Point shear-wave elastography for the diagnosis of veno-occlusive disease in children and young adults.

BACKGROUND: Hepatic veno-occlusive disease or sinusoidal obstruction syndrome is a potentially life-threatening complication of hematopoietic stem cell transplantation. OBJECTIVE: To assess the usefulness of point shear-wave elastography (pSWE) for the early diagnosis of sinusoidal obstruction syndrome (SOS) in children. MATERIALS AND METHODS: A retrospective study was carried out in 43 patients with suspected SOS assessed between March 2018 and November 2021. Diagnosis of SOS was confirmed in 28 patients based on the European Society for Blood and Marrow Transplantation diagnostic criteria. Abdominal ultrasound and pSWE of the liver were performed before and after hematopoietic stem cell transplantation on first suspicion of SOS. RESULTS: Liver stiffness on initial suspicion was higher in patients diagnosed with SOS and these values increased compared to the pre-transplantation values. A cutoff value of 1.37 m/s was found for the diagnosis of SOS, with an area under the curve of 0.779 (95% CI 0.61-0.93). CONCLUSION: Point shear wave elastography of the liver is a promising technique for the early diagnosis of pediatric SOS.

Extracorporeal photopheresis in paediatric patients: A retrospective comparison between different 'off-line' protocols.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) has been shown to be an effective treatment for graft-versus-host disease (GvHD). However, information regarding lymphocyte collection for ECP in children is limited. The aim of this study was to analyse and compare lymphocyte collection for ECP in children using different devices and protocols. Moreover, we have studied both safety and variables of the infused product related to treatment efficacy. PATIENTS AND METHODS: This was a retrospective study of 91 patients who underwent 1524 apheresis procedures with either the COBE Spectra or Spectra Optia system. The comparison study between the Optia protocols (MNC and CMNC) was prioritized. We analysed 578 procedures using the Optia blood cell separator: 204 and 374 using the MNC and the CMNC protocol, respectively. RESULTS: The Optia CMNC protocol showed better collection efficiency, with increased lymphocyte collection per kg of body weight (p < 0.001). On multivariate analysis, the type of protocol showed no relationship with haematocrit or platelet loss. Most procedures were well-tolerated, with the most frequent adverse events related to venous access (21.7%). Seventy-one percent of patients had either partial or complete clinical GvHD response. In the multivariate model, only two variables were associated with a better response to ECP, younger age and a greater increase of B lymphocytes after treatment. CONCLUSION: Lymphocyte collection for ECP is well-tolerated in most children, achieving complete or partial response in more than half of GvHD patients. CMNC is the optimal software to perform lymphocyte collection in children.

Mobilization with high-dose granulocyte colony-stimulating factor alone at 12 µg/kg twice a day in high-risk pediatric patients: A retrospective analysis of the experience in a single center.

INTRODUCTION: Mobilization regimes in pediatric patients at high risk for poor mobilization are not standardized across different institutions. We present a retrospective analysis of our experience with a high-dose granulocyte colony-stimulating factor (G-CSF) regime of 12 µg/Kg per body weight (BW) twice a day for 4 days used in high-risk patients. MATERIAL AND METHODS: We report the results of all pediatric patients mobilized with high-dose G-CSF between January 1999 and February 2021 in our center. A successful mobilization was defined as a peripheral blood (PB) CD34+ cell count of ≥10 CD34+ cells/µl on the fifth day of mobilization immediately before leukapheresis. A minimum cell yield of ≥2 × 106 CD34+ cells/Kg of BW was required for a successful collection. RESULTS: Of the 262 patients included in the analysis, mobilization failure was found in 27 (10.3%). In a univariate analysis, this was associated with age, weight, baseline diagnosis, and having undergone a previous mobilization cycle, the latter being the only factor that remained significantly associated in a multivariate analysis (P = 0.03). The 54 patients (20.6%) did not reach the minimum required CD34+ cell yield. 50.4% of the patients reported adverse events (AEs) during the mobilization period, and 23 (9.1%) reported 3 or more concomitant AEs. However, all of them were mild and did not affect the mobilization schedule. CONCLUSIONS: Although most high-risk pediatric patients are successfully mobilized with the high-dose G-CSF regime, this approach does not salvage all of them and significantly increases the presence of AEs in comparison to standard-dose regimes.

