6,759 results on '"Bone Marrow Transplantation adverse effects"'
Search Results
2. Lower incidence of grade II-IV acute Graft-versus-Host-Disease in pediatric patients recovering with high Vδ2+ T cells after allogeneic stem cell transplantation with unmanipulated bone marrow grafts: a prospective single-center cohort study.
- Author
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Müller T, Alasfar L, Preuß F, Zimmermann L, Streitz M, Hundsdörfer P, Eggert A, Schulte J, von Stackelberg A, and Oevermann L
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- Humans, Child, Male, Female, Adolescent, Child, Preschool, Prospective Studies, Incidence, Bone Marrow Transplantation adverse effects, Infant, Receptors, Antigen, T-Cell, gamma-delta metabolism, Receptors, Antigen, T-Cell, gamma-delta immunology, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Immune Reconstitution, Acute Disease, Graft vs Host Disease immunology, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Transplantation, Homologous
- Abstract
Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCR αβ , TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Müller, Alasfar, Preuß, Zimmermann, Streitz, Hundsdörfer, Eggert, Schulte, von Stackelberg and Oevermann.)
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- 2024
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3. Reconstituted CD74 + NK cells trigger chronic graft versus host disease after allogeneic bone marrow transplantation.
- Author
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Dou Y, Nian Z, Wang D, Sun G, Zhou L, Hu Z, Ke J, Zhu X, Sun R, Tian Z, Fu B, Zhou Y, and Wei H
- Subjects
- Animals, Mice, Humans, Chronic Disease, Male, Female, Histocompatibility Antigens Class II immunology, Histocompatibility Antigens Class II metabolism, Disease Models, Animal, Hematopoietic Stem Cell Transplantation adverse effects, Mice, Inbred C57BL, Immune Reconstitution, Bronchiolitis Obliterans Syndrome, Graft vs Host Disease etiology, Graft vs Host Disease immunology, Killer Cells, Natural immunology, Killer Cells, Natural metabolism, Bone Marrow Transplantation adverse effects, Transplantation, Homologous
- Abstract
Chronic graft-versus-host disease (cGVHD) is the most common long-term complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The patients with pulmonary cGVHD in particular have a very poor prognosis. NK cells are the first reconstituted lymphocyte subset after allo-HSCT; however, the impact of reconstituted NK cells on cGVHD is unclear. Here, we found allogeneic recipients showed obvious pulmonary cGVHD. Surprisingly, deletion of reconstituted NK cells resulted in maximal relief of pulmonary cGVHD. Mechanistically, reconstituted NK cells with donor profiles modulated the pulmonary inflammatory microenvironment to trigger cGVHD. Reconstituted NK cells secreted IFN-γ and TNF-α to induce CXCL10 production by epithelial cells, which recruited macrophages and CD4
+ T cells to the lungs. Then macrophages and CD4+ T cells were activated by the inflammatory microenvironment, thereby mediating lung injury. Through assessment of differences in cellular energy, we found that CD74+ NK cells with high mitochondrial potential and pro-inflammatory activity triggered pulmonary cGVHD. Furthermore, targeted elimination of CD74+ NK cells using the anti-CD74 antibody significantly alleviated pulmonary cGVHD but preserved the CD74- NK cells to exert graft-versus-leukemia (GVL) effects. Data from human samples corroborated our findings in mouse models. Collectively, our results reveal that reconstituted CD74+ NK cells trigger pulmonary cGVHD and suggest that administration of CD74 antibody was a potential therapeutic for patients with cGVHD., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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4. Pre-frailty after blood or marrow transplantation and the risk of subsequent mortality.
- Author
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Balas N, Richman JS, Landier W, Shrestha S, Bruxvoort KJ, Hageman L, Meng Q, Ross E, Bosworth A, Wong FL, Bhatia R, Forman SJ, Armenian SH, Weisdorf DJ, and Bhatia S
- Subjects
- Humans, Male, Female, Middle Aged, Risk Factors, Aged, Adult, Survivors, Follow-Up Studies, Survival Rate, Young Adult, Adolescent, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation mortality, Frailty mortality
- Abstract
We examined the prevalence, risk factors, and association between pre-frailty and subsequent mortality after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 3346 individuals who underwent BMT between 1974 and 2014 at one of three transplant centers and survived ≥2 years post-BMT. Participants completed the BMTSS survey at a median of 9 years from BMT and were followed for subsequent mortality for a median of 5 years after survey completion. Closest-age and same-sex biological siblings also completed the survey. Previously published self-reported indices (exhaustion, weakness, low energy expenditure, slowness, unintentional weight loss) classified participants as non-frail (0-1 indices) or pre-frail (2 indices). National Death Index was used to determine vital status and cause of death. Overall, 626 (18.7%) BMT survivors were pre-frail. BMT survivors had a 3.2-fold higher odds of being pre-frail (95% CI = 1.9-5.3) compared to siblings. Compared to non-frail survivors, pre-frail survivors had higher hazards of all-cause mortality (adjusted hazard ratio [aHR] = 1.6, 95% CI = 1.4-2.0). Female sex, pre-BMT radiation, smoking, lack of exercise, anxiety, and severe/life-threatening chronic health conditions were associated with pre-frailty. The novel association between pre-frailty and subsequent mortality provides evidence for interventions as pre-frail individuals may transition back to their robust state., (© 2024. The Author(s).)
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- 2024
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5. Liver Transplantation for Nijmegen Breakage Syndrome With Hepatic Malignancy and Hepatopulmonary Syndrome After Bone Marrow Transplantation: A Case Report.
- Author
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Şal O, Erbey F, Armutlu A, Karasu G, Demir B, Kızılkan NU, Akbulut A, Kanmaz T, and Alim A
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- Humans, Adolescent, Female, Bone Marrow Transplantation adverse effects, Living Donors, Liver Transplantation, Liver Neoplasms surgery, Nijmegen Breakage Syndrome complications, Hepatopulmonary Syndrome surgery, Hepatopulmonary Syndrome etiology, Hepatopulmonary Syndrome therapy
- Abstract
Background: Nijmegen breakage syndrome (NBS) is an autosomal recessive DNA repair disorder that manifests through increased genomic instability, malignancy, and cellular and humoral immunodeficiencies. The prognosis for NBS patients is poor due to their increased susceptibility to fatal infections and lymphoproliferative malignancies. Currently, there is no specific treatment for NBS, though allogeneic hematopoietic stem cell transplantation (HSCT) has been performed and documented as case series to demonstrate the utility of transplantation., Methods: A 14-year-old girl with NBS and haploidentical HSCT from her older brother due to recurrent lung infection was referred for liver transplantation (LT) due to liver cirrhosis, hepatopulmonary syndrome (HPS), and suspicion of liver malignancy. It was decided to perform LT using the living donor who had previously donated for HSCT., Results: Living donor left lobe LT was successfully performed from her brother. The patient experienced no complications in the early postoperative period and was discharged on the seventh postoperative day. Pathological examination of extracted liver has shown "intermediate cell carcinoma" in two foci. After 1 year LT, the patient has had an uneventful course in terms of LT complications and infection, with minimal immunosuppression., Conclusions: NBS patients have an increased prevalence of malignancies, including primary hepatic malignancy, but most are managed medically or with limited resections. Transplantation in these patients can be curative for hepatic malignancy with a favorable safety profile., (© 2024 Wiley Periodicals LLC.)
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- 2024
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6. An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease.
- Author
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Kassim AA, de la Fuente J, Nur E, Wilkerson KL, Alahmari AD, Seber A, Bonfim C, Simões BP, Alzahrani M, Eckrich MJ, Horn B, Hanna R, Dhedin N, Rangarajan HG, Gouveia RV, Almohareb F, Aljurf M, Essa M, Alahmari B, Gatwood K, Connelly JA, Dovern E, Rodeghier M, and DeBaun MR
- Subjects
- Humans, Male, Female, Child, Adolescent, Adult, Child, Preschool, Young Adult, Cyclophosphamide therapeutic use, Cyclophosphamide administration & dosage, Transplantation Conditioning methods, Middle Aged, Thiotepa administration & dosage, Thiotepa therapeutic use, Bone Marrow Transplantation methods, Bone Marrow Transplantation adverse effects, Anemia, Sickle Cell therapy, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Transplantation, Haploidentical methods
- Abstract
Abstract: In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative-related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on the conditioning protocol. Graft failure occurred in 8 of 70 (11.4%) and only in participants aged <18 years; all had autologous reconstitution. After a median follow-up of 2.4 years, the 2-year Kaplan-Meier-based probability of event-free survival was 82.6%. The 2-year overall survival was 94.1%, with no difference between children and adult participants. After excluding participants with graft failure (n = 8), participants with engraftment had median whole blood donor chimerism values at days +180 and +365 after transplant of 100% (n = 58), respectively, and 96.6% (57/59) were off immunosuppression 1 year after transplant. The 1-year grade 3 to 4 acute graft-versus-host disease (GVHD) rate was 10%, and the 2-year moderate-severe chronic GVHD rate was 10%. Five participants (7.1%) died from infectious complications. We demonstrate that nonmyeloablative haploidentical BMT with thiotepa and PTCy is a readily available curative therapy for most adults, even those with organ damage, compared to the more expensive myeloablative gene therapy and gene editing. Additional strategies are required for children to decrease graft failure rates. The trial was registered at www.clinicaltrials.gov as #NCT01850108., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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7. Effectiveness and Complications of Bone Marrow Aspirate Concentrate in Patients with Knee Osteoarthritis of Kellgren-Lawrence Grades II-III.
- Author
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Baek JH, Lee SC, Lee DN, Ahn HS, and Nam CH
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Aged, Treatment Outcome, Adult, Pain Measurement, Bone Marrow Transplantation methods, Bone Marrow Transplantation adverse effects, Injections, Intra-Articular, Aged, 80 and over, Osteoarthritis, Knee complications
- Abstract
This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren-Lawrence (K-L) grades II-III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K-L grades II-III OA. The exclusion criteria were age of <40 years or >80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6-8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up ( p < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 ( p < 0.05) and from 68.4 to 83.3 points ( p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K-L grades II-III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.
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- 2024
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8. Effects of female bone marrow transplantation on male reproductive organs.
