Ten-year experience of allogeneic haploidentical hematopoietic stem cell transplantation with non-manipulated grafts in children and adolescents with high-risk acute leukemia

Paina, Olesya V.; Боровкова, А С; Frolova, A. S.; Ekushov, Kirill Alexandrovich; Быкова, Т А; Rakhmanova, Zhemal Zarifovna; Galas, Mariya A.; Khabirova, A.G.; Markova, Inna V.; Семенова, Е. В.; Bondarenko, Sergey N.; Babenko, Elena