Effective and Elaborative Induction Program for Mitigating Myths and Misconceptions Linked to Hematopoietic Stem Cell Transplantation in a Resource Limited Setting.

Since the first transplant in 1957 and hematopoietic stem cell transplantation (HSCT) is the curative modality for numerous hematological disorders. Nevertheless, it is not available for all patients. Besides unavailability of matched donors a lot of factors could hinder HSCT in a resource limited setting, as financial and administrative factors. In our daily practice we noticed other factors that hinder HSCT in our center, the common myths and misconceptions about HSCT and donation. This quasi-experimental study assessed, for the first time, common myths and misconceptions about HSCT among 218 medical and nursing students before and after an interventional educational program. The study tool was an investigators' developed self-administered questionnaire. Participants' male to female ratio was 1:2.5, and FAS was middle in 52.7%. Pretest high myths scores were reported in 53.4% and 90% of medical and nursing students that was reduced to 0% and 4% post-test, respectively. Pretest, 26.3% and 7% of medical and nursing students welling to donate HSC, that increased to 66% and 39% post-test, respectively. Rural residency, low and middle FAS associated with higher myths scores. Myths score is an independent effector of willingness to donate HSC among participants. In conclusion medical/nursing students had significant myths and misconceptions about HSCT that was corrected with the educational program. Thus, wide based educational programs about HSCT are mandatory to correct myths and augment HSC donation. www.clinicaltrrial.gov: clinical trial ID NCT05151406. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01634-5.

Anticipation of Relapse and Acute Graft-Versus-Host Disease after Allogeneic Peripheral Blood Stem Cell Transplantation: The Fundamental Role of Antigen-Presenting (Dendritic) Cells.

Background: Dendritic cells (DCs) are antigen-presenting cells. In humans two distinct lineages of DCs exist: DC1 and DC2. Efforts to explore the role of DCs in acute graft-versus-host disease (aGVHD) after allogeneic peripheral blood stem-cell transplantation (PBSCT) are gaining traction. However, further research is needed to identify particular lineages and their values in terms of developing an evidence-based aGVHD- or relapse-prevention strategy. We monitored DC counts and subsets in PBSC grafts while harvesting stem cells in recipients to elucidate their value in anticipating disease relapse or aGVHD. Methods: We enrolled 29 participants. Using fluorescence-activated cell sorting, total counts/kg of CD34+, DCs, and DC subsets were analyzed in 29 PBSC-graft components using CMRF44, CD11c, and CD4 monoclonal antibodies (MoAbs). Results: In the 29 grafts, we detected a significant positive correlation (P<0.01) between DCs and both DC1 and DC2. Significantly higher counts (P<0.01) of DCs and DC1 in those who had developed aGVHD (nine cases) were also observed. Relapsed cases (two) were also associated with higher counts of DCs and DC2. A significant positive correlation (P<0.05), was recorded between DCs and DC1 counts and the day of myeloid engraftment, while this was not detected on the day of platelet engraftment. Myeloid engraftment transpired earlier in patients without aGVHD. Increased DC-graft numbers, particularly DC1 measured by CD11c Moabs, were associated with aGVHD. Recipients of higher numbers of CD4bright DCs had an increased risk of relapse after allogeneic PBSCT. Conclusion: This study analyzed DCs in PBSC grafts, using novel specific MoAbs and flow cytometry. Our data showed that higher donor DC1 counts were linked to the incidence of aGVHD and DC2 with relapse. We propose a fundamental role for DC-graft monitoring in anticipating aGVHD and disease relapse.

Hematological, Biochemical Properties, and Clinical Correlates of Hemoglobin S Variant Disorder: A New Insight Into Sickle Cell Trait.

