Stem Cell Transplantation Research Articles

Female-to-male allogeneic transplantation affects outcomes differently according to the type of haplo-transplantation

Allogeneic hematopoietic stem cell transplantation from a female donor to a male recipient (female-to-male allo-HCT) is a well-established risk factor for chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM). The inferior outcomes of female-to-male allo-HCT are considered to be due to allo-immunity against H-Y antigens. However, the influence of minor histocompatibility antigens in haplo-identical allo-HCT remains to be elucidated. We investigated the impact of female-to-male allo-HCT according to the haplo-HCT subtype. In the post-transplant cyclophosphamide (PTCY) cohort (n = 660), a female-to-male sex-mismatch was significantly associated with a decreased risk of relapse (HR: 0.70 [95% CI: 0.49–0.99], P = 0.045), but not with overall survival (OS) or NRM (HR: OS 0.89 [95% CI: 0.68–1.16], P = 0.40; NRM 0.98 [95% CI: 0.68–1.41], P = 0.90). On the other hand, in the non-PTCY cohort (n = 219), a female-to-male sex-mismatch was associated with inferior risks of OS and NRM, but was not associated with relapse. These results suggested that the survival impact of the haplo-HCT subtype differed according to the presence of a sex-mismatch. PTCY might be feasible for overcoming the inferiority of female-to-male allo-HCT and might preserve a GVL effect against H-Y antigens.

A Systematic Review on the Epidemiology and Treatment Options of Multiple Myeloma in Asia

Multiple myeloma (MM) accounts for almost 15% of all neoplastic malignancies around the globe. This systematic review intends to analyse data on the treatment and management of MM in selected regions in Asia to identify and prioritize areas that need attention. A comprehensive review of original articles, published in English from 2005 to 2022, derived from the PubMed/MEDLINE database was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. There were 98 studies from select regions of Asia (China, India, Taiwan, Hong Kong, and Singapore) on newly diagnosed MM and relapsed/refractory MM. This review evaluated the trends in disease outcomes with the gradual shift in treatment regimens from doublet to triplet. Additionally, this review also explored autologous stem cell transplant outcome and anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in MM patients. This is the first systematic review attempting to collect data on the utility and comparison of innovative agents and modifications in treatment regimens in the context of the Asian population. This review established that the body of evidence for the management of MM was generally of poor quality and there is a need for more versatile studies in the region. Novel and innovative drug regimens may help in combating the illness but consorted efforts by researchers, industry partners, policymakers, and the government are key factors in the long-term survival of MM patients. In the current systematic review, the authors have tried to give a comprehensive account of the available treatments, trends in MM management and prognosis for MM in Asia.

Photobiomodulation therapy to prevent oral mucositis and functional impairment in adult patients with haematological cancer undergoing haematopoietic stem cell transplantation: randomised trial protocol

IntroductionOral mucositis is a highly prevalent condition in individuals treated for haematological neoplasms, primarily during haematopoietic stem cell transplantation (HSCT). The condition is known to delay recovery processes, increasing the...

CRISPR/Cas9 in the treatment of sickle cell disease (SCD) and its comparison with traditional treatment approaches: a review.

Sickle cell disease (SCD) is a common hereditary blood disorder that profoundly impacts individuals' health, causing chronic pain, anemia, organ damage, increased susceptibility to infections, and social and psychological effects. Over the years, advances in treatment have improved the long-term outcomes of SCD patients. However, problems such as limited access to hematopoietic stem cell transplantation (HSCT) and potential complications associated with the available therapies underscore the importance of continued research and development. The recent FDA approval of Casgevy (Exagamglogene autotemcel), a genetic therapy based on CRISPR/Cas9 technology, demonstrates a comprehensive effort to address the complexity of SCD using new technologies. This review explores the potential of CRISPR/Cas9 for treating SCD and evaluates its efficacy, safety, and long-term outcomes compared to traditional treatment approaches. Long-term research is needed to comprehensively assess the safety, effectiveness, and inclusion of CRISPR/Cas9, ensuring its overall efficacy.