"Ex-vivo" T-cell depletion in allogeneic hematopoietic stem cell transplantation: New clinical approaches for old challenges.

Allogeneic transplantation still remains as standard of care for patients with high-risk hematological malignancies at diagnosis or after relapse. However, GvHD remains yet as the most relevant clinical complication in the early post-transplant period. TCD allogeneic transplant is now considered a valid option to reduce severe GvHD and to provide a platform for cellular therapy to prevent relapse disease or to treat opportunistic infections.

Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH).

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

Plerixafor-based mobilization in pediatric healthy donors with unfavorable donor/recipient body weight ratio resulted in a better CD34+ collection yield: A retrospective analysis.

INTRODUCTION: In order to propose risk-adapted mobilization algorithms, several authors have tried to look for predictive factors of the CD34+ yield in healthy pediatric donors. Donor recipient body weight ratio (D/R ratio) was identified as one of the main variables related with the success to achieve the target cell dose for transplantation. According to this variable we modified the mobilization schedule. MATERIAL AND METHODS: We report the results of 46 mobilizations and apheresis procedures performed in our center with unfavorable D/R ratio. Mobilization was attempted by the standard regime of G-CSF (10 mcg/kg/24 hours) in 28 cases (60.9%), with high dose G-CSF (10 mcg/kg/12 hours) in 9 cases (19.6%), and with plerixafor and G-CSF single dose regime in 9 cases (19.6%). RESULTS: CD34+ cell quantification before apheresis is closely related to CD34+ yield, being the only factor related to collected CD34+ cells (beta .71; P < .0001). The mobilization efficiency was higher in plerixafor group compared to the other two schedules (P < .0001). By using plerixafor for mobilization, we achieved the target CD34+ cell dose of ≥2 × 106 /kg per recipient body weight in all cases with unfavorable D/R ratio. It was observed that 17.4% of cases that not reached the established target cell dose were located in the standard or high-dose mobilization regimes. This difference is even greater for optimal collections (≥5 × 106 /kg), since of the 54.3% cases that did not reach this goal none was mobilized by plerixafor. CONCLUSION: Tailoring the mobilization regime we can reach the target cell dose, even in those cases with the worst D/R ratio.

Kinetics and Risk Factors of Relapse after Allogeneic Stem Cell Transplantation in Children with Leukemia: A Long-Term Follow-Up Single-Center Study.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established treatment for high-risk hematological malignancies in the pediatric population, but relapse remains the leading cause of death. We analyzed risk factors associated with relapse. Data from 353 allo-HSCTs from 1989 to 2015 in our center were studied retrospectively. We performed a multivariate analysis of pre- and postransplantation variables and developed a predictive risk score for relapse using the significant factors in this training cohort. The results were confirmed in a validation cohort of 90 allo-HSCTs done in our institution from 2016 to the present. A total of 104 patients relapsed after allo-HSCT, with a relapse cumulative incidence of 31 ± 2%. In multivariate analysis, only 2 variables influenced relapse: disease phase (advanced versus early, HR, 2.84; 95% CI, 1.76 to 4.57; P = .001) and presence of chronic graft-versus-host disease (GVHD) (acute GVHD versus chronic GVHD [HR, 4.27; 95% CI, 1.99 to 9.15; P = .0001] and no GVHD versus chronic GVHD [HR, 6.86; 95% CI, 3.63 to 12.97] P = .0001]. Applying the personalized risk score (0 to 3), the relapse cumulative incidence was 70 ± 5% in patients with a score of 3 (without GVHD and in the advanced phase) compared with 6 ± 4% in patients with a score of 0 (with chronic GVHD and in an early phase). This score has been verified in the validation set. With a median follow-up of 54 months, the disease-free survival (DFS) and overall survival rate were 37 ± 3% and 45 ± 4%, respectively. The association of GVHD with the graft-versus-leukemia effect is clearly established in our study, and the form of GVHD associated with less relapse and the best DFS is the classical form of chronic GVHD according to the National Institutes of Health classification. The proposed relapse risk score was validated in an independent cohort and allows personalization of the prognosis.

Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results.

Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 ± 9%and 28 ± 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 ± 11% and 58 ± 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.

Use of Eculizumab in Pediatric Patients with High-Risk Transplantation-Associated Thrombotic Microangiopathy: Outcomes and Risk Factors Associated with Response and Survival. A Retrospective Study on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).

Transplantation-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although survival has improved significantly with the introduction of eculizumab, the need for improvement remains, especially in high-risk patients. This study aimed to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment. We designed a national multicenter retrospective study of children treated with eculizumab for high-risk TA-TMA. The study cohort comprised 29 patients who had undergone a first (n = 28) or second (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for malignant (n = 17) or nonmalignant (n = 12) disease. The median time from HSCT to TA-TMA diagnosis was 154 days (interquartile range [IQR], 103 to 263 days). Eleven patients (38%) who were initially diagnosed with low- to intermediate-risk TA-TMA progressed to high-risk TA-TMA (hrTA-TMA), within a median time of 4 days (IQR, 1 to 33 days). SC5b-9 was increased in 90% of 20 patients in whom it was measured. Renal (n = 12), pulmonary (n = 1), and intestinal (n = 1) biopsy confirmed the diagnosis in 12 of 14 patients (85%). Seventeen patients (58%) had extrarenal involvement with serositis (n = 13; 44,8%), pulmonary (n = 12; 41,4%), gastrointestinal (n = 8; 27.6%), cardiovascular (n = 7; 24.1%), or central nervous system (CNS) (n = 2; 6.9%) involvement. The median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR, 1 to 8 days). Overall, 19 patients (65.5%) responded to eculizumab, of whom 17 (58.6%) achieved a complete response and 2 (6.9%) achieved a partial response. The remaining 10 patients (34.5%) did not show any of response. The overall response rate to eculizumab for TA-TMA was 27.59% (95% confidence interval [CI], 14.87% to 47.66%) at 1 month, 55.17% (95% CI, 38.43% to 73.48%) at 3 months, and 62.07% (95% CI, 45.10% to 79.13%) at 6 months after eculizumab initiation. In multivariate analysis, the pulmonary involvement decreased the probability of response (hazard ratio [HR], .18; P = .0298). The 1-year overall survival (OS) was 55.2% (95% CI, 35.6% to 71.0%) for the whole cohort and 83.3% (95% CI, 56.7% to 94.3%) for patients who responded to eculizumab. Pulmonary involvement (HR, 14.93; P = .0043) and CNS involvement (HR, 8.63; P = .0497) were associated with a statistically significant decrease in survival. We found that patients diagnosed with hrTA-TMA with pulmonary involvement had a poor response to eculizumab, and that patients with pulmonary and CNS involvement had significantly decreased survival. Given these results, we hypothesize that providing eculizumab therapy at an early stage of the disease before organ damage is established might significantly improve the response and, consequently, survival.

Haploidentical versus Cord Blood Transplantation in Pediatric AML. A Retrospective Outcome Analysis on Behalf of the Pediatric Subcommittee of GETH (Grupo Español de Trasplante Hematopoyético).