Background: The sickle cell trait (SCT) disorder possesses a clinical heterogeneity ranging from a symptomless condition to sudden death. This study aimed to develop a diagnostic approach that helps the characterization and identification of SCT from normal subjects and sickle cell disease (SCD) patients, and to assess its severity. Methods: Sixty controls, 24 SCD patients and 31 SCT subjects were assessed clinically, radiologically and by laboratory investigations. Results: Of the SCT subjects, 12.8% were symptomatic (3.2% anemic, 6.4% hemolytic crisis, and 3.2% painful crises). Anemia was normocytic in 66.6%, and normochromic and polychromatic in 33.4%. Significantly lower red blood cells (RBCs), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hematocrit (Hct), Shine and Lal index (SL), and hemoglobin A (Hb A), and higher mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), Ricerca index (RI), and Huber-Herklotz index (HH) were found in SCT subjects compared with the controls. Hb A and hemoglobin S (Hb S) were excellent in discriminating SCT from SCD (cut-off for SCT > 50% and < 40%) followed by Hct, MCHC, Hb, Green and King index (GK), and England and Fraser index (EF) (cut-off for SCT > 33%, > 32, > 11, < 71, and < 10, respectively). Radiologically normal findings were detected in 87% of SCT subjects; they had nearly normal liver and renal function tests (except one case each). A schematic diagnostic paradigm for SCT was proposed. Conclusion: This study allowed understanding of SCT in various aspects, i.e., clinical, hematological, biochemical and radiological. Thus, it could help prevention of the Hb S variant disorder and proper management of carriers. This might be applied in pre-marital screening, particularly in those with family history of Hb S disorder.

Platelet indices parameters in the new disease activity score of rheumatoid arthritis with ankle involvement: A comparative analytic study.

BACKGROUND: Platelet indices (PIs) are platelet parameters that are correlated with platelet activity. Despite being widely available, inexpensive, and feasible; their use in clinical settings is limited. Recently, we developed a new score (EgyDAS), which relies on PIs and assesses disease activity in rheumatoid arthritis (RA). OBJECTIVES: This study explored the practicability and validity of EgyDAS in RA with ankle involvement, considering that ankle is neglected in the commonly used DAS28 score. METHODS: This comparative case-control study included 2-groups of RA patients, group1 (control): without and group 2: with ankle involvement. RESULTS: Ankle involvement in RA showed no gender or age differences, however, it was associated with higher platelet count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet distribution width (PDW), visual analogue scale (VAS), tender joint count (TJC), and lower hemoglobin (Hb) and mean platelet volume (MPV). DAS28 categorized a higher proportion of patients to have high disease activity compared with EgyDAS; moreover, it did not detect those in remission in group 2 patients. Highly significant differences in the 2-scores were observed between the two groups. Further analyses revealed superiority of EgyDAS in assessing disease activity in group 2 patients. Finally, both scores were found correlated together in the study groups. CONCLUSIONS: Over or underestimation of RA disease activity could occur when using DAS28. PIs were found correlated with ankle involvement in RA. PIs and EgyDAS are the best tools to assess disease activity in RA patients with ankle involvement. However, the study recommended the use of both scores together.

Genotyping versus phenotyping of non-ABO erythrocyte antigens in patients with the Mediterranean hemopathic syndromes: Effect of transfusion therapy.

The Mediterranean hemopathic syndromes (MHS) are the most prevalent hemoglobinopathies in the Mediterranean basin. Transfusion therapy is the main therapy for these disorders, particularly for severe forms of the disease. Currently, pre-transfusion serological typing of erythrocyte antigens is the standard tool for reducing complications of transfusion in those patients. This study compared genotyping with phenotyping of non-ABO erythrocyte antigens in patients with MHS and assessed the effect of transfusion therapy on their results. One-hundred ninety-eight MHS patients were recruited, screened, and proven negative for allo-antibodies. They were grouped into two groups: (1) 20 newly diagnosed patients with no transfusion history and (2) 178 previously diagnosed patients undergoing transfusion therapy. Patients were interviewed and clinically examined. Full blood count (FBC) and high performance liquid chromatography (HPLC) were done for group 1 only. Genotyping and phenotyping of non-ABO erythrocyte antigens were performed for group 1, and 25 patients out of group 2 were propensity score-matched (PSM) with group 1. Both groups were gender and age matched; 55% and 74% of groups 1 and 2 had major disease, respectively. Insignificant differences were observed between genotyping and phenotyping of non-ABO erythrocyte antigens in group 1, while significant discrepancies and mixed field results were noted in group 2 patients. Discrepancies were obvious with JKa, JKb, and little c antigens. Conclusively, molecular typing is a powerful tool for pre-transfusion testing in chronically transfused MHS patients. This testing reduces incidence of transfusion reactions. JKa, JKb and little c antigens are the most clinically significant non-ABO erythrocyte antigens.