Healthcare Resource Utilization and Associated Costs in Patients With Chronic Graft-Versus-host Disease Postallogeneic Hematopoietic Stem Cell Transplantation in England

Limited evidence suggests chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases healthcare resource utilization (HCRU) and costs. However, this burden has not been well characterized in England. This study assesses secondary care HCRU and costs for patients following allo HSCT in England with cGvHD and patients who did not develop graft-versus-host disease (GvHD). Further stratification was performed among patients who did or did not subsequently receive high-cost therapies for the treatment of cGvHD. This descriptive, retrospective cohort study used Hospital Episode Statistics (HES) data from April 2017 to March 2022. HES data captures information on reimbursed diagnoses and procedures from all National Health Service (NHS) secondary care admissions and attendances in England. High-cost drugs as defined by NHS England are recorded in HES, these drugs and other procedures including plasma exchange, were used to identify patients with cGvHD who were in receipt of high-cost therapies. HCRU and costs were described for patients with cGvHD following allo-HSCT (n = 721) and were matched with patients with no evidence of GvHD following allo-HSCT (n = 718). HCRU and costs were also described for the subset of patients with cGvHD (n = 198) following receipt of high-cost therapies and patients with cGvHD prior to or without such therapies (n = 523). A higher proportion of patients with cGvHD had at least one inpatient or intensive care unit (ICU) admission or emergency care attendance than patients without GvHD (inpatient: 74.6% versus 66.6%; emergency care: 39.3% versus 30.5%; ICU: 7.4% versus 4.7%; respectively); whilst the proportion of patients with an outpatient attendance were similar for both groups (outpatient: 80.3% versus 84.1%; respectively). The cost across all secondary care settings was higher for patients with cGvHD than patients without GvHD, with a mean cost of inpatient admissions of £17,339 ppy for those with cGvHD versus £8548 ppy in patients without GvHD. A higher proportion of patients who received high-cost therapies for the treatment of cGvHD had at least one secondary care admission or attendance, than patients who did not (inpatient: 85.4% versus 66.4%; ICU: 7.1% versus 5.4%; outpatient: 87.9% versus 76.7%; emergency care: 44.4% versus 36.5%; respectively). Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean number (14.6 versus 8.2 ppy, respectively) for all-cause inpatient admissions after treatment than patients who did not. In all secondary care settings, the total cost ppy was higher for patients who received high-cost therapies for the treatment of cGvHD, than for those who did not. Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean cost (£21,137 versus £15,956 ppy, respectively) for all-cause inpatient admissions than patients who did not. This study demonstrates that cGvHD and the use of associated high-cost therapies impacts healthcare activity and costs across various secondary care settings in England more than patients without GvHD and patients with cGvHD who received no high-cost therapies.

Ex vivo-generated human CD1c+ regulatory B cells by a chemically defined system suppress immune responses and alleviate graft-versus-host disease

IL-10+ regulatory B cells (Bregs) show great promise in treating graft versus host disease (GVHD), a life-threatening complication of post-hematopoietic stem cell transplantation. However, obtaining high-quality human IL-10+ Bregs in vitro remains a challenge due to the lack of unique specific marker and the triggering of pro-inflammatory cytokines expression. Here, by uncovering the critical signaling pathways in Bregs induction by mesenchymal stromal cells (MSCs), we firstly established an efficient Bregs induction system based on MSCs and GSK-3β blockage (CHIR-99021), which had a robust capacity to induce IL-10+ Bregs while suppress TNF-α expression. Furthermore, these Bregs population could be identified and enriched by CD1c+. Mechanistically, MSCs induced the expansion of Bregs through the PKA-mediated phosphorylation of cAMP response element binding protein (CREB). Thus, we developed a chemical-defined inducing protocol by PKA-CREB agonist, instead of MSCs, which can also effectively induce CD1c+ Bregs with lower TNF-α expression. Importantly, induced CD1c+ Bregs suppressed the proliferation of PBMC and the inflammatory cytokines secretion of T cells. When adoptive transferred to a humanized mouse model of GVHD, induced CD1c+ Bregs effectively alleviated GVHD. Overall, we establish an efficient ex vivo induction system for human Bregs, which has implications in developing novel Bregs-based therapies for GVHD.

Real-World Outcomes of Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma with Deletion 17p

