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Treatment of patients with high-risk neuroblastoma (NB) is a complex challenge, and it is based on response to certain elements of therapy. The development and introduction of new treatment approaches, such as GD2-targeted immunotherapy (IT), leads to improved survival in this cohort of patients. The aim of the study was to retrospectively assess the effectiveness of therapy in patients with high-risk NB before the introduction of IT into clinical practice. We retrospectively analyzed the data of 151 NB patients stratified into a high-risk group who had received treatment in accordance with the modified NB2004 protocol of the German Society for Pediatric Oncology and Hematology (GPOH) at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology from 01.2012 to 12.2017. This study was approved by the Independent Ethics Committee and the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. All the study subjects (or their legal representatives) signed a voluntary informed consent form indicating their agreement to treatment and use of their data for research purposes. Overall survival (OS), event-free survival (EFS), and risk factors were analyzed in the patients with high-risk NB including those who had completed multimodal therapy with autologous hematopoietic stem cell transplantation and post-consolidation therapy with isotretinoin and had achieved a satisfactory response to induction therapy (complete response (CR), very good partial response (VGPR), partial response (PR)) (population of special interest). The main unfavorable prognostic clinical and molecular genetic factors affecting survival in the high-risk NB patients were older age, MYCN gene amplification, and stage 4 of the disease. The use of the modified GPOH NB2004 protocol resulted in a satisfactory response (CR/VGPR/PR) to the induction therapy in most patients: 124/151 (82.1 %). Surgery (other than primary tumor biopsy) led to improved survival, with no statistical difference between macroscopic radical surgery and macroscopic residual tumor. At the same time, radiation therapy (RT), as the second element of local control, had a significant impact on EFS in the group of the patients with stage 4 disease: the 3-year EFS was 39.4 % (95 % confidence interval (CI) 23.1–55.4) in the patients with RT versus 25.7 % (95 % CI 17.5–34.7) in the patients without RT (p = 0.0295). The introduction of a new high-dose TreoMel chemotherapy regimen did not result in worse survival rates but led to a decrease in transplant-related toxicity. The 5-year OS and 5-year EFS were 49.4 % (95 % CI 40.9–57.3 %) and 33.3 % (95 % CI 25.9–40.9) respectively for all the study subjects, and 81.6 % (95 % CI 70.3–88.9) and 55.1 % (95 % CI 43.1–65.5) respectively for the patients from the population of special interest. The analysis of the results of therapy in the high-risk NB patients who had received treatment at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, yielded results comparable to those of the original GPOH NB2004 protocol. The patients with CR/VGPR/PR to the induction therapy who had completed the protocol treatment with autologous hematopoietic stem cell transplantation and isotretinoin post-consolidation therapy demonstrated higher 5-year EFS rates. However, there remains a need to develop more effective treatment regimens for high-risk NB.

Pure red cell aplasia (PRCA) is a rare complication of AB0-incompatible allogeneic hematopoietic stem cell transplantation, which manifests as a partial or complete absence of erythroid lineage in recipients with normal function of other hematopoietic lineages. There is a hypothesis, that lysis of erythroid precursors occurs because of antibody formation by population of residual B-lymphocytes and/or long-lived recipient’s plasma cells, which are capable for proliferation and active expression of the CD38 marker. That is why the invention of the IgG1 monoclonal antibody to CD38 presented as a new potentially effective targeted therapeutic option for patients with refractory PPCA. The article summarize clinical data on daratumumab for the therapy of PRCA in pediatric allogeneic hematopoietic stem cell transplantation recipients. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications.

We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin (hATG) and cyclosporin A (CsA) with (n = 49) or without (n = 49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR + IST and IST groups was similar (65% vs 53%; P = .218); however, the complete response (CR) rate was significantly higher in the ELTR + IST group (31% vs 12%; P = .027). In severity subgroups, the ORR was 89% vs 57% (P = .028) in favor of IST + ELTR in SAA, but it did not differ in patients with vSAA (52% vs 50%; P = .902). At 6 months after the crossover, 61% of initial ELTR(−) patients achieved a response compared with 17% of initial ELTR(+) patients (P = .016). No significant difference in ELTR + IST and IST groups was observed in the 3-year overall survival (OS) (89% vs 91%; P = .673) or the 3-year event-free survival (EFS) (53% vs 41%; P = .326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(−) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. This trial was registered at Clinicaltrials.gov as #NCT03413306.

This article discusses the potential of droplet digital polymerase chain reaction (PCR) for the diagnostic detection and monitoring of the allelic load of the BRAF V600E mutation in circulating cell-free DNA and myeloid progenitor cell population in the bone marrow of patients with Langerhans cell histiocytosis (LCH). Droplet digital PCR may serve as a useful tool for the monitoring of minimal residual disease and improve our understanding of the pathogenesis of Langerhans cells histiocytosis. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

Here we report a clinical case of a patient with BRAF-positive Langerhans cell histiocytosis treated with combination therapy including trametinib. As the patient was undergoing long-term therapy with a BRAF inhibitor, his underlying disease reactivated. Hence it was suggested that the child might have become resistant to the treatment as a result of a subclonal mutation. It was concluded that this event undermined the efficacy of long-term therapy with BRAF inhibitors and highlighted the need for further study of possible molecular genetic mechanisms involved in the pathogenesis of Langerhans cell histiocytosis, as well as the need for the development of new treatment approaches. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Graft failure (GF) remains a serious issue of hematopoietic stem cell transplantation (HSCT) in inborn errors of immunity (IEI). Second HSCT is the only salvage therapy for GF. There are no uniform strategies for the second HSCTs and limited data are available on the second HSCT outcomes. 48 patients with various IEI received second allogeneic HSCT from 2013 to 2020. Different conditioning regimens were used, divided into two main groups: containing myeloablative doses of busulfan/treosulfan (n = 19) and lymphoid irradiation 2–6 Gy (n = 22). Irradiation-containing conditioning was predominantly used in suspected immune-mediated rejection of the first graft. Matched unrelated donor was used in 28 patients, mismatched related in 18, and matched related in 1. 35 patients received TCRαβ/CD19 graft depletion. The median follow-up time was 2.4 years post-HSCT. One patient died at conditioning. The OS was 0.63 (95% CI: 0.41–0.85) after busulfan/treosulfan and 0.68 (95% CI: 0.48–0.88) after irradiation-based conditioning, p = 0.66. Active infection at HSCT significantly influenced OS: 0.43 (95% CI: 0.17–0.69) versus 0.73 (95% CI: 0.58–0.88) without infection, p = 0.004. The cumulative incidence of GF was 0.15 (95% CI: 0.08–0.29). To conclude, an individualized approach is required for the second HSCT in IEI. Low-dose lymphoid irradiation in suspected immune-mediated GF may be a feasible option.

