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).