BackgroundDespite tremendous advancements in multiple myeloma (MM) therapeutics, outcomes remain heterogeneous, heavily influenced by clinical and cytogenetic factors. Among these, deletion of the short arm of chromosome 17 (del(17p)) is a strong predictor of poor prognosis. ObjectiveThe aim of this study was to evaluate real-world outcomes in patients with newly-diagnosed multiple myeloma (NDMM) with del(17p) undergoing upfront auto-HCT. Study DesignWe conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-HCT at MD Anderson Cancer Center between 2008 and 2018. Primary endpoints were progression-free survival (PFS) and overall survival (OS), with secondary endpoints being hematological response and minimal residual disease (MRD) status post-auto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. ResultsOne hundred and fifteen patients were included (55% male). Median age at auto-HCT was 62 years (range 34-83). The median del(17p) clone size was 20%, with 51 (53%) patients having clone sizes >20% and 15 (15%) patients having clone sizes >55%. Additional high-risk cytogenetic abnormalities included t(4;14) in 15 (13%) patients, t(14;16) in 8 (7%) patients, and 1q21+ in 25 (22%) patients. After induction, 10% of patients achieved ≥ CR and 50% achieved ≥ VGPR, with 25% having MRD-negative ≥ VGPR. Post-transplant, 42% achieved ≥ CR and 83% achieved ≥ VGPR as best response, with 55% (48/87) having MRD-negative ≥ VGPR. With a median follow-up of 31.4 months (range 3.1–199.1), median PFS and OS for the entire cohort were 19.9 and 71.5 months, respectively, and 5-year OS was 53%. Concurrent del(17p) and t(4;14) were associated with significantly worse outcomes, with median PFS and OS of 11.5 and 22.4 months, respectively. For the subset of patients with del(17p) and t(4;14), median PFS and OS were 11.5 months and 22.4 months, respectively. In multivariable analysis (MVA), female sex was associated with worse PFS (HR [95% CI] 2.87 [1.75-4.72], p<0.001), while MRD negative CR post-transplant (0.35 [0.18-0.68], p=0.002) and maintenance therapy (0.46 [0.27-0.77], p=0.003) were associated with better PFS. In MVA for OS, female sex (2.22 [1.18-4.17], p=0.013) and the presence of t(4;14)(2.55 [1.09-5.95], p=0.030) were associated with worse OS, whereas Karnofsky Performance Status of ≥90 (0.47 [0.23-0.94], p=0.034) was associated with better OS. ConclusionThis study affirms del(17p) as a high-risk abnormality with unfavourable outcomes despite modern therapies. The co-occurrence of del(17p) and t(4;14) was associated with particularly poor outcomes. Novel approaches are needed for this high-risk subgroup.

Changes in energy expenditure and body composition following allogeneic stem cell transplant

Changes in energy expenditure and body composition following allogeneic stem cell transplant

Post-transplantation Cyclophosphamide-Based Regimen for Graft-vs.-Host Disease Prophylaxis Reduces Risk of CKD in Allogenic Stem-Cell Transplant Recipients

Post-transplantation Cyclophosphamide-Based Regimen for Graft-vs.-Host Disease Prophylaxis Reduces Risk of CKD in Allogenic Stem-Cell Transplant Recipients

Efficacy of thiotepa-conditioned autologous stem-cell transplantation as consolidation therapy for primary leptomeningeal malignant lymphoma: a case report and review of literature.

Primary leptomeningeal malignant lymphoma (PLML) is a rare subtype of primary central nervous system lymphoma (PCNSL). Treatment is often based on PCNSL, but currently there is no established treatment strategy due to its rarity. We report a case of a 46-year-old male diagnosed with PLML through cerebrospinal fluid cytology and flow cytometry, presenting with multiple cranial nerve palsies and L5 radiculopathy. The patient achieved complete remission (CR) with R-MPV (rituximab, methotrexate, procarbazine, and vincristine) combined with intrathecal chemotherapy (methotrexate, cytarabine, and prednisolone). This was followed by autologous stem-cell transplantation (ASCT) using a thiotepa-based conditioning regimen, resulting in sustained CR. A literature review on the use of ASCT for PLML revealed three reported cases, including ours, all achieving CR with ASCT and minimal adverse events. These findings suggest that ASCT can be a promising consolidation therapy for PLML. Further studies are needed to establish standardized treatment protocols for this rare condition.

Late Kidney and Blood Pressure Outcomes after Pediatric Hematopoietic Stem-Cell Transplant: A Systematic Review and Meta-Analysis

Late Kidney and Blood Pressure Outcomes after Pediatric Hematopoietic Stem-Cell Transplant: A Systematic Review and Meta-Analysis

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

Kidney Recovery Prognosis after Allogeneic Hematopoietic Stem-Cell Transplantation

An Unprecedented Case of Autologous Stem-Cell Transplant in a Patient with Multiple Myeloma with ESKD on Peritoneal Dialysis

An Unprecedented Case of Autologous Stem-Cell Transplant in a Patient with Multiple Myeloma with ESKD on Peritoneal Dialysis

Cystatin C as a Superior Biomarker for Melphalan Dosing in Patients with Multiple Myeloma Undergoing Autologous Stem-Cell Transplant: A Single-Center Retrospective Analysis

Cystatin C as a Superior Biomarker for Melphalan Dosing in Patients with Multiple Myeloma Undergoing Autologous Stem-Cell Transplant: A Single-Center Retrospective Analysis

Improving risk stratification for 2022 European LeukemiaNet favorable-risk patients with acute myeloid leukemia

Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) Favorable genetic-risk group has important clinical implications, as allogeneic stem-cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all Favorable genetic-risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged <60 years with de novo AML classified as 2022 ELN Favorable genetic-risk who achieved a CR and had RNA-seq and gene mutation data from diagnostic samples available (Alliance trial A152010). To identify prognostically relevant transcripts that can distinguish patients cured from patients susceptible to lower- or higher-risk of relapse or death, we fit a regularized mixture cure model (MCM), where RNA-seq expression values were our candidate covariates. To validate the identified transcripts, we analyzed 75 patients with de novo AML aged <60 years included in the 2022 ELN Favorable genetic-risk group who achieved a CR in an independent test set from Gene Expression Omnibus (GSE37642). Our MCM identified 145 transcripts associated with cure, or long-term RFS, and 149 transcripts associated with latency, or shorter-term time-to-relapse. The area under the curve and C-statistic were, respectively, 0.946 and 0.856 for our training and 0.877 and 0.857 for our test sets. Our results suggest that the Favorable-risk group includes distinct transcriptionally defined subgroups with different biological properties, which may be useful for refining this genetic-risk category.

The Future of Regenerative Medicine: Stem Cell Research in Pakistan

The landscape of medicine is being revolutionized by the recent breakthroughs in stem cell research that offer new possibilities for treating diseases that were once deemed degenerative, incurable, or irreversible. In low and middle-income countries like Pakistan stem cell therapy holds promise for cost-effective solutions to non-communicable diseases. However, these advancements are hindered by ongoing debates, legal challenges, and public controversies. Stem cells can differentiate into various cell types and self-renew themselves, making them appealing for regenerative medicine. Unlike traditional therapies, regenerative medicine focuses on the restoration of optimal functioning of the damaged tissues and organs. Stem cells can be categorized as embryonic and adult stem cells. Adult stem cells such as mesenchymal stem cells can differentiate into various cell types. These can be obtained from bone marrow, adipose tissue, umbilical cord tissue, and amniotic fluid. Research shows that stem cells have the potential to treat cancers and advance regenerative medicine. Genetically modified stem cells can act as delivering systems for the treatment of genetic disorders and the development of therapeutic agents directly targeted to organs. Successful differentiation of stem cells into neurons, cardiomyocytes, insulin-producing cell clusters, hepatocytes, and hematopoietic precursors. These achievements are powerful tools that can help in combating human diseases. In Pakistan, while the potential of stem cell therapy has generated significant excitement, the progress is hindered by regulatory and infrastructure challenges. Addressing these concerns and fostering a supportive research environment is essential for advancing stem cell and regenerative medicine in the country. According to the WHO International Clinical Trials Registry, there are over 3000 trials on adult stem cells in progress [1]. These trials are essential in advancing the knowledge of stem cell therapies and for the establishment of realistic expectations for their outcomes. The transplantation of stem cells into non-native environments can pose risks, including tumor formation and other complications. These risks underscore the importance of rigorous evaluation and monitoring to ensure that these promising therapies are both safe and effective before they become widely available. In conclusion, stem cell research has great potential to revolutionize healthcare in Pakistan, but ethical, regulatory, and infrastructure challenges must be overcome before its benefits can be fully realized in regenerative medicine. An environment that is supportive and safe is imperative for clinical trials and research to ensure safe and effective therapies in the future.

An unusual case of thrombotic microangiopathy following autologous stem cell transplantation: A case report

Thrombotic microangiopathy (TMA) is a rare but potentially life-threatening complication following autologous stem cell transplantation (ASCT). The incidence is extremely low. Here, we present the case of a 54-year-old male with relapsed diffuse large B-cell lymphoma (DLBCL) who developed TMA within 92 days after ASCT. The patient exhibited signs of hemolysis, thrombocytopenia and rapid renal function deterioration, and necessitating initiation of hemodialysis. Kidney biopsy confirmed TMA and Genetic testing revealed Complement H factor deficiency. Treatment with plasma exchange and corticosteroids resulted in no significant response. The patient was ultimately managed with ravulizumab. Transplant associated TMA (TA-TMA) is a an entity in which TMA occurs following stem cell transplant. This case highlights the importance of considering TMA in the differential diagnosis of renal failure following ASCT and initiating prompt treatment as delayed management can lead to devastating outcomes.

Real-world treatment trends and triple class exposed status in newly diagnosed multiple myeloma patients in Japan: A retrospective claims database study.