The problem of extramedullary (EM) involvement in acute myeloid leukemia (AML) in children is of considerable relevance since its pathogenesis remains understudied and the impact on prognosis is still unclear. The variability of tissue and organ involvement depends on immunophenotypic, cytogenetic, and molecular features of myeloid cells and can cause difficulties in diagnosis, thus making it necessary to combine imaging and laboratory tools for timely and accurate diagnosis of EM disease. The prognostic significance of EM involvement has not been established unequivocally, thus the need for intensification of chemotherapy, as well as for allogeneic hematopoietic stem cell transplantation in first remission, remain debatable. The results of target therapy in EM AML are encouraging and may reduce the risk of AML relapse. This article describes the clinical features of EM AML in children and reviews the diagnostic approaches as well as the advantages and limitations of existing laboratory and imaging methods. The molecular features of EM AML, current treatment options and prognosis have also been analyzed. The patients' parents gave their consent to the use of their children's data, including photographs, for research purposes and in publications.

Acute graft-versus-host disease (GVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation determining the prognosis of hematopoietic stem cell recipients because of the impairment of multiple organs and systems and subsequent secondary immunodeficiency caused by combination immunosuppressive therapy. Current strategies are focused on the prevention of this life-threatening complication and on the timely start of treatment with appropriate selection of medications based on the knowledge of acute GVHD pathogenesis and grading as well as of risk factors for its development / progression in different patients. Here we provide a brief overview of acute GVHD and the existing approaches to its prevention and treatment.

Our previous experience of using plerixafor and granulocyte colony stimulating factor (G-CSF) in addition to treosulfan-based conditioning in patients with Wiscott–Aldrich syndrome (WAS) demonstrated efficacy and a decreased risk of severe graft failure after hematopoietic stem cell transplantation (HSCT) with TCRab + /CD19 + graft depletion. Because of the remaining risk of graft failure in WAS patients following HSCT with unmanipulated grafts reported in a number of large-scale retrospective studies, we used plerixafor and G-CSF in conditioning regimens in 6 WAS patients who received native bone marrow as a graft source. None of the patients developed severe organ toxicity in the early post-transplantation period. All of them had long-term full donor chimerism in whole blood and the CD3 + line and a good graft function. At the last follow-up, 5 patients are alive at 3.7 to 74.7 months after HSCT (median follow-up time: 24.0 months). One patient died of chronic lung graft-versus-host-disease at 18 months after the transplantation. Despite limited experience, we believe that additional hematopoietic stem cell mobilization with plerixafor and G-CSF in treosulfan-based conditioning regimens may be effective in WAS patients undergoing HSCT with an unmanipulated graft. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Key words: plerixafor, conditioning regimen, hematopoietic stem cell transplantation, Wiscott–Aldrich syndrome, unmanipulated graft

Kaposiform lymphangiomatosis (KLA) is an aggressive lymphatic anomaly associated with bone involvement, serositis occurring at various sites, the development of Kasabach–Merritt phenomenon, and frequent infectious complications. The International Society for the Study of Vascular Anomalies classifies KLA as a subtype of generalized lymphatic anomaly. The mTOR-inhibitor rapamycin in combination with symptomatic treatment is the most common specific treatment. However, there are no standard approaches to the management of KLA. Even with modern diagnostic tools and combination therapy, the 5-year survival rate is 51 %, and the average life expectancy is 2.75 years. This article presents a classic case of KLA associated with Kasabach–Merritt phenomenon that was successfully managed with rapamycin and a liposomal form of doxorubicin as specific therapy. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Multicolor flow cytometry is now routinely used in laboratory practice for the minimal residual disease (MRD) monitoring in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Wide application of CD19-directed immunotherapy leads to frequent loss of CD19 expression, that hampers significantly the flow cytometric MRD detection methodology. We developed an antibody panel and data analysis algorithm for multicolor flow cytometry, which is a reliable method for MRD detection in patients with BCP-ALL treated with CD19-directed therapy. We recommend a single-tube 11-color panel for MRD detection, which is adapted for the case of possible CD19 loss. Based on patterns of antigen expression changes and the relative expansion of normal CD19-negative BCPs, guidelines for multicolored flow cytometry data analysis and interpretation are established. The recommended approach is reliable tool for therapy response monitoring displaying the same effectiveness with the more laborious and costly molecular techniques.