- Author
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Takahashi T, Nagahori K, Omotehara T, Kuramasu M, Ogawa Y, Wu X, Natsuyama Y, Kawata S, Yakura T, Miyaso H, Li ZL, and Itoh M
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- Animals, Male, Female, Mice, Genitalia, Male immunology, Genitalia, Male pathology, Mice, Inbred C57BL, Humans, Mice, Inbred BALB C, Testis immunology, Testis pathology, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha immunology, Bone Marrow Transplantation adverse effects, Graft vs Host Disease immunology
- Abstract
Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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9. Successful haploidentical bone marrow transplantation in Griscelli syndrome type 2 with non-busulfan-based regimen and post-transplantation cyclophosphamide: a case report and review of the literature.
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Yamada S, Maruyama Y, Saito S, Komori K, Morokawa H, Okura E, Hirabayashi K, Furui Y, Kurata T, Nishioka M, Fukuyama T, Sakashita K, and Nakazawa Y
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Cyclophosphamide therapeutic use, Transplantation Conditioning adverse effects, Primary Immunodeficiency Diseases complications, Lymphohistiocytosis, Hemophagocytic complications, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects, Piebaldism
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- 2024
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10. Assessment of Corneal Epithelial Changes and Related Factors in Ocular Chronic Graft-Versus-Host Disease (GVHD) by in Vivo Confocal Microscopy.
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Liu S, Peng R, Ma J, Shen Z, Hu B, Zhao Y, and Hong J
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- Adolescent, Adult, Female, Humans, Male, Middle Aged, Young Adult, Bone Marrow Transplantation adverse effects, Chronic Disease, Cytokines metabolism, Corneal Diseases diagnosis, Corneal Diseases etiology, Corneal Diseases metabolism, Epithelium, Corneal pathology, Graft vs Host Disease diagnosis, Microscopy, Confocal, Tears metabolism
- Abstract
Purpose: To evaluate corneal epithelial changes and related factors in chronic ocular graft-versus-host disease (oGVHD) patients., Methods: 21 patients (35 eyes) with chronic oGVHD and 8 patients (12 eyes) without oGVHD after bone marrow transplantation were recruited for assessment involving in vivo confocal microscopy (IVCM) analysis, ocular surface parameter determination and tear cytokine level analysis. The IVCM corneal epithelial scoring system was used to evaluate corneal epithelial changes., Results: There was a significant difference in the corneal epithelial score ( p = .001) between the two groups. The corneal epithelial scores were significantly correlated with the corneal fluorescein staining scores (CFS, r = 0.463, p < .001), Schirmer's test (r = -0.389, p = .009) and tear cytokine levels of EGF (r = -0.491, p < .001) and APRIL (r = -0.318, p = .030)., Conclusions: The depth of corneal epithelial defects can be estimated by the CFS. Corneal epithelial changes of chronic oGVHD are considered to be associated with lacrimal deficiency and a lack of EGF.
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- 2024
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11. Effects of CD34 + cell dose on engraftment and long-term outcomes after allogeneic bone marrow transplantation.
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Oyama T, Fujiwara SI, Tominaga R, Yokoyama D, Noguchi A, Furuki S, Koyama S, Murahashi R, Nakashima H, Hyodo K, Ikeda T, Kawaguchi SI, Toda Y, Nagayama T, Umino K, Minakata D, Morita K, Ashizawa M, Yamamoto C, Hatano K, Sato K, Otsuki I, Ohmine K, and Kanda Y
- Subjects
- Adult, Humans, Bone Marrow Transplantation adverse effects, Retrospective Studies, Antigens, CD34, Recurrence, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Background: The number of CD34
+ cells in the graft is generally associated with time to engraftment and survival in transplantation using cord blood or allogeneic peripheral blood stem cells. However, the significance of abundant CD34+ in bone marrow transplantation (BMT) remained unclear., Methods: We retrospectively reviewed 207 consecutive adult patients who underwent their first BMT at Jichi Medical University between January 2009 and June 2021., Results: The median nucleated cell count (NCC) and CD34+ cell dose were 2.17 × 108 /kg (range .56-8.52) and 1.75 × 106 /kg (.21-5.84), respectively. Compared with 104 patients in the low CD34+ group (below the median), 103 patients in the high CD34+ group (above the median) showed faster engraftment at day +28 in terms of neutrophil (84.6% vs. 94.2%; p = .001), reticulocyte (51.5% vs. 79.6%; p < .001), and platelet (39.4% vs. 72.8%; p < .001). There were no significant differences in overall survival, relapse, nonrelapse mortality, acute or chronic graft-versus-host disease, or infectious complications between the two groups in univariate and multivariate analyses. Low or high NCC had no significant effect on overall survival, nonrelapse mortality, cumulative incidence of relapse and graft-versus-host disease, either. While a positive correlation was observed between NCC and the CD34+ cell dose, a high CD34+ cell dose was associated with rapid hematopoietic recovery, even in patients with NCC below the median., Conclusion: Measurement of CD34+ cell dose in addition to NCC was useful for predicting hematopoietic recovery, but seemed to have little influence on the long-term outcome in BMT., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)- Published
- 2024
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12. Acute Graft versus Host Disease in Beta Thalassemia Patients Following Allogeneic Haematopoietic Stem Cell Transplantation.
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Rafique N, Ali A, Ghaffor T, Khattak TA, Asghar MB, and Chaudhry QU
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- Humans, Male, Female, Child, Adolescent, Infant, Newborn, Infant, Child, Preschool, Bone Marrow Transplantation adverse effects, Pakistan epidemiology, Retrospective Studies, beta-Thalassemia complications, beta-Thalassemia therapy, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Objective: To analyse the frequency, risk factors, and clinical symptoms of acute graft-versus-host disease (aGvHD) in patients with beta-thalassemia major after allogeneic haematopoietic stem cell transplantation (HSCT)., Study Design: Descriptive study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from January 2017 to December 2021., Methodology: Data were obtained from patients diagnosed with bone and tissue malignancies (BTM) who had undergone haematopoietic stem cell transplantation (HSCT) and experienced aGVHD. Patients who experienced initial graft failure and individuals who underwent subsequent bone marrow transplantation were excluded., Results: Total of 117 patients diagnosed with BTM underwent fully matched HSCT, including 76 (65%) males, and 41 (35%) females. The median age of the patients undergoing transplantation was 7.34±7.32 years and the donors' median age was 7.6±9.85 years. Among the donors, 53 (45.3%) were males and 64 (54.7%) were females. Gender disparity was observed in 46 (39.3%) instances as a female donor matched with a male recipient. A total of 106 individuals underwent bone marrow harvest (BMH); with 5 (4.3%) patients receiving peripheral blood stem cells (PBSC) and 6 (5.2%) patients receiving both BMH and PBSC. Acute GvHD was observed in 50 (42.7%) patients, including 30 (60%) males and 20 (40%) females. Grade I GvHD occurred in 32 (27.3%) individuals, Grade II GvHD in 16 (13.7%) patients, and Grade III GvHD in one (0.8%) patient. It had no statistically significant association with recipient/donor age, gender disparity, the source of the graft source, the dose of stem cells, or the presence of thymoglobulin (TG)., Conclusion: Acute GvHD was observed in high frequency in Beta-thalassemia patients receiving morrow harvesting proportional to their gender distribution. Associated factors were GvHD prophylaxis measure, mucositis and, CMV reactivation., Key Words: Beta thalassemia major patients, Acute graft versus host disease, Allogeneic haematopoietic stem cell.
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- 2024
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13. Bone Density and Trabecular Bone Score Decline Rapidly in the First Year After Bone Marrow Transplantation with a Marked Increase in 10-Year Fracture Risk.
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Gong JY, Chiang C, Wark JD, Ritchie D, Panek-Hudson Y, Le MV, Limbri L, Fabila N, Fourlanos S, and Yates CJ
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- Humans, Male, Cancellous Bone, Bone Marrow Transplantation adverse effects, Absorptiometry, Photon, Lumbar Vertebrae, Femur Neck, Risk Assessment, Bone Density, Osteoporotic Fractures epidemiology
- Abstract
As outcomes from allogeneic bone marrow transplantation (BMT) have improved, prevention of long-term complications, such as fragility fractures, has gained importance. We aimed to assess areal bone mineral density (aBMD) and trabecular bone score (TBS) changes post BMT, and determine their relationship with fracture prevalence. Patients who attended the Royal Melbourne Hospital (RMH) BMT clinic between 2005-2021 were included. Patient characteristics and dual-energy X-ray absorptiometry (DXA) values were collected from the electronic medical record and a survey. TBS iNsight™ was used to calculate TBS for DXA scans performed from 2019 onwards. 337 patients with sequential DXAs were eligible for inclusion. Patients were primarily male (60%) and mean age ± SD was 45.7 ± 13.4 years. The annualised decline in aBMD was greater at the femoral neck (0.066g/cm
2 (0.0038-0.17)) and total hip (0.094g/cm2 (0.013-0.19)), compared to the lumbar spine (0.049g/cm2 (- 0.0032-0.16)), p < 0.0001. TBS declined independently of aBMD T-scores at all sites. Eighteen patients (5.3%) sustained 19 fractures over 3884 person-years of follow-up post-transplant (median follow-up 11 years (8.2-15)). This 5.3% fracture prevalence over the median 11-year follow-up period is higher than what would be predicted with FRAX® estimates. Twenty-two patients (6.5%) received antiresorptive therapy, and 9 of 18 (50%) who fractured received or were on antiresorptive therapy. In BMT patients, aBMD and TBS decline rapidly and independently in the first year post BMT. However, FRAX® fracture probability estimates incorporating these values significantly underestimate fracture rates, and antiresorptive treatment rates remain relatively low., (© 2024. Crown.)- Published
- 2024
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14. IL-6-mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation.
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Zhang P, Fleming P, Andoniou CE, Waltner OG, Bhise SS, Martins JP, McEnroe BA, Voigt V, Daly S, Kuns RD, Ekwe AP, Henden AS, Saldan A, Olver S, Varelias A, Smith C, Schmidt CR, Ensbey KS, Legg SR, Sekiguchi T, Minnie SA, Gradwell M, Wagenaar I, Clouston AD, Koyama M, Furlan SN, Kennedy GA, Ward ES, Degli-Esposti MA, Hill GR, and Tey SK
- Subjects
- Antiviral Agents, Immunoglobulin G, Animals, Mice, Bone Marrow Transplantation adverse effects, Cytomegalovirus Infections immunology, Cytomegalovirus Infections metabolism, Immunity, Humoral, Interleukin-6 metabolism
- Abstract
Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.
