Efficiency of second allogeneic HSCT in the children with acute leukemias with relapses after first transplantation

Kozhokar, P.V.; Paina, Olesya V.; Frolova, A. S.; Rakhmanova, Zhemal Zarifovna; Боровкова, А С; Семенова, Е. В.; Osipova, Anna A.; Ekushov, Kirill Alexandrovich; Слесарчук, О. А.; Ovechkina, Varvara N.; Babenko, Elena V.; Vitrishchak, Alina A.; Смирнов, Б. И.; Zubarovskaya, Ludmila; Afanasyev, Boris

doi:10.18620/ctt-1866-8836-2019-8-4-33-40

Cited by 4 publications

(3 citation statements)

References 15 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Повторные алло-ТГСК, также как и при остром лейкозе, могут быть эффективны у некоторых пациентов с Р-Р ЛЛ [21]. Так, в представленной работе у 2 пациентов проведение повторной алло-ТГСК привело в одном случае к достижению длительной ремиссии, в другом -к появлению донорского гемопоэза после первичного неприживления.…”

Section: рисунокunclassified

Allogeneic hematopoietic stem cell transplantation in children with lymphoblastic lymphoma

Kozlov

Казанцев

Юхта

et al. 2021

Voprosy gematologii/onkologii i immunopatologii v pediatrii

View full text Add to dashboard Cite

Lymphoblastic lymphoma (LBL) in children is curable in most cases, but there is still a significant proportion of patients in whom standard therapy is ineffective. Thus, patients develop a relapse or a primary refractory disease in about 10% of cases (R/R). In this case, the main treatment method is allogeneic hematopoietic stem cell transplantation (allo-HSCT). The choice in favor of transplantation is predominantly based on the experience in adult patients. A small number of pediatric patients accounts for the limited data in pediatrics. The prognosis of these patients is always extremely poor. It has been shown that the survival of patients after allo-HSCT is higher only if remission is achieved prior to the transplantation. In order to provide more evidence in support of allo-HSCT, randomized clinical trials are needed. However, such studies in the field of allo-HSCT are quite difficult to conduct, and this necessitates the search for alternative methods of evidence-based medicine in this area. Probably, the achievement of high survival rates could be considered a sufficient argument in favor of this method. This study was approved by the Independent Ethics Committee and the Scientific Council of the I.P. Pavlov First Saint-Petersburg State Medical University of the Ministry of Healthcare of Russia. In this work, we summarize the experience in allo-HSCT in children with R/R LBL obtained at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University. This work is one of the few ones devoted exclusively to the role of alloHSCT in the treatment of pediatric R/R LBL. From 2006 to 2020, at the R.M. Gorbacheva Research Institute for Pediatric Oncology, Hematology and Transplantation, I.P. Pavlov First Saint-Petersburg State Medical University, allo-HSCT was performed in 13 children and adolescents with R/R LBL (2 patients underwent 2 transplantations). Repeated transplantations were performed due to progression and primary graft failure. The median number of prior lines of therapy was 2.5 (2–4). Remission prior to alloHSCT was observed in 7 cases. The graft sources were a fully HLA-matched related donor (n = 3), a fully HLA-matched unrelated donor (n = 4), and a haploidentical donor (n = 8). The following schedules were used as a conditioning regimen: fludarabine 150 mg/m2 + busulfan 8–14 mg/kg (n = 8), fludarabine 150 mg/m2 + melphalan 140 mg/m2 (n = 5), fludarabine 150 mg/m2 + treosulfan 30 mg/m2 (n = 2). In most cases, the prevention of “graft versus host” disease (GVHD) was based on post-transplant cyclophosphamide (n = 11). Cyclophosphamide alone was used in fully matched related transplantation (n = 2), in combination with tacrolimus and cellsept – in unrelated transplantation (n = 1), and in combination with sirolimus and tacrolimus – in haploidentical transplantation (n = 8). A combination of ATGAM, methotrexate and cyclosporin A was used three times in alloHSCT from an unrelated donor for the prevention of GVHD. In one allo-HSCT from a fully matched related donor, cyclosporin A alone was used for the prevention of GVHD. The graft sources were bone marrow (n = 9) and peripheral blood stem cells (n = 4). The median CD34+ cells/kg was 3.8 (1.1–10.0). At the median follow-up of 651 (106–3034) days, the 3-year event-free survival rate was 52% (95% CI: 25–74), the incidence of relapse/progression was 48% (95% CI: 26–76). Five out of thirteen patients died during the study period. The cause of death was the underlying disease in all cases. The cumulative incidence of acute and chronic GVHD was 28% (95% CI: 11–58%) and 24% (95% CI: 5–48), respectively. This work is one of the largest in terms of the number of transplanted children with R/R LBL. Our results are superior to those obtained in case of using only chemotherapy in comparison with the historical control and are comparable with the few previously published data on allo-HSCT in children. In this study, we included patients who underwent allo-HSCT. Among them, there were also children out of remission of LBL which implies that there was no selection of patients, and thus our study settings were close to the so-called real clinical settings. The drawbacks of this work include the following: the study was carried out at a single transplant center, there was no comparison group, the number of patients was low. Nevertheless, considering the complexity of conducting randomized trials in the field of allo-HSCT, the presented data serve as an important confirmation of the effectiveness of transplantation in R/R LBL.

