%). The number of patients with acute leukemia diagnosis was 14(0.8%) in the group in which the mean corpusculer volume was either microcytic or normocytic. The incidence of acute leukemia and bone marrow failure was significantly higher in the group with macrocytosis compared between the two groups. Conclusion: although vitamin B12 deficiency is considered firstly in patients who have undergone cytopenia and macrocytosis in our country, haematological malignancies, bone marrow failures, myelodysplasia and myeloproliferative diseases should be remembered especially in the individuals with Down syndrome at the same time. [ABSTRACT FROM AUTHOR]

Abstract: Childhood acute lymphoblastic leukemia is one of the most frequent cancers of that age range. Tremendous progress has been achieved in the treatment of these diseases, and increasing numbers of patients are actually cured and live normal lives thereafter. The treatment however remains a complex and serious ordeal. Although statistics are more than encouraging, the specific care of any given patient must be considered with a personalized approach. Among modern tools of disease monitoring, minimal residual disease assessment has earned increasing appeal and now tends to be rather dubbed “measurable” residual disease as the major goal of therapy was the complete eradication of the pathological clone. In this review, the basic characteristics of ALL diagnosis will be briefly recalled, before summarizing available techniques and providing some considerations on the clinical relevance and strategies of childhood ALL MRD evaluation. [ABSTRACT FROM AUTHOR]

Introduction: Abnormal serum lipids profiles have been reported in human malignancies. Attempts have been made to correlate serum lipids in leukemia patients with the disease activity and response to chemotherapy. Material and Methods: The aim of this study was to evaluate a possible prognostic significance of serum lipid profile in patients with acute leukemia before and after chemotherapy. Methods: Fasting blood samples were obtained from 78 previously untreated patients at Tehran University of Medical Sciences hospitals at the time of diagnosis and after chemotherapy with complete remission. Total cholesterol, serum triglyceride, HDL-C and LDL-C were estimated by enzymatic kits. Results: A total of Seventy eight proved cases of ALL and AML with mean age of 24.87 years were studied out of which 53.8% were males and 46.2% were females. An altered serum lipid profile was observed at the time of diagnosis of patients. Statistically significant values included elevated TG(194.41±18.28mg%), reduced TC (128.97±8.53mg%),LDLC (82.84±6.76mg%) and HDLC(25.30± 1.22 mg %).After complete remission the lipid profile significantly was different, a reduction in TG (127.84±8.59mg%) and elevated TC(168.01±11.66mg%),LDLC(105.10±6.41mg%),and HDLC (37.38±1.78mg%) were observed.Values are given as mean±SD. Conclusion: These results support the idea that cholesterol and its fractions(LDLC, HDLC), and TG determination might be considered as useful biochemical and prognostic markers in hematologic neoplasms. [ABSTRACT FROM AUTHOR]

Leukemic cells acquire complex and often multifactorial mechanisms of resistance to treatment, including various metabolic alterations. Although the use of metabolic modulators has been proposed for several decades, their use in clinical practice has not been established. Natural products, the so-called botanical drugs, are capable of regulating tumor metabolism, particularly in hematopoietic tumors, which could partly explain the biological activity attributed to them for a long time. This review addresses the most recent findings relating to metabolic reprogramming-Mainly in the glycolytic pathway and mitochondrial activity-Of leukemic cells and its role in the generation of resistance to conventional treatments, the modulation of the tumor microenvironment, and the evasion of immune response. In turn, it describes how the modulation of metabolism by plant-derived extracts can counteract resistance to chemotherapy in this tumor model and contribute to the activation of the antitumor immune system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Arévalo, Cruz-Rodriguez, Quijano and Fiorentino.)

Aim. To study the pattern of complex chromosome damages (CCD) in acute leukemias (AL) and their place in the development of post-transplant recurrences (PTR) of AL. Materials and methods. Cytogenetic and partially molecular biological studies of bone marrow cells were conducted in 10 patients with PTR. Of them, 6 patients were diagnosed as having acute lymphoblastic leukemia (ALL), including T-ALL and Ph-positive ALL in 2 and 4 patients, respectively; and 4 patients had acute non-lymphoblastic leukemia (ANLL), including one case secondarily induced by previous polychemotherapy (PCT) and irradiation. The standard G-band staining technique complemented by multicolor fluorescence in situ hybridization in one of the cases was used. Results. It was shown that CCD had the similar pattern in 4 patients before transplantation and in PTR, progressed in 4 more patients, was absent or unnoticed in the early stage of the disease. The other recurrent chromosomal abnormalities that are worthy of notice are as follows: a) the presence of two Ph chromosomes in the cells of two of the 4 patients with Ph+ ALL; b) the frequent involvement of chromosome pairs 9, 19, 5, and 7 into the numerical and structural rearrangements. Conclusion. The important feature of PTR of AL is cellular CCDs, a portion of which is clearly related to previous PCT and may be of pathogenetic value for the development of recurrences.

