Background: Conditioning regimens for allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) in adult Acute Lymphoblastic Leukemia (ALL) typically involve administering a ≥ 12 Gy dose of Total Body Irradiation (TBI), offering survival benefits but with potential acute and long-term complications. Within Myeloablative Conditioning (MAC) regimens, the optimal TBI dose in terms of outcomes and safety remains unknown, and the economic challenges of the standard approaches are pronounced in Low-middle Income Countries (LMIC). To address this gap, this study analyzes the outcomes of high-dose versus low-dose TBI in adult ALL patients undergoing allo-HSCT in Cali, Colombia. Objectives: To compare the clinical outcomes of Myeloablative Conditioning (MAC) regimens based on a standard-dose TBI of ≥ 12 Gy (SD-TBI) versus regimens with low-dose TBI ≤ 4 Gy (LD-TBI) in adult patients with ALL and identical and haploidentical allo-HSCT.Patients and methods: A retrospective cohort study was conducted with adult patients (≥18 years of age) with ALL between 2012 and 2021, who underwent allo-HSCT at a single center, in Cali-Colombia. The study population was divided into two MAC therapy groups: SD-TBI (≥ 12 Gy TBI) plus Flu and LD-TBI (≤ 4 Gy TBI) plus Bu and Flu. The primary outcome was Overall Survival (OS). Secondary outcomes included Disease-free Survival (DFS), Cumulative Incidence of Relapse (CIR), non-relapse mortality (NRM), Transplant-related Mortality (TRM), and acute and long-term transplant-associated complications. Outcomes were assessed at 12 months.Results: A total of 100 patients were included, 39 received SD-TBI and 61 LD-TBI. Median age was 30 years, 97% of patients were classified as high risk, and only 49% were in first Complete Response (CR1). OS at 12 months was 59% and 47% in the SD-TBI and LD-TBI groups, respectively (p = 0.305). Relapse incidence at 12 months was 29% and 38.5% (p = 0.442). The incidence of grade II-IV acute graft versus host disease (aGVHD) was 24% in the SD-TBI vs. 46% in the LD-TBI group (p = 0.028). The relative risk (RR) for GVHD in the SD-TBI group was 0.52 (95% CI 0.27-0.98). The adjRR for donor type was 0.9 (95% CI 0.45-1.9) for haploidentical transplantation and RR 0.3 (95% CI 0.08 - 0.82) for HLA identical. Conclusion: In ALL patients taken to allo-HSCT between 2012 and 2021, we found no significant differences in OS, DFS, TRM, or relapse incidence between SD-TBI and LD-TBI MAC regimens. The risk of aGVHD was lower in patients with SD-TBI, particularly those with HLA-identical donors. These results enhance Latin American representation in transplantation studies and have potential clinical implications. This study also serves as a base for future prospective studies and cost-effectiveness analyses needed for optimization of allo-HSCT conditioning regimens for ALL in LMIC.
Background: Outcomes of chemotherapy in adults with ALL in resource-poor countries are reportedly worse compared with outcomes in resource-rich countries. There are few comparative data on transplants in these settings. Methods: Retrospective analysis of 102 consecutive subjects > 18 years with ALL receiving an allotransplant from Jan 2007 to Sept 2022 in Jordan. Results: Median follow-up is 38 mo ([IQR] 16-80 mo). 81 subjects were men. The median age was 29 y(IQR 22-36 y). 63 were B-cell and 38, were T-cell lineage. 31 had the Ph-chromosome. 68 were in 1st and 34, ≥ 2nd histological complete remission. 97 received intensive conditioning. Donors were an HLA-identical sibling (N = 88) or an HLA-mis-matched relative (N = 14). Grafts were blood cells. Subjects received conventional GvHD prophylaxis, cyclophosphamide (N = 11) or ATG (N = 3). All subjects recovered bone marrow function with complete donor chimerism. 5-year leukemia-free survival (LFS), 58% (47, 69%) and survival, 45% (34, 56%). 45 subjects developed acute and 44, cGvHD. 3-year cumulative incidence of cGvHD was 28% (15, 42%). 5-year CIR was 32% (18, 45%) and 3-year NRM, 25% (15, 35%). Conclusion: Allotransplant outcomes in adults with ALL in Jordan, a resource-poor country, seem comparable to those reported in resource-rich countries.