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- 2024
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15. Eltrombopag improves platelet engraftment after haploidentical bone marrow transplantation: Results of a Phase II study.
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Ahmed S, Bashir Q, Bassett RL Jr, Ullah F, Aung F, Valdez BC, Alousi AM, Hosing C, Kebriaei P, Khouri I, Marin D, Nieto Y, Olson A, Oran B, Qazilbash MH, Rezvani K, Mehta R, Shpall EJ, Ciurea S, Andersson BS, Champlin RE, and Popat UR
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Prospective Studies, Cyclophosphamide therapeutic use, Retrospective Studies, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Graft vs Host Disease drug therapy, Benzoates, Hydrazines, Pyrazoles
- Abstract
Slow platelet recovery frequently occurs after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with bone marrow graft and post-transplant cyclophosphamide (PCy)-based graft-versus-host disease (GVHD) prophylaxis. Improved platelet recovery may reduce the need for transfusions and improve outcomes. We investigated the safety and efficacy of eltrombopag, a thrombopoietin receptor agonist, at enhancing platelet recovery post-haplo-HSCT. The prospective study included patients ≥18 years of age who received haplo-HSCT with bone marrow graft and PCy. Patients received eltrombopag 300 mg/day starting on Day +5. The primary objective was to estimate platelet engraftment (>50 000/μL by Day 60). In a post hoc analysis, they were compared to a contemporary matched control group who did not receive eltrombopag. One hundred ten patients were included in the analysis (30 eltrombopag and 80 control). Seventy-three percent and 50% of patients in the eltrombopag group and control group, respectively, attained >50 000/μL platelet count by Day 60 (p = .043). No eltrombopag-related grade ≥4 adverse events were observed. Median time to platelet recovery (>20 000/μL) was 29 days with eltrombopag and 31 days for controls (p = .022), while its cumulative incidence was 90% (95% confidence interval [CI]: 78%-100%) with eltrombopag versus 67.5% (95% CI: 57%-78%) for controls (p = .014). Number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and non-relapse mortality were similar between groups. Overall, eltrombopag is safe and improves platelet recovery in patients undergoing haplo-HSCT with bone marrow graft and PCy., (© 2024 Wiley Periodicals LLC.)
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- 2024
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16. Secondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication.
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Keller MD, Schattgen SA, Chandrakasan S, Allen EK, Jensen-Wachspress MA, Lazarski CA, Qayed M, Lang H, Hanley PJ, Tanna J, Pai SY, Parikh S, Berger SI, Gottschalk S, Pulsipher MA, Thomas PG, and Bollard CM
- Subjects
- Infant, Humans, Bone Marrow Transplantation adverse effects, Bone Marrow, Immunotherapy, Adoptive, T-Lymphocytes transplantation, Virus Diseases, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Virus-specific T cells (VST) from partially-HLA matched donors have been effective for treatment of refractory viral infections in immunocompromised patients in prior studies with a good safety profile, but rare adverse events have been described. Here we describe a unique and severe adverse event of VST therapy in an infant with severe combined immunodeficiency, who receives, as part of a clinical trial (NCT03475212), third party VSTs for treating cytomegalovirus viremia following bone marrow transplantation. At one-month post-VST infusion, rejection of graft and reversal of chimerism is observed, as is an expansion of T cells exclusively from the VST donor. Single-cell gene expression and T cell receptor profiling demonstrate a narrow repertoire of predominantly activated CD4
+ T cells in the recipient at the time of rejection, with the repertoire overlapping more with that of peripheral blood from VST donor than the infused VST product. This case thus demonstrates a rare but serious side effect of VST therapy., (© 2024. The Author(s).)- Published
- 2024
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17. Editorial: How often can we get the right diagnosis after bone marrow transplant in patients with abnormal liver function tests? Authors' reply.
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Dezan MGF, Cavalcante LN, Silva HRC, de Moura Almeida A, de Assis LHDS, de Freitas TT, de Araújo MAS, Cotrim HP, and Lyra AC
- Subjects
- Humans, Liver Function Tests, Bone Marrow Transplantation adverse effects, Liver Diseases
- Published
- 2024
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18. Comparative Analysis of Allogeneic Bone Marrow Transplantation Outcomes Between Japanese and Non-Japanese Populations.
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Yanagisawa R, Shindo M, Shinohara A, Kuwatsuka Y, Nakase K, Kimura F, Shingai N, Nishida T, Fukuda T, Sakurai M, Kurokawa M, Koike T, Ota S, Takada S, Onizuka M, Uchida N, Tanaka M, Noguchi M, Maruyama Y, Hagihara M, Ichinohe T, Atsuta Y, Kanda J, Nakasone H, and Toubai T
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Japan, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease epidemiology
- Abstract
Background: As the Japanese population may have less genetic diversity than other ethnic groups, treatment outcomes may be affected when allogeneic hematopoietic cell transplantation is performed in other races. However, evidence explaining the effect of racial differences is limited., Methods: We used the Japanese National Database to examine the outcomes of first allogeneic bone marrow transplantations (BMTs) performed between Japanese and non-Japanese patients from 1996 to 2021. We performed propensity score matching using sex, age group, underlying disease group, HLA mismatch, conditioning regimen intensity, and BMT implementation age to select Japanese-to-Japanese BMT patients as the controls., Results: The numbers of non-Japanese-to-Japanese and Japanese-to-non-Japanese BMT cases included in the analysis were 48 and 75, respectively, and the following outcomes were compared: overall survival, non-relapse mortality, acute graft-vs-host disease (GVHD) ≥ grade II, chronic GVHD, and engraftment of neutrophils and platelets. Most parameters did not differ when comparing BMTs according to ethnicity; only platelet engraftment was delayed in Japanese-to-non-Japanese BMT but not in non-Japanese-to-Japanese BMT., Conclusions: The results of this study suggested that BMT performed in Japanese and non-Japanese patients has little effect on treatment outcomes. The results of this study may be useful for donor selection in Japan, where internationalization has progressed in recent years., Competing Interests: Declaration of competing interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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19. Scoring system for optimal cord blood unit selection for single cord blood transplantation.
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Watanabe M, Konuma T, Imahashi N, Terakura S, Seo S, Morishima S, Uchida N, Doki N, Tanaka M, Nishida T, Kawakita T, Eto T, Takahashi S, Sawa M, Uehara Y, Kim SW, Ishimaru F, Ichinohe T, Fukuda T, Atsuta Y, and Kanda J
- Subjects
- Adult, Humans, Male, Female, Bone Marrow Transplantation adverse effects, Retrospective Studies, Fetal Blood, Antigens, CD34, Cord Blood Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Background: We conducted a retrospective study to categorize the cord blood unit (CBU)s to identify the optimal units., Methods: A total of 8503 adults (female, n = 3592; male, n = 4911) receiving their first single cord blood transplantation (CBT) in 2000-2019 were analyzed. Factors associated with CBUs affecting overall survival (OS) and neutrophil engraftment were selected to create ranked categorization for each outcome, followed by comparison with transplantation using HLA-matched bone marrow (BMT)/peripheral blood stem cell (PBSCT) from unrelated (n = 6052) and related donors (n = 4546)., Results: Sex-mismatch, CD34+ cell and CFU-GM counts were selected in the OS analysis. Considering the strong interaction between sex mismatch and CD34+ cell counts, we analyzed females and males separately. For females, female CBU with CD34+ cell counts {greater than or equal to} 0.5 × 10e5/kg and CFU-GM counts {greater than or equal to} 15 × 10e3/kg offered the best OS (Group I), followed by other groups with any (Groups II-IV) or all (Group V) of the risk factors. Group I consistently showed favorable OS (Group IV: HR1.22, P = 0.027; Group V: HR1.31, P = 0.047), comparable to those of rBMT/PBSCT (OS: HR1.02, P = 0.654) and uBM/PBSCT in patients with higher rDRI (HR1.07, P = 0.353). Male patients lacked significant factors affecting OS. Categorization for neutrophil engraftment consisting of CD34+ cell and CFU-GM counts, sex-mismatch, presence of donor-specific antibodies, and the number of HLA-mismatches was effective but not predicted OS., Conclusion: Our ranked categorizations sufficiently predicted female OS and engraftment. The best-ranked CBUs offered preferable outcomes comparable to conventional BM/PB donors in female but not in male patients., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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20. Editorial: How often can we get the right diagnosis after bone marrow transplant in patients with abnormal liver function tests?
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Gaume C, Moluçon Chabrot C, Chabrot P, and Abergel A
- Subjects
- Humans, Liver Function Tests, Bone Marrow Transplantation adverse effects, Liver Diseases
- Published
- 2024
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21. Late morbidity and mortality after autologous blood or marrow transplantation for lymphoma in children, adolescents and young adults-a BMTSS report.
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Holmqvist AS, Meng Q, Dai C, Hageman L, Landier W, Wu J, Francisco LF, Ross ES, Balas N, Bosworth A, Te HS, Bhatia R, Rosenthal J, Wong FL, Weisdorf D, Armenian SH, and Bhatia S
- Subjects
- Child, Humans, Adolescent, Young Adult, Adult, Bone Marrow, Neoplasm Recurrence, Local, Transplantation, Autologous adverse effects, Morbidity, Bone Marrow Transplantation adverse effects, Lymphoma therapy
- Abstract
We determined the risk of late morbidity and mortality after autologous blood or marrow transplantation (BMT) for lymphoma performed before age 40. The cohort included autologous BMT recipients who had survived ≥2 years after transplantation (N = 583 [HL = 59.9%; NHL = 40.1%]) and a comparison cohort (N = 1070). Participants self-reported sociodemographics and chronic health conditions. A severity score (grade 3 [severe], 4 [life threatening] or 5 [fatal]) was assigned to the conditions using CTCAE v5.0. Logistic regression estimated the odds of grade 3-4 conditions in survivors vs. comparison subjects. Proportional subdistribution hazards models identified predictors of grade 3-5 conditions among BMT recipients. Median age at BMT was 30.0 years (range: 2.0-40.0) and median follow-up was 9.8 years (2.0-32.1). Survivors were at a 3-fold higher adjusted odds for grade 3-4 conditions (95% CI = 2.3-4.1) vs. comparison subjects. Factors associated with grade 3-5 conditions among BMT recipients included age at BMT (>30 years: adjusted hazard ratio [aHR] = 2.31; 95% CI = 1.27-4.19; reference: ≤21 years), pre-BMT radiation (aHR = 1.52; 95% CI = 1.13-2.03; reference: non-irradiated), and year of BMT (≥2000: aHR = 0.54; 95% CI = 0.34-0.85; reference: <1990). The 25 years cumulative incidence of relapse-related and non-relapse-related mortality was 18.2% and 25.9%, respectively. The high risk for late morbidity and mortality after autologous BMT for lymphoma performed at age <40 calls for long-term anticipatory risk-based follow-up., (© 2024. The Author(s).)