Relevance. Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytic disorder. Cutaneous forms of the disease spontaneously regress within a few years, while systemic forms of JXG require treatment and may pose a threat to the lives of patients. Due to the lack of unified approach to the treatment of multisystem forms of JXG, the question of effective therapy tactics remains unresolved. The most common approach is to use Langerhans cell histiocytosis (LCH) treatment regimens for JXG. With the understanding of the leading role of mutations in the MEK-ERK signaling pathway in the pathogenesis of JXG, targeted therapy, BRAF- and MEK-inhibitors, are increasingly being considered in the treatment of JXG.Clinical cases. We present two cases of multisystem JXG with central nervous system (CNS) lesions. The first patient with CNS and skin lesions was treated with chemotherapy, developed for the treatment of multisystem LCH, which allowed us to obtain an effect “active disease better” (AD better). The second JXG patient with brain, lungs, bones, and adrenal gland lesions, combined targeted therapy with BRAF- and MEKinhibitors, vemurafenib and cobimetinib, resulted in a “non active disease” (NAD) effect.Conclusion. Multisystem form of JXG with CNS involvement is a rare oncological disease, the therapy of which has not been developed. With the introduction of molecular genetic profiling technology, it became possible to obtain NAD effect using targeted therapy.

Hematopoietic stem cell transplantation (HSCT) from an allogeneic donor is a standard treatment for high-risk leukemia that makes it possible to cure patients with chemotherapy-resistant leukemia. “Graft-versus-host” disease (GVHD) is the key biological and clinical problem associated with HSCT. Ex vivo depletion of ab-T cells has been used at the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology since 2012 as a means to prevent GVHD after HSCT. The successful application of this approach to GVHD prevention has reduced the risk of clinically significant acute GVHD and chronic GVHD to 15–20 %, and transplant-related mortality – to 5–10 %. The risk of relapse is 20–30 %, but when HSCT is performed in active disease, it increases to 50 %. The role of epigenetic mechanisms in the formation of the tumor phenotype has been established, and pharmacological approaches have been proposed. New drug classes include proteasome inhibitors such as bortezomib. The relatively low toxicity of epigenetic therapy and proteasome inhibitors makes their use in the post-transplant period an attractive approach to relapse prevention. We regarded prophylaxis after HSCT as one of the possible approaches that could help reduce relapse rate. Here we explore the effects of hypomethylation therapy (azacitidine) combined with an HDAC inhibitor (valproic acid) and a proteasome inhibitor (bortezomib). The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Combination therapy cycles were carried out after engraftment and in some patients, were accompanied by infusions of modified donor lymphocytes enriched in NK cells or memory T cells. The experimental group included 35 pediatric patients with hemoblastoses who had received HSCT from March 2013 to November 2016. The median age was 6.9 years. Twenty-three children had acute myeloid leukemia (AML), 11 patients – acute lymphoblastic leukemia (ALL), and one patient was diagnosed with juvenile myelomonocytic leukemia (JMML). Twenty-one patients were in complete clinical and hematologic remission at the time of HSCT while 14 patients (AML – 12, ALL – 1, JMML – 1) underwent HSCT in active disease. The patients were conditioned with treosulfan and melphalan (n = 26), thiotepa (n = 8), or etoposide (n = 1). Post-transplantation chemotherapy included azacitidine at a dose of 30 mg/m 2 IV for 5 days, bortezomib at a dose of 1.3 mg/m 2 s.c. (No. 2), and valproic acid at a dose of 250 mg 3 times a day р.о. (No. 6). The patients were planned to receive 3 cycles of post-transplantation chemotherapy with a break of 30 days between each treatment. Donor lymphocyte infusions were given on Day 7 of each cycle. A total of 92 cycles were conducted after HSCT. The most common side effect of treatment was hematologic toxicity. Transient visceral toxicity was registered after 46 (50 %) chemotherapy cycles. There were no cases of acute GVHD after donor lymphocyte infusions. At the time of the analysis, the median follow-up was 6.5 years. The cumulative risk of grade II–IV acute GVHD was 19% (95 % confidence interval (CI) 12–32). Nineteen patients relapsed at a median of 6 months after HSCT. Sixteen patients died of disease progression or complications related to subsequent treatment at a median of 11.76 months. The cumulative probability of relapse was 54% (95% CI 40–73). The cumulative probability of relapse in the patients transplanted in clinical and hematologic remission and those in active disease was 48% (95% CI 30–75) and 64 % (95 % CI 43–95), respectively. The event-free survival in the entire group of patients was 46 % (95 % CI 29–62). The event-free survival rates in the patients transplanted in remission and in active disease were 52% (95% CI 31–73) and 36 % (95 % CI 10–60), respectively. There were no deaths of complications of HSCT that were not associated with the recurrence of the disease in the experimental group. The cumulative risk of relapse among the AML patients in clinical and hematologic remission at the time of HSCT and those with advanced stage of the disease was 45 % (95 % CI 40–74) and 58 % (95 % CI 36–94), respectively. The overall survival was 53 % (95 % CI 31–73); the overall survival for the patients transplanted in remission and those who received HSCT in active disease was 63% (95 % CI 35–92) and 41% (95% CI 14–70), respectively. The event-free survival was 54% (95% CI 30–62) in the remission group and 41% (95 % CI 14–69) in the relapse group. In the ALL patients, the cumulative risk of relapse was 54 % (95 % CI 31–93); the overall and event-free survival rates were 72 % (95 % CI 46–91) and 45 % (95 % CI 16–75), respectively. Our analysis of the overall experience of prophylactic treatment with decitabine and azacitidine after ab-T cell-depleted HSCT suggests that this approach should be considered purely experimental and acceptable for prospective clinical studies in clearly defined cohorts of patients.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite remarkable improvements in the treatment of pediatric acute lymphoblastic leukemia over last years, relapse still carries a poor prognosis with considerable morbidity and mortality. New immunotherapeutic approaches will change the way we treated our patients and the results we had. Blinatumomab is a bispecific T-cell-engaging antibody indicated for the treatment of relapsed/refractory B-cell lymphoblastic leukemia. The use of Blinatumomab in relapsed B-cell ALL has shown promising effects, especially as a bridging tool to hematopoietic stem cell transplantation. The therapy results for patients in the high risk group remain far from optimal due to refractoriness to chemotherapy, death from infectious complications, as well as acute chemotherapy toxicity. This article demonstrates the results of our experience of using Blinatumomab in children with the high-risk group relapsed B-cell ALL treated according to the ALL-REZ 2016 protocol. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The efficacy and toxicity of innovational blocks with the use of fludarabine and clofarabine with subsequent Blinatumomab infusion are shown. And we present the efficacy of autologous CD3+ lymphocytes infusion once a week during the continuous blinatumomab therapy. Also we demonstrate the results of using Blinatumomab for the treatment of patients with refractory to the first line therapy relapsed B-lymphoblastic leukemia and patients with a second relapse of B-cell ALL. The first line therapy in these patients was carried out according to the ALL-REZ 2014 protocol. Our results show an improved reduction in minimal residual disease in patients with refractory relapsed B-cell ALL as well as an increased event free survival in children with the high-risk group relapsed B-cell ALL.

