Dual T-cell depletion with individually tailored anti-thymocyte globulin and attenuated dose of post-transplant cyclophosphamide in haploidentical peripheral stem cell transplantation.

This study aimed to assess the efficacy of dual T-cell suppression using individually tailored doses of antithymocyte globulin (ATG) and attenuated dose of post-transplant cyclophosphamide (PTCy) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We conducted a retrospective analysis of 78 adults with acute leukemia or myelodysplastic syndrome who underwent haplo-HSCT using intravenous busulfan and fludarabine conditioning. Thirty-two patients received attenuated ATG/PTCy, while 46 patients received ATG (7.5 mg/kg) as GVHD prophylaxis. The 100-day cumulative incidence of grade III-IV (9.7% vs. 32.4%, P = 0.018) acute GVHD, as well as 2-year moderate-severe chronic GVHD (13.9% vs. 43.9%, P = 0.018) in the ATG/PTCy group were significantly lower than those in the ATG group. The 2-year overall survival was comparable between the two groups. However, 2-year GVHD-free, relapse-free survival in the ATG/PTCy group was significantly higher compared to that in the ATG group (38.9% vs. 21.7%, P = 0.021). Moreover, during post-engraftment period, the ATG/PTCy group exhibited lower incidences of life-threatening bacterial (12.5% vs. 37%, P = 0.033) and viral infection (0% vs. 17.4%, P = 0.035) than the ATG group. In conclusion, the combination of individually tailored ATG and low-dose PTCy appears to be a promising strategy in haplo-HSCT.

IL-6 inhibition prevents costimulation blockade-resistant allograft rejection in T cell-depleted recipients by promoting intragraft immune regulation in mice.

The efficacy of costimulation blockade with CTLA4-Ig (belatacept) in transplantation is limited due to T cell-mediated rejection, which also persists after induction with anti-thymocyte globulin (ATG). Here, we investigate why ATG fails to prevent costimulation blockade-resistant rejection and how this barrier can be overcome. ATG did not prevent graft rejection in a murine heart transplant model of CTLA4-Ig therapy and induced a pro-inflammatory cytokine environment. While ATG improved the balance between regulatory T cells (Treg) and effector T cells in the spleen, it had no such effect within cardiac allografts. Neutralizing IL-6 alleviated graft inflammation, increased intragraft Treg frequencies, and enhanced intragraft IL-10 and Th2-cytokine expression. IL-6 blockade together with ATG allowed CTLA4-Ig therapy to achieve long-term, rejection-free heart allograft survival. This beneficial effect was abolished upon Treg depletion. Combining ATG with IL-6 blockade prevents costimulation blockade-resistant rejection, thereby eliminating a major impediment to clinical use of costimulation blockers in transplantation.

Interruption of anti-thymocyte globuline treatment in solid organ transplantation is effectively monitored through a low total lymphocyte count.

Introduction: Anti-Thymocyte Globulin (ATG) is a cornerstone in immune suppression for solid organ transplantation. The treatment is a delicate balance between complications arising from over-immunosuppression such as infections and cancer versus rejection stemming from under-immunosuppression. CD3+ T-lymphocyte measurements are frequently employed for treatment monitoring. However, this analysis is costly and not always accessible. The aim of this study was to investigate whether the total count of lymphocytes could replace CD3+ T-lymphocyte measurements based on data from our transplantation center combined with a review of the literature. The hypothesis was that the total lymphocyte count could serve as a diagnostic surrogate marker for CD3+ T-lymphocytes. Methods: A retrospective cohort study was conducted, including patients who underwent kidney and/or a pancreas transplantation and received ATG as induction therapy or for rejection treatment. The inclusion criterium was that the total lymphocyte count and CD3+ T-lymphocyte measurements were measured simultaneously on the same day. Additionally, PubMed and Embase were searched up to 18/10/2023 for published studies on solid organ transplantation, ATG, T-lymphocytes, lymphocyte count, and monitoring. In the retrospective cohort study, a total of 91 patients transplanted between 2016 and 2023, with 487 samples, were included. Results: Total lymphocyte counts below 0.3 x 109/L had a high sensitivity (86%) as a surrogate marker of CD3+ T-lymphocytes below 0.05 x 109/L, but the specificity was low (52%) for total lymphocyte counts above 0.3 x 109/L as a surrogate marker for CD3+ T-lymphocytes above 0.05 x 109/L. A review of the literature identified seven studies comparing total lymphocyte counts and CD3+ T-lymphocytes in ATG monitoring. These studies supported the use of a low total lymphocyte count as a surrogate marker for CD3+ T-lymphocytes and an indicator to omit ATG treatment. However, there was no consensus regarding high total lymphocyte counts as an indicator for continued treatment. Discussion: Results supports that the total lymphocyte count can be used to omit ATG treatment when below 0.3 x 109/L whereas the CD3+ T-lymphocyte analysis should be reserved for higher total lymphocyte counts to avoid ATG overtreatment.