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- 2024
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22. Lung Injury Prediction Model in Bone Marrow Transplantation: A Multicenter Cohort Study.
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Herasevich S, Schulte PJ, Hogan WJ, Alkhateeb H, Zhang Z, White BA, Khera N, Roy V, Gajic O, and Yadav H
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Cohort Studies, Lung Injury complications, Respiratory Distress Syndrome therapy, Respiratory Distress Syndrome complications, Respiratory Insufficiency therapy
- Abstract
Rationale: Pulmonary complications contribute significantly to nonrelapse mortality following hematopoietic stem cell transplantation (HCT). Identifying patients at high risk can help enroll such patients into clinical studies to better understand, prevent, and treat posttransplantation respiratory failure syndromes. Objectives: To develop and validate a prediction model to identify those at increased risk of acute respiratory failure after HCT. Methods: Patients underwent HCT between January 1, 2019, and December 31, 2021, at one of three institutions. Those treated in Rochester, MN, formed the derivation cohort, and those treated in Scottsdale, AZ, or Jacksonville, FL, formed the validation cohort. The primary outcome was the development of acute respiratory distress syndrome (ARDS), with secondary outcomes including the need for invasive mechanical ventilation (IMV) and/or noninvasive ventilation (NIV). Predictors were based on prior case-control studies. Measurements and Main Results: Of 2,450 patients undergoing stem cell transplantation, there were 1,718 hospitalizations (888 patients) in the training cohort and 1,005 hospitalizations (470 patients) in the test cohort. A 22-point model was developed, with 11 points from prehospital predictors and 11 points from posttransplantation or early (<24-h) in-hospital predictors. The model performed well in predicting ARDS (C-statistic, 0.905; 95% confidence interval [CI], 0.870-0.941) and the need for IMV and/or NIV (C-statistic, 0.863; 95% CI, 0.828-0.898). The test cohort differed markedly in demographic, medical, and hematologic characteristics. The model also performed well in this setting in predicting ARDS (C-statistic, 0.841; 95% CI, 0.782-0.900) and the need for IMV and/or NIV (C-statistic, 0.872; 95% CI, 0.831-0.914). Conclusions: A novel prediction model incorporating data elements from the pretransplantation, posttransplantation, and early in-hospital domains can reliably predict the development of post-HCT acute respiratory failure.
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- 2024
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23. Allogeneic bone marrow transplantation for aplastic anemia.
- Author
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Storb R
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Unrelated Donors, Transplantation Conditioning methods, Anemia, Aplastic etiology, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
After more than 60 years of intense research in allogeneic hematopoietic cell transplantation (HCT), this therapy has progressed from one that was fraught with seemingly insurmountable complications to a standard treatment of patients with aplastic anemia. During the 1970s and 1980s, HCT donors were almost exclusively HLA-identical siblings. Subsequent advances in the understanding of the complexity of the HLA region along with the development of molecular HLA typing and the establishment of unrelated volunteer donor registries have resulted in an ever-increasing use of such donors. Most recent breakthroughs have enabled HLA-haploidentical HCT and, thereby, finding donors for nearly every patient. The outstanding outcomes reported with any of the donor options have made allogeneic HCT the preferred treatment over immunosuppressive therapy., (© 2022. Japanese Society of Hematology.)
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- 2024
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24. Reduced toxicity matched sibling bone marrow transplant results in excellent outcomes for severe congenital neutropenia.
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Oved JH, Gibson NM, Venella K, Elgarten CW, Wray L, Warren JT, and Olson TS
- Subjects
- Humans, Child, Bone Marrow Transplantation adverse effects, Congenital Bone Marrow Failure Syndromes, Busulfan therapeutic use, Busulfan pharmacology, Siblings, Prospective Studies, Cyclophosphamide therapeutic use, Granulocyte Colony-Stimulating Factor therapeutic use, Hematopoietic Stem Cell Transplantation methods, Neutropenia complications, Neutropenia congenital, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Severe congenital neutropenia (SCN) is caused by germline mutations, most commonly in ELANE , impacting neutrophil maturation and leading to high risk of life-threatening infections. Most patients with ELANE- mutant SCN can achieve safe neutrophil counts with chronic Granulocyte-Colony Stimulating Factor (G-CSF). However, up to 10% of patients have neutropenia refractory to G-CSF and require allogeneic stem cell transplant. Traditional conditioning for these patients includes busulfan and cyclophosphamide which is associated with significant toxicities. We present five patients with SCN without myeloid malignancy transplanted using a reduced toxicity regimen of busulfan, fludarabine and thymoglobulin. 5 pediatric patients with SCN underwent matched sibling donor bone marrow transplant (MSD-BMT) between 2014-2022 on or per CHP14BT057 (NCT02928991), a prospective, single center trial testing elimination of cyclophosphamide from conditioning in pediatric patients with single lineage inherited BMF syndromes. All patients had MSDs and no evidence of MDS. Conditioning consisted of PK-adjusted busulfan, fludarabine, and thymoglobulin, with calcineurin inhibitor and mycophenolate mofetil GVHD prophylaxis. With median follow-up of 48.4 months, overall and event-free survival were 100%. There was no acute GVHD and one instance of chronic limited GVHD. Patients exhibited >95% donor myeloid chimerism at 5 years post-BMT. Two patients experienced CMV reactivation without end-organ disease, and no other viral reactivation or significant infections occurred. MSD-BMT with reduced toxicity myeloablation for SCN provides excellent outcomes while minimizing toxicity. These data suggest that busulfan, fludarabine, and ATG can be considered an efficacious, low-toxicity standard of care regimen for patients with SCN undergoing MSD-BMT., Competing Interests: JO consults for Emendo Biotherapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oved, Gibson, Venella, Elgarten, Wray, Warren and Olson.)
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- 2024
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25. Immunological dynamic characteristics in acute myeloid leukemia predict the long-term outcomes and graft-versus host-disease occurrences post-transplantation.
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Wang W, Li H, Guo Y, Zhang L, Jiang W, Zheng N, Peng S, Guan X, Fan G, and Shen L
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation methods, Transplantation, Homologous, Retrospective Studies, Leukemia, Myeloid, Acute, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation methods
- Abstract
To investigate the relationship between immune dynamic and graft-versus-host-disease (GVHD) risk, 111 initial diagnostic acute myeloid leukemia patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in bone marrow (BM) from 60 transplant patients at four different time points were analyzed. Additionally, 90 immune subsets in peripheral blood (PB) of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer OS compared to non-transplant patients (P < 0.001). Among transplant patients, those who developed GVHD showed longer OS than those without GVHD (P < 0.05). URD donors and CMV-negative status donors were associated with improved OS in transplant patients (P < 0.05). Importantly, we observed a decreased Th/Tc ratio in BM at initial diagnostic in patients with GVHD compared to those without GVHD (P = 0.034). Receiver operating characteristic analysis indicated that a low Th/Tc ratio predicted an increased risk of GVHD with a sensitivity of 44.44% and specificity of 87.50%. Moreover, an increased T/NK ratio in BM of post-induction chemotherapy was found to be associated with GVHD, with a sensitivity of 75.76% and specificity of 65.22%. Additionally, we observed a decreased percentage of NK1 (CD56-CD16+NK) in PB on day 100 post-transplantation in the GVHD group (P < 0.05). These three indicators exhibit promising potential as specific and useful biomarkers for predicting GVHD. These findings provide valuable insights for the early identification and management of GVHD risk, thereby facilitating the possibility of improving patient outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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26. Peripheral blood stem cell transplantation from haploidentical related donor could achieve satisfactory clinical outcomes for intermediate- or high-risk adult acute myeloid leukemia patients.
- Author
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Cao LQ, Huo WX, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Huang XJ, and Mo XD
- Subjects
- Humans, Adult, Bone Marrow Transplantation adverse effects, Recurrence, Retrospective Studies, Peripheral Blood Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology, Leukemia, Myeloid, Acute complications
- Abstract
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most important curative method for intermediate- and high-risk adult acute myeloid leukemia (AML) patients. We aimed to identify the clinical outcomes of haploidentical related donor (HID) peripheral blood stem cell transplantation (PBSCT) who receiving peripheral blood (G-PB) harvest, and the patients receiving bone marrow (BM) plus G-PB harvest (BM + PB) as grafts were enrolled as control. The engraftments of neutrophil and platelet in G-PB group were both faster than those in BM + PB group. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGVHD), and moderate to severe chronic GVHD (cGVHD) were all comparable between G-PB and BM + PB groups. The cumulative incidence of relapse and non-relapse mortality at 3 years after HID HSCT was 12.6% versus 13.7% (p = 0.899) and 3.6% versus 7.3% (p = 0.295), respectively, in G-PB and BM + PB group. While the probabilities of GVHD-free/relapse-free survival, leukemia-free survival, and overall survival at 3 years after HID HSCT were 60.6% versus 53.4% (p = 0.333), 83.8% versus 79.0% (p = 0.603), and were 87.3% versus 82.9% (p = 0.670), respectively. We confirmed the safety and efficacy of HID PBSCT in intermediate- and high-risk AML patients in a large cohort., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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27. Acute esophageal stricture after bone marrow transplant.
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Pang S, Saleh H, Ailawadhi S, Edgar M, and Pang M
- Subjects
- Male, Humans, Middle Aged, Bone Marrow Transplantation adverse effects, Bone Marrow, Combined Modality Therapy, Esophageal Stenosis etiology, Esophageal Stenosis therapy, Multiple Myeloma drug therapy
- Abstract
Esophageal stricture after bone marrow transplantation (BMT) is exceptionally rare, with only a few cases reported in the literature. We present an interesting case of a 58-year-old male with refractory multiple myeloma who developed dysphagia five days following his second bone marrow transplantation. He was found to have a severe esophageal stricture. The patient was treated with multiple esophageal dilations and triamcinolone injections in the following weeks to months, resulting in an improvement in symptoms. Although the exact underlying mechanism remains unknown, high-dose chemotherapy conditioning with melphalan prior to BMT likely contributed to the stricture. Our case highlights the importance of heightened post-bone marrow transplantation management for rare complications, such as an esophageal stricture., (© 2023. Japanese Society of Gastroenterology.)
