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Expert Review of Hematology 2024Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the...
The long-term outcomes and safety of severe aplastic anemia treated with porcine antilymphocyte globulin plus cyclosporine, with or without thrombopoietin receptor agonists: a double-center retrospective study.
BACKGROUND
Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA).
RESEARCH DESIGN AND METHODS
We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023.
RESULTS
The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 10/L was a simple predictor of favorable response at 6 months ( = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1-95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6-78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS ( = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment.
CONCLUSIONS
p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.
Topics: Humans; Anemia, Aplastic; Cyclosporine; Male; Female; Retrospective Studies; Middle Aged; Antilymphocyte Serum; Adult; Receptors, Thrombopoietin; Treatment Outcome; Animals; Adolescent; Aged; Swine; Young Adult; Drug Therapy, Combination; Child; Severity of Illness Index; Immunosuppressive Agents
PubMed: 38687471
DOI: 10.1080/17474086.2024.2350527 -
Annals of Hematology Jun 2024This study aimed to investigate the prognosis of unrelated umbilical cord blood transplantation (UCBT) using low-dose anti-thymocyte globulin (ATG) in children diagnosed...
OBJECTIVE
This study aimed to investigate the prognosis of unrelated umbilical cord blood transplantation (UCBT) using low-dose anti-thymocyte globulin (ATG) in children diagnosed with severe aplastic anemia (SAA).
METHODS
This retrospective case series study was conducted involving pediatric SAA patients treated at the Capital Institute of Pediatrics from January 2020 to February 2023. All patients underwent a reduced-intensity conditioning (RIC) regimen alongside low-dose ATG.
RESULTS
The study comprised nine patients (five males) with a median age of 5 years (range: 1.7 to 7 years). The median follow-up duration was 799 days (range: 367 to 1481 days), during which all patients survived. The median time interval from diagnosis to transplantation was 3 months (range: 1 to 9 months). The median dosage of ATG administered was 5 mg/kg (range: 2.5 to 7.5 mg/kg). The median durations for granulocyte and platelet engraftment were 15 days (range: 12 to 23 days) and 26 days (range: 12 to 41 days), respectively. Three patients experienced grade 2-4 acute graft-versus-host disease (aGVHD). Epstein-Barr virus (EBV) reactivation was observed in three patients, while cytomegalovirus (CMV) reactivation occurred in seven patients, with no cases of CMV disease or post-transplant lymphoproliferative disorder (PTLD). One patient experienced recurrence 15 months after transplantation due to influenza A infection.
CONCLUSION
These findings indicate that SAA patients may attain a favorable prognosis following UCBT with a RIC regimen combined with low-dose ATG.
Topics: Humans; Anemia, Aplastic; Antilymphocyte Serum; Male; Female; Child, Preschool; Child; Cord Blood Stem Cell Transplantation; Retrospective Studies; Infant; Graft vs Host Disease; Transplantation Conditioning; Unrelated Donors
PubMed: 38656370
DOI: 10.1007/s00277-024-05756-2 -
Frontiers in Immunology 2024Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against... (Review)
Review
Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient's age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies.
Topics: Humans; Anemia, Aplastic; Hematopoietic Stem Cell Transplantation; Adult; Child; Immunotherapy; Antilymphocyte Serum; Immunosuppressive Agents; Treatment Outcome; Animals
PubMed: 38646536
DOI: 10.3389/fimmu.2024.1378432 -
American Journal of Hematology Jul 2024
Comparative Study
Topics: Humans; Antilymphocyte Serum; Anemia, Aplastic; Cyclosporine; Child; Immunosuppressive Agents; Horses; Animals; Male; Rabbits; Female; Adolescent; Child, Preschool; Treatment Outcome; Infant; Retrospective Studies
PubMed: 38622880
DOI: 10.1002/ajh.27334 -
Pediatric Transplantation May 2024We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD).
OBJECTIVE
We investigated the safety and efficacy of haploidentical stem cell transplantation (SCT) in pediatric patients with X-linked adrenoleukodystrophy (ALD).
METHODS
A retrospective analysis of transplantation data from 29 cases of ALD, treated between December 2014 and April 2022, was conducted. Neurologic function scores (NFS) were assessed. The conditioning regimen was busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg, and fludarabine 90 mg/m (BFC). Graft-versus-host disease prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil, and short course of methotrexate.
RESULTS
Among the 29 cases, 14 cases (NFS = 0) were asymptomatic, and 15 (NFS ≥ 1) were symptomatic. The median age at SCT was 8 years (range: 4-16 years); the median follow-up time was 1058 days (range: 398-3092 days); 28 cases were father donors and 1 case was a grandfather donor. Hematopoietic reconstitution was successful in all patients, and all of them achieved complete donor chimerism at the time of engraftment. The leading cause of death was still primary disease progression (n = 4). Survival free of major functional disabilities was 100% in asymptomatic patients versus 66.67% in the symptomatic group (p = .018).