Effects of Antithymocyte Globulin, Basiliximab, and Induction-Free Treatment in Living Donor Kidney Transplant Recipients on Tacrolimus-Based Immunosuppression.

OBJECTIVES: Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment. MATERIALS AND METHODS: We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections. RESULTS: We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group. CONCLUSIONS: In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.

Pediatric renal transplantation: a single center experience.

INTRODUCTION: The rising prevalence of global end-stage renal disease (ESRD) is a significant health concern, especially among children. Although renal replacement therapy is available, children with ESRD are at an increased risk of mortality. Kidney transplantation is the preferred modality of treatment and surpasses renal replacement therapy in terms of survival. However, pediatric renal transplantation could prove difficult due to factors like smaller recipients and donor-recipient mismatches leading to higher complications. MATERIALS AND METHODS: A retrospective single-group case series study was conducted on children with ESRD who were planned to undergo kidney transplantation from living donors between 2015 and 2021. The data was collected from two centers in the city of Sulaymaniyah. RESULTS: The study comprised a predominantly male patient population, with a total of 39 individuals (n = 39) and 13 female patients. The donors were mostly males between 25-40 years old. The majority of participants were 15-18 years old. In majority of the patients Thymoglobulin was the immunosuppressive agent used in induction. The most common etiology for renal failure was reflux nephropathy and artery anastomosis was performed to the external iliac artery in the majority of patients. Only 9 patients had complications following the transplantation and 3 patients had an episode of acute rejection. CONCLUSIONS: Renal transplantation is the preferred treatment of renal failure in pediatric patients in the city of Sulaymaniyah. The most common etiology for pediatric renal failure was reflux nephropathy which was different from the findings of North American Pediatric Renal Trials and Collaborative Studies.

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: A UNOS database study.

BACKGROUND AND OBJECTIVES: The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. MATERIALS AND METHODS: We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. RESULTS: Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p < 0.001), 3-year (6.0 vs. 4.3%, p < 0.001) and 5-year follow-up (7.7 vs. 6.4%, p = 0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p = 0.0005), 3-year (7.6 vs. 5.5%, p < 0.001) and 5-year follow-up (11.5 vs. 8.8%, p < 0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p = 0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p = 0.53) or 5-year follow-up (7.2 vs. 8.1%, p = 0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p = 0.98) and at 3 years (5.5 vs. 5.4%, p = 0.45), respectively. CONCLUSION: Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

European Survey on Clinical Practice of Detecting and Treating T-Cell Mediated Kidney Transplant Rejection.

The KDIGO guideline for acute rejection treatment recommends use of corticosteroids and suggests using lymphocyte-depleting agents as second line treatment. Aim of the study was to determine the current practices of detection and treatment of TCMR of kidney allografts amongst European kidney transplant centres. An invitation was sent through ESOT/EKITA newsletters and through social media to transplant professionals in Europe for taking part in the survey. A total of 129 transplant professionals responded to the survey. There was equal representation of small and large sized transplant centres. The majority of centres treat borderline changes (BL) and TCMR (Grade IA-B, IIA-B) in indication biopsies and protocol biopsies with corticosteroids as first line treatment. Thymoglobulin is used mainly as second line treatment for TCMR Grade IA-B (80%) and TCMR IIA-B (85%). Treatment success is most often evaluated within one month of therapy. There were no differences observed between the large and small centres for the management of TCMR. This survey highlights the common practices and diversity in clinics for the management of TCMR in Europe. Testing new therapies for TCMR should be in comparison to the current standard of care in Europe. Better consensus on treatment success is crucial for robust study designs.

Assessment of immunosuppression induction with basiliximab compared to antithymocyte-globulin in adult heart transplant patients.