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- 2024
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28. Haploidentical bone marrow transplantation in a pediatric patient with Wiskott-Aldrich syndrome. A case report.
- Author
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Pury S, López Orozco M, Pichichero G, Sasia LV, Morell D, Álvarez MS, Basquiera AL, Mas ME, and Salvucci K
- Subjects
- Male, Child, Humans, Infant, Bone Marrow Transplantation adverse effects, Cyclophosphamide, Wiskott-Aldrich Syndrome therapy, Wiskott-Aldrich Syndrome diagnosis, Wiskott-Aldrich Syndrome genetics, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder caused by mutations in the gene that encodes the Wiskott-Aldrich syndrome protein (WASp). Here, we report the clinical case of an 18-month-old boy diagnosed with Wiskott-Aldrich syndrome, who did not have an HLA-matched related or unrelated donor and was treated successfully with a hematopoietic stem cell transplant (HSCT) from a haploidentical family donor. Graft-versus-host disease (GvHD) prophylaxis included post-transplant cyclophosphamide (PT-Cy). At day +30, the peripheral blood-nucleated cell chimerism was 100% and the WAS protein had a normal expression. Currently, at month 32 post-transplant, the patient has hematological and immune reconstitution and complete donor chimerism without evidence of GvHD. HSCT with PT-Cy was a feasible and safe option for this patient with WAS, in which an HLA matched donor was not available., (Sociedad Argentina de Pediatría.)
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- 2024
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29. Cardiovascular Risk Stratification of Patients Undergoing Hematopoietic Stem Cell Transplantation: The CARE-BMT Risk Score.
- Author
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Vasbinder A, Catalan T, Anderson E, Chu C, Kotzin M, Murphy D, Cheplowitz H, Diaz KM, Bitterman B, Pizzo I, Huang Y, Xie J, Hoeger CW, Kaakati R, Berlin HP, Shadid H, Perry D, Pan M, Takiar R, Padalia K, Mills J, Meloche C, Bardwell A, Rochlen M, Blakely P, Leja M, Banerjee M, Riwes M, Magenau J, Anand S, Ghosh M, Pawarode A, Yanik G, Nathan S, Maciejewski J, Okwuosa T, and Hayek SS
- Subjects
- Adult, Humans, Middle Aged, Bone Marrow Transplantation adverse effects, Risk Factors, Retrospective Studies, Cardiovascular Diseases diagnosis, Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Hematopoietic Stem Cell Transplantation adverse effects, Heart Failure epidemiology, Heart Failure therapy, Heart Failure complications
- Abstract
Background: Evidence guiding the pre-hematopoietic stem cell transplantation (HSCT) cardiovascular evaluation is limited. We sought to derive and validate a pre-HSCT score for the cardiovascular risk stratification of HSCT candidates., Methods and Results: We leveraged the CARE-BMT (Cardiovascular Registry in Bone Marrow Transplantation) study, a contemporary multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019 (N=2435; mean age at transplant of 55 years; 4.9% Black). We identified the subset of variables most predictive of post-HSCT cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, heart failure, stroke, atrial fibrillation or flutter, and sustained ventricular tachycardia. We then developed a point-based risk score using the hazard ratios obtained from Cox proportional hazards modeling. The score was externally validated in a separate cohort of 919 HSCT recipients (mean age at transplant 54 years; 20.4% Black). The risk score included age, transplant type, race, coronary artery disease, heart failure, peripheral artery disease, creatinine, triglycerides, and prior anthracycline dose. Risk scores were grouped as low-, intermediate-, and high-risk, with the 5-year cumulative incidence of cardiovascular events being 4.0%, 10.3%, and 22.4%, respectively. The area under the receiver operating curves for predicting cardiovascular events at 100 days, 5 and 10 years post-HSCT were 0.65 (95% CI, 0.59-0.70), 0.73 (95% CI, 0.69-0.76), and 0.76 (95% CI, 0.69-0.81), respectively. The model performed equally well in autologous and allogeneic recipients, as well as in the validation cohort., Conclusions: The CARE-BMT risk score is easy to calculate and could help guide referrals of high-risk HSCT recipients to cardiovascular specialists before transplant and guide long-term monitoring.
- Published
- 2024
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30. Hepatobiliary disease after bone marrow transplant: A cross-sectional study of 377 patients.
- Author
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Dezan MGF, Cavalcante LN, Silva HRC, de Moura Almeida A, Dos Santos de Assis LH, de Freitas TT, de Araújo MAS, Cotrim HP, and Lyra AC
- Subjects
- Humans, Female, Bone Marrow Transplantation adverse effects, Cross-Sectional Studies, Bone Marrow, Transplantation, Homologous adverse effects, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Hepatitis complications
- Abstract
Background: Bone marrow transplantation (BMT) is a standard treatment for several haematologic conditions. Following BMT, patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischaemic hepatitis, and fulminant hepatitis., Aims: To evaluate the frequency, clinical characteristics, and outcomes of patients with hepatobiliary alterations associated with BMT in a tertiary referral centre., Methods: This was a cross-sectional study with data collected from the medical records of patients undergoing BMT between January 2017 and June 2022. We diagnosed hepatobiliary complications based on established criteria., Results: We included 377 patients; 55.7% had hepatobiliary complications. Female gender, pre-BMT hepatobiliary alteration, and haploidentical allogeneic transplantation were associated with increased risk with odds ratios (OR) of 1.8 (p = 0.005), 1.72 (p = 0.013) and 3.25 (p = 0.003), respectively. Patients with hepatobiliary complications spent longer in the hospital than those without (27.7 × 19.3 days, respectively; p < 0.001). Among 210 patients with hepatobiliary complications, 28 died compared to 5 of 167 without complications (OR 4.98; p = 0.001)., Conclusions: Hepatobiliary complications are frequent in patients undergoing BMT. There is a greater risk of their occurrence in women, people with pre-BMT liver alterations, and in haploidentical transplants. The occurrence of these complications increases the length of stay and is associated with a higher risk of death., (© 2023 John Wiley & Sons Ltd.)
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- 2024
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31. Unusual presentations of chronic graft versus host disease.
- Author
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Okorie CL, Salem I, Scripture AJ, Simmons BJ, Momtahen S, and Yan S
- Subjects
- Female, Humans, Bone Marrow Transplantation adverse effects, Skin pathology, Chronic Disease, Bronchiolitis Obliterans Syndrome, Psoriasis complications, Graft vs Host Disease pathology, Exanthema
- Abstract
Skin is commonly affected by graft versus host disease (GVHD), a complication of bone marrow transplantation (BMT). One-third of hematopoietic cell transplantation recipients develop acute eruption classically described as folliculocentric, maculopapular, or morbilliform, in contrast to the more common chronic presentations of sclerotic, poikilodermic, or lichenoid dermatitides. With the wider use of non-myeloablative (reduced-intensity) transplant therapy, various atypical presentations can occur, representing a diagnostic challenge. Herein, we report an unusual case of chronic GVHD manifested by two distinct clinical and histopathological features lacking the classical presentation. Five months after her BMT, the patient presented with a papulosquamous eruption on her neck, trunk, and arms showing a psoriasiform histopathological pattern of chronic GVHD. She also demonstrated multiple small flesh-colored papules on her distal extremities showing a solitary syringotropic pattern of GVHD, demonstrated by interface dermatitis involving the superficial eccrine duct, as the only diagnostic histopathological feature of GVHD. This report, with review of literature, highlights the uncommon psoriasiform GVHD and the novel description of isolated syringotropic chronic GVHD., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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32. Fall risk factors in hospitalized bone marrow transplant patients: A systematic review.
- Author
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Turkoglu NM and Shang J
- Subjects
- Adult, Humans, Infant, Bone Marrow Transplantation adverse effects, Accidental Falls prevention & control, Risk Factors, Steroids, Diarrhea etiology, Hypnotics and Sedatives, Muscle Weakness etiology, Anti-Anxiety Agents, Neoplasms
- Abstract
Background: Certain types of cancer and treatment increase the risk of falls among cancer patients, particularly patients with hematologic cancer undergoing bone marrow transplant (BMT). Nurses are integral to preventing falls and maintaining patient safety. Understanding patients undergoing BMT fall risk factors may help nurses identify high fall risk patients and develop fall prevention interventions., Purpose: This systematic review aims to identify risk factors for falls among hospitalized adult patients receiving BMT treatment., Methods: Guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review of the literature was conducted by searching databases PubMed and CINAHL. Study quality was evaluated using the Crowe Critical Appraisal Tool form (v1.4)., Findings: An initial search yielded 829 articles; six were included for final review after removing duplicates and screening for inclusion criteria: specific to patients undergoing BMT, measure fall outcome, in hospital, and original research. The identified risk factors include age of 65 and older, leukemia diagnosis, days of diarrhea, incontinence of urine or stool, increased pulse rate, muscle weakness, hypnotic, anxiolytic medication, recent steroid use, allogenic transplant, and post-engraftment period., Conclusions: Risk factors for falls among patients undergoing BMT are multifactorial and are related to muscle weakness, medication administration, pulse rate, type of transplant, age, engraftment period, and bathroom use., Implications for Nursing: Nurses providing care to patients undergoing BMT need to assess and increase nurse surveillance on allogeneic transplant patients, specifically those on anxiolytic, hypnotic, and steroid medications. Nurses providing care to patients undergoing BMT should implement more fall prevention strategies in patients undergoing BMT who develop diarrhea and urine or stool incontinence. Identifying specific patients undergoing BMT fall risk factors and applying multifaceted individualized fall prevention strategies has the potential to improve allogeneic transplant patient care and prevent fall-related complications., (© 2022 NANDA International, Inc.)
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- 2024
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33. Evaluation of the quality of life of adult patients admitted to the bone marrow transplantation unit.