Direct myocardial transplant of HFDSCs (human fetal derived stem cells) by open chest surgical procedure was performed in 10 patients with Heart Failure (HF) due to no ischemic, no chagasic dilated cardiomyopathy. All 10 patients survived the operation. At 40 months, the mean (±SD) NYHA class decreased from 3.4 ± 0.5 to 1.33 ± 0.5 (p = .001); the mean EF increased 31%, from 26.6% ± F) 34.8% ± 7.2% (p = .005); and the mean ETT increased 291.3%, from 4.25 minutes to 16.63 minutes (128.9% increase in metabolic equivalents, from 2.46 to 5.63) (p < .0001); the mean LVEDD decreased 15%, from 6.85 ± 0.6 cm to 5.80 ± 0.58 cm (p < .001); mean performance in the 6-minute walk test increased by 43.2%, from 251 ± 113.1 seconds to 360 0 seconds (p = .01); the mean distance increased 64.4%, from 284.4 144.9 m to 468.2 ± 89.8 m (p = .004); and the mean result in the Minnesota test decreased from 71 ± 27.3 to 6 ± 5.9 (p < .001). Six patients survived after 40 months; 5 of them had complete reverse remodeling after 3 months after transplants. The average age at the moment of the transplants was 62 years (s/d 11.6). Results: The first patient died at 5,4 years for an infection; the second patient died at,7,4 years for heart failure; the third patient died at 8,4 years for heart failure; the fourth patient died at 10 years for heart failure and the fifth patient died at 14,4 years after transplant at the age of 83 for heart failure. The average age at the moment of death was 70 years (s/d12.9). The survival rate at 4 years was 100% (K/M) and at 14 years (25%K/M). Conclusion: These initial worldwide experiences with the surgical direct transplant of liver fetal stem cells in patients with end-stage HF shows clearly the positive effect in the reverse remodeling of the left ventricle of 50% of the cohort and excellent long-term results in these types of patients opening a new avenue for treating end-stage HF patients without any other option of treatment.
Objective: To retrospectively analyze the effects of (bone marrow platelet-rich plasma BMPRP) precise pancreatic infusion therapy versus conventional treatment. Methods: Bone marrow was collected from the iliac crest anterior superior spine, and platelet-rich plasma was separated by centrifugation. BMPRP was infused into the pancreas under ultrasound guidance. It was compared with conventional hypoglycemic drugs and insulin therapy. Results: In the BMPRP treatment group of 32 cases, the fasting blood sugar and hemoglobin A1c were significantly lower than pre-treatment levels, while the C-peptide level did not change significantly. The insulin dose was reduced. In the conventional treatment group of 28 cases, the fasting blood sugar, hemoglobin A1c, and C-peptide levels did not change significantly after continuous treatment for one year, and the insulin dose was not reduced. Conclusion: BMPRP precise pancreatic infusion therapy can improve pancreatic function, reduce insulin resistance, lower blood sugar, and reduce the required insulin dosage.
Apoptosis, or programmable necrosis, can be induced by miscellaneous factors such as radiation, chemicals, and physiological and pathological conditions. Apoptosis is required for many processes, such as the turning over of normal cells, and the growth of the immune system and functions, unfair apoptosis either too little or too much has been linked to several clinical circumstances, accompanied by cancer, diabetes, and neurodegenerative spoiling. The harm of β-cell cytoplasm owing to pancreatic cells dying (T2DM) is a complicated etiology of Non-insulin-dependent diabetes mellitus (type II). To halt the normal progression of pancreatic cell disorders, it may be required to modulate the apoptosis and proliferation processes of these cells. Apoptosis is a complex process with four major components: induction, detection, effectors, and eradication. Each step necessitates the coordinated action of multiple molecules, the most noteworthy of which are caspases, the Bcl-2 protein family, and p53 (tumor suppressor gene).
More than 60 million persons all over the world are living with the diagnosis of “Autism”, in accordance with the UNO. According to the WHO, almost every hundredth child is a sufferer of ASD. Such figures emphasize globalization of the problem, and its impact not only on the child’s family but also on the economies of entire countries. Autism diagnosis is difficult and based on the general symptoms in kids. Today, the neuroimaging techniques (methods of functional Magnetic Resonance Imaging (MRI) and MRI tractography), Electroencephalography (EEG), evoked cognitive potentials and dynamic monitoring of the results help with an objective evaluation of stem cell therapy. Treatment options in modern pharmacology and rehabilitation psychotherapy for ASD kids are limited. Therapy methods do not ensure a full integration into social life and personality awareness. To alleviate likely problems in society, different therapeutic approaches exist that might reduce the manifestation of the various autism symptoms. FSC therapy is one such innovative method that has recently become enough popular. We inform about the clinical case of successful treatment using fetal stem cells for a child with autism followed by the period of 1-year follow-up showing significant clinical results. Over one year, the positive changes that had been proved by the ATEC questionnaire, the EEG results, and MRI-tractography were noted for the patient’s family. As emphasized in the clinical case report, fetal stem cell therapy is a promising and efficient treatment for children with autism. All that was sufficiently confirmed by the results acquired because we saw an overall improvement in this patient.