Haploidentical stem cell transplantation (Haplo-SCT) and cord blood transplantation (CBT) are both effective alternative treatments in patients suffering from acute myeloid leukemia (AML) and lacking a matched HLA donor. In the last years, many centers have abandoned CBT procedures mostly due to concern about poorer immune recovery compared with Haplo-SCT. We conducted a retrospective multicenter study comparing the outcomes using both alternative approaches in AML. A total of 122 transplants (86 Haplo-SCTs and 36 CBTs) from 12 Spanish centers were collected from 2007 to 2021. Median age at hematopoietic stem cell transplantation (HSCT) was 7 years (0.4-20). Thirty-nine patients (31.9%) showed positive minimal residual disease (MRD) at HSCT and a previous HSCT was performed in 37 patients (30.3%). The median infused cellularity was 14.4 × 106/kg CD34+ cells (6.0-22.07) for Haplo-SCT and 4.74 × 105/kg CD34+ cells (0.8-9.4) for CBT. Median time to neutrophil engraftment was 14 days (7-44) for Haplo-SCT and 17 days (8-29) for CBT (P = .03). The median time to platelet engraftment was 14 days (6-70) for Haplo-SCT and 43 days (10-151) for CBT (P < .001). Graft rejection was observed in 13 Haplo-SCTs (15%) and in 6 CBTs (16%). The cumulative incidence of acute graft versus host disease (GvHD) grades II-IV was 54% and 51% for Haplo-SCT and CBT, respectively (P = .50). The cumulative incidence of severe acute GvHD (grades III-IV) was 22% for Haplo-SCT and 25% for CBT (P = .90). There was a tendency to a higher risk of chronic GvHD in the Haplo-SCT group being the cumulative incidence of 30% for Haplo-SCT and 12% for CBT (P = .09). The cumulative incidence of relapse was 28% and 20% for Haplo-SCT and CBT, respectively (P = .60). We did not observe statistically significant differences in outcome measures between Haplo-SCT and CBT procedures: 5-year overall survival (OS) was 64% versus 57% (P = .50), 5-year disease-free survival (DFS) 58% versus 57% (P = .80), GvHD-free and relapse-free survival (GFRFS) 41% versus 54% (P = .30), and cumulative incidence of transplant-related mortality (TRM) 14% versus 15% (P = .80), respectively. In the multivariate analysis, MRD positivity and a disease status >CR1 at the time of HSCT were significantly associated with poorer outcomes (P < .05). In conclusion, our study supports that both haploidentical and cord blood transplantation show comparable outcomes in pediatric AML patients. We obtained comparable survival rates, although CBT showed a trend to lower rates of chronic GvHD and higher GFRFS, demonstrating that it should still be considered a valuable option, particularly for pediatric patients.

Very late isolated CNS relapse of acute myeloid leukemia.

Isolated central nervous system (CNS) relapse in acute myeloid leukemia (AML) rarely occurs later than 2 years after remission. We present a child diagnosed with AML (FAB M5) without CNS involvement at diagnosis who was treated with chemotherapy and consolidated with autologous hematopoietic stem cell transplantation. He was in complete remission for >6 years until he had an isolated CNS relapse. He was treated with only intrathecal chemotherapy and achieved a second complete remission, but relapsed in the bone marrow 5 months after the CNS relapse. Treatment of late isolated CNS relapse of AML is discussed.

Qualitative and Economic Impact of Standardized and Digitalized Operation Room Processes in Obesity Surgery.

PURPOSE: The introduction of innovative digital solutions in healthcare lags compared to other industries but promises high potential to create value in efficiency and quality. Increasing economic pressure forces hospitals to optimize operating room (OR) processes, in which such solutions might provide additional support. MATERIALS AND METHODS: This retrospective case-control and monocentric study investigated if digitalized and standardized intraoperative surgical workflows of laparoscopic Roux-en-Y gastric bypass (LRYGB) have a significant impact on efficiency, quality, and economics. Logistic and linear regression models were used to apply propensity score matching (PSM) for efficiency and odds ratio for the quality analysis. RESULTS: The study included 49 patients per group. The results demonstrate a significant increase in efficiency and cost-effectiveness in the treatment group. Length of stay (LoS) was 1.2 days less than in the control group (5.6 vs. 4.4). The mean of total OR and skin-to-skin time increased by 3.7% (142.00 vs. 136.80) and 8.5%, respectively (93.88 vs. 85.94). The standard deviation (SD) of total OR and skin-to-skin time decreased by 7.36 min (26.86 vs. 34.22) and 8.98 min (23.20 vs. 32.18) in the treatment group. The results of the odds ratio did not provide any conclusions on quality. Overall, costs were reduced by 318 € per patient and total revenue improved by 10,073 €. CONCLUSION: The implementation of digital workflow management systems in obesity surgery improves economic efficiency. Hospital management and payors should evaluate further support in research of the digitization of the OR, followed by reimbursement to increase and facilitate the accessibility to digital support systems.