Acute human parvovirus B19 infection triggers immune-mediated transient bone marrow failure syndrome, extreme direct hyperbilirubinaemia and acute hepatitis in patients with hereditary haemolytic anaemias: multicentre prospective pathophysiological study.

A total of 244 patients with hereditary haemolytic anaemias (HHA) were screened for acute symptomatic human parvovirus B19 infection (HPV-B19) in a prospective study. To assess the risks associated with HPV-B19 infection, patients were classified into Group I and Group II according to presence or absence (symptoms, signs and specific serology) of acute HPV-B19 infection respectively. In all, 131 (53·7%) patients had ß-thalassaemia, 75 (30·7%) hereditary spherocytosis (HS), 27 (11·1%) sickle cell anaemia (SCA) and 11 (4·5%) glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 33 (13·5%) patients who presented with symptomatic HPV-B19 infection, 19 (57·5%) had HS, nine (27·3%) had ß-thalassaemia and five (15·2%) had SCA. In Group I, there were significant differences in the mean white blood cell, red blood cell and platelet counts, haemoglobin concentration, total bilirubin (TB), alanine aminotransferase, aspartate aminotransferase and serum creatinine (all P < 0·001) compared to Group II. In all, 27 (81·8%) patients had arthropathy and bone marrow failure (BMF); 13 (39·4%) had acute kidney injury (AKI), more in SCA (80%); and 12 (36·4%) patients had hepatitis, more in HS (66·8%). Five (15·2%) patients with HS had BMF, AKI, nervous system involvement and extreme hyperbilirubinaemia (TB range 26·3-84·7 mg/dl). Five (15·2%) patients had haemophagocytic syndrome. Two patients with HS combined with Type-I autoimmune hepatitis presented with transient BMF. Complete recovery or stabilisation was noted at 12 months in every patient except for one patient with SCA who died during the infection. HPV-B19 must be suspected and screened in patients with HHA with typical and atypical presentations with careful follow-up.

Value of Platelet Distribution Width and Mean Platelet Volume in Disease Activity Score of Rheumatoid Arthritis.

BACKGROUND AND OBJECTIVE: Disease activity score 28 (DAS28) for rheumatoid arthritis (RA) is the commonly used DAS; it relies on clinical parameters that could be subjective. This work aimed to create a more accurate DAS for RA and assess its validity. PATIENTS AND METHODS: The study included 98 RA patients and 53 matched controls; they were interviewed, clinically examined, their visual analogue scales (VAS) were reported, and then blood samples were withdrawn for erythrocyte sedimentation rate (ESR), complete blood count (CBC), and C-reactive protein (CRP). Platelet indices (PIs) were obtained from the CBC including Plt (platelet count), mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT). DAS28 was calculated for each patient using RheumaHelper mobile software. Minitab Statistical Package® and SPSS v20 software were used for data analysis. RESULTS AND CONCLUSIONS: Results revealed perfect matching between patients and controls as regarding age and gender. ESR, CRP and PDW were significantly higher in patients than controls; also positive correlations were detected among these variables. A new DAS for RA was developed; ESR, CRP, PDW and MPV were the components for this index. Further analyses showed that this new score was significantly higher in patients than controls and correlated with DAS28 of the patients. Furthermore the new score could identify RA patients from healthy subjects (cut off value < -0.79) and stratified RA patients according to their disease activity into low, intermediate, high, or in remission. Conclusively, we developed a more precise, easily obtained new DAS for RA. This new DAS has both diagnostic/prognostic values in patients with RA.

Is it the time to implement the routine use of distress thermometer among Egyptian patients with newly diagnosed cancer?