Langerhans cell histiocytosis (LCH) is a disorder with a variety of clinical signs. The most severe forms affect "risk organs" (RO). The established role of BRAF V600E mutation in LCH led to a targeted approach. However, the targeted therapy can't cure the disease and the cessation leads to quick relapses. In our study, we combined cytarabine (Ara-C) and 2'-chlorodeoxyadenosine (2-CdA) with targeted therapy to achieve stable remission. Nineteen children were enrolled in the study: 13 RO+ and 6 RO-. Five patients received the therapy upfront, while the other 14 - as the second or third line. The protocol starts with 28 days of vemurafenib (20 mg/kg) which is followed by 3 courses of Ara-C and 2-CdA (100 mg/m2/every 12 h, 6 mg/m2/day, Days 1-5) with concomitant vemurafenib therapy. After that, vemurafenib therapy was stopped, and 3 courses of mono 2-CdA followed. All patients rapidly responded to vemurafenib: the median DAS decreased from 13 to 2 points in the RO+ group and from 4.5 to 0 points in the RO- group on Day 28. All patients except one received complete protocol treatment, and 15 of them didn't have disease progression. The 2-year relapse-free survival (RFS) for RO+ was 76.9% with a median follow-up of 21 months and 83.3% with a median follow-up of 29 months for RO-. Overall survival is 100%. Importantly, 1 patient experienced secondary MDS (sMDS) after 14 months from vemurafenib cessation. Our study demonstrates that combined vemurafenib plus 2-CdA and Ara-C is effective in a cohort of children with LCH, and the toxicity is manageable. This trial is registered at www.clinicaltrials.gov as NCT03585686.

Contemporary therapy of acute promyelocytic leukemia (APL) is based on the use of all-trans retinoic acid, which is effective against tumor cells harboring RARa gene rearrangements (most common – t(15;17)(q24;q21)/PML::RARa). In several studies, it was suggested to use typical immunophenotypic features of APL (HLA-DR-negativity, etc) for prediction of RARa rearrangements presence. In this study, we aimed to evaluate the range of genetic aberrations that could be found in the HLA-DR-negative acute myeloid leukemia (AML). Our study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Among studied 806 pediatric AML patients, HLA-DR-negativity was found in 253 cases. Only in 45.4% of them t(15;17)(q24;q21)/PML::RARa was found, while in remaining 54.6% normal karyotype or other genetic aberrations without RARa involvement. Frequency of the most common immunophenotypic features of APL, such as total CD117, CD33 and MPO expression with the lack of CD34, was higher in patients with t(15;17)(q24;q21)/PML::RARa, although only two thirds of APL cases were found to have all these signs. Moreover, the percentage of cells positive or negative for mentioned antigens varied significantly in APL group. Thus we can conclude, that all “typical” immunophenotypic characteristics of APL including HLA-DR-negativity, are very unspecific and cannot be used for reliable prediction of presence of t(15;17)(q24;q21)/PML::RARa.

Over the past years, the outcomes of patients with acute myeloid leukemia (AML) have significantly improved due to the use of intensive chemotherapy, more effective supportive therapy, and the availability of allogeneic hematopoietic stem cell transplantation. This article presents the outcomes of children with AML treated in accordance with the AML-MM-2006 protocol. Our study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The study included 233 patients with a median age of 6.5 years (7 days – 18 years) who were stratified into the following risk groups: standard risk, intermediate risk, and high risk. The 5-year event-free survival (EFS) was 0.64 ± 0,14, 0.49 ± 0.05, and 0.43 ± 0.05 for standard-risk (n = 12), intermediate-risk (n = 106), and high-risk (n = 115) patients, respectively (p = 0.14), while the 5-year overall survival (OS) was 1.0 year, 0.7 ± 0.05 and 0.55 ± 0.05, respectively (p = 0.001). The OS in the entire cohort was 0.68 ± 0.032. Factors associated with poor prognosis included hyperleukocytosis, the presence of extramedullary lesions, and age < 1 year. The overall survival rates in these patient groups were 0.55 ± 0.08, 0.39 ± 0.09 and 0.49 ± 0.08, respectively. The worst prognosis was for patients with monosomy 7 and t(7;12) whose OS rates were 0.25 ± 0.2 and 0.4 ± 0.2, respectively. For non-responders and patients with relapsed AML, the OS was 0.33 ± 0.08 and 0.54 ± 0.06, respectively. Early death (before remission could be achieved) occurred in 4% of patients, and 3.8% of patients died in first remission. Sixtytwo percent of deceased patients died of disease progression. In the entire cohort of patients, the five-year EFS was 0.53 ± 0.047, the cumulative risk of relapse after 3 years of remission was 40%, the confidence interval was 23–89%.

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal disease of the blood system characterized by intravascular hemolysis, bone marrow dysfunction and an increased risk of thrombotic and organ complications.Aim — to provide relevant clinical recommendations for the provision of medical care to adults and children with PNH.Basic information. Experts from the National Hematological Society association which is focused on the promotion of hematology, transfusiology and bone marrow transplantation along with experts from the public organization, National Society of Pediatric Hematologists and Oncologists, have developed current clinical recommendations for providing medical care to adults and children with PNH. The recommendations address in detail the issues of etiology, pathogenesis, epidemiology, and clinical manifestations of the disease. Special attention is paid to the diagnosis, differential diagnosis, and treatment of PNH based on the principles of evidence.