- Author
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Ozturk GS, Ratip S, Umar RM, and Tezcan S
- Subjects
- Adult, Humans, Middle Aged, Hospitalization, Prospective Studies, Quality of Life psychology, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation psychology, Multiple Myeloma drug therapy, Multiple Myeloma psychology
- Abstract
Introduction: The complexity of treatment and extended therapy duration associated with bone marrow transplantation directly affect the psychological well-being of the patients, create anxiety, and reduce their quality of life. The aim of our study was to evaluate the quality of life of patients admitted to the bone marrow transplantation unit., Methods: This prospective and descriptive study was conducted between January and June 2021 in an adult BMT unit in Turkey. The sociodemographic characteristics of the patients were recorded. The patient's quality of life was measured twice using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) scale at the beginning of the study and 30 days later. SPSS 15 was used for the analysis., Results: A total of 40 patients were included in the study. The mean age was 46 years. Most of the patients were diagnosed with multiple myeloma and 58% had at least one comorbid disease. Most of the patients (78%) were receiving myeloablative therapy. High dose melphalan regimen was the most commonly applied regimen (25%). Thrombocytopenia was the most common side effect (14%). Although there was no change in the quality of life, it was found that the social/family well-being scores increased ( p < 0.05)., Conclusions: In our study, it was observed that the number of comorbid diseases was higher in patients with bone marrow transplantation. The incidence of side effects may be high in these patients. We believe that clinical pharmacists have an important role in monitoring adverse effects and improving the quality of life in bone marrow transplantation units., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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34. Enteral nutrition optimization program for children undergoing blood & marrow transplantation: A quality improvement project.
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Murphy JD, Cooke KR, Symons HJ, and VanGraafeiland B
- Subjects
- Child, Young Adult, Humans, Bone Marrow, Quality Improvement, Bone Marrow Transplantation adverse effects, Enteral Nutrition methods, Malnutrition etiology
- Abstract
Background: Malnutrition in children and young adults undergoing blood and marrow transplantation (BMT) increases morbidity and mortality. Addressing this via optimization of enteral nutrition can potentially improve outcomes., Methods: This Quality Improvement project utilized pre-post-intervention design and post-intervention survey to evaluate a novel program optimizing enteral nutrition support in children undergoing BMT. All patients aged 0-18 who were admitted during the 16-week implementation period followed the Enteral Nutrition Optimization Program from pre-BMT through discharge. Data on biometric indicators, complications, and post-transplant milestone time markers were evaluated via Mann-Whitney U, Fisher's exact, and Chi-square tests as indicated using SPSS™ Version 27. A separate sample of clinical providers completed a post-intervention survey to evaluate the feasibility and acceptance of the intervention., Findings: Six patients received the intervention, with 12 patients evaluated. There were no statistical differences between groups on measured evaluations of weight loss (0.15 kg vs +0.4 kg, p = 0.39), malnutrition (2 vs 3, p = 0.545), graft-versus-host-disease (2 vs 2, p = 1), time to engraftment (platelets day 22 vs 20.5, p = 0.589), infections (p = 0.368), and length of stay (32.5 days vs 31 days, p = 1). The provider sample of 45 participants showed overall feasibility and acceptance of the intervention (88.9% agreed or strongly agreed)., Discussion: Feasibility and acceptance were high, resulting in increased use of nasogastric and gastrostomy tubes. Though no clinical significance, interpretation is limited due to the small sample size., Practice Implications: Implementing a novel nutritional support program resulted in a culture shift towards enteral nutrition optimization. Further studies are needed to determine clinical impacts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. No funding was received for this project., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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35. Effect of graft-versus-host disease on outcomes of HLA-haploidentical peripheral blood transplantation using post-transplant cyclophophamide.
- Author
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Shimomura Y, Komukai S, Kitamura T, Sobue T, Akahoshi Y, Kanda J, Ohigashi H, Nakamae H, Hiramoto N, Nagafuji K, Tanaka T, Eto T, Ota S, Maruyama Y, Akasaka T, Matsuoka KI, Mori Y, Fukuda T, Atsuta Y, and Terakura S
- Subjects
- Humans, Cyclophosphamide therapeutic use, Bone Marrow Transplantation adverse effects, Transplantation Conditioning, Recurrence, Retrospective Studies, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
There is limited evidence regarding the association between graft-versus-host disease (GVHD) and reduced relapse in patients who undergo allogeneic hematopoietic stem cell transplantation from haploidentical donors (haplo-HSCT) using post-transplant cyclophosphamide (PTCY). We investigated the association between GVHD and transplant outcomes in 938 patients who received haplo-HSCT using PTCY. Overall survival (OS), relapse rate, and non-relapse mortality (NRM) were evaluated using landmark analysis at the landmark points at 100 and 360 days after HSCT for acute and chronic GVHD, respectively. Grade I-II acute GVHD was not associated with OS (adjusted hazard ratio: 1.15, 95% confidence interval: 0.85-1.57), relapse (1.03, 0.74-1.45) and NRM (1.15, 0.74-1.77). Conversely, grade III-IV acute GVHD was associated with higher NRM (3.16, 1.61-6.19), but no other outcomes. Limited chronic GVHD was not associated with OS (1.11, 0.48-1.95), relapse (1.05, 0.30-3.75) and NRM (1.30, 0.45-3.79). Extensive chronic GVHD was associated with higher NRM (2.40, 1.03-5.57), but no other outcome. In conclusion, any GVHD was not associated with a reduced relapse rate and improved OS, and Grade III-IV acute GVHD and extensive chronic GVHD were associated with higher NRM in patients who received haplo-HSCT using PTCY., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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36. Response to Haspel and McKenna 'Major incompatible red blood cell transfusions prior to bone marrow transplantation: Not worth the risk'.
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Jarisch A and Bonig H
- Subjects
- Humans, Transplantation, Homologous, Blood Group Incompatibility, Bone Marrow Transplantation adverse effects, Erythrocyte Transfusion adverse effects
- Published
- 2023
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37. Understanding and treatment of cutaneous graft-versus-host-disease.
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Hong J, Fraebel J, Yang Y, Tkacyk E, Kitko C, and Kim TK
- Subjects
- Humans, Quality of Life, Skin, Bone Marrow Transplantation adverse effects, Skin Diseases etiology, Skin Diseases therapy, Skin Diseases diagnosis, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease therapy, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
The skin is the outermost mechanical barrier where dynamic immune reactions take place and is the most commonly affected site in both acute and chronic graft-versus-host disease (GVHD). If not properly treated, pain and pruritis resulting from cutaneous GVHD can increase the risk of secondary infection due to erosions, ulcerations, and damage of underlying tissues. Furthermore, resulting disfiguration can cause distress and significantly impact patients' quality of life. Thus, a deeper understanding of skin-specific findings of GVHD is needed. This review will highlight some promising results of recent pre-clinical studies on the pathophysiology of skin GVHD and summarize the diagnostic and staging/grading procedures according to the clinical manifestations of skin GVHD. In addition, we will summarize outcomes of various GVHD treatments, including skin-specific response rates., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2023
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38. Major incompatible red blood cell transfusions prior to bone marrow transplantation: Not worth the risk.
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Haspel RL and McKenna DH
- Subjects
- Humans, Transplantation, Homologous, Blood Group Incompatibility, ABO Blood-Group System, Erythrocytes, Bone Marrow Transplantation adverse effects, Erythrocyte Transfusion adverse effects
- Published
- 2023
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39. Allogeneic T cells cause acute renal injury after hematopoietic cell transplantation.
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Miyata M, Matsuki E, Ichikawa K, Takehara T, Hosokawa Y, Sekiguchi E, Peltier D, Reddy P, Ishizawa K, Watanabe M, and Toubai T
- Subjects
- Mice, Animals, Transplantation, Homologous adverse effects, Bone Marrow Transplantation adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease prevention & control, Acute Kidney Injury etiology
- Abstract
Acute kidney injury (AKI) is a frequent complication of allogeneic hematopoietic cell transplantation (allo-HCT). There are many causes of AKI after allo-HCT, but it is unknown whether renal acute graft-versus-host disease (aGVHD) caused by direct allogeneic donor T-cell-mediated renal damage contributes. Here, we tested whether allogeneic donor T cells attack kidneys in murine models of aGVHD. To avoid confounding effects of nephrotoxic agents, we did not administer immunosuppressants for GVHD prophylaxis. We found that urinary N-acetyl-β-D-glucosaminidase, a marker of tubular injury, was elevated in allogeneic recipients on day 14 after allogeneic bone marrow transplantation. Donor major histocompatibility complex-positive cells were present and CD3+ T cells were increased in the glomerulus, peritubular capillaries, interstitium, and perivascular areas in the kidneys of allo-HCT recipient mice. These T cells included both CD4+ and CD8+ cells with elevated activation markers, increased exhaustion markers, and greater secretion of proinflammatory cytokines and cytotoxic proteins. Consistent with allo-T-cell-mediated renal damage, expression of neutrophil gelatinase-binding lipocalin, a marker of AKI, and elafin, a marker of aGVHD, were increased in renal tissue of allogeneic recipients. Because apoptosis of target cells is observed on histopathology of aGVHD target tissues, we confirmed that alloreactive T cells increased apoptosis of renal endothelial and tubular epithelial cells in cytotoxic T-lymphocyte assays. These data suggest that immune responses induced by donor T cells contribute to renal endothelial and tubular epithelial cell injury in allo-HCT recipients and that aGVHD may contribute to AKI after allo-HCT., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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40. Unrelated female-to-male bone marrow transplantation would be preferred over cord blood transplantation in male patients.