Adverse events related to central venous catheters (CVC) and the influence of CVC characteristics on peripheral blood hematopoietic progenitor cell collection in children.

Introduction: The use of peripheral blood progenitor cells (PBPCs) as a source for hematopoietic stem cell transplantation (HSCT) in pediatric healthy donors is still under debate. The risk of a central venous catheter (CVC) placement and catheter-related complications continue to be the main arguments to discourage its use. Methods: we present a retrospective analysis of 140 PBPC collections in pediatric patients and donors, describing adverse events (AE) related to CVCs as well as the influence of catheterrelated variables on the efficiency of the leukapheresis. Results: 14 CVC-related AEs were recorded (10%). The most common was fever in 5 patients, 4 of which had a catheter-related bacteriemia. Thrombotic events were only observed in 3 patients with active malignancy. A healthy donor presented a moderate bleeding after catheter withdrawal that resolved with local measures, and none of the rest presented any AE. Regarding variables related to the development of AEs, the subject group (patient or donor) was the only one significantly associated (p < 0.0001). Of interest, efficiency was also related to catheter location, being worse in those located in the femoral vein than in into the jugular or the subclavian veins (p < 0.05). In a multivariate analysis, the only variable significantly associated was catheter size (beta 0.238, p < 0.01). Discussion: Placing a CVC for PBPC collection in pediatric subjects is overall safe; CVC-related complications in pediatric healthy donors are very rare. Furthermore, we should try to place catheters of the largest caliber possible, since the efficiency of the collection is related to this variable.

Treosulfan-Based Conditioning Regimen In Pediatric Hematopoietic Stem Cell Transplantation: A Retrospective Analysis on Behalf of the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC).

Increasing data on treosulfan-based conditioning regimens before hematopoietic stem cell transplantation (HSCT) demonstrate the consistent benefits of this approach, particularly regarding acute toxicity. This study aimed to describe the results of treosulfan-based conditioning regimens in children, focusing on toxicity and outcomes when used to treat both malignant and nonmalignant diseases. This retrospective observational study of pediatric patients treated in Spain with treosulfan-based conditioning regimens before HSCT was based on data collection from electronic clinical records. We studied a total of 160 treosulfan-based conditioning HSCTs to treat nonmalignant diseases (n = 117) or malignant diseases (n = 43) in 158 children and adolescents. The median patient age at HSCT was 5.1 years (interquartile range, 2 to 10 years). The most frequent diagnoses were primary immunodeficiency (n = 42; 36%) and sickle cell disease (n = 42; 36%) in the nonmalignant disease cohort and acute lymphoblastic leukemia (n = 15; 35%) in the malignant disease cohort. Engraftment occurred in 97% of the patients. The median times to neutrophil engraftment (17 days versus 14 days; P = .008) and platelet engraftment (20 days versus 15 days; P = .002) were linger in the nonmalignant cohort. The 1-year cumulative incidence of veno-occlusive disease was 7.98% (95% confidence interval [CI], 4.6% to 13.6%), with no significant differences between cohorts. The 1-year cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was higher in the malignant disease cohort (18% versus 3.2%; P = .011). Overall, the malignant cohort had both a higher total incidence (9% versus 3%; P < .001) and a higher 2-year cumulative incidence (16% versus 1.9%; P < .001) of total chronic GVHD. The 2-year cumulative transplantation-related mortality was 15%, with no difference between the 2 cohorts. The 5-year overall survival was 80% (95% CI, 72% to 86%) and was higher in the nonmalignant cohort (87% versus 61%; P = .01). The 2-year cumulative incidence of relapse was 25% in the malignant cohort. The 5-year cumulative GVHD-free, relapse-free survival rate was 60% (95% CI, 51% to 70%) and was higher in the nonmalignant cohort (72% versus 22%; P < .001). A treosulfan-based radiation-free conditioning regimen is feasible, achieving a high engraftment rate and 5-year overall survival, and is an emerging option for the first HSCT in nonmalignant diseases.