Introduction. The tactics of therapy for elderly comorbid patients with mantle cell lymphoma with unfavorable prognosis factors (complex karyotype, 17p13 deletion, mutations in the TP53 gene) have not been developed. The use of intensive chemotherapy regimens and transplantation of allogeneic hematopoietic stem cells (allo-HSCT) is impossible due to severe comorbidity in elderly patients. A rational approach is the use of a combination of ibrutinib and venetoclax. As an alternative to allo-HSCT, a new option for elderly patients with poor prognostic factors is Chimeric Antigen Receptor T-cell therapy (CAR-T) cell therapy.Aim — to present the experience of using ibrutinib and venetoclax with CAR-T-cell therapy in the first line of treatment in an elderly patient with MCL with a mutation in the TP53 gene and hyperleukocytosis.Main findings. Patient M., 68 years old. The examination revealed hyperleukocytosis 978 × 109/L, anemia (55 g/L), thrombocytopenia (30 × 109/L), and splenomegaly 250 × 180 mm. According to the results of laboratory studies, the diagnosis of lymphoma from mantle cells with a complex karyotype, deletion 17p13, 13q14 and mutation p.R248W in exon 7 of the TP53 gene (VAF = 26 %) was verified. For cytoreductive purposes, two sessions of leukocytapheresis and prephase with cyclophosphamide (200 mg/m2) and dexamethasone (10 mg/m2) were performed. From day 3, therapy with ibrutinib 420 mg/day and venetoclax 100 mg/day was started. After 2 days, the leukocytes were 0.7 × 109/L, and the size of the spleen decreased, as a result of which the development of tumor lysis syndrome was noted. As a result of intensive therapy, the patient’s condition stabilized, which allowed him to resume treatment. After 7 days, the number of leukocytes was 2.5 × 109/L, neutrophils — 70 %, platelets — 90 × 109/L, hemoglobin — 95 g/L. According to immunophenotyping, the population of B-lymphocytes was 4 %. According to NGS data, the allelic load of the mutation in the TP53 gene is 0.8 %. The patient underwent anti-CD19 CAR-T-cell therapy and achieved complete remission. Three months after therapy, MRD remains-negative remission and the persistence of CAR-T cells is determined.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the gold standard curative therapy for infants and children with many inborn errors of immunity (IEI), but adolescents and adults with IEI are rarely referred for transplant. Lack of published HSCT outcome data outside small, single-center studies and perceived high risk of transplant-related mortality have delayed the adoption of HSCT for IEI patients presenting or developing significant organ damage later in life. This large retrospective, multicenter HSCT outcome study reports on 329 IEI patients (age range, 15-62.5 years at HSCT). Patients underwent first HSCT between 2000 and 2019. Primary endpoints were overall survival (OS) and event-free survival (EFS). We also evaluated the influence of IEI-subgroup and IEI-specific risk factors at HSCT, including infections, bronchiectasis, colitis, malignancy, inflammatory lung disease, splenectomy, hepatic dysfunction, and systemic immunosuppression. At a median follow-up of 44.3 months, the estimated OS at 1 and 5 years post-HSCT for all patients was 78% and 71%, and EFS was 65% and 62%, respectively, with low rates of severe acute (8%) or extensive chronic (7%) graft-versus-host disease. On univariate analysis, OS and EFS were inferior in patients with primary antibody deficiency, bronchiectasis, prior splenectomy, hepatic comorbidity, and higher hematopoietic cell transplant comorbidity index scores. On multivariable analysis, EFS was inferior in those with a higher number of IEI-associated complications. Neither age nor donor had a significant effect on OS or EFS. We have identified age-independent risk factors for adverse outcome, providing much needed evidence to identify which patients are most likely to benefit from HSCT. ispartof: BLOOD vol:140 issue:14 pages:1635-1649 ispartof: location:United States status: published

The COVID-19 pandemic continues to be a major public health threat worldwide. The course of this disease in immunocompromised patients is significantly different from that in healthy subjects, which is associated with the impossibility of virus elimination through their own adaptive immune response. Delayed immune reconstitution after hematopoietic stem cell transplantation (which may take months after the procedure) increases the risk of life-threatening COVID-19 infection necessitating a search for and application of new methods of treatment. T lymphocytes are critically important for viral infection control, and are necessary both for the direct elimination of Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications.

Survival after Allo-HSCT for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, GVHD and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the SAAWP of the EBMT included 479 patients with idiopathic SAA who underwent Allo-HSCT in 2 conventional situations: i) upfront Allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) Allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GVHD, extensive chronic GVHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late Allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (HR: 4.08, 95% CI [1.41-11.83], p=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR: 1.04, 95% CI [1.02-1.06], p