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Tamaki M, Akahoshi Y, Okada Y, Uchida N, Tanaka M, Doki N, Sawa M, Maruyama Y, Ueda Y, Miyakoshi S, Katayama Y, Kawakita T, Kimura T, Onizuka M, Fukuda T, Atsuta Y, Yanagisawa R, Yakushijin K, Kanda J, and Nakasone H
- Subjects
- Humans, Male, Female, Bone Marrow Transplantation adverse effects, Unrelated Donors, Recurrence, Chronic Disease, Retrospective Studies, Cord Blood Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Background Aims: Allogeneic hematopoietic stem cell transplantation from female donors to male recipients (female-to-male allo-HCT) is a well-established risk factor for a greater incidence of non-relapse mortality (NRM) and chronic graft-versus-host disease (GVHD). In contrast, unrelated cord blood transplantation (UCBT) is associated with a lower incidence of chronic GVHD. In this study, survival outcomes were compared between the UCBT and unrelated female-to-male bone marrow transplantation (UFMBMT) groups., Methods: We evaluated male allo-HCT recipients who underwent UCBT or UFMBMT between 2012 and 2020 in Japan. There were 2517 cases in the UCBT group, 456 cases in the HLA-matched UFMBMT group and 457 cases in the HLA-mismatched UFMBMT group., Results: HLA-mismatched UFMBMT was significantly associated with a decreased risk of relapse (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.57-0.98], P = 0.033) and HLA-matched UFMBMT had the tendency of a decreased risk of relapse (HR 0.78; 95% CI 0.61-1.01, P = 0.059). HLA-matched UFMBMT was also associated with favorable OS (HR 0.82; 95% CI 0.69-0.97, P = 0.021). The relationship between the donor sources and relapse was similarly observed in the lymphoid malignancy cohort., Conclusions: The difference of graft-versus leukemia effect by H-Y immunity according to donor sources might contribute to the difference in clinical impact. It might be desirable for patients who could sufficiently wait for donor coordination to select BMT rather than UCBT, even if only unrelated female donors are available for male recipients., Competing Interests: Declaration of Competing Interest M Tanaka received a grant from Chugai Pharmaceutical and received honoraria from AbbVie GK, Kyowa-Kirin, Daiichi-Sankyo, Sumitomo Pharma, Astellas Pharma, Pfizer, Otsuka Pharmaceutical and MSD. MS received honoraria from Chugai Pharmaceutical Co., Pfizer, Astellas Pharma, Nippon Shinyaku, Ono Pharma, MSD, Bristol-Myers Squibb, Kyowa-Kirin, Asahi Kasei, Novartis, Eisai, Otsuka Pharmaceutical, Sumitomo Dainippon Pharma, Sanofi, Takeda Pharmaceuticals, Mochida Pharmaceutical Co., Shire, Mundi Pharma, AbbVie, CSL Behring, SymBio Pharmaceuticals, Janssen Pharmaceuticals, Astra Zeneca, Daiichi-Sankyo and GlaxoSmithKline. JK received a grant from Eisai, received consulting fees from AbbVie GK, Megakaryon Corp., SymBio Pharmaceuticals, Daiichi-Sankyo, Novartis, Janssen Pharmaceutical and Astellas Pharma and received honoraria from CSL Behring, Daiichi-Sankyo, MSD, Sumitomo Dainippon Pharma, Astellas Pharma, Takeda Pharmaceuticals, AbbVie GK, Chugai Pharmaceutical Co., Amgen Pharma, Novartis, Otsuka Pharmaceutical, Bristol-Myers Squibb, Ono Pharma, Janssen Pharmaceutical, Sanofi, Asahi Kasei Pharma, Kyowa-Kirin, CareNet, Nippon Shinyaku and Nippon Kayaku. HN received honoraria from Takeda Pharmaceuticals, Otsuka Pharmaceutical Co., Bristol-Myers Squibb, Celgene, Pfizer, Novartis, Janssen Pharmaceuticals, Eisai, Chugai Pharmaceutical Co., Meiji Seika Pharma and Nippon Shinyaku., (Copyright © 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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41. Haploidentical bone marrow transplants with post transplant cyclophosphamide on day + 3 + 5: The Genova protocol.
- Author
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Raiola AM, Angelucci E, Sica S, and Bacigalupo A
- Subjects
- Humans, Middle Aged, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation methods, Bone Marrow, Cyclophosphamide therapeutic use, Recurrence, Transplantation Conditioning methods, Leukemia, Myeloid, Acute drug therapy, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation methods
- Abstract
We report 634 patients who underwent unmanipulated haploidentical (HAPLO) bone marrow transplantation (BMT) in two Centers. The diagnosis was acute myeloid leukemia (AML) (n = 251), acute lymphoblastic leukemia (ALL)(n = 107), myelodysplastic syndrome and myelofibrosis (MDS + MF) (n = 125) and chronic lymphoproliferative disorders (n = 151). Median age was 52 years (16-74). Graft versus host disease (GvHD) prophylaxis was intravenous cyclosporin (CSA) starting on day 0, oral mycophenolate on day +1, and post-transplant cyclophosphamide (PTCY) on days +3 + 5. Primary graft failure was seen in 23 patients (3,6%); 17 /23 (74%) were rescued with second HAPLO graft, and were alive at one year. The cumulative incidence of acute GvHD grade II-IV was 29% and 3% for grade III-IV; the cumulative incidence of moderate severe chronic GvHD was 23%: older donor and patients age were significant predictors of both acute and chronic GvHD. The overall non relapse mortality (NRM) at 2 years was 19%: 8%, 21% and 30% in patients aged <40, 41-60 > 60 years. Disease free survival (DFS) at 5 years was 64% for acute leukemia in first remission, 51% for acute leukemia CR2, 25% for acute leukemia advanced disease and 49% for MDS/MPN. We confirm, on a relatively large number of patients, that unmanipulated HAPLO BMT with PTCY on days +3 + 5, mostly after a myeloablative conditioning regimen, is followed by a low incidence of graft failure and grade III-IV GvHD; moderate severe chronic GvHD is 23% and NRM at 2 years 19%; 5 year DFS is influenced by remission status of the underlying disease., Competing Interests: Declaration of Competing Interest No conflicts to disclosure., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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42. Impact of HLA disparity on overall mortality risk in patients with extensive chronic GVHD: The HLA Working Group of Japanese Society for Transplantation and Cellular Therapy.
- Author
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Fuji S, Hakoda A, Kanda J, Fukuda T, Doki N, Katayama Y, Uchida N, Ozawa Y, Kanda Y, Tanaka M, Kataoka K, Ara T, Sawa M, Onizuka M, Onishi Y, Kimura T, Ichinohe T, Atsuta Y, Shintani A, and Morishima S
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Histocompatibility Testing, HLA Antigens, Japan, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation adverse effects
- Published
- 2023
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43. The development of post-transplant cyclophosphamide: Half a century of translational team science.
- Author
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O'Donnell PV and Jones RJ
- Subjects
- Animals, Humans, Interdisciplinary Research, Cyclophosphamide therapeutic use, Bone Marrow Transplantation adverse effects, Unrelated Donors, Transplantation Conditioning adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control
- Abstract
Close HLA matching of donors and recipients has been the dogma for successful allogeneic blood or marrow transplantation (alloBMT), to limit the complications of graft-versus-host disease (GVHD). However, many patients in need, especially those within certain ethnic groups such as those of African-Americans and Hispanics, remain unable to find a match even with the increased availability of unrelated donors. Over half a century ago, investigators at Johns Hopkins found that cyclophosphamide's immunosuppressive properties made it the ideal replacement for total body irradiation in alloBMT conditioning regimens. They also found it to be the best chemotherapeutic for preventing GVHD in animal models, but its cytotoxic properties scared them from using it clinically in the high doses successful in animal models. Subsequent work showed that cyclophosphamide spared hematopoietic and other stem cells including memory lymphocytes, prompting re-examination at high doses for GVHD prophylaxis. Animal and extensive human studies demonstrated that high-dose post-transplantation cyclophosphamide (PTCy) effectively and safely limited GVHD such that mismatched transplants are now considered standard-of-care worldwide. The beneficial effects of PTCy on GVHD appears to be independent of donor type, graft source, or conditioning regimen intensity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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44. Estimating the effect of active detection and isolation on Clostridioides difficile infections in a bone marrow transplant unit.
- Author
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Reagan KA, Chan DM, Vanhoozer G, and Bearman G
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Infection Control methods, Hospital Units, Clostridioides difficile isolation & purification, Clostridium Infections diagnosis, Clostridium Infections epidemiology, Cross Infection diagnosis, Cross Infection epidemiology
- Abstract
Objective: To model the effects of active detection and isolation (ADI) regarding Clostridioides difficile infection (CDI) in the bone marrow transplant (BMT) unit of our hospital., Setting: ADI was implemented in a 21-patient bone marrow unit., Patients: Patients were bone marrow recipients on this unit., Interventions: We compared active ADI, in which patients who tested positive for colonization of C. difficile before their hospital stay were placed under extra contact precautions, with cases not under ADI., Results: Within the BMT unit, ADI reduced total cases of CDI by 24.5% per year and reduced hospital-acquired cases by ∼84%. The results from our simulations also suggest that ADI can save ∼$67,600 per year in healthcare costs., Conclusions: Institutions with active BMT units should consider implementing ADI.
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- 2023
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45. Prospective PTCTC trial of myeloablative haplo-BMT with posttransplant cyclophosphamide for pediatric acute leukemias.
- Author
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Fierro-Pineda JC, Tsai HL, Blackford A, Cluster A, Caywood E, Dalal J, Davis J, Egeler M, Huo J, Hudspeth M, Keating A, Kelly SS, Krueger J, Lee D, Lehmann L, Madden L, Oshrine B, Pulsipher MA, Fry T, and Symons HJ
- Subjects
- Young Adult, Humans, Child, Prospective Studies, Cyclophosphamide therapeutic use, Bone Marrow Transplantation adverse effects, Acute Disease, Recurrence, Graft vs Host Disease etiology, Leukemia complications, Myelodysplastic Syndromes therapy, Myelodysplastic Syndromes complications
- Abstract
Promising results have been reported for adult patients with high-risk hematologic malignancies undergoing haploidentical bone marrow transplant (haploBMT) with posttransplant cyclophosphamide (PTCy). To our knowledge, we report results from the first multicenter trial for pediatric and young adult patients with high-risk acute leukemias and myelodysplastic syndrome (MDS) in the Pediatric Transplantation and Cellular Therapy Consortium. Nine centers performed transplants in 32 patients having acute leukemias or MDS, with myeloablative conditioning (MAC), haploBMT with PTCy, mycophenolate mofetil, and tacrolimus. The median patient age was 12 years. Diagnoses included AML (15), ALL (11), mixed-lineage leukemia (1), and MDS (5). Transplant-related mortality (TRM) at 180 days was 0%. The cumulative incidence (CuI) of grade 2 acute graft-versus-host disease (aGVHD) on day 100 was 13%. No patients developed grades 3-4 aGVHD. The CuI of moderate-to-severe chronic GVHD (cGVHD) at 1 year was 4%. Donor engraftment occurred in 27 patients (84%). Primary graft failures included 3 patients who received suboptimal bone marrow grafts; all successfully engrafted after second transplants. The CuI of relapse at 1 year was 32%, with more relapse among patients MRD positive pre-BMT vs MRD negative. Overall survival rates at 1 and 2 years were 77% and 73%, and event-free survival rate at 1 and 2 years were 68% and 64%. There was no TRM or severe aGVHD, low cGVHD, and favorable relapse and survival rates. This successful pilot trial has led to a phase 3 trial comparing MAC haploBMT vs HLA-matched unrelated donor BMT in the Children's Oncology Group. This trial was registered at www.clinicaltrials.gov as #NCT02120157., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
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46. Varicella vaccine meningoencephalitis in a child receiving autologous bone marrow transplantation.
