HLA-B*58 and HLA-B*27 Play a Role in the Development of Acute Leukemia: A Case Control Study.

BACKGROUND: Acute leukemia (AL) constitutes a group of malignant hematological diseases with multifactor origins. Some human leukocyte alleles (HLA) may be important genetic risk factors for development of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). It is still unknown whether there is a relationship between ALL and AML with some alleles of the major histocompatibility complex. Our study looks specifically at western and southwest Algerian populations. METHOD: Using the polymerase chain reaction with the sequence specific probe (PCR- SSP) method, we investigated the relationship of HLA-B alleles in 163 Algerian AL patients and 293 controls from the same ethnic origin. The study ran from 2013 - 2020. RESULTS: Allele frequencies of HLA-B*27 and HLA-B*58 was higher in AL patients compared with control individuals; p=0.05 and p=0.03 respectively. Interestingly, all patients carrying HLA-B*27 allele and 88% of patients carrying HLA-B*58 allele had AML. However, there were no significant differences when we compared these results with the rest of AL group (HLA-B*X allele) (p=0.387). Response to induction chemotherapy treatment were comparable between the two patient groups 67% and 65% (p=0.978) respectively. CONCLUSION: These results suggest that the HLA-B*27 and HLA-B*58, may be factors predisposing individuals to acute leukemia, in west and southwest Algerian patients. A large-scale study is still needed to confirm these findings.

Impact of the Major BCR-ABL1 Transcript Type on Clinical and Biological Parameters and Molecular Response in Patients With Chronic Myeloid Leukemia.

AIM: In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib as frontline therapy. METHODS: This is six years prospective study started in March 1 st, 2013. 67 patients with newly CP-CML were treated by Imatinib as frontline therapy. Clinical and biological characteristics disease were collected for all patients. Molecular typing was performed by multiplex RT-PCR and quantification of transcripts by real-time quantitative PCR (qRT-PCR). The cumulative incidence of deep molecular response (DMR) was estimated by the Kaplan-Meier method. The comparison was made using the parametric Log-Rank test. A value of P ≤ 0.05 is considered significant. RESULTS: 61% of patients expressed b3a2, 35.82% b2a2 and 2.98% expressed a rare transcript of type e19a2. At diagnosis, the b2a2 type had a higher level of expression than that of b3a2 (67.92 vs 53.79%; P = 0.03). This insignificant difference between the two transcript subgroups was also observed for rates below 1% at 6 months (54 vs 39; P = 0.26) and below 0.1% (54 vs 44 %; P = 0.50), (77 vs 50%; P = 0.09) and (81 vs 78 %; P = 0.52) at 12, 18 and 24 months respectively. The two types of transcript had almost the same kinetics. Nevertheless, the absolute value of the BCR-ABL1/ABL ratio decrease was faster in the group of patients expressing b3a2, than in those expressing b2a2. At 18 months post IM therapy, patients with a b3a2 transcript have a trend of better MMR that those with b2a2 (77 vs 50%; P = 0.09). The DMR was not significantly different between two groups at 24 months (50 vs 32%; P = 0.20) and 36 months (75 vs 70%; P = 0.54) respectively. The cumulative probability of achieving MRD at 5 years was higher in patients with b3a2 type but not statistically significant; (85 vs. 68%; P = 0.17). CONCLUSION: Patients with b3a2 transcript may be associated with a better response to Imatinib therapy.

Efficacy and safety of autologous transplant with non-cryopreserved peripheral blood stem cells in myeloma and lymphoma in Algeria. 10 years' experience.