Introduction. The introduction of chimeric antigen receptor (CAR) T-cell therapy is a promising treatment of patients with relapsed or refractory (R/R) B-cell lymphoproliferative diseases (LPDs).Aim — to present the results of CAR-T-cell therapy of 6 adult patients with B-cell LPDs.Materials and methods. This is a pilot study conducted in adult patients with R/R or persistent minimal residual disease B-cell LPDs treated with CAR-T-cells. The study was approved by a local ethical committee of National Research Center for Hematology. Patients did not have alternative options for effective and safe treatment. All patients signed an informed consent. All patients were lymphodeplated with fl udarabine and cyclophosphamide for 4 days before the introduction of CAR-T-lymphocytes. Cytokine release syndrome (CRS) was prevented by tocilizumab on the day of CAR-T-cell administration. The effi cacy and safety of CAR-T-cell therapy was evaluated.Results. From 01.01.2020 to 01.01.2022, 10 CAR-T-cell infusions were performed for 6 adult patients (age 19–68 years, median — 32 years) with B-cell LPDs: 4 — R/R B-acute lymphoblastic leukemia, 1 — R/R diffuse large B-cell lymphoma, 1 — persistence of MRD in mantle cell lymphoma. In all patients with a R/R, median — 4 (2–5) lines of chemotherapy and/ or immunotherapy were performed before CAR-T-cell therapy. CD19 CAR-T-cells received 3 patients, CD19/CD22 CAR-Tcells — 2 patients, CD19 and CD20 CAR-T-cells received 1 patient. Autologous CAR-T-cells received 4 (66 %) patients, allogeneic CAR-T-cells received 1 patient, and one patient had two CAR-T-cell administrations — 1 autologous and 1 allogeneic. The median number of CAR-T-cells was 0.5 × 106 /kg (from 0.1 × 106 /kg to 3 × 106 /kg). In 7 (87.5 %) of the 8 cases after CAR-T-cell administration, overall response to therapy (complete or partial remission) was achieved, and complete remission was achieved in 6 (75 %) cases. Side effects were noted after 8 of 10 CAR-T-cell transfusions: CRS in 40 % (CRS 1 — 10 %, CRS 2 — 20 %, CRS 3 — 10 %), ICANS in 10 %, tumor lysis syndrome in 20 %, multi-organ dysfunction syndrome in 10 %. There were no lethal complications due to CAR-T-cell administrations. The median follow-up period was 6 (1–16) months. Of the 6 patients, 2 (33 %) died from relapses and progression of LPD. One (17 %) patient died in complete remission from infectious complications. Three (50 %) patients are observed till now. The median time of CAR-T-cell circulation was 33 (6– 60) days.Conclusion. CAR-T-cell therapy is a promising treatment for R/R B-cell LPDs and LPDs with persistence of MRD after cytoreductive therapy. This type of therapy requires a multidisciplinary approach.

Langerhans cell histiocytosis (LCH) is a disease that arises from myeloid cells that phenotypically resemble Langerhans cells (LC), which is typically driven by the BRAF V600E mutation. High-risk LCH has a poor prognosis. Fifteen children with BRAF V600E + LCH received vemurafenib between March 2016 and February 2020. The median age at LCH onset was 2 months and the median age at the start of vemurafenib treatment was 22 months. The median disease activity score (DAS) at the start of vemurafenib treatment was 12 points. The median duration of vemurafenib treatment was 29 months. All patients responded to treatment, with median DAS of 4 points at week 4 and 1 point at 6 months. Two patients died: 1 of hepatic failure after NSAID overdose and 1 of neutropenic sepsis. Cessation of vemurafenib resulted in relapse in 5 patients and was only possible for 1 patient. Serial measurements of BRAF V600E using cell-free circulating DNA revealed that 7 patients had persistently high mutant allele levels. Vemurafenib is effective in children with BRAF V600E + LCH. However, treatment with vemurafenib does not eradicate the disease and its long-term toxicity has not been established.

Presently, there is no consensus on the best treatment for relapsed B-cell acute lymphoblastic leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in patients with extramedullary lesions. There are certain anti-tumor drugs that can be used in case of relapse after allo-HSCT, however, prospective randomized studies directly comparing different chemotherapy and immunotherapy approaches are generally lacking. Retrospective studies exploring therapy for relapsed disease are difficult to compare due to the inhomogeneity of patient populations and the diversity of treatment approaches. In such situations, the treatment choice is influenced by the characteristics of the tumor population, particularly, its immunophenotype, available drugs, and the experience of a healthcare facility and physicians. This clinical case report describes the process of treating a patient with B-lymphoblastic lymphoma and shows the possibility of using donor CD19-specific CAR-T cells as a treatment for isolated CNS relapse after allo-HSCT. The patient's parents gave their consent to the use of their child's data, including photographs, for research purposes and in publications.

The aim of this study was to describe the immunophenotype of leukemic cells in acute myeloid leukemia (AML) with inv(16) (p13.1q22)/CBFb-MYH11 and t(16;16)(p13.1;q22)/CBFb-MYH11 in children. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. We investigated bone marrow samples from 36 pediatric patients with initially diagnosed AML with inv(16)(p13.1q22)/t(16;16)(p13.1;q22)/CBFb-MYH11. Immunophenotypic profile of leukemic cells was very heterogeneous: cells expressed antigens of early stages of differentiation (CD34, CD117, CD123) as well as markers of mature monocytes (CD11c, CD14, CD64) and neutrophils (CD65, CD15). Moreover, in 55.6% of cases lymphoid coexpressions were noticed (CD2 – the most frequent one). Furthermore, in 83.3% of cases we detected the separation of leukemic cells population into two parts: more “immature” – myeloblastic, which expressed early markers of differentiation (CD34, CD117), and more “mature” part, expressing monocytic antigens (CD11b, CD14, CD33). There was no clear separation between these parts of population. Despite the immunophenotypic similarity between monocytic part of leukemic population and normal monocytes, in 87.5% of studied cases there were same lymphoid coexpressions on these cells as on leukemic myeloblasts. Moreover, we showed that levels of CBFb-MYH11 expression in leukemic monocytes and myeloblasts were comparable. Presence of these characteristics in monocytes allows to consider them as part of leukemic cells population and take into consideration during the total immunophenotype reporting.