Aim. To perform a dynamic study of Β-endorphin, hypoxia-inducible factor-1α (HIF-1α), and cytokines in hematologic patients. Subjects and methods. Fifty-nine patients with different types of acute leukemia (AL), 30 with anaplastic anemia (AA), 24 with thrombocytopenic purpura, and 20 healthy volunteers were examined during their 40-day stay at 3200 m above sea level. Β-Endorphin and HIF-1α were measured by a sandwich-type enzyme immunoassay using the Abcam antibodies. Cytokines (interleukin (IL)-2, IL-6, and tumor necrosis factor-α) were estimated by enzyme immunoassay applying the Pro Con kits (Saint Petersburg). Results. Serum Β-endorphin concentrations were 1.5-2-fold above the normal values in the majority of patients with AL. The patients with initial leukocytosis at onset of disease were noted to have elevated white blood cell Β-endorphin concentrations up to 85.9±22.4 pg/ml; moreover, during chemotherapy this index increased about two times (170.74±33.8 pg/ml). There was a direct correlation between the concentrations of Β-endorphin and HIF-1α (r = 0.9) and an inverse correlation between the levels of IL-6 and Β-endorphin (r = -0.7). On ascending to 3200 m, under the conditions of hypoxic hypoxia the patients with AA or idiopathic thrombocytopenic purpura showed a considerable increase in serum Β-endorphin concentrations, mainly in the acute period of being at high altitudes. Conclusion. Stress factors (tumor, use of cytostatics, pain, anemia, hypoxia, high environment temperature) stimulate the elaboration of Β-endorphin, particularly in the white blood cells of patients with AL during chemotherapy. The highest elevation in the index was seen during acute adaptation to hypoxic hypoxia.

Aim. To study the deposition of donor platelets (DP) in myelosuppressive thrombocytopenia (TP) in patients with acute leukemia (AL) or lymphosarcoma (LSA), by using a radionuclide label (51Cr) for DP. Subjects and methods. Complex clinical, hematological and radionuclide studies were conducted in 63 patients divided into 3 groups: 1) 7 healthy volunteers (a control group); 2) 37 patients with AL; 3) 19 patients with LSA. Results. Changes were found in the deposition of labeled DPs used to prevent and treat hemorrhagic syndrome in myelosuppressive TP in patients with AL or LSA. In AL, this function was established to be virtually completely suppressed whereas in LSA, some functional activity of mononuclear phagocytes was preserved. Different degrees of suppression of this function were probably related to the nature of these diseases and particularly due to varying degrees of leukemic infiltration of depot organs. A mechanism for increased consumption of transfused DP in profound TP, one of the causes of which is the myelosuppression as a result of programmed polychemotherapy, cannot be ruled out. Conclusion. By and large, the radionuclide labeling technique for DP may be useful in specifying a number of uncertain mechanisms for derangements of the thrombocytic component of hemostasis in oncohematologic diseases.

ntroduction: Despite all improvement in the treatment of acute myeloid leukemia (AML) patients, the management in relapsed or refractory disease is still controversial. The use of multiple chemotherapeutic agents will induce more toxicity and morbidity in patients. Fludarabin- containing therapy (FLAG and FLANG) mostly has been used in the treatment of relapsed or refractory AML patients.Methods: In this retrospective study, we evaluated the response of treatment in 40 adult leukemia patients treated with these regimens from October 2007 to December 2011 in our center. They took FLAG (fludarabine, cytarabine, GCSF) and FLANG (fludarabine, cytarabine, mitoxantrone) according to the approved protocol. They were taken packed cells or platelets as needed and antibiotics in cases of established or highly suspicious infections. After these therapies, 12 patients with suitable donor made ready for allogeneic hematopoietic stem cell transplantation (HSCT) and one patient without donor underwent autologous HSCT.Results: The median age of patients was 29.5 (range: 16- 50) years old. The male to female ratio was 30:10. The patients were diagnosed with ALL (15, 37.5%) and AML (25, 62.5%). The most common subtype of leukemia was ALL- L2 and AML- M4. The most common disease treated was AML-M4. Two patients had secondary leukemia (breast cancer and MDS). Except two patients which treated with FLAG regimen, others received FLANG. Most patients were primary refractory (18, 45%), first relapse (17, 42.5%) or second relapse (5, 12.5%) before this treatment. Thirteen patients underwent hematopoietic stem cell transplantation after FLANG. Four patients received FLANG as relapse treatment after transplantation. Pulmonary aspergillus infection occurred in 13 patients and aspergillus sinusitis in two after FLANG/ FLAG treatment. White blood cells and platelet recovery observed in 30 patients with a median time of 20 days after treatment. Treatment resulted in complete response (n=19), partial response (n=1) and no response (n=11) in patients. Early death (before 60 days) after treatment occurred in 9 (22.5%) patients. The most common causes of death were primary disease (relapse) (24, 60%) and infection (5, 12.5%). The one- year overall survival was 21.4% (SE: 7.1%). Among the survivors, only 5 patients received transplantation and 5 patients are alive without transplantation.Conclusion: The study shows that refractory and relapsed leukemia patients can achieve complete remission with FLAG/ FLANG treatment. The side effects include serious fungal infections and sepsis. Moreover, high mortality during these treatments was observed.