- Author
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Coralie R, Ziad C, Christian R, Pierre T, Chantal B, Bruce T, and Philippe O
- Subjects
- Female, Humans, Child, Infant, Bone Marrow Transplantation adverse effects, Retrospective Studies, Chickenpox Vaccine adverse effects, Herpesvirus 3, Human, Acyclovir therapeutic use, Vaccines, Attenuated, Chickenpox diagnosis, Chickenpox etiology, Herpes Zoster, Meningoencephalitis
- Abstract
Background: Varicella vaccine, a live-attenuated Oka-strain of varicella zoster virus (VZV), is a recommended childhood vaccine by many countries. As with wild varicella strain, after primary infection, the live-attenuated virus can establish latency in sensory ganglia and reactivate causing vaccine-strain illnesses: herpes zoster (HZ), visceral or peripheral and central nervous system dissemination. We report a case of early reactivation of live-attenuated virus-HZ and meningoencephalitis-in an immunocompromised child., Methods: This is a retrospective descriptive report of a case, in a tertiary pediatric hospital, CHU Sainte-Justine (Montréal, Canada)., Results: An 18 month-year old girl diagnosed with a primitive neuro-ectodermal tumor (PNET) received the day prior to diagnosis, a first varicella vaccine (MMRV). She received chemotherapy 20 days post MMRV vaccine and autologous bone marrow transplantation 3 months post vaccination. She was considered not eligible, to acyclovir prophylaxis prior transplantation (positive for VZV IgG and negative for herpes simplex virus IgG by ELISA). At day 1 post transplantation, she developed dermatomal HZ and meningoencephalitis. Oka-strain varicella was isolated, she was treated with acyclovir and foscarnet. Neurologic status improved in 5 days. Control of VZV viral load in cerebrospinal fluid showed a slow decrease to from 5.24 log 10 copies/mL to 2.14 log 10 copies/mL in 6 weeks. No relapse was observed. She recovered without neurological sequelae., Conclusions: Our experience highlights the importance of conducting a thorough medical history regarding vaccination and serological status of newly immunocompromised patients. Intensive chemotherapy succeeding live vaccine administration <4 weeks could have influenced early and severe viral reactivation. Early initiation of prophylactic antiviral treatment is questioned in such circumstances., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)
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- 2023
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47. Epidemiology of cytomegalovirus antiviral resistance testing for solid organ and bone marrow transplant patients from 2011 - 2019.
- Author
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Li L, Lowe CF, McLachlan E, Romney MG, Wright A, and Matic N
- Subjects
- Humans, Bone Marrow Transplantation adverse effects, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Drug Resistance, Viral, Cytomegalovirus, Cytomegalovirus Infections
- Abstract
Background: CMV reactivation post-transplantation is common, with need for prompt identification of patients most at-risk for CMV antiviral drug resistance (AVDR)., Objectives: This study describes CMV AVDR frequencies, antiviral prescribing practices, and AVDR risk factors in patients from 2011 to 2019 in British Columbia, Canada., Study Design: Retrospective review of demographics, transplant type, viral loads, antiviral exposure duration, and 12-month mortality was conducted for all patients with samples submitted for CMV AVDR testing from 2011 to 2019. Genotyping of AVDR mutations occurred at the national reference laboratory. Mann-Whitney U, T-test or Fisher's exact tests examined differences between patients with and without AVDR., Results: Fifty-three plasma and three tissue/fluid specimens successfully underwent CMV AVDR testing; of these samples, 27/56 (48%) had AVDR mutations detected. The commonest AVDR mutations were at UL97 loci A594 (20%), H596 (12%) and L595 (12%). Mutations occurred more frequently in requests from solid organ than hematopoietic stem cell transplant patients (58% vs. 27%, p = 0.05). Previous resistance testing was a significant risk factor for AVDR (p < 0.001). Patients with AVDR had approximately 51 more days of antiviral therapy (p = 0.007) and took 9 days longer to clear viremia (p = 0.23). The median turnaround time from sample send-out to reporting was nine days. However, empiric use of second-line antivirals occurred in most cases (39/53, 74%) before results were available., Discussion: Laboratories should strive to provide timely CMV AVDR testing for transplant patients, to minimize unnecessary exposure to second-line antiviral agents. The findings of this study may help guide clinicians when selecting empiric antiviral therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)
- Published
- 2023
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48. A Multicenter Prospective Interventional Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans.
- Author
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Fujioka A, Yanishi K, Yukawa A, Imai K, Yokota I, Fujikawa K, Yamada A, Naito A, Shoji K, Kawamata H, Higashi Y, Ishigami T, Sasaki KI, Tara S, Kuwahara K, Teramukai S, and Matoba S
- Subjects
- Humans, Male, Middle Aged, Female, Bone Marrow, Prospective Studies, Ischemia etiology, Ischemia therapy, Transplantation, Autologous, Pain, Treatment Outcome, Bone Marrow Transplantation adverse effects, Bone Marrow Transplantation methods, Thromboangiitis Obliterans therapy
- Abstract
Background: Thromboangiitis obliterans (TAO) can lead to the development of critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients (<50 years) still require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has been tested and shown to have reasonable efficacy in CLTI. In this multicenter prospective clinical trial, we evaluated the safety and efficacy of BM-MNC implantation in CLTI patients with TAO., Methods and results: We enrolled 22 CLTI patients with skin perfusion pressure (SPP) <30 mmHg. The primary endpoint of this trial is the recovery of SPP in the treated limb after a 180-day follow-up period. Secondary endpoints include the pain scale score and transcutaneous oxygen pressure (TcPO
2 ). One patient dropped out during follow-up, leaving 21 patients (mean age 48 years, 90.5% male, Fontaine Class IV) for analysis. BM-MNC implantation caused no serious adverse events and increased SPP by 1.5-fold compared with baseline. Surprisingly, this effect was sustained over the longer term at 180 days. Secondary endpoints also supported the efficacy of this novel therapy in relieving pain and increasing TcPO2 . Major amputation-free and overall survival probabilities at 3 years among all enrolled patients were high (95.5% and 89.5%, respectively)., Conclusions: BM-MNC implantation showed safety and significant efficacy in CLTI patients with TAO.- Published
- 2023
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49. Genetic manipulation resulting in decreased donor chondroitin sulfate synthesis mitigates hepatic GVHD via suppression of T cell activity.
- Author
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Tamura S, Ishiguro H, Suwabe T, Katagiri T, Cho K, Fuse K, Shibasaki Y, Mikami T, Shindo T, Kitagawa H, Igarashi M, Sone H, Masuko M, and Ushiki T
- Subjects
- Mice, Animals, Chondroitin Sulfates, Transplantation, Homologous adverse effects, Bone Marrow Transplantation adverse effects, Mice, Inbred C57BL, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology
- Abstract
Donor T cell activation, proliferation, differentiation, and migration are the major steps involved in graft-versus-host disease (GVHD) development following bone marrow transplantation. Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and causes immune modulation by interacting with cell growth factors and inducing cell adhesion. However, its precise effects on immune function are unclear than those of other proteoglycan families. Thus, we investigated the significance of CS within donor cells in acute GVHD development utilizing CSGalNAc T1-knockout (T1KO) mice. To determine the effects of T1KO, the mice underwent allogenic bone marrow transplantation from major histocompatibility complex-mismatched donors. While transplantation resulted in hepatic GVHD with inflammatory cell infiltration of both CD4
+ and CD8+ effector memory T cells, transplantation in T1KO-donors showed milder cell infiltration and improved survival with fewer splenic effector T cells. In vitro T-cell analyses showed that the ratio of effector memory T cells was significantly lower via phorbol myristate acetate/ionomycin stimulation. Moreover, quantitative PCR analyses showed significantly less production of inflammatory cytokines, such as IFN-γ and CCL-2, in splenocytes of T1KO mice. These results suggest that reduction of CS in donor blood cells may suppress the severity of acute GVHD after hematopoietic stem cell transplantation., (© 2023. Springer Nature Limited.)- Published
- 2023
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50. Cytokine release syndrome in haploidentical stem cell transplant may impact T-cell recovery and relapse.
- Author
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Shapiro RM, Kim HT, Ansuinelli M, Guleria I, Cutler CS, Koreth J, Gooptu M, Antin JH, Kelkar A, Ritz J, Wu CJ, Soiffer RJ, Ho VT, Nikiforow S, and Romee R
- Subjects
- Humans, Cytokine Release Syndrome etiology, Retrospective Studies, Bone Marrow Transplantation adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease epidemiology
- Abstract
Cytokine release syndrome (CRS) following haploidentical hematopoietic cell transplantation (HCT) resembles CRS after chimeric antigen receptor-T therapy. We conducted this single-center retrospective study to evaluate the association of posthaploidentical HCT CRS with clinical outcomes and immune reconstitution. One hundred sixty-nine patients who underwent haploidentical HCT between 2011 and 2020 were identified. Of these, 98 patients (58%) developed CRS after HCT. CRS was diagnosed based on the presence of fever within the first 5 days after HCT without evidence of infection or infusion reaction and was graded according to established criteria. The development of posthaploidentical HCT CRS was associated with a lower incidence of disease relapse (P = .024) but with an increased risk of chronic graft-versus-host disease GVHD (P = .01). The association of CRS with a lower incidence of relapse was not confounded by graft source or disease diagnosis. Neither CD34 nor total nucleated cell dose was associated with CRS independently of graft type. In patients developing CRS, CD4+ Treg (P < .0005), CD4+ Tcon (P < .005), and CD8+ T cells (P < .005) increased 1 month after HCT compared with those who did not develop CRS, but not at later time points. The increase in CD4+ regulatory T cells 1 month after HCT was most notable among patients with CRS who received a bone marrow graft (P < .005). The development of posthaploidentical HCT CRS is associated with a reduced incidence of disease relapse and a transient effect on post-HCT immune reconstitution of T cells and their subsets. Therefore, the validation of these observations in a multicenter cohort is required., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2023
- Full Text
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