Serotherapy-Free Regimen Improves Non-Relapse Mortality and Immune Recovery Among the Recipients of αβ TCell–Depleted Haploidentical Grafts: Retrospective Study in Childhood Leukemia

Shelikhova, Larisa; Glushkova, Svetlana; Nikolaev, Ruslan; Дунайкина, М. А.; Zhekhovtsova, Zhanna; Blagov, Sergey; Khismatullina, Rimma; Balashov, Dmitriy; Kurnikova, Elena; Pershin, Dmitriy; Muzalevskii, Yakov; Kazachenok, Alexei; Osipova, E. Yu.; Trakhtman, Pavel; Maschan, Alexei; Maschan, Michael

doi:10.1016/j.jtct.2021.01.010

Cited by 15 publications

(18 citation statements)

References 25 publications

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“…All three are widely adopted when treating leukemia and autoimmune diseases, but because the toxicity of 6-TG is higher compared to of 6-MP and AZA, 6-TG is generally only adopted in patients with failed or intolerant treatment of 6-MP and AZA. Thiopurine drugs are prodrugs, and their metabolism in vivo is a complex process [ 5 ]. AZA can be rapidly converted to 6-mercaptopurine under the action of glutathione S-transferase.…”

Section: Introductionmentioning

confidence: 99%

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

Zhang

et al. 2022

BioMed Research International

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Objective. To explore the efficacy, safety, and clinical value of 6-TG versus 6-MP when treating childhood acute lymphoblastic leukemia (ALL). Methods. The study period was from January 2017 to June 2021. The subjects of this study were 100 children with ALL who were treated in our hospital. According to different intervention methods, the children who received 6-MP maintenance therapy were selected as the control group, with a total of 57 cases. Children with TG maintenance therapy were included in the research group, a total of 43 cases. The ICNS recurrence rate, non-ICNS recurrence rate, first remission mortality rate, secondary malignant tumor, and other indicators were compared. Results. First of all, we compared the effective rate: complete remission (CR), partial remission, and nonremission in the study group, and the effective rate was 87.5%. In the control group, there were CR, partial remission, and no remission, and the effective rate was 65.5%. The effective rate of the study group was higher, and the difference between groups was statistically significant ( P < 0.05 ). There were 55 cases of failure in the study group, with an incidence of 21.91%. There were 42 cases of total failure events in the control group, the incidence rate was 18.02%, and there exhibited no remarkable difference ( P > 0.05 ). In the study group, 6 cases died in the first remission, with a fatality rate of 2.39%, while there exhibited no death in the control group. The mortality in the first remission period in the study group was lower ( P < 0.05 ). The overall recurrence rate of the study group was 5.57%, while that of the control group was 11.15%. The overall recurrence rate of the study group was lower, and the difference between groups was statistically significant ( P < 0.05 ). The recurrence rate of ICNS was 2.14% in the study group and 2.98% in the control group, and there exhibited no remarkable difference ( P > 0.05 ). The non-ICNS recurrence rate was 3.43% in the study group and 7.17% in the control group. There exhibited no remarkable difference ( P > 0.05 ). The incidence of secondary malignant tumor events was 0.85% in the study group and 1.59% in the control group. There exhibited no remarkable difference ( P > 0.05 ). The incidence of hepatic vein occlusive disease was 7.29% in the study group and 2.39% in the control group. The incidence of hepatic vein occlusive disease in the study group was higher, and the difference between groups was statistically significant ( P < 0.05 ). Finally, we compared the incidence of adverse reactions. In the study group, there were 12 cases of oral mucosal damage, 7 cases of liver function damage, 6 cases of infection, 10 cases of myelosuppression, 9 cases of gastrointestinal reaction, and 4 cases of skin damage; the incidence rate was 23.17%. In the control group, there were 12 cases of oral mucosal damage, 7 cases of liver function damage, 6 cases of infection, 10 cases of myelosuppression, 9 cases of gastrointestinal reaction, and 4 cases of skin damage, with an incidence of 19.12%. There exhibited no remarkable difference in the incidence of adverse reactions ( P > 0.05 ). Conclusion. 6-TG maintenance therapy in children with ALL can enhance the overall effective rate, can reduce the first remission mortality and the total recurrence rate, and will not increase the overall incidence of adverse reactions, but the incidence of reversible or irreversible hepatic veno-occlusive disease is remarkably increased, which has a certain clinical value. Background. Treatment-related hepatotoxicity and myelosuppression remain formidable challenges for clinicians. Pharmacokinetic studies found that 6-TG has a more direct intracellular activation pathway, shorter cytotoxic time, and stronger potency than 6-MP. Therefore, this study investigated the efficacy, safety, and clinical value of 6-TG and 6-MP in the treatment of children with ALL.