Pure Red Cell Aplasia (PRCA) is a well-recognized complication of Major ABO-incompatible allogeneic stem cell transplantation. It is featured by anemia, Reticulocytopenia, and the absence of erythroblasts in a normal-appearing bone marrow biopsy. The mechanism for PRCA is presumed to be the persistence of recipient isoagglutinins, produced by residual host B lymphocytes or plasma cells, which probably interfere with the engraftment of donor erythroid cells. Several risk factors for PRCA have been reported, such as the presence of Anti-A Isoagglutininsbefore transplantation, reduced intensity conditioning, absence of Graft Versus Host Disease (GVHD), sibling donor and Cyclosporin A(CsA) as GVHD prophylaxis. PRCA is not a barrier to going ahead with Hematopoietic Stem Cell Transplantation (HSCT). There are many therapeutic options however few recover spontaneously, among the available options include high-dose steroids, Erythropoietin(EPO), Plasma exchange, Donor lymphocyte Infusion (DLI), treatment with Rituximab, Bortezomib, Daratumumab and tapering or discontinuation of immunosuppression. All these options have variable success in the literature ranging from 30% - 70%, Non-responders become red cell transfusion dependent and their quality of life is impaired. We are reporting a novel therapeutic option, Ibrutinib as an armamentarium in treating the PRCA post-HSCT, which works by blocking the Bruton Tyrosine Kinase (BTK) pathway thereby inhibiting the host B cell isoagglutinins production and good clinical response.
The stem cell secretome is a collective mixture of soluble and insoluble factors released by stem cells during paracrine communication and/or autocrine signaling. In addition to intracellular communication, these paracrine factors play an integral role in tissue development and generation, acting as the primary driving force in the regenerative properties of stem cells. Despite such great potential of stem cell secretome in therapeutic applications, the lack of secretome-based treatments available for the public at the time of writing is odd and puzzling. Hence, this review aims to provide insights into recent advancements in understanding the stem cell secretome, as well as discuss future possibilities and current limitations that must be overcome for the proper development of secretome-based therapies. Through utilizing the MEDLINE database from the National Library of Medicine® (NLM), we found that while there is much evidence of the therapeutic effects of secretome-based therapy, flaws involving regulations and standardization hinder it from revolutionizing regenerative medicine at present. It is cardinal to emphasize that while secretome-based therapy may be the solution for many untreatable conditions, much research is still required before it is approved for clinical practice.
Autologous Hematopoietic Stem Cell Transplantation (AHSCT) performed after induction therapy is the standard of care for newly diagnosed Multiple Myeloma (MM) patients who qualify. Our institution has performed AHSCT for MM since 1991, and in this study, we sought to retrospectively examine the outcomes of 303 MM patients who underwent AHSCT from 1991-2021. We focused on Overall Survival (OS) and Progression-Free Survival (PFS) in patients in addition to Landmark survival (1-year post-transplantation). We found that in elderly patients > 70 years of age there was no significant difference in OS at 12 years, with 51% for patients < 70 years of age and 50% > 70; these were the same numbers for PFS at 12 years as well. We also found that median overall survival is improving overall with each decade in our transplanted MM patients with patient survival improved to over > 80% regardless of age at 7 years, when the previous median overall survival was 6 - 6.6 years before 2001. Given our findings, supported by others, we show that survival is continually improving over time in MM AHSCT patients and that AHSCT can be performed safely with equivalent landmark and long-term PFS and OS in patients of advanced age.
We reviewed our outcomes of patients with relapsed/refractory Hodgkin Lymphoma treated with autologous stem cell transplant over a 30-year period, 1992 to 2022 and are reporting 15-year Disease-Free Survival (DFS) and Overall Survival (OS) of the 36 patients treated (19 men, 17 women, median age 41). Over the years there were different preparative regimens employed (carmustine, etoposide, melphalan and BCNU, etoposide, cytarabine, and melphalan) as well as post-transplant consolidation therapy (brentuximab). With a median follow-up of 15 years, the DFS is 52% and OS is 64%. Long-term complications include cardiomyopathy and second malignancies. The use of better salvage regimens and post-transplant consolidation therapy should lead to better outcomes.