Treatment trends for newly diagnosed multiple myeloma (NDMM) are not fully evaluated in real-world settings in the Japanese population. Triple-class exposed (TCE) patients with relapsed or refractory MM have a poor prognosis and limited treatment options. To clarify characteristics, treatment trends, and TCE status in Japanese patients with MM, we conducted a retrospective, non-interventional study. Data from patients with MM were extracted from a Japanese claims database between 2015 and 2022: this study identified patients with NDMM prescribed daratumumab (D), lenalidomide (R), and/or bortezomib (V) as 1st-line treatment. The patient characteristics and treatment trends were analyzed for non-transplant and transplant groups. Of 1,784 patients, non-transplant patients (n = 1,656, median age 75 years [range: 37-94]) received R+dexamethasone (Rd) (24.7%), Vd (23.8%), and RVd (15.6%) and transplant patients (n = 128, median age 61 years [range: 35-73]) received RVd (49.5%), Vd (18.7%), and DVd (8.4%) in 1st line. In the non-transplant group, the commonly prescribed treatment regimens were Rd for patients aged ≥75 years, Vd for patients aged 65-74 years, and RVd for patients aged <65 years. Patients with renal or cardiac dysfunction commonly received Vd or Rd, respectively. In the transplant group, 107 (83.6%) and 20 (15.6%) patients received transplantation in the 1st and 2nd lines, respectively. The top three regimens as induction therapy before stem cell transplantation were RVd (49.5%), Vd (18.7%), or DVd (8.4%) in 1st line. Cumulative TCE patients by 5th line were 351 (21.2%) and 56 (43.8%) for non-transplant and transplant patients, respectively. TCE ratio at each line gradually increased from 1st to 5th line (11.1-69.2% in the non-transplant group and 21.1-100% in the transplant group, respectively). Of 184 TCE patients in the non-transplant group, 89.7% received sequencing treatments including DRd, RVd, and DVd, and 10.3% received D-RVd in 1st line.

The Role of MicroRNAs and Stem cells in Rheumatoid Arthritis: A Therapeutic and Diagnostic Approach.

In autoimmune illnesses like Rheumatoid Arthritis (RA), the synovium is constantly inflamed, and joints are ruptured. It is becoming increasingly clear that stem cells, especially notably mesenchymal stem cells (MSCs) and microRNAs (miRNAs), play important roles in the onset and amelioration of RA. There is mounting evidence from both animal and human studies that suggests a potentially safe and effective method to treat RA and other intractable diseases by reducing chronic inflammation and spurring tissue regeneration through the transplantation of multipotent adult stem cells, such as mesenchymal stromal/stem cells. To control gene expression, which impacts immune cell differentiation and inflammatory pathways, microRNAs (miRNAs) are crucial, even though MSCs can self-renew and modify inflammatory reactions. The pathophysiology of RA is marked by the dysregulation of immunological responses and the proliferation of fibroblast-like synoviocytes, which are linked to the aberrant expression of specific microRNAs (miRNAs). This study mainly aims to examine the therapeutic implications of these microRNAs (miRNAs) in relation to RA, as they can function as diagnostic and prognostic indicators. This study explores the functions of microRNAs (miRNAs) and stem cells in rheumatoid arthritis (RA), drawing attention to the relevance of these biological processes and the potential for creating novel therapeutic strategies to improve patient outcomes.

Expression of Anti- Apoptotic Gene ( BARF1) and Immunomodulatory Gene (BCRF1) For Epstein Barr Virus in Chronic Active EBV Patients

Epstein Barr virus (EBV) is a herpes virus with double-stranded DNA enclosed by proteins. The envelope of the virus has glycoproteins, which are important for attachment and entry into the host cells (B cells and epithelial cells). EBV targets B cells by utilizing their molecular machinery to replicate the viral genome. The virus causes B cells to differentiate into memory B cells, which then can move into the circulatory system, or become latent until a trigger causes reactivation. The transmission of the Epstein Barr virus occurs in several ways, such as deep kissing or food-sharing. Increased levels of viral DNA are found in salivary secretions after the initial infection. Children can be infected after eating food that has already been chewed by an EBV infected individual. The transmission has occurred through stem cell and organ transplantation, as well as blood transfusion. EBV has several associated complications, One dangerous complication is splenic rupture due to infectious mononucleosis. Aim of the Study: To Estimation the immunemodulatory and Oncogenes for Epstein Barr Virus Associated with Viral Tumorigenesis in Chronic Active EBV Patients By Detection of EBV IgG in all samples , Estimation the expression of antiapoptotic gene ( BARF1) and immunomodulatory gene (BCRF1). Result: The study showed there are high significant between the patient group with different inflammation disease in addition infected with virus compare with have not disease When detection genetically about the virus in sample of infected by EBV the presence of genes has been diagnosed BARF1 and BCRF1 in patient's group.