79 research outputs found
BTK, NuTM2A, and PRPF19 are Novel KMT2A Partner Genes in Childhood Acute Leukemia
Chromosomal rearrangements of the human KMT2A/MLL gene are associated with acute leukemias, especially in infants. KMT2A is rearranged with a big variety of partner genes and in multiple breakpoint locations. Detection of all types of KMT2A rearrangements is an essential part of acute leukemia initial diagnostics and follow-up, as it has a strong impact on the patientsβ outcome. Due to their high heterogeneity, KMT2A rearrangements are most effectively uncovered by next-generation sequencing (NGS), which, however, requires a thorough prescreening by cytogenetics. Here, we aimed to characterize uncommon KMT2A rearrangements in childhood acute leukemia by conventional karyotyping, FISH, and targeted NGS on both DNA and RNA level with subse-quent validation. As a result of this comprehensive approach, three novel KMT2A rearrangements were discovered: ins(X;11)(q26;q13q25)/KMT2A-BTK, t(10;11)(q22;q23.3)/KMT2A-NUTM2A, and inv(11)(q12.2q23.3)/KMT2A-PRPF19. These novel KMT2A-chimeric genes expand our knowledge of the mechanisms of KMT2A-associated leukemogenesis and allow tracing the dynamics of minimal residual disease in the given patients. Β© 2021 by the authors. Licensee MDPI, Basel, Switzerland.Funding: KMT2A rearrangement assessment was supported by the Russian Science Foundation (grant no. 19-75-10056). Quantitative RT-PCR for MRD monitoring was supported by Russian Presidential (grant no. MK-1645.2020.7)
Hematopoietic stem cell transplantation with alpha/beta T-lymphocyte depletion and short course of eculizumab in adolescents and young adults with paroxysmal nocturnal hemoglobinuria
The main goal is to optimize hematopoietic stem cell transplantation (HSCT) approach among adolescents and young adults with paroxysmal nocturnal hemoglobinuria (PNH) by means of Graft-versus-host disease (GVHD) and post-transplant complications risk lowering. Materials and methods. We report our experience of HSCT from HLA-matched unrelated donors using TCR alfa/beta and CD19 depletion in 5 pts (1M/4F) with PNH, developed after successful immunosuppressive therapy (IST) of acquired aplastic anemia (AA). Median age of pts at the moment of transplantation was 17,8 years (range 14,5-22,7), median interval from IST to PNH was 4 years (5mo - 6,5 y). In all patients non-severe pancytopenia was present: granulocytes 0,8Ρ
109/l (0,8-1,8 Ρ
109/l) platelets 106 Ρ
109/l (27-143 Ρ
109/l) and Hb -78 g/l, median PNH clone size in granulocytes was 94 (range 75-99)%. One pts previously developed sinus thrombosis. Conditioning consisted of thoraco-abdominal irradiation 4-6 Gy, cyclophosphamide 100 mg/kg, fludarabine 150 mg/m2 and anti-thymocyte globulin (ATG) or alemtuzumab. Eculizumab was given from day (-7) till day (+14) (every 7 days, only 4 times). GVHD prophylaxis was tacrolimus Β± methotrexate. Results. Infusedgraft characteristics were: CD34+ - 8,1Ρ
106/kg, CD3TCRabΒ·150Ρ
103/kg, CD3gd+ - 7,3Ρ
106/kg, Π‘D19+ - 221Ρ
103/kg, NK -6,4Ρ
108/kg. Engraftment was achieved in all 5 pts with a median of 15(12-18) ΠΈ 13(10-18) days for granulocytes and platelets, respectively. Skin acute GVHD grade I developed in only 1 pt, and subsided with short course of glucocorticoids. CMV reactivation occurred in 1 pt; there were no episodes of Epstein-Barr Virus (EBV) o rAdenovirus (AdV) reactivation. Full donor myeloid chimerism was established in all pts by day +30. Immune reconstitution was delayed until 6 months after transplant but no severe infections occurred. All pts are alive 1,7-5,5 years (med 4 years) after HSCT with normal hematopoiesis and immune function, full donor chimerism and no late sequelae. Conclusions. Transplantation of TCRalfa/beta and CD19 depleted hematopoietic cells from matched unrelated donor after immunoablative conditioning and supported with short course of eculizumab is perfectly safe and efficient technology leading to cure in young patients with PNH
Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation
Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source
Clinical applications of donor lymphocyte infusion from an HLA-haploidentical donor: consensus recommendations from the Acute Leukemia Working Party of the EBMT
Donor lymphocyte infusion has been used in the management of relapsed hematologic malignancies after allogeneic hematopoietic cell transplantation. It can eradicate minimal residual disease or be used to rescue a hematologic relapse, being able to induce durable remissions in a subset of patients. With the increased use of haploidentical hematopoietic cell transplantation, there is renewed interest in the use of donor lymphocytes to either treat or prevent disease relapse post transplant. Published retrospective and small prospective studies have shown encouraging results with therapeutic donor lymphocyte infusion in different haploidentical transplantation platforms. In this consensus paper, finalized on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, we summarize the available evidence on the use of donor lymphocyte infusion from haploidentical donor, and provide recommendations on its therapeutic, pre-emptive and prophylactic use in clinical practice
The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01
Hepatotoxicity induced by horse ATG and reversed by rabbit ATG: a case report
<p>Abstract</p> <p>Background</p> <p>The use of antilymphocyte agents has improved patient and graft survival in hematopoietic stem cell and solid organ transplantation but has been associated with the development of short-term toxicities as well as long-term complications.</p> <p>Case presentation</p> <p>We report a young female with Fanconi anemia who received antithymocyte globulin as part of the conditioning regimen prior to her planned allogeneic hematopoietic stem cell transplant at King Faisal Specialist Hospital and Research Centre in Riyadh. She developed sudden and severe hepatotoxicity after receiving the first dose of horse antithymocyte globulin, manifested by marked elevation of serum transaminases and mild elevation of serum bilirubin level. Immediately after withdrawal of the offending agent and shifting to the rabbit form of antithymocyte globulin, the gross liver dysfunction started to subside and the hepatic profile results returned to the pre-transplant levels few weeks later. The patient had her allogeneic hematopoietic stem cell transplant as planned without any further hepatic complications. After having a successful allograft, she was discharged from the stem cell transplant unit. During her follow up at the outpatient clinic, the patient remained very well and no major complication was encountered.</p> <p>Conclusion</p> <p>Hepatotoxicity related to the utilization of antithymocyte globulin varies considerably in severity and may be transient or long standing. There may be individual or population based susceptibilities to the development of side effects and these adverse reactions may also vary with the choice of the agent used. Encountering adverse effects with one type of antithymocyte agents should not discourage clinicians from shifting to another type in situations where continuation of the drug is vital.</p
The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience
Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34Β±8% vs 8Β±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51Β±10%, 50Β±10% and 39,1Β±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials
Graft-versus-host disease and relapse/rejection-free survival after allogeneic transplantation for idiopathic severe aplastic anemia: a comprehensive analysis from the SAAWP of the EBMT.