INTRODUCTION: The storage of harvested stem cells, in standard refrigerators at +4°C, is a simple and inexpensive alternative to cryopreservation for most patients living in countries with limited resources. We present the 10 years' experience of our single center from Oran in Algeria using non-cryopreserved stem cells after conditioning with high dose chemotherapy, in a large group of myeloma and lymphoma patients. METHODS: From May 2009 to December 2019, autologous stem cell transplantation (ASCT) was carried out in our center, of which 420 with multiple myeloma (MM) and 154 patients with lymphoma. The source of stem cells in all patients consisted of mobilized autologous peripheral blood stem cells (PBSCs). A median of one cytapherisis was performed (range, 1-3) and the products of the aphaeresis were stored in a conventional blood bank refrigerator at +4°C, in 300-mL transfer packs (Baxter Healthcare) composed of impermeable gas, polyvinyl chloride plastic film. The viability of the harvested cells is assessed by flow cytometry using 7'AAD (7 Amino-Actinomycine D) and was determined by a trypan blue dye exclusion test. The chemotherapy conditioning regimen (Mel200, BEAM, CBV, EAM, BeEAM) started once a minimum of 2×106 CD34+cell/kg in MM or 3x106 CD34+cell/kg in lymphoma was obtained. RESULTS: In MM patients, the median age at ASCT was 54 years (range; 27-73). The median harvested CD34+ cell count was 3,2x106/kg (range; 1, 22 to 13, 22) and the viability in all cases being >90%. All patients had engraftment on the median of day 9 (range; 7 to 24) and platelet transfusion independence on the median of day 13 (range; 9 to 39). There was no graft failure. Transplant related mortality (TRM) at 100 days was 3,5%. The overall response to transplant was 99% (complete remission (CR) =64,5%; very good partial remission (VGPR) =34%, partial remission (PR) =1,5%). The estimated overall survival (OS) at 5 years was 68% and the median post-transplant progression-free survival (PFS) was 47 months. On December 31th 2021, 41% patient relapsed and 28% died after disease progression. 305 (75%) patients are alive and 237 (59%) without disease activity after a median follow-up of 52 months (range; 13 to 149). In lymphoma patients, 98 Hodgkin`s lymphoma (HL) and 56 non-Hodgkin´s lymphoma (NHL), were auto grafted. The median age at ASCT was 28 years (range; 16-55) and 33 years (17-61) respectively. After mobilization a median of 4,25x106/kg (NHL) and 4,14x106/kg (HL) of CD34+ was infused and the median viability of the cells after 7 days of refrigeration (trypan blue exclusion) was 82%. The median time to achieve 0,5 G/L neutrophil or more was 14 days (9-44) and 15 days (11-27) in HL and NHL, median time to achieve 20 G/L platelets or more at a median of 16 days (10-37) and 17 days (15-28) in HL and NHL. The OS at 5 years was 76% and 67% for patients with HL and NHL respectively. Transplant related mortality at 100 days was 5% in HL and 12,5% in NHL. CONCLUSION: This study demonstrates the feasibility of intensified therapy followed by autologous non-cryopreserved PBSCs infusion in MM and lymphoma patients. This method of ASCT is cheaper, and may potentially enable the widespread use of ASCT activities in other hematology centers in Algeria and in developing countries.

Aspirin enhances regulatory functional activities of monocytes and downregulates CD16 and CD40 expression in myocardial infarction autoinflammatory disease.

BACKGROUND: Exacerbation of CD16 as molecule marker of both intermediate and non-classical monocytes (MOs) has been shown to be involved in the pathogenesis of myocardial infarction (MI). In this study, we have tried to evaluate the aspirin (acetylsalicylic acid, ASA) treatment effect on the CD16-expressed MOs and activation-associated CD40 in MI. METHODS: MOs were isolated from the whole blood of healthy controls and patients with MI. The cells were stimulated and treated with different doses of ASA. RESULTS: ASA significantly decreased nitric oxide (NO) production and inducible NO synthase (iNOS) activity, but significantly increased arginase activity. Levels of interleukin (IL)-1ß, IL-6 and interferon-γ (IFN-γ) were downregulated, whereas those of IL-10 were upregulated. Additionally, ASA induced a markedly increase in both phagocytosis and intracellular pathogen killing activities. Moreover, ASA treatment induced significantly upregulation of intracellular levels of glucose (iGlu), and free calcium ions (ifCa2+), and, covertly, significantly downregulation of total cellular cholesterol content (tccCHOL). Furthermore, the expression levels of CD16 and CD40 were significantly downregulated in ASA-treated MOs. CONCLUSIONS: We show for the first time that ASA immunomodulates the functional activities of MOs during MI and promotes their switching toward a classical phenotype, exhibiting low CD16 expression levels and thereby anti-inflammatory properties.