BACKGROUND: The distress thermometer (DT) is an effective tool for identifying distress among cancer patients worldwide. However, DT has not been studied in Egyptian patients. We aimed to study the prevalence of distress among Egyptian patients with different types of cancers using DT. METHODS: A total of 550 patients with newly diagnosed hematological and solid cancers who were followed up at 3 Oncology Centers in Egypt were enrolled. They completed a sociodemographic and clinical status questionnaire, the DT and the Problem List (PL) scale. RESULTS: At a DT cut-off score of ≥4, 46% of patients had significant distress, which was related to the tumor site and stage. The most frequent problems reported were treatment decision (64.4%), worry (47%), and fears (44.5%). In univariate logistic regression analysis, participants who had significant distress described 23 out of 36 problems in the practical, family, emotional, and physical areas. After adjustment to sociodemographic and clinical characteristics, multivariable analysis confirmed that insurance, depression, fear, sadness, worry, loss of interest in usual activity, and sleep were independent factors associated with significant distress in cancer patients. CONCLUSIONS: Almost half of Egyptian patients newly diagnosed with cancer reported significant distress. Those who had significant distress described extra problems in the practical, family, emotional, and physical areas. We recommend the routine use of DT for screening Egyptian patients with cancer, as well as the involvement of the psycho-oncology and social services, at the time of their initial diagnosis.

Aplastic anemia and COVID-19: how to break the vicious circuit?

Aplastic anemia (AA) is a type of anemia that is caused by an intrinsic defect of hematopoietic progenitors or an extrinsic immune mediated destruction of stem cells. Patients commonly presented with pancytopenia, particularly leukopenia that renders patient susceptible to various infections. COVID-19 is one of these infections that could be life threatening and highly contagious. Infection with COVID-19 is expected in a patient who developed fever, respiratory manifestations, leukopenia and lymphopenia together with history suggestive of exposure to infection. Furthermore COVID-19 was found associated with thrombocytopenia, agranulocytosis and monocytopenia in severe cases. Thus the relationship between COVID-19 infection and AA would be a vicious circle as both cause leukopenia and lymphopenia. This study aimed to break this circle, through proposing risk stratification of vulnerability to COVID-19 in AA patients who were admitted in our institution in the period from Mar. 2018 to Mar. 2020 followed by a strict preventive plan tailored for each risk group. 79% of AA patients were at high risk of acquiring COVID-19 infection if exposed. This group of patients have to be targeted with more aggressive preventive plan than normal healthy persons. In conclusion this study proposed next step in combating COVID-19 infection through mass survey of high risk people then application of specific precautions to them, perhaps they could be candidate for future vaccine or prophylactic treatment.

Interleukin-27 and interleukin-35 in de novo acute myeloid leukemia: expression and significance as biological markers.

BACKGROUND AND OBJECTIVES: IL27 and IL35 are regulatory T cells (T-regs) related cytokines; they were accused in eukemogenesis of acute myeloid leukemia (AML). This study aimed to assess the expression of these cytokines in de novo AML and investigate their role as biomarkers. SUBJECTS AND METHODS: Seventy newly diagnosed patients with primary AML and 30 matched healthy volunteers were recruited. AML diagnosis was confirmed with flowcytometric and immunophenotypic analyses, while ELISA was used to assess serum levels of IL27 and IL35 in patients and controls. Receiver operating characteristic curve analysis was used to estimate IL27 and IL35 optimum cutoff values for predicting AML. RESULTS: Serum levels of both cytokines were significantly higher in AML patients than controls (P<0.001), with no effect of gender or French-American-British subtypes. Significant correlations of IL27 and IL35 with poor prognostic factors and with each other were detected in patients only. IL27 optimum cutoff for predicting AML was >43, AUC (0.926) with a sensitivity 74% and specificity 96.6% (P<0.001), while for IL35>27.8, AUC (0.972) with 88% and 98% sensitivity and specificity, respectively (P<0.001). CONCLUSION: Conclusively, this study proved that IL27and IL35 could identify AML patients from healthy subjects, and their overexpression denotes poor prognosis. Based on the simplicity and wide availability of their detection technique we recommend the inclusion of IL27 and IL35 in the diagnostic/prognostic workup of AML; however, further longitudinal research is needed to prove their exact prognostic value.

Myeloid Leukemias: A Glance at Middle Eastern Centers.