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Section: Introductionmentioning

confidence: 99%

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

Zhang

et al. 2022

BioMed Research International

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“…The incidence of CMV reactivation was 45-50% in the experimental mDLI arm and 54-55% in the control arm. The median duration of CMV viremia was 3 weeks (range, 1-9) in the prospective cohort and 4 weeks (range, 1-26) in the historical cohort (105). Memory DLI was associated with improved CMVspecific T-cell reconstitution in a subcohort of CMV IgG seropositive recipients.…”

Section: Prophylactic DLImentioning

confidence: 87%

“…Prophylactic and therapeutic DLI are administered to improve posttransplant immune restoration to reduce both infectious complications and disease relapse. Michael Maschan et al investigated low-dose memory (CD45RA-depleted) donor lymphocyte infusion (mDLI) after ab T-cell depleted HSCT (103)(104)(105). The incidence of CMV reactivation was 45-50% in the experimental mDLI arm and 54-55% in the control arm.…”

Section: Prophylactic DLImentioning

confidence: 99%

“…Analysis of a subcohort of CMV seropositive recipients indicated remarkably better CMVspecific T-cell reconstitution on day 30 in the experimental arm (104). Compared to that of the historical cohort, restoration of CMV-specific immunity at day 30 was significantly enhanced in the prospective cohort (40% versus 25%) (105). Luca Castagna et al prospectively evaluated a CD45RA+ depleted DLI in terms of reducing viral infection early after PTCy-haploSCT (106).…”

Section: Prophylactic DLImentioning

confidence: 99%

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CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

et al. 2021

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Haploidentical stem cell transplantation (haploSCT) has advanced to a common procedure for treating patients with hematological malignancies and immunodeficiency diseases. However, cure is seriously hampered by cytomegalovirus (CMV) infections and delayed immune reconstitution for the majority of haploidentical transplant recipients compared to HLA-matched stem cell transplantation. Three major approaches, including in vivo T-cell depletion (TCD) using antithymocyte globulin for haploSCT (in vivo TCD-haploSCT), ex vivo TCD using CD34 + positive selection for haploSCT (ex vivo TCD-haploSCT), and T-cell replete haploSCT using posttransplant cyclophosphamide (PTCy-haploSCT), are currently used worldwide. We provide an update on CMV infection and CMV-specific immune recovery in this fast-evolving field. The progress made in cellular immunotherapy of CMV infection after haploSCT is also addressed. Groundwork has been prepared for the creation of personalized avenues to enhance immune reconstitution and decrease the incidence of CMV infection after haploSCT.

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“…Одним із факторів, що впливають на термін експлуатації інструменту гарячого деформування, є температура [12][13][14][15][16][17], зокрема її вплив на процеси в поверхневому та підповерхневому шарах [18][19][20][21][22][23][24][25]:…”

Section: аналіз публікаційunclassified

Influence of structure and phase composition of economically alloyed steels on wear resistance

Hlushkova,

Bagrov,

Volchuk

2023

Bulletin of KhNAHU

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Problem. The paper considers the influence of wear on the formation of a "white band" in metastable austenitic, martensitic-austenitic and secondary hardening steels of the Cr-Mn-Ti system additionally alloyed with Mo, B, V., the influence of the structure and phase composition on the wear resistance of sparing. Goal. Based on the above, the purpose of this work was to study the influence of structure and phase composition on the wear resistance of economically alloyed metastable and secondary hardening steels. Methodology. Surfacing of the studied materials was carried out in copper molds with different rates of forced cooling. Metastable austenitic, martensitic-austenitic and secondary hardening steels of the Cr-Mn-Ti system additionally alloyed with Mo, B, V were studied. Additional alloying of these steels with titanium in an amount of 2...5% contributed to the prevention of spalling along the fusion zone. Near the fusion line there is a base metal zone with a width of 7...15 µm. Results. After testing at the volume temperature of the working part of the specimen ТV=553…573 K in the contact volumes of the deposited metal of the 30Kh2V8F type, broadening of the grain boundaries, shear lines, finer grains compared to the underlying layers were revealed. Outside the zone of plastic deformation, the size of the grains corresponds to their sizes before the start of testing, the grain boundaries are relatively thin. The number and location of carbides observed at X430, X80O magnifications are also similar to the structural characteristics of the deposited metal of the 30Kh2V8F type. Originality. At close values of the contact pressure in the friction pair, the time of formation of a crack of critical length increases with an increase in the effective surface energy γе (including the energy of plastic deformation). Thus, the crack resistance indices (CR, j-integral, δС) and, consequently, the wear resistance of maraging steels are higher than those of metastable and tool steels. Practical value. The crack resistance indices (CR, j-integral, δС) and, consequently, the wear resistance of maraging steels are higher than those of metastable and tool steels. Conclusions. The conducted studies confirm the possibility of the formation of a "white band" both in alloys with a high concentration of elements - austenitizers (Mn, C, Ni), and when alloyed with carbide-forming elements with a relatively low affinity for carbon (V, Mo).

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Serotherapy-Free Regimen Improves Non-Relapse Mortality and Immune Recovery Among the Recipients of αβ TCell–Depleted Haploidentical Grafts: Retrospective Study in Childhood Leukemia

Cited by 15 publications

References 25 publications

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

A Retrospective Cohort Study of the Efficacy, Safety, and Clinical Value of 6-TG versus 6-MP Maintenance Therapy in Children with Acute Lymphoblastic Leukemia

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update

Influence of structure and phase composition of economically alloyed steels on wear resistance

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