Background. Extramedullary infiltration (EI) is relatively common in children with acute myeloid leukemia (AML) (up to 20-25 %). However, its clinical and prognostic significance remains poorly understood.Objective: to describe clinical features and to define prognostic significance of EI in children with AML.Materials and methods. The subjects of retrospective observational study were 228 children with de novo AML. The median age was 6.6 years. All of them were treated according to the protocol AML-MM-2006 from April 2007 to June 2018.All patients with EI were divided into three cohorts according to the localization of the lesions: 1) central nervous system (CNS) involvement (CNS group), 2) other localizations apart from CNS (myelosarcomas (MS) group), 3) combined lesions (CNS + MS group).Results. EI was diagnosed in 84 patients (36.84 %) with de novo AML. Among them 47 (55.95 %) had CNS involvement, 20 (23.81 %) had MS, 15 (17.86 %) had both CNS involvement and MS. 5-year overall survival (OS) rate was slightly higher in patients with CNS involvement than in children without EI - 80 ± 12 % vs 71 ± 9 %, p = 0.26, however OS in patients with MS was significantly lower - 45 ± 16 % vs 71 ± 9 %, p p = 0.004. 5-year event-free survival in patients with MS was also lower than in children without EI - 38 ± 16 % vs 51 ± 8 %, p = 0.011.Conclusion. Patients with MS had worse 5-year OS and EFS than children without EI according to our study. Moreover allogenic HSCT conducted in first clinical remission did not improve the survival rate. Neuroleukemia as the only EI was not an unfavorable prognostic factor in our cohort of AML patients and was more often associated with inv(16).

BACKGROUND Collection of a large number of early hematopoietic progenitors is essential for allogeneic apheresis products intended for TCR-alpha/beta depletion. MATERIALS AND METHODS We added plerixafor 0.24 mg/kg body weight (bw) on day 4 of high-dose filgrastim mobilization 10 hours prior to apheresis in 16 (30.5%) pediatric allogeneic donors who failed to recover a sufficient number of CD34+ cells. RESULTS On day 4 of G-CSF, the median CD34+ cell count in peripheral blood was 6 per μL (range 4-9 per μL) in 6 poor mobilizers and 16 per μL (range 12-19 per μL) in insufficient mobilizers. In all donors, the threshold of 50 CD34+ cells/μL was achieved, and the median increase was 14.8-fold in poor mobilizers and 6.5-fold in insufficient mobilizers, whereas it was 3.45-fold increase in those mobilized with G-CSF alone. DISCUSSION In all donors, a predefined number of >10 × 106 CD34+ cells/kg of recipient bw before depletion was reached in the apheresis product. The use of plerixafor did not affect the purity of further TCR-alpha/beta depletion. Side effects were mild to moderate and consisted of nausea and vomiting. CONCLUSION Thus, the safety and high efficacy of plerixafor was proven in healthy pediatric allogeneic hematopoietic cell donors.

Cystic angiomatosis is a rare disease characterized by disseminated multifocal hemangiomatous and/or lymphangiomatous cystic lesions of the skeleton with possible visceral organ involvement. Only a few dozens of such patients worldwide have been described in the literature. This article presents two case reports of the patients admitted to the D. Rogachev NRMCPHOI with suspected Langerhans cell histiocytosis. The patient’s parents gave their consent to the use of their child’s data, including photographs, for research purposes and in publications. During the investigation, multiple cysts of the skull bones, spine, pelvic bones and limbs, as well as of the spleen were found in both patients. A biopsy of the bone cysts of the skull revealed no data in favor of histiocytosis or other neoplasms. Cystic angiomatosis was diagnosed in both cases. This is a rare disease that should be kept in mind in the differential diagnosis in patients with cystic lesions of the bones and visceral organs.

Introduction Accurate detection of GATA1 mutation is highly significant in patients with acute myeloid leukemia (AML) and trisomy 21 as it allows optimization of clinical protocol. This study was aimed at (a) enhanced search for GATA1 mutations; and (b) characterization of molecular landscapes for such conditions. Methods The DNA samples from 44 patients with newly diagnosed de novo AML with trisomy 21 were examined by fragment analysis and Sanger sequencing of the GATA1 exon 2, complemented by targeted high-throughput sequencing (HTS). Results Acquired GATA1 mutations were identified in 43 cases (98%). Additional mutations in the genes of JAK/STAT signaling, cohesin complex, and RAS pathway activation were revealed by HTS in 48%, 36%, and 16% of the cases, respectively. Conclusions The GATA1 mutations were reliably determined by fragment analysis and/or Sanger sequencing in a single PCR amplicon manner. For patients with extremely low blast counts and/or rare variants, the rapid screening with simple molecular approaches must be complemented with HTS. The JAK/STAT and RAS pathway-activating mutations may represent an extra option of targeted therapy with kinase inhibitors.

Thrombopoietin receptor agonists (TPO-RA) – romiplostim and eltrombopag – changed considerably the therapeutic options for severe persistent and chronic immune thrombocytopenia (ITP). The article presents the results of a retrospective study of TPO-RA efficacy and safety in patients under 18 years of age. The study was approved by the Independent Ethics Committee and Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. Sixty-eight children had a total of 89 courses of TPO-RA (44 romiplostim and 45 eltrombopag). Their median age was 6.5 years. The median ITP duration was 15.8 months. All patients received previous ITP therapy (1–6 lines). Before the initiation of TPO-RA, the majority of patients had thrombocytopenia with bleeding. In most cases, the platelet response was achieved within the first 2 months of treatment. The average effective doses of romiplostim and eltrombopag were 10 mg/kg per week and 75 mg per day, respectively. Half of patients in romiplostim group and 62% of patients in eltrombopag group did not require extra therapy. The majority of patients (75.6–81.8%) achieved an overall response, but only near 50% achieved a durable (more than 24 weeks) platelet response. Six patients sustained the response after TPO-RA discontinuation. The most common adverse events (AE) of TPO-RA therapy were transient elevation in hepatic enzymes in eltrombopag group (28.9%) and thrombocytosis (18.2–22.2%) in both groups. In 6 cases the therapy was discontinued due to AEs. Two AEs were serious. Our results demonstrate that TPO-RA could safely increase platelet counts and decrease the risk of spontaneous life-threatening bleeding in nearly half of children with severe persistent and chronic ITP. TPO-RA could help to avoid long-term immunosuppressive therapy and splenectomy or delay them and the ITP remission is possible in some cases.