The Injection of autologous Adipose-Derived Stem Cells (ADSCs) and Stromal Vascular Fraction (SVF) into dermal and subdermal layers can improve skin volume and rejuvenation. The SEFFI (Superficial Enhanced Fluid Fat Injection) technique, which involves minimal manipulation of autologous microfragmented adipose tissue, was utilized for harvesting and re-injection, using the SEFFILLER™ disposable medical device. Mechanical fragmentation of adipose tissue is a well-established surgical technique that stimulates tissue regeneration, filler, and biological activity. The study evaluated the biological properties (regenerative and anti-aging) of different harvest and processing fat graft methods among which the fragmented adipose tissue, specifically focusing on the presence of exosomes. Exosomes, nanometer-sized vesicles produced by cells for cellular communication, were found to contain miRNAs with anti-inflammatory, regenerative, and vascular content. The products’ contained exosomes were confirmed in the study through electron microscopy, Western Blotting, gene expression, and sequencing of miRNA content.
Gynecological laparoscopy has to be analyzed also in the context of complications that occur during the surgical procedures. Complications occur daily. For this reason, emphasis should be placed on lifelong continuous education and training. Given the risks and complications we face, we must be trained to deal with them. This improves the safety of laparoscopic operations. Without such certainty, gynecological laparoscopy would not be the method of choice in a minimally invasive approach. This requires significant commitment, effort, and responsibility. In this way, we provide our patients with the best and highest quality healthcare service. Likewise, with such an approach, the frequency of complications is reduced to a minimum. New perspectives and possibilities are associated with the application of robotic surgery.
Mesenchymal Stromal/Stem Cells (MSCs); which can be isolated from Bone Marrow (BM) in addition to several tissues and body fluids; have the following characteristic features: self-renewal, differentiation into various cell types, plastic adherence, and specific surface markers on flow cytometry [1-3].
Background: Autologous hematopoietic stem cell transplants (HSCT) is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (MM) and patients with relapsed and refractory Hodgkin lymphoma (R/R-HL) who achieve chemosensitivity after salvage therapy. Although autologous HSCT is routinely performed in an inpatient setting, the procedure can safely be performed in an outpatient setting. Methods and materials: A retrospective study of patients with MM and R/R- HL who received outpatient autologous HSCT at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia between the first of April 2017 and the 31st of January 2022 was performed. Results: Over the study period of 4 years and 10 months, a total of 90 outpatient autologous HSCTs were performed for 79 patients (54 patients with MM; 4 of them received planned tandem autografts and 7 other myeloma patients received second autologous HSCTs for relapsed or progressive disease; and 25 patients with R/R-HL) at our institution. The median ages of patients with MM and those with R/R-HL at HSCT were 50.4 years and 27.8 years respectively. At the presentation of their MM, the following high-risk (HR) features were encountered: stage II and III diseases according to the revised international scoring system (RISS) in 53.7%; adverse cytogenetics in 42.6% and extensive bone involvement in 53.7% of patients. In patients with HL at presentation, 48% of patients had stage IV disease according to Ann Arbor staging classification and 84% of patients had B symptoms. Survival for 100 days post-HSCT for all patients with MM and HL who received outpatient autologous transplants was 100%. For patients with MM, the overall survival (OS) rates at 3 years and 4 years post-HSCT were 80% and 67%, while the progression-free survival (PFS) rates over 3 years and 4 years were 58% and 38% respectively. For patients with HL, the OS at 6 years post-HSCT was 95% while the PFS rates at 3 years and 6 years post-HSCT were 84% and 62% respectively. Conclusion: Outpatient autologous HSCT for patients with MM and HL is safe, and feasible and can lead to short-term as well as long-term outcomes that are comparable to autologous transplantation performed in an inpatient setting. Additional benefits of outpatient autologous include saving beds and reducing hospital costs.