Hematopoietic stem cell transplantation in Algeria.

INTRODUCTION: Algeria is a country of 40.4 million inhabitants and half of which is under 30years. In Algeria, Health-care insurance covered, 90% of the population. Health care is free and it is supported by the Ministry of Health. 16 university hospitals exist in Algeria and only two (Algiers and Oran) practicing bone marrow transplant. Adult hematologic malignancies account for 10% (about 4000 new cases/year) of the malignancy affecting in most cases young patients under 65years of age. In 2016, 270 transplants were performed in total (Algiers+Oran), including 149 allografts (related donor transplants: 99%) and 121 autografts. 98% of transplants are done in adults and only 2% in children with cord blood transplants. In summary for the two transplant centers, the predominant types of transplantation performed are allogeneic transplant in 55% and autologous transplant in 45%. The particularity of EHU1st November in Oran, is the use of non-cryopreserved stem cells. Stem cell was mobilized using G-CSF alone and the grafts were kept in a conventional blood bank refrigerator at +4°C until reinfusion on day 0. The outcome with non-cryopreserved stem cells are the same as those with cryopreserved stem cells and we conclude that autologous transplant with non cryopreserved hematopoietic stem cells (HSC) is a simple, effective and safe method and the cryopreservation is not necessary in our work conditions in developing countries. The projects are achieving the autograft in all University Hospitals with non cryopreserved HSC, achieving a center allograft in the east of the country and the development of bone marrow transplantation in children. CONCLUSION: Currently in Algeria, the number of transplantation is insufficient and the development of new transplant centers is essential. In the future, we hope to implement the National Society of Bone Marrow transplant and also the National recipient registry and Donor registry in Algeria.

Epidemiological, clinical and pronostic aspects of multiple myeloma eligible for therapeutic intensification followed by autologous hematopoietic stem cell in the Algerian West: report of 147 cases.

BACKGROUND: Multiple Myeloma (MM) represent about 1 to 2% of cancers and 15% of all hematological malignancies. It is characterized by malignant proliferation of plasmocytes in bone marrow and an excess of secreted monoclonal immunoglobulins (Ig) Objective: Describe the epidemiological, clinical, biological and prognosis of patients with MM treated with autologous peripheral hematopoietic stem cell transplantation (APHSCT) in the Algerian West. METHODS: It is a retrospective descriptive study covering all MM patients treated with APHSCT over a period of 7 years (2008-2015) at service of Haematology and Cell Therapy of the EHU "1er November 1954 of Oran, Algeria. RESULTS: During the study, we collected 147 MM patients treated with APHSCT. The median age of the population was 53 years with a male predominance and a sex ratio of 1.53. Clinically, bone syndrome was found in 75.51% of cases. Paraclinaclly, anemia was found in 78.52% of patients, hyperprotidemy in 59.06%. A monoclonal peak in serum protein electrophoresis was noted in 80.54% of cases. Isotype repartition was: IgG (61.04%), IgA (19.17%), monoclonal light chains (16.11%). A plasmocytosis more than 10% was detected in 89.79% of cases. According to the Durie and Salmon classification, all of our patients were classified as stage III. The average survival time was thirty months. CONCLUSION: The majority of our patients had advanced stage of MM to the presentation and the median survival was not reached thus emphasizing a high rate of remission and marks an important advance in the care of MM in Algeria.

Can sex be determined from a blood smear?