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<0.001), acute GVHD (HR: 1.03, 95% CI [1.00-1.07], p=0.041), and chronic GVHD (HR: 1.04 95% CI [1.01-1.08], p=0.032) as the cause of GRFS failure. GRFS after upfront MRD Allo-HSCT was very good, notably with early Allo-HSCT, confirming that younger patients with a MRD should be transplanted immediately. GRFS was worse in cases of salvage Allo-HSCT, most notably in older patients, questioning the utility of Allo-HSCT earlier in the disease course
ΠΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈ ΡΠ΅ΡΠ΅Π½ΠΈΡ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Π΄ΠΈΡΡΠ΅ΠΌΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π²Π½ΡΡΡΠΈΡΠΎΡΡΠ΄ΠΈΡΡΠΎΠ³ΠΎ ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ ΠΏΡΠΈ Ρ ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π²ΠΌΠ΅ΡΠ°ΡΠ΅Π»ΡΡΡΠ²Π°Ρ Ρ Π΄Π΅ΡΠ΅ΠΉ Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΌΠΈ
Coagulopathy always accompanies blood loss, and its transformation into disseminated intravascular coagulation syndrome (DIC) is associated with increased morbidity and mortality.Objective: to characterize the features of the development and course of DIC during bleeding, as well as identify the main predictors of its formation during surgical interventions in children with oncological diseases.Material and Methods. A retrospective study of children under 18 years of age with oncological pathology who received surgical treatment for the period from 2017 to 2019 years. Children who received blood transfusion and hemostatic therapy with intraoperative bleeding were selected. The resulting cohort (n=207) was divided into two groups using the modified ISTH assessment system: children with DIC (n=59), without DIC (n=148). Demographic, clinical, and laboratory factors were compared between groups. The final model of multivariate logistic regression included signs that were before the development of DIC on the second day after the operation and were selected as a result of univariate analysis (P<0.05), had less than 10% missing data and were clinically plausible. The prediction accuracy of the multivariate model was checked by analyzing the area under the ROC curve.Results. DIC was found to develop often in children with cancer during surgical operations in the retroperitoneal space (OR=2.09 [1.07; 4.05]; P=0.03) and liver (OR=3.86 [1.72; 8.67]; P=0.001). Multiple organ failure (MOF) was more severe and was represented by pulmonary, hepatic and renal failure in the group with identified DIC. The development of MOF was accompanied by a decrease in tissue perfusion and an increase in D-dimer. The probability of detecting acute thrombosis after surgery was 4.5 times higher in the group of patients with DIC than in the group without DIC (OR=4.5 [1.4; 14.3]; P=0.01). 