Mesenchymal Stem Cells (MSCs) have antimicrobial, anti-inflammatory, immunomodulatory, and regenerative potentials. Additionally, utilization of MSCs in the clinical arena has been shown to be safe and well tolerated. Hence, this form of cellular therapy has gained particular attention in the treatment of several infectious disorders and their complications. MSCs have been successfully used in the treatment of the following infections and their complications: bacterial infections including complicated sepsis; viral infections including Human Immunodeficiency Virus (HIV), hepatitis B and C viruses, and Coronavirus disease (COVID-19) complicated by acute respiratory distress syndrome; parasitic infections including schistosomiasis, malaria, and Chagas disease; and mycobacterial infections including tuberculosis. The use of MSCs derived from certain sources and Extracellular Vesicles (ECVs) derived from MSCs has improved their efficacy and reduced their side effects. However, the clinical application of MSCs in the treatment of several infectious diseases still faces real challenges that need to be resolved. The current status of MSCs and the controversies related to their utilization in various infections will be thoroughly discussed in this review.
Graft Versus Host Disease (GVHD) is a major limitation to the success of allogeneic Hematopoietic Stem Cell Transplantation (HSCT) as Steroid-Refractory (SR) acute GVHD carries poor prognosis due to the absence of an efficacious second-line therapy. Mesenchymal Stem Cells (MSCs) which have immunosuppressive, immunomodulatory, and regenerative properties may become a highly effective therapeutic modality for SR-GVHD in the near future. MSCs have already been approved to treat childhood SR-GVHD in Japan, and they have been conditionally licensed in New Zealand and Canada. It is expected that MSCs will be approved for the treatment of SR-GVHD in adults in Europe, North America, and other parts of the world within a few years. Utilization of the recently introduced techniques including the use of MSC products such as exosomes and Extracellular Vesicles (ECVs) instead of the parent MSCs, robotic manufacturing technology, and genetic engineering of MSCs will ultimately overcome the remaining obstacles facing the widespread utilization of MSCs and their products as therapeutics not only in HSCT but also in other medical fields. The aim of this review is to provide an update on the remarkable progress achieved in the use of MSCs and their products in the field of HSCT.
Mesenchymal stem cells are heterogenous adult multipotent stromal cells that can be isolated from various sources including bone marrow, peripheral blood, umbilical cord blood, dental pulp, and adipose tissue. They have certain regenerative, anti-inflammatory, immunomodulatory, immunosuppressive, antimicrobial, and other properties that enable them to have several therapeutic and clinical applications including treatment of various autoimmune disorders; role in hematopoietic stem cell transplantation and regenerative medicine; treatment of skin, pulmonary and cardiovascular disorders; treatment of neurological and eye diseases; as well as treatment of various infections and their complications. Different factors including donor age, biological source, route of administration, and signaling pathways have an impact on the functions and consequently the clinical applications of mesenchymal stromal cells. The products of mesenchymal stem cells such as extracellular vesicles and exosomes reproduce the biological effects and most of the therapeutic actions of the parent stem cells. Genetic engineering and the use of specific mesenchymal stromal cell products have improved their clinical efficacy and decreased their adverse effects. However, despite the recent progress in the use of mesenchymal stem cells, the clinical application of these cells in the treatment of several diseases still faces real challenges that need to be resolved. The current status of mesenchymal stem cells and the controversies related to their clinical utilization in various disease conditions will be thoroughly discussed in this review.
Background: Aautologous hematopoietic stem cell transplants (HSCT) is the standard of care for newly diagnosed patients with multiple myeloma (MM) who are eligible for autologous transplantation. Although cryopreservation is routinely employed, autologous HSCT can be performed using non-cryopreserved stem cells. Methods and materials: A retrospective study of patients with MM who received autologous HSCT between the 10th of October 2010 and the 31st of January 2022 at King Fahad Specialist Hospital (KFSH) in Dammam, Saudi Arabia was performed. Results: Over 11 years and 113 days, a total of 135 autologous HSCTs were performed for 119 patients with MM at our institution. Single autologous HSCTs were performed for 119 patients, while 16 of these patients received either planned tandem autologous transplants or second autografts due to either progression or relapse of their myeloma. The median age of patients with MM at autologous HSCT was 51.5 years. At presentation of their MM, the following high-risk (HR) features were encountered: stage III disease according to the revised international scoring system (RISS) in 12.3%; adverse cytogenetics in 31.93% of patients; advanced bone disease in 60.50%; and renal dysfunction or failure in 11.76% of patients. A total of 104 autologous HSCTs (77.04%) were performed without cryopreservation while 31 autografts (22.96%) were performed using cryopreserved apheresis stem cell products. Additionally, 54 autologous HSCTs (40.00%) were done at outpatient while 81 autografts (60.00%) were performed in an inpatient setting. Survival for 100 days post-HSCT for all patients with MM who received autologous transplants including those done at outpatient was 100%. The 4 years overall survival (OS) an progression-free survival (PFS) for patients with MM who received non- cryopreserved or fresh autologous HSCTs were 82% and 68% respectively. Conclusion: Autologous HSCT without cryopreservation is safe, and feasible and can lead to short-term as well as long-term outcomes that are comparable to autologous transplantation with cryopreservation. Non- cryopreserved autologous grafts allow the performance of autologous transplants in an outpatient setting to save beds and reduce costs.