OBJECTIVE: Originally, this blind study was designed to check whether blood smears constitute reliable tools to determine sex. However, when we analyzed our data some interesting findings immerged and in this paper we try to highlight them. MATERIAL AND METHODS: 74 blood smears (35 women and 39 men) have been performed and then stained. 200 polynuclearneutrophils were examined for nuclear appendages and classified into four groups: neutrophils with form A, B or C appendages and neutrophils without any appendage.The difference (A-C) was calculated for each slide. The "cytologic sex" was defined as a male in case of a negative value and as a female otherwise. RESULTS: Neutrophils bear the same amount of appendages in both genders (p=0.37). But the number of form A is greater in females (p<0.0001) and form C is much more frequent in males (p<0.0001), that is why, the difference A-C is the best way to differentiate between both sexes.The distribution histogram of A-C in women shows a multimodal histogram contrary to men's graphwhich is a bell-shaped curve. The menstrual cycle was incriminated in this feature. CONCLUSION: Blood smear is a reliable tool to determine gender. CONFLICT OF INTEREST: None declared.

The impact of Immigration and Customs Enforcement on immigrant health: perceptions of immigrants in Everett, Massachusetts, USA.

U.S. immigrants have faced a changing landscape with regard to immigration enforcement over the last two decades. Following the passage of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996, and the creation of the Immigration and Customs Enforcement (ICE) agency after the attacks of September 11, 2001, detention and deportation activity increased substantially. As a result, immigrants today are experiencing heightened fear of profiling and deportation. Little research exists on how these activities affect the health and well-being of U.S. immigrant communities. This study sought to address this gap by using community-based participatory research to investigate the impact of enhanced immigration enforcement on immigrant health in Everett, Massachusetts, USA, a city with a large and diverse immigrant population. Community partners and researchers conducted 6 focus groups with 52 immigrant participants (documented and undocumented) in five languages in May 2009. The major themes across the groups included: 1) Fear of deportation, 2) Fear of collaboration between local law enforcement and ICE and perception of arbitrariness on the part of the former and 3) Concerns about not being able to furnish documentation required to apply for insurance and for health care. Documented and undocumented immigrants reported high levels of stress due to deportation fear, which affected their emotional well-being and their access to health services. Recommendations from the focus groups included improving relationships between immigrants and local police, educating immigrants on their rights and responsibilities as residents, and holding sessions to improve civic engagement. Immigration enforcement activities and the resulting deportation fear are contextual factors that undermine trust in community institutions and social capital, with implications for health and effective integration processes. These factors should be considered by any community seeking to improve the integration process.

The estimation of platelet count from a blood smear on the basis of the red cell: platelet ratio.

OBJECTIVE: The estimation of platelet count from blood smears is a daily routine laboratory test, which should be systematic each time the automated count is erroneous. In our laboratory, we estimate the platelet count indirectly by using the automated red blood cell (RBC) and calculating the platelet count on the basis of the red cell: platelet ratio in a stained blood film. In this study, we attempted to verify the reliability of this technique. MATERIAL AND METHODS: One hundred ninety-one platelet counts were executed by two laboratory methods: an automated count using an impedance cell counter and then a manual method by reviewing microscopic blood smears. The number of platelets per 1000 erythrocytes was multiplied by the automated RBC (x106 cells/µl) to give an approximate manual count (x103 cells/µl). Two paired t-test was used for comparison of the two methods. RESULTS: The regression analyses for the entire data set collected in our study with the two laboratory methods gave the following least squares equation by comparing the automated (y) to the manual method (x): y=0.8548x + 12.013 (r=0.908). The paired t-test showed no significant difference between the two methods (p>0.05) and the Intra-class Correlation Coefficient (ICC) was equal to 0.905. The plot of the differences between the automated and manual values against their means according to Band and Altman design showed that the difference mean was 3.209 with a standard deviation SD=46.331. We noticed that 93% of the differences were within the agreement limits (mean±2SD), and that 77% of the differences were less than 20,000 platelets/µl. CONCLUSION: Estimating platelet count on the basis of the red cell: platelet ratio is a reliable technique and it should be proposed as a method of reference.