BACKGROUND: Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant reduces the early risk and has additional benefits. The induction agent of choice within our program was changed from rabbit antithymocyte-globulin (rATG) to basiliximab, so it was necessary to evaluate whether this had any impact on patient outcomes. OBJECTIVES: Our primary objective was to describe rejection, infection, and other outcomes in adult heart transplant patients at the University of Alberta Hospital in Edmonton, Canada. METHODS: This study was a nonrandomized, retrospective cohort study. RESULTS: Sixty-three patients were included with median ages 50 years versus 54 years. More female patients received rATG (20% vs. 42.4%). The most common indication for transplant in both cohorts was ICM (63.3% vs. 57.6%). Patients who received rATG had significantly higher PRA (0% vs. 43%, p < .001). Acute rejection episodes were similar between basiliximab and rATG at 3 months (16.7% vs. 15.1%; p = 1.0) and 6-months (30.0% vs. 18.1%; p = .376). Infections were not statistically different with basiliximab compared to rATG at 3-months, 43.3% vs. 63.6% and at 6-months 60.0% vs. 66.7%). There were no fatalities in either group. CONCLUSIONS: Our study did not demonstrate differences in rejection with basiliximab compared to rATG. Mortality did not differ, but basiliximab-treated patients had fewer infections and infection-related hospitalizations than those treated with rATG. Larger studies with longer durations are needed to more completely describe the differences in rejection and infectious outcomes.

Post-transplant cyclophosphamide at 80 mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning.

While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), its dose remains a matter of debate due to side effect concerns. Standard dose of 100 mg/kg associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced-intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80 mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score >2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8% ± 3.4% and 19.9% ± 7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80 mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients.

Post-transplant cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil compared to anti-thymocyte globulin, calcineurin inhibitor, and methotrexate combinations as graft-versus-host disease prophylaxis post allogeneic stem cell transplantation from sibling and unrelated donors in patients with acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

Post-transplant cyclophosphamide plus calcineurin inhibitor (CNI)(tacrolimus or cyclosporine A) plus mycophenolate mofetil (PTCy/TAC or CSA/MMF) and anti-thymocyte globulin plus CNI (tacrolimus or cyclosporine A) plus methotrexate (ATG/TAC or CSA/MTX) are common graft-versus-host disease (GVHD) prophylaxis regimens. We compared the two regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic transplantation from matched siblings or unrelated donors. 402 received PTCy/TAC or CSA/MMF and 5648 received ATG/TAC or CSA/MTX. Patients in the PTCy-based group were younger (48.7 vs. 51.5 years, p = 0.024) and there was a higher frequency of patient cytomegalovirus seropositivity and female donor to male patient combination in this group (77.8% vs. 71.8%, p = 0.009 and 18.4% vs. 14.4%, p = 0.029, respectively). More patients in the PTCy-based group received reduced-intensity conditioning (51.5% vs. 41%, p < 0.0001). No differences were observed in the incidence of acute GVHD grade II-IV and III-IV (21.2% vs. 20.4%, p = 0.92 and 8.1% vs. 6%, p = 0.1) or 2-year total and extensive chronic GVHD (33.7% vs. 30%, p = 0.09 and 10.7% vs. 11.2%, p = 0.81) between the groups. In the multivariate analysis, all transplant outcomes did not differ between the groups. PTCy/CNI/MMF and ATG/CNI/MTX are alternative regimens for GVHD prophylaxis in AML patients.

Immune reconstitution after single-unit umbilical cord blood transplantation using anti-thymoglobulin and myeloablative conditioning in adults with hematological malignancies.

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3+ T cells, CD8+ T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4+ T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4+ T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning.

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 × 109/L was a simple predictor of favorable response at 6 months (p = 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 (p = 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.

The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults.

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.

Haploidentical hematopoietic stem cell transplantation with busulfan, cyclophosphamide, and fludarabine conditioning for X-linked adrenal cerebral leukodystrophy.

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/m2 (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.

Unrelated umbilical cord blood transplantation with low-dose anti-thymocyte globulin for children with severe aplastic anemia: A case series.

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.

Comparable outcomes of allogeneic peripheral blood versus bone marrow hematopoietic stem cell transplantation from a sibling donor for pediatric patients.

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.

Current use of antithymoglobulin as induction regimen in kidney transplantation: A review.

Currently, various immunosuppressive drugs are used in organ transplantation. In particular, antithymoglobulin is a widely used drug in kidney transplantation in Korea, accounting for 20% of all induction therapy. According to existing studies, antithymoglobulin induction therapy has several advantages and disadvantages compared with other immunotherapies depending on the kidney transplant situation (dead donor, living donor, low-risk recipient, and high-risk recipient) or antithymoglobulin dose. In this review, we summarize the research conducted so far on antithymoglobulin and hope that antithymoglobulin research on kidney transplantation will be actively conducted in the future.