BACKGROUND AND OBJECTIVES: Myeloid leukemias (MLs) are clonal stem cell disorders affecting myeloid lineage cells. Advances in cytogenetic and molecular studies partially disclosed the mystery about risk factors and pathophysiology of MLs. Regarding incidence, risk factors, response to treatment, and overall survival of patients, research showed differences among different countries. However, the Western registry data are the basis for the documented description of MLs in medical textbooks. This research aimed to study MLs in Middle Eastern health centers. Egypt has the highest population in the Middle East; furthermore, 96.6% of the population is native Egyptians; accordingly the study focused on Egypt. PATIENTS AND METHODS: Data of 468 patients with MLs were collected from hospital records at two big tertiary health centers. They were grouped into group 1 (chronic myeloid leukemia, CML) and group 2 (acute myeloid leukemia, AML); the latter was subgrouped into 2a (primary AML) and 2b (secondary AML). RESULTS AND CONCLUSIONS: The median age of patients was 43 years; males predominate in group 2a and females in groups 1 and 2b. 37.2% of group 1 patients were treated with Gleevec. Hematopoietic stem cell transplantation was planned for only 5% of group 2 and 18% relapsed. Of groups 1 and 2 patients, 25% and 12%, respectively, stopped follow up, and 15% and 35% died. ORR and overall survival were 53%, 27% and 7%, 0.4% for groups 1 and 2, respectively. Conclusively, this study showed a young age of ML patients, with female predominance in CML, and poor outcome. This reflected racial, ethnic and risk factor differences in incidence of MLs.

Quantitative Assay of Mutated Nucleophosmin in Acute Myeloid Leukemia.

BACKGROUND: In our previous work, we provided strong evidence that nucleophosmin (NPM) gene mutation has an important role in leukemogenesis of primary acute myeloid leukemia (AML). Furthermore, we speculated a new targeted therapy in patients with primary AML and bearing mutated NPM (mNPM). Based on these results together with findings of other researchers, it was essential to develop a method for accurate detection of mNPM. METHODS: Our method based on utilizing the most recent flow cytometeric techniques and instruments in measuring mNPM. Attributed to their availability and technical feasibility, we used human leukemia cell lines to validate our method. RESULTS: The main findings were differential expression of wild-type NPM (wtNPM) within the same sample. Furthermore flow cytometry (FCM) was a simple straightforward tool for quantitative assay of mNPM. CONCLUSIONS: In this work we developed an innovative technique that could enable quantitative assay of mNPM, and ease its use as a biomarker in cytogenetic and molecular prognostication of primary AML. In addition the study suggested that FCM could differentiate mNPM expression within cells of the same patient thus could be used for monitoring of minimal residual disease.

Role of Nucleophosmin Gene Mutation in Leukemogenesis of Acute Myeloid Leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a hematopoietic stem cell disorder that carries very poor prognosis. Understanding molecular basis of AML leukemogenesis could lead to the emergence of effective targeted therapies for AML. AML bearing nucleophosmin (NPM) gene mutation has distinct features. This study was conducted to investigate the role of mutated (m) NPM in pathogenesis of de novo AML through studying its contribution in proliferation of AML cell line cells. METHODS: Two types of human leukemia cell lines were used. One of them was a model for AMLs with mNPM and the other for AMLs with wild type (wt) NPM. Assessment of the proliferative role of mNPM in AML was carried out using cell culture and viability studies. The obtained results were reaffirmed by immunocytochemical and immunoblotting techniques. RESULTS: Analysis of results was done with the appropriate computer software. It showed higher proliferative potential of cells with mNPM compared to those bearing wtNPM only. Furthermore, the immunocytochemical studies demonstrated subcellular localization of NPM isoforms during various phases of mitosis. Mitosis was associated with cytoplasmic translocation of wtNPM in certain phases, while localization of mNPM remained unchanged throughout the cell cycle. Results of immunoblotting showed little or no change in protein expression of either NPM moieties during mitosis. CONCLUSIONS: The current study demonstrated important contribution of NPM gene mutation in enhancing proliferation of AML cell lines. These results confirmed the role of mNPM in AML leukemogenesis, and highlighted the importance of targeting mNPM in new evolving AML therapies.