Background: Measurable residual disease (MRD) status before allogeneic hematopoietic stem cell transplantation (AHSCT) is commonly associated with a high risk of relapse. It is still uncertain whether AHSCT could overcome the negative impact of MRD positivity (MRD+), especially in patients with high-risk Philadelphia negative acute lymphoblastic leukemia (Ph-negative ALL). Materials and methods: An observational retrospective study was conducted on patients with high-risk Ph-negative ALL who underwent AHSCT between January 2005 and June 2022. The patients selected were in complete remission (CR): with 80% in CR1 (n = 69) and 20% in CR2 (n = 17). Graft sources were bone marrow (BM) in 71% of patients and peripheral blood stem cells in 29% of patients. The conditioning regimen was TBI or chemotherapy-based (CT). Bone marrow MRD level was quantified using 4-6 color multiparametric flow cytometry (MFC). The threshold for MRD positivity was ≥ 0.1%. Results: The study included 86 patients (45 B-ALL and 41 T-ALL) with a median age of 18 years (range, 4–55 years). The median level of MRD pre-AHSCT (pre-MRD) was 0.4×10-3 (range, 0.01-75.6×10-3). After a median follow-up of 25 months (range 1-205 months), the cumulative incidence of relapse (CIR) was significantly higher in the MRD+ group (39% vs. 20%, p = 0.04). The median time of relapse post-AHSCT was 14 months (range, 1-203 months) in the MRD+ group and 32 months (range, 4-209 months) in the MRD- group (p = 0.28). Non-relapse mortality (NRM) was 15% in both groups (p = 0.97). The 2-year estimated overall survival (OS) and event-free survival (EFS) were 61% vs. 74% (p = 0.07) and 58% vs. 70% (p = 0.10) in the MRD+ and MRD- groups, respectively. A subgroup analysis in MRD+ patients showed that a TBI-based conditioning regimen was distinctly associated with lower CIR (22% vs. 60% respectively, p = 0.04), improved OS (82% vs. 36% respectively, p = 0.007) and better EFS (73% vs. 38%, p = 0.04) compared to CT-based. In a multivariate analysis, pre-AHSCT MRD+ status and non-TBI-based conditioning were significantly associated with inferior OS (OR, 2.30; 95% CI, [1.027-5.168], p = 0.04 and OR, 3.91; 95% CI, [1.624-9.418], p = 0.002, respectively). The only predicting factor of lower EFS was the non-TBI-based regimen (OR, 2.82; 95% CI, [1.308-6.097], p = 0.008). Non-TBI-based and CR2 were significantly associated with higher CIR (OR, 6.25; 95% CI, [1.947-20.055], p = 0.002 and OR, 4.74; 95% CI, [1.197-18.791], p = 0.03, respectively). Peripheral stem cell source was significantly associated with higher NRM (OR, 6.55; 95% CI, [1.488-28.820], p = 0.01). Conclusion: High-risk Ph-negative ALL patients with MRD ≥ 10-3 prior AHSCT had lower OS compared to MRD- patients and may benefit from TBI as a conditioning regimen before AHSCT.
angiopathy supports the importance of complementmediated mechanisms for this clinical entity [4].The excess in complement activation produces a systemic proin lammatory response to SARS-CoV infection [5] and is associated with signi icant thrombophilia, with endothelial cell integrity disruption, contributing to thrombotic occlusions in the microand even macro-vasculature.Thus, this aberrant complement cascade must be regarded as a crucial therapeutic target in facing SARS-CoV-2-induced pneumonia, as also reported on the activity of an anti-C5a monoclonal antibody in two critical COVID-19 patients [6].However, it should be considered that different Human Leukocyte Antigen (HLA) molecules are involved in presenting peptides derived from pathogens to T-lymphocytes.It has been reported [7] that triggering an immune reaction and contemporarily being an HLA-DQA1 carrier may induce the production of anti-drug antibodies against anti-TNF drugs, which could represent a tool in the management of COVID-19, thus resulting in their failure against SARS-CoV-2-induced complications.