CONCLUSION
BFC regimen used in haploidentical SCT was administered safely without major transplant-related complications even in symptomatic patients, and neurological symptoms were stabilized after SCT.
Topics: Humans; Child; Child, Preschool; Adolescent; Busulfan; Retrospective Studies; Graft vs Host Disease; Transplantation Conditioning; Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Antilymphocyte Serum; Adrenoleukodystrophy; Vidarabine
PubMed: 38602169
DOI: 10.1111/petr.14735 -
Annals of Hematology Jun 2024Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral... (Comparative Study)
Comparative Study
Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral blood SCs (PBSC) has recently increased. With advancing graft-versus-host disease (GVHD) prophylaxis, whether the BM is still a better SC source than PB in sibling donor HSCT remains controversial. Here, we compared the results of BM transplantation (BMT) and PBSC transplantation (PBSCT) in pediatric patients with malignant or non-malignant diseases receiving sibling HSCT using a total of 7.5 mg/kg of anti-thymocyte globulin (ATG). We retrospectively reviewed children who received HSCT from a sibling donor between 2005 and 2020 at Seoul National University Children's Hospital. Of the 86 patients, 40 underwent BMT, and 46 underwent PBSCT. Fifty- six patients had malignant diseases, whereas thirty patients had non-malignant diseases. All conditioning regimens comprised ATG. Busulfan-based myeloablative conditioning regimens were administered to patients with malignant diseases and approximately half of those with non-malignant diseases. The remaining half of the patients with non-malignant diseases were administered cyclophosphamide-based reduced- intensity conditioning regimens. According to studies conducted at our center, all BM donors received G-CSF before harvest to achieve early engraftment. In all 86 patients (47 males and 39 females), the median age at the time of HSCT was 11.4 (range, 0.7 - 24.6) years. The median follow-up period was 57.9 (range, 0.9-228.6) months, and the corresponding values for those with BM and PBSC were 77 (range, 2.4-228.6) months and 48.7 (range, 0.9-213.2) months, respectively. Engraftment failure occurred in one patient with BM and no patient with PBSC. The cumulative incidence of acute GVHD with grades II-IV was higher in PBSC (BM 2.5%, PBSC 26.1%, p = 0.002), but there was no significant difference in those with grades III-IV acute GVHD (BM 0%, PBSC 6.5%, p = 0.3703) and extensive chronic GVHD (BM 2.5%, PBSC 11.6%, p = 0.1004). There were no significant differences in treatment-related mortality (TRM) (BM 14.2%, PBSC 6.8%, p = 0.453), 5-year event-free survival (EFS) (BM 71.5%, PBSC 76.2%, p = 0.874), and overall survival (OS) rates (BM 80.8%, PBSC 80.3%, p = 0.867) between BM and PBSC in the univariate analysis. In the multivariate analysis, which included all factors with p < 0.50 in the univariate analysis, there was no significant prognostic factor for EFS or OS. There was no significant difference in the relapse incidence between BM and PBSC among patients with malignant diseases (BM 14.2%, PBSC 6.8%, p = 0.453). Additionally, there were no significant differences in the TRM, 5-year EFS, and OS rates between malignant and non-malignant diseases nor between the busulfan-based myeloablative regimen and reduced-intensity chemotherapy using cyclophosphamide. In this study, we showed no significant differences in EFS, OS, TRM, and GVHD, except for acute GVHD grades II-IV, between BMT and PBSCT from sibling donors, using ATG (a total of 7.5 mg/kg). Therefore, PB collection, which is less invasive for donors and less labor-intensive for doctors, could also be considered an acceptable SC source for sibling donor HSCT in children.
Topics: Humans; Child; Male; Female; Child, Preschool; Adolescent; Retrospective Studies; Siblings; Bone Marrow Transplantation; Infant; Peripheral Blood Stem Cell Transplantation; Graft vs Host Disease; Transplantation Conditioning; Hematopoietic Stem Cell Transplantation; Tissue Donors; Treatment Outcome; Antilymphocyte Serum; Transplantation, Homologous
PubMed: 38594416
DOI: 10.1007/s00277-024-05737-5 -
Journal of Hematopathology Jun 2024
Topics: Humans; Antilymphocyte Serum; T-Lymphocytes; CD5 Antigens; Male; Female
PubMed: 38573562
DOI: 10.1007/s12308-024-00581-y -
Pediatric Transplantation May 2024This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney...
Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.
BACKGROUND
This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs).
METHODS
This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate.
RESULTS
A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m, p = .614).
CONCLUSIONS
These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.