90-daily survival was 84.41Β±6.49% [71.69%; 97.13%] in the group of patients with DIC, and 96.22Β±3.12 [90.1%; 100%] in the group without DIC. Multivariate analysis showed that age less than 8 years, platelet count less than 150X109/l, hypocalcemia less than 1 mmol/l and the period of intraoperative critical hypotension for more than 25 minutes are predictors of the development of DIC after surgery. ROC analysis showed excellent quality of the obtained predictive model (AUC=0,94 [0,9; 0,97]).Conclusion. In children with oncological diseases, in the presence of bleeding, coagulopathy in the postoperative period is transformed into a DIC-syndrome, proceeding clinically with the development of organ failure. Age less than 8 years, platelet count less than 150X109/l, hypocalcemia less than 1 mmol/L and a period of intraoperative critical hypotension of more than 25 minutes are predictors of the development of DIC. The extreme expression of the Β«organΒ» type DIC is the progression of thrombotic syndrome to life threatening complications, which reduces the 90-day survival by 12%.ΠΡΠΎΠ²ΠΎΠΏΠΎΡΠ΅ΡΠ΅ Π²ΡΠ΅Π³Π΄Π° ΡΠΎΠΏΡΡΡΡΠ²ΡΠ΅Ρ ΠΊΠΎΠ°Π³ΡΠ»ΠΎΠΏΠ°ΡΠΈΡ, Π° Π΅Π΅ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠ°ΡΠΈΡ Π² ΡΠΈΠ½Π΄ΡΠΎΠΌ Π΄ΠΈΡΡΠ΅ΠΌΠΈΠ½ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π²Π½ΡΡΡΠΈΡΠΎΡΡΠ΄ΠΈΡΡΠΎΠ³ΠΎ ΡΠ²Π΅ΡΡΡΠ²Π°Π½ΠΈΡ (ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌ) ΡΠ²ΡΠ·Π°Π½Π° Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½Π½ΡΠΌ ΡΡΠΎΠ²Π½Π΅ΠΌ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π΅ΠΌΠΎΡΡΠΈ ΠΈ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΠΈ.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΡ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΠΎΠ²Π°ΡΡ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΈ ΡΠ΅ΡΠ΅Π½ΠΈΡ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΏΡΠΈ ΠΊΡΠΎΠ²ΠΎΡΠ΅ΡΠ΅Π½ΠΈΡΡ
, Π° ΡΠ°ΠΊΠΆΠ΅ Π²ΡΡΠ²ΠΈΡΡ ΠΎΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΎΡΡ Π΅Π³ΠΎ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΈ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠ²Π½ΡΡ
Π²ΠΌΠ΅ΡΠ°ΡΠ΅Π»ΡΡΡΠ²Π°Ρ
Ρ Π΄Π΅ΡΠ΅ΠΉ Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΌΠΈ.ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. Π Π΅ΡΡΠΎΡΠΏΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Ρ Π΄Π΅ΡΠ΅ΠΉ Π² Π²ΠΎΠ·ΡΠ°ΡΡΠ΅ Π΄ΠΎ 18 Π»Π΅Ρ Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΌΠΈ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
Ρ
ΠΈΡΡΡΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π»Π΅ΡΠ΅Π½ΠΈΠ΅ Π² ΠΏΠ΅ΡΠΈΠΎΠ΄ Ρ 2017 ΠΏΠΎ 2019 Π³ΠΎΠ΄Ρ. ΠΡΠΎΠ±ΡΠ°Π»ΠΈ Π΄Π΅ΡΠ΅ΠΉ, ΠΏΠΎΠ»ΡΡΠ°Π²ΡΠΈΡ