show abstract

Section: рисунокunclassified

Allogeneic hematopoietic stem cell transplantation in children with lymphoblastic lymphoma

Kozlov

Казанцев

Юхта

et al. 2021

Voprosy gematologii/onkologii i immunopatologii v pediatrii

View full text Add to dashboard Cite

show abstract

“…However, relapse aft er haplo-HSCT has limited options for cure [2]. Second transplantation could be eff ective in patients that achieved remission [3]. Th e currently available immunotherapies, e.g., blinatumomab, a bispecific T-cells engager (BITE) antibody, or conjugate antibody inotuzumab ozogamicin have provided curative strategy in some patients to achieve remission before second haplo-HSCT with acceptable toxicity.…”

Section: Introductionmentioning

confidence: 99%

Successful treatment of relapsed/refractory B-Acute lymphoblastic leukemia with Inotuzumab ozogamicin after blinatumomab failure

Bondarenko

Smirnova

Moiseev

et al. 2020

CTT

Self Cite

View full text Add to dashboard Cite

Blinatumomab, a bispecific T-cell engaging CD3-CD19 antibody, is highly effective in patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, patients who failed with Blina have a dismal outcome. Inotuzumab ozogamicin is one of the therapeutic options after blinatumomab failure. We report a young man who exhibited bone marrow (BM) relapse of B-ALL following haploidentical stem cell transplantation (haplo-HSCT). Remission was not achieved after Blinotumomab treatment, thus Inotuzumab was administered. A complete remission with no signs of minimal residual disease was achieved after a single cycle of Inotuzumab. The second haplo-HSCT from another donor was successful. Conclusion The present case demonstrate an opportunity of successful inotuzumab therapy after failure of allo-HSCT and blinotumomab treatment.

show abstract

“…Опубликованные данные об эффективности комбинированной профилактической терапии у детей с ЮММЛ отсутствуют. В случае развития рецидива повторная алло-ТГСК со сменой донора или без нее может быть «терапией спасения» у 30-40% пациентов [3,9,10].…”

unclassified

The prophylaxis of severe hemophilia A with inhibitors in children in the Republic of Belarus: a 12-year experience

Dmitriev,

Volkova,

Aleinikova

et al. 2023

Voprosy gematologii/onkologii i immunopatologii v pediatrii

View full text Add to dashboard Cite

The development of inhibitory antibodies against FVIII is the most serious complication associated with the use of FVIII concentrates in hemophilia A patients. There is a need for more research on measures that could reduce the risk of inhibitor formation in previously untreated patients (PUPs) with severe hemophilia A. The purpose of this study was to determine the effectiveness of the prevention of clotting inhibitor development in PUPs (or minimally treated patients) with severe hemophilia A by administering plasma-derived factor VIII concentrate (pdFVIII) at a dose of 25 IU/kg once a week for a year. The study was approved by the Independent Ethics Committee and the Scientific Council of the Belarusian Research Center for Pediatric Oncology, Hematology and Immunology (the Republic of Belarus). Between 2010 and 2022, 56 boys were newly diagnosed with severe hemophilia A. Twenty-one of them received pdFVIII as on-demand treatment to stop bleeding (Group 1). Thirty-five boys received pdFVIII at a dose of 25 IU/kg body weight once a week during the first 50 weeks of treatment for the prevention of inhibitor development (Group 2). The administration of pdFVIII at a dose of 25 IU/kg once a week in the PUPs (or minimally treated patients) contributed to a decrease in the cumulative incidence of inhibitors to 15.9 ± 7.7% (4 out of the 35 patients who had been treated prophylactically) compared with 43.7 ± 11.8% (8 out of the 21 patients who had received hemostatic therapy to stop bleeding) (log-rank test, p = 0.041). Thus, the administration of pdFVIII concentrate at a dose of 25 IU/kg once a week for the first 50 weeks of treatment lead to a decrease (p = 0.009) in the cumulative incidence of inhibitors against the administered coagulation factor VIII to 15.9 ± 7.7%.

show abstract

Efficiency of second allogeneic HSCT in the children with acute leukemias with relapses after first transplantation

Cited by 4 publications

References 15 publications

Allogeneic hematopoietic stem cell transplantation in children with lymphoblastic lymphoma

Allogeneic hematopoietic stem cell transplantation in children with lymphoblastic lymphoma

Successful treatment of relapsed/refractory B-Acute lymphoblastic leukemia with Inotuzumab ozogamicin after blinatumomab failure

The prophylaxis of severe hemophilia A with inhibitors in children in the Republic of Belarus: a 12-year experience

Contact Info

Product

Resources

About