Topics: Humans; Child; Basiliximab; Antilymphocyte Serum; Antibodies, Monoclonal; Prednisone; Kidney Transplantation; Retrospective Studies; Cohort Studies; Azathioprine; Induction Chemotherapy; Graft Rejection; Immunosuppressive Agents; Recombinant Fusion Proteins; Transplant Recipients
PubMed: 38553819
DOI: 10.1111/petr.14713 -
Annals of Hematology May 2024Rabbit anti-human T lymphocyte globulin (ATLG) and anti-thymocyte globulin (ATG) are commonly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic...
Rabbit anti-human T lymphocyte globulin (ATLG) and anti-thymocyte globulin (ATG) are commonly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (HSCT). Yet, their efficacy and safety have seldom been compared in hematological malignancies with haploidentical HSCT. A retrospective analysis with 28 ATLG (total dosage, 20-30 mg/kg) and 18 ATG (total dosage, 8-10 mg/kg) patients were performed. The cumulative incidences of chronic GVHD and relapse were comparable between both groups. ATLG showed a trend towards a lower acute GVHD incidence (28.6% vs. 44.4%, P = 0.242) and 3-year non-relapse mortality (10.7% vs. 27.8%, P = 0.160), and had a significantly higher 3-year overall survival (OS, 64.3% vs. 33.3%, P = 0.033) and GVHD-free and relapse-free survival (GRFS, 32.1% vs. 11.1%, P = 0.045) compared with ATG. Multivariate Cox regression analysis demonstrated ATLG was independently associated with a favorable OS (hazard ratio [HR] = 0.37, 95% confidence interval [CI]: 0.16-0.86, P = 0.020) and GRFS (HR = 0.51, 95%CI: 0.26-1.00, P = 0.051). Furthermore, ATLG had a lower risk of fever (25.0% vs. 61.1%, P = 0.014) and hemorrhage cystitis (7.1% vs. 38.9%, P = 0.008) than ATG-T. In conclusion, ATLG confers more survival benefit and a better safety profile than ATG and can be used in hematological malignancies with haploidentical HSCT. Prospective designed trials with a larger sample size are warranted to confirm the results in the future.
Topics: Animals; Humans; Rabbits; Antilymphocyte Serum; Prospective Studies; Retrospective Studies; Neoplasm Recurrence, Local; Hematopoietic Stem Cell Transplantation; Hematologic Neoplasms; Graft vs Host Disease; Chronic Disease; Transplantation Conditioning
PubMed: 38538977
DOI: 10.1007/s00277-024-05724-w -
Leukemia May 2024There is a high risk of GVHD and non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) from unrelated donors. Prophylaxis with rabbit...
There is a high risk of GVHD and non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) from unrelated donors. Prophylaxis with rabbit anti-thymocyte globulin (rATG) is standard in Europe but post-transplantation Cyclophosphamide (PTCy) is an emerging alternative. We analyzed outcomes of rATG (n = 7725) vs. PTCy (n = 1039) prophylaxis in adult patients with hematologic malignancies undergoing peripheral blood alloSCT from 10/10 antigen-matched unrelated donors (MUD) between January 2018 and June 2021 in the EBMT database. The provided P-values and hazard ratios (HR) are derived from multivariate analysis. Two years after alloSCT, NRM in the PTCy group was 12.1% vs. 16.4% in the rATG group; p = 0.016; HR 0.72. Relapse was less frequent after PTCy vs. rATG (22.8% vs. 26.6%; p = 0.046; HR 0.87). Overall survival after PTCy was higher (73.1% vs. 65.9%; p = 0.001, HR 0.82). Progression free survival was better after PTCy vs. rATG (64.9% vs. 57.2%; p < 0.001, HR 0.83). The incidence of chronic GVHD was lower after PTCy (28.4% vs. rATG 31.4%; p = 0.012; HR 0.77), whereas the incidence and severity of acute GVHD were not significantly different. GVHD-free relapse-free survival was significantly higher in the PTCy arm compared to the rATG arm (2 y incidence: 51% vs. 45%; HR: 0.86 [95% CI 0.75-0.99], p = 0.035). In the absence of evidence from randomized controlled trials, our findings support a preference for the use of PTCy in adult recipients of peripheral blood alloSCTs from MUD.
Topics: Humans; Cyclophosphamide; Graft vs Host Disease; Antilymphocyte Serum; Male; Middle Aged; Female; Adult; Hematologic Neoplasms; Unrelated Donors; Hematopoietic Stem Cell Transplantation; Immunosuppressive Agents; Transplantation, Homologous; Aged; Young Adult; Transplantation Conditioning; Adolescent; Survival Rate; Follow-Up Studies; Retrospective Studies
PubMed: 38538862
DOI: 10.1038/s41375-024-02225-7