Aim. To analyze the causes of prolonged hematopoietic tissue aplasias in patients with acute leukemias (AL) after chemotherapy courses. Materials and methods. Data on 7 patients with acute myeloid leukemia, followed up at the Hematology Departments, Hematology Research Center, Russian Academy of Medical Sciences, over the period 2003 to 2007, who had developed deep bone marrow aplasia (BMA) inadequate to cytostatic drug exposure during chemotherapy, were analyzed. The authors compared in all the patients the values of peripheral blood and bone marrow (BM) puncture specimens and the results of blood tests using the polymerase chain reaction at different AL development stages with the results of an immunohistochemical study using the markers of viruses of hepatitis C and B, a herpes group (EBV, CMV, HSV-1, HSV-2) and parvovirus B19. Results. The marker of hepatitis C was detected in 6 of the 7 patients with prolonged BMA; 3 of these 6 patients showed a simultaneous infection with hepatitis B. Six of the 7 patients were found to have concomitant BM lesion with various herpes group viruses. Two patients had a resistant form of AL. Conclusion. Hepatitis C virus infection in patients and the resistant form of the disease were the principal causes of the development of BMA inadequate to cytostatic drug exposure. Affliction of abundant bone marrow cells with herpes group viruses was not a direct cause, but might substantially aggravate BMA.

Malignancy is the second most common cause of mortality in the reproductive period and it complicates up to one out of every 1000 pregnancies. When cancer is diagnosed during pregnancy, the management approach must take into consideration both the mother and her fetus. Hematologic cancers diagnosed in pregnancy are not common, resulting in paucity of randomized controlled trials. Diagnosis of such malignancies may be missed or delayed, as their symptoms are similar to those encountered during normal pregnancy. Also, many imaging studies may be hazardous during pregnancy. Management of these malignancies during pregnancy induces many treatment-related risks for mother and baby and should consider patient’s preferences for pregnancy continuation. In this article, hematologic malignancies diagnosed in pregnant patients including acute leukemias, chronic myeloid leukemia, lymphomas, multiple myeloma and myeloproliferative neoplasms, will be reviewed, including diagnostic and management strategies and their impact on the pregnant patient and the developing fetus. [ABSTRACT FROM AUTHOR]

Background Acute myeloid leukemia and acute lymphoid leukemia differ substantially in response to therapy and course, and accurate differentiation of the two is fundamental to therapeutic decisions. Immunophenotyping is used for this purpose, and various guidelines have been proposed regarding a minimal screening antibody panel. Most of them have been found inefficient. Methods Eighty-two cases of consecutive acute leukemias reporting to this hospital over a period of two years were included in the study. Peripheral blood smear, bone marrow aspirate, and bone marrow biopsy were studied using morphology, cytochemical stains, and relevant immunohistochemical stains on selected biopsy specimens. Flowcytometry analysis was carried out using Indian consensus screening panel and our proposed minimal screening panel (PMSP) for comparison. Result Immunophenotyping using PMSP resulted in 95.12% accurate diagnosis versus Indian consensus minimal screening panel (ICMSP) with an accuracy of 92.68%. This result was statistically significant as per Chi Square tests. Conclusion PMSP can be used as a substitute for ICMSP, since it includes lineage-specific cytoplasmic antibodies, as well as lesser number of monoclonal antibodies, and enables us to diagnose mixed lineage leukemia. Fewer markers can be linked to a lower cost as well, which is relevant in a developing economy. [ABSTRACT FROM AUTHOR]

It is well established that natural killer (NK) cells play an important role in the immunity against cancer, while the involvement of other recently identified, NK-related innate lymphoid cells is still poorly defined. In the haploidentical hematopoietic stem cell transplantation for the therapy of high-risk leukemias, NK cells have been shown to exert a key role in killing leukemic blasts residual after conditioning. While the clinical results in the cure of leukemias are excellent, the exploitation of NK cells in the therapy of solid tumors is still limited and unsatisfactory. In solid tumors, NK cell function may be inhibited via different mechanisms, occurring primarily at the tumor site. The cellular interactions in the tumor microenvironment involve tumor cells, stromal cells and resident or recruited leukocytes and may favor tumor evasion from the host's defenses. In this context, a number of cytokines, growth factors and enzymes synthesized by tumor cells, stromal cells, suppressive/regulatory myeloid and lymphoid cells may substantially impair the function of different tumor-reactive effector cells, including NK cells. The identification and characterization of such mechanisms may offer clues for the development of new immunotherapeutic strategies to restore effective anti-tumor responses. In order to harness NK cell-based immunotherapies, several approaches have been proposed, including reinforcement of NK cell cytotoxicity by means of specific cytokines, antibodies or drugs. These new tools may improve NK cell function and/or increase tumor susceptibility to NK-mediated killing. Hence, the integration of NK-based immunotherapies with conventional anti-tumor therapies may increase chances of successful cancer treatment. [ABSTRACT FROM AUTHOR]