Once-daily intravenous busulfan for 47 pediatric patients undergoing autologous hematopoietic stem cell transplantation: a single center study.

We report our results using once-daily intravenous (IV) busulfan (Bu)-based conditioning adjusted by weight without drug monitoring as myeloablative conditioning in 47 pediatric patients undergoing first autologous hematopoietic transplantation from 2006 to 2010. Median age was 4 years (range, 1 to 22 y). There were 35 boys and 12 girls. Conditioning was Bu-based in all patients. In medulloblastoma patients (n=12), IV thiotepa at 5 mg/kg/d×2 days was associated with Bu. In solid tumors other than medulloblastoma, IV melphalan was used at 140 mg/m/d×1 day. In lymphoma patients (n=9), IV cyclophosphamide was used at 60 mg/kg/d×2 days. Median number of CD34 cells infused was 4.65×10/kg (range, 1.7 to 58.7×10/kg). Median times to neutrophil and platelet recovery (>20×10/L) were 11 days (range, 8 to 16 d) and 12 days (range, 7 to 135 d), respectively. Median hospitalization time was 14 days (range, 9 to 92 d). Sixteen patients developed grades III and IV mucositis. Only 1 patient developed mild sinusoidal obstruction syndrome. No patient developed seizures or severe neurological complications. With a median follow-up of 18 months, probability of transplantation-related mortality and disease-free survival were 0% and 70%±8%, respectively. In conclusion, in our experience, once-daily IV Bu-based conditioning without drug monitoring for autologous hematopoietic transplantation in pediatric patients is a safe and effective regimen with no mortality.

Long-term transplant outcomes after allogeneic hematopoietic transplant in pediatric patients with hematological malignancies are influenced by severe chronic graft vs. host disease and immune reconstitution.

Long-term follow-up studies are crucial to ensure surveillance and intervention for late complications after allogeneic stem cell transplantation, but they are scarce on the pediatric population. This study aims to analyze risk factors for long-term transplant outcomes. We report a landmark analysis of 162 pediatric patients who underwent allogeneic transplantation between 1991 and 2016, and survived for at least 12 months after the transplant. With a median follow-up time of 10 years for the survivors, the probability of disease-free survival (DFS) and overall survival (OS) is 81 ± 3 and 88 ± 2%, respectively. Variables that influenced DFS in the univariate analysis were: disease phase (early phase 87 ± 3% vs. advanced phase 74 ± 5%; p = 0.04), acute graft vs. host disease (aGvHD; yes 73 ± 5% vs. no 87 ± 3%; p = 0.038), severe chronic GvHD (cGvHD; yes 41 ± 13% vs. no 85 ± 3%; p = 0.0001), and CD4+ lymphocytes 2 years after the transplant (above the median of 837/µl 98 ± 2% vs. below the median 82 ± 6%, p = 0.026). However, in the multivariate analysis, the only variable that influenced DFS was presence of severe chronic GvHD (yes vs. no, HR 6.25; 95% CI, 1.35-34.48; p = 0.02). Transplant strategies should aim to reduce the risk of severe cGvHD. Immune reconstitution surveillance may help clinicians to better deal with late transplant complications.