Primary immune thrombocytopenia is a benign and self-limiting process in the majority of children. Severe life-threatening hemorrhages, including intracranial, develop rarely. Risk factors predisposing for development of severe hemorrhagic complications have not been determined. In order to decrease the severity of neurological consequences and mortality in intracranial hemorrhages, timely combined urgent therapy is neсessary. There are four clinical cases of intracranial hemorrhage in immune thrombocytopenia in children with different outcomes in this article. The parents of the patients agreed to use the information, including photos of children, in scientific research and publications.

The delayed recovery of adaptive immunity underlies transplant-related mortality (TRM) after αβ T cell-depleted hematopoietic stem cell transplantation (HSCT). We tested the use of low-dose memory donor lymphocyte infusions (mDLIs) after engraftment of αβ T cell-depleted grafts. A cohort of 131 pediatric patients (median age 9 years) were grafted with αβ T cell-depleted products from either haplo (n = 79) or unrelated donors (n = 52). After engraftment, patients received mDLIs prepared by CD45RA depletion. Cell dose was escalated monthly from 25 × 103 to 100 × 103/kg (haplo) and from 100 × 103 to 300 × 103 /kg (MUD). In a subcohort of 16 patients, T-cell receptor (TCR) repertoire profiling with deep sequencing was used to track T-cell clones and to evaluate the contribution of mDLI to the immune repertoire. In total, 343 mDLIs were administered. The cumulative incidence (CI) of grades II and III de novo acute graft-versus-host disease (aGVHD) was 5% and 2%, respectively, and the CI of chronic graft-versus-host disease was 7%. Half of the patients with undetectable CMV-specific T cells before mDLI recovered CMV-specific T cells. TCR repertoire profiling confirmed that mDLI-derived T cells significantly contribute to the TCR repertoire up to 1 year after HSCT and include persistent, CMV-specific T-cell clones.

BACKGROUND: In addition to treatment response, cytogenetic and molecular aberrations are the most important prognostic factors in children with de novo acute myeloid leukemia (AML). However, little is known about cytogenetics at the time of relapse.METHODS: This international study analyzed the prognostic value of cytogenetic profiles and karyotypic changes in pediatric relapsed AML in relation to the probability of event-free (pEFS) and overall survival (pOS). For this purpose, cytogenetic reports from all patients registered on the Relapsed AML 2001/01 Study were reviewed and classified.RESULTS: Cytogenetic information at relapse was available for 403 (71%) of 569 registered patients. Frequently detected aberrations at relapse were t(8;21)(q22;q22) (n = 60) and inv(16)(p13.1q22)/t(16;16)(p13.1;q22) (n = 24), both associated with relatively good outcome (4-year pOS 59% and 71%, respectively). Monosomy 7/7q-, t(9;11)(p22;q23), t(10;11)(p12;q23), and complex karyotypes were associated with poor outcomes (4-year pOS 17%, 19%, 22%, and 22%, respectively). Of 261 (65%) patients for whom cytogenetic data were reliable at both diagnosis and relapse, pEFS was inferior for patients with karyotypic instability (n = 128, 49%), but pOS was similar. Unstable karyotypes with both gain and loss of aberrations were associated with inferior outcome. Early treatment response, time to relapse, and cytogenetic profile at time of relapse were the most important prognostic factors, both outweighing karytoypic instability per se.CONCLUSION: The cytogenetic subgroup at relapse is an independent risk factor for (event-free) survival. Cytogenetic assessment at the time of relapse is of high importance and may contribute to improved risk-adapted treatment for children with relapsed AML.

Blinatumomab with subsequent haematopoietic stem cell transplantation was applied in 13 infants with acute lymphoblastic leukaemia (ALL). Eight patients were treated in first remission due to slow clearance of minimal residual disease (MRD); one for MRD-reappearance after long MRD negativity, one for primary refractory disease and three during relapse treatment. In slow MRD responders, complete MRD response was achieved prior to transplantation, with an 18-month event-free survival of 75%. In contrast, only one of five patients with relapsed/refractory ALL is still in complete remission. These data provide a basis for future studies of immunotherapy in very high-risk infant ALL.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged

Romiplostim is a thrombopoietin (TPO) receptor agonist approved for children and adults with immune thrombocytopenia (ITP) for ≥6 months, recommended as second-line treatment. This phase 3b, single-arm, multicenter study investigated long-term efficacy and safety of romiplostim in children ≥1 to

Background Ineffective erythropoiesis (IE) is the most prominent feature of transfusion-dependent beta-thalassemia (TDT), which leads to extramedullary hemopoiesis. The rejection rate in allogeneic hematopoietic stem cell transplantation (HSCT) is high in heavily transfused patients with TDT accompanied by prominent IE. Therefore, a pretransplantation treatment bridging to HSCT is often used to reduce allosensitization and IE. Ruxolitinib is a JAK-1/JAK-2 inhibitor and has showed its efficacy in suppressing IE and the immune system. A previously published study on RUX in adult patients with TDT has revealed that this treatment significantly reduces spleen size and is well tolerated. Procedure Ten patients (5-14 years old) with TDT and an enlarged spleen were enrolled. The dose of ruxolitinib was adjusted for age: for patients 11 years: 20-30 mg/m2 total daily dose. HSCT was performed in 8 of 10 patients. Results After the first 3 months of ruxolitinib therapy, spleen volume decreased in 9 of 10 cases by 9.1%-67.5% (M = 35.4%) compared with the initial size (P = 0.003). The adverse events of ruxolitinib (infectious complications, moderate thrombocytopenia, and headache) were successfully managed by reducing the dose. The outcomes of HSCT were favorable in seven of eight cases. Conclusion Ruxolitinib is promising as a short-term pre-HSCT treatment for pediatric patients with TDT and pronounced IE.