Π³Π΅ΠΌΠΎΡΡΠ°Π½ΡΡΡΠ·ΠΈΠΈ ΠΈ Π³Π΅ΠΌΠΎΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ ΠΏΡΠΈ ΠΈΠ½ΡΡΠ°ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΊΡΠΎΠ²ΠΎΡΠ΅ΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ ΠΊΠΎΠ³ΠΎΡΡΡ (n=207) ΡΠ°Π·Π΄Π΅Π»ΠΈΠ»ΠΈ Π½Π° Π΄Π²Π΅ Π³ΡΡΠΏΠΏΡ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΌΠΎΠ΄ΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΠΎΡΠ΅Π½ΠΊΠΈ ISTH: Π΄Π΅ΡΠΈ Ρ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ (n=59), Π±Π΅Π· ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° (n=148). ΠΡΠΎΠ²Π΅Π»ΠΈ ΡΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ Π΄Π΅ΠΌΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ
, ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ
ΡΠ°ΠΊΡΠΎΡΠΎΠ² ΠΌΠ΅ΠΆΠ΄Ρ Π³ΡΡΠΏΠΏΠ°ΠΌΠΈ. Π ΠΎΠΊΠΎΠ½ΡΠ°ΡΠ΅Π»ΡΠ½ΡΡ ΠΌΠΎΠ΄Π΅Π»Ρ ΠΌΠ½ΠΎΠ³ΠΎΡΠ°ΠΊΡΠΎΡΠ½ΠΎΠΉ Π»ΠΎΠ³ΠΈΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΠΈ Π²ΠΊΠ»ΡΡΠΈΠ»ΠΈ ΠΏΡΠΈΠ·Π½Π°ΠΊΠΈ, ΠΊΠΎΡΠΎΡΡΠ΅ Π±ΡΠ»ΠΈ Π΄ΠΎ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΠΠ‘-ΡΠΈΠ½-Π΄ΡΠΎΠΌΠ° Π½Π° 2-Π΅ ΡΡΡΠΊΠΈ ΠΏΠΎΡΠ»Π΅ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΈ ΠΈ Π±ΡΠ»ΠΈ ΠΎΡΠΎΠ±ΡΠ°Π½Ρ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΎΠ΄Π½ΠΎΡΠ°ΠΊΡΠΎΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° (p<0,05), ΠΈΠΌΠ΅Π»ΠΈ ΠΌΠ΅Π½Π΅Π΅ 10% ΠΏΡΠΎΠΏΡΡΠ΅Π½Π½ΡΡ
Π΄Π°Π½Π½ΡΡ
ΠΈ Π±ΡΠ»ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈ ΠΏΡΠ°Π²Π΄ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΡΠΌΠΈ. Π’ΠΎΡΠ½ΠΎΡΡΡ ΠΏΡΠΎΠ³Π½ΠΎΠ·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ½ΠΎΠ³ΠΎΡΠ°ΠΊΡΠΎΡΠ½ΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ ΠΏΡΠΎΠ²Π΅ΡΠΈΠ»ΠΈ ΠΏΠΎ Π°Π½Π°Π»ΠΈΠ·Ρ ΠΏΠ»ΠΎΡΠ°Π΄ΠΈ ΠΏΠΎΠ΄ ΠΊΡΠΈΠ²ΠΎΠΉ ROC.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π£ΡΡΠ°Π½ΠΎΠ²ΠΈΠ»ΠΈ, ΡΡΠΎ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌ Ρ Π΄Π΅ΡΠ΅ΠΉ Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΌΠΈ ΡΠ°ΡΡΠΎ ΡΠ°Π·Π²ΠΈΠ²Π°Π΅ΡΡΡ ΠΏΡΠΈ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΡΡ
Π² ΠΎΠ±Π»Π°ΡΡΠΈ Π·Π°Π±ΡΡΡΠΈΠ½Π½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π° (OR=2,09 [1,07; 4,05]; p=0,03) ΠΈ ΠΏΠ΅ΡΠ΅Π½ΠΈ (OR=3,86 [1,72; 8,67]; p=0,001). ΠΠΎΠ»ΠΈΠΎΡΠ³Π°Π½Π½Π°Ρ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡ (ΠΠΠ) Π±ΡΠ»Π° Π±ΠΎΠ»Π΅Π΅ ΡΡΠΆΠ΅Π»ΠΎΠΉ ΠΈ Π±ΡΠ»Π° ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Π° Π»Π΅Π³ΠΎΡΠ½ΠΎΠΉ, ΠΏΠ΅ΡΠ΅Π½ΠΎΡΠ½ΠΎΠΉ ΠΈ ΠΏΠΎΡΠ΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΡΡ Π² Π³ΡΡΠΏΠΏΠ΅ Ρ Π²ΡΡΠ²Π»Π΅Π½Π½ΡΠΌ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎ-ΠΌΠΎΠΌ. Π Π°Π·Π²ΠΈΡΠΈΠ΅ ΠΠΠ ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π»ΠΎΡΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ ΡΠΊΠ°Π½Π΅Π²ΠΎΠΉ ΠΏΠ΅ΡΡΡΠ·ΠΈΠΈ ΠΈ ΡΠΎΡΡΠΎΠΌ D-Π΄ΠΈΠΌΠ΅ΡΠ°. ΠΠ΅ΡΠΎΡΡΠ½ΠΎΡΡΡ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΎΡΡΡΠΎΠ³ΠΎ ΡΡΠΎΠΌΠ±ΠΎΠ·Π° ΠΏΠΎΡΠ»Π΅ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΈ Π±ΡΠ»Π° Π² 4,5 ΡΠ°Π·Π° Π²ΡΡΠ΅ Π² Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ, ΡΠ΅ΠΌ Π² Π³ΡΡΠΏΠΏΠ΅ Π±Π΅Π· ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° (OR=4,5 [1,4; 14,3]; p=0,01). 90-Π΄Π½Π΅Π²Π½Π°Ρ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° Π² Π³ΡΡΠΏΠΏΠ΅ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ β 84,41Β±6,49% [71,69%; 97,13%], Π° Π² Π³ΡΡΠΏΠΏΠ΅ Π±Π΅Π· ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° β 96,22Β±3,12% [90,1%; 100%]. ΠΠ½ΠΎΠ³ΠΎΡΠ°ΠΊΡΠΎΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ Π²ΠΎΠ·ΡΠ°ΡΡ ΠΌΠ΅Π½Π΅Π΅ 8 Π»Π΅Ρ, ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠΎΠ² ΠΌΠ΅Π½Π΅Π΅ 150Π₯109/Π», Π³ΠΈΠΏΠΎΠΊΠ°Π»ΡΡΠΈΠ΅ΠΌΠΈΡ ΠΌΠ΅Π½Π΅Π΅ 1 ΠΌΠΌΠΎΠ»Ρ/Π» ΠΈ ΠΏΠ΅ΡΠΈΠΎΠ΄ ΠΈΠ½ΡΡΠ°ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΊΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠΈ Π±ΠΎΠ»Π΅Π΅ 25 ΠΌΠΈΠ½ΡΡ ΡΠ²Π»ΡΡΡΡΡ ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΎΡΠ°ΠΌΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° ΠΏΠΎΡΠ»Π΅ ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΈ. ROC-Π°Π½Π°Π»ΠΈΠ· ΠΏΠΎΠΊΠ°Π·Π°Π» ΠΏΡΠ΅Π²ΠΎΡΡ
ΠΎΠ΄Π½ΠΎΠ΅ ΠΊΠ°ΡΠ΅ΡΡΠ²ΠΎ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠΉ ΠΏΡΠΎΠ³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠΎΠ΄Π΅Π»ΠΈ (AUC=0,94 [0,9; 0,97]).ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. Π£ Π΄Π΅ΡΠ΅ΠΉ Ρ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΠΌΠΈ, ΠΏΡΠΈ Π½Π°Π»ΠΈΡΠΈΠΈ ΠΊΡΠΎΠ²ΠΎΡΠ΅ΡΠ΅Π½ΠΈΡ, ΠΊΠΎΠ°Π³ΡΠ»ΠΎ-ΠΏΠ°ΡΠΈΡ Π² ΠΏΠΎΡΠ»Π΅ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅ ΡΡΠ°Π½ΡΡΠΎΡΠΌΠΈΡΡΠ΅ΡΡΡ Π² ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌ, ΠΏΡΠΎΡΠ΅ΠΊΠ°ΡΡΠΈΠΉ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΈ Ρ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌ ΠΎΡΠ³Π°Π½Π½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈ. ΠΠΎΠ·ΡΠ°ΡΡ ΠΌΠ΅Π½Π΅Π΅ 8 Π»Π΅Ρ, ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠΎΠ² ΠΌΠ΅Π½Π΅Π΅ 150Π₯109/Π», Π³ΠΈΠΏΠΎΠΊΠ°Π»ΡΡΠΈΠ΅ΠΌΠΈΡ ΠΌΠ΅Π½Π΅Π΅ 1 ΠΌΠΌΠΎΠ»Ρ/Π» ΠΈ ΠΏΠ΅ΡΠΈΠΎΠ΄ ΠΈΠ½ΡΡΠ°ΠΎΠΏΠ΅ΡΠ°ΡΠΈΠΎΠ½Π½ΠΎΠΉ ΠΊΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ Π³ΠΈΠΏΠΎΡΠΎΠ½ΠΈΠΈ Π±ΠΎΠ»Π΅Π΅ 25 ΠΌΠΈΠ½ΡΡ ΡΠ²Π»ΡΡΡΡΡ ΠΏΡΠ΅Π΄ΠΈΠΊΡΠΎΡΠ°ΠΌΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ°. ΠΡΠ°ΠΉΠ½ΠΈΠΌ Π²ΡΡΠ°ΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΠΠΠ‘-ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Β«ΠΎΡΠ³Π°Π½Π½ΠΎΠ³ΠΎ ΡΠΈΠΏΠ°Β» ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΈΠ½Π΄ΡΠΎΠΌΠ° Π΄ΠΎ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠΉ, ΡΠ³ΡΠΎΠΆΠ°ΡΡΠΈΡ
ΠΆΠΈΠ·Π½ΠΈ, ΡΡΠΎ ΠΈ ΡΠΌΠ΅Π½ΡΡΠ°Π΅Ρ 90-Π΄Π½Π΅Π²Π½ΡΡ Π²ΡΠΆΠΈΠ²Π°Π΅ΠΌΠΎΡΡΡ Π½Π° 12%
Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis
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 6 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 = 5 years remains a risk factor for overall survival.Transplantation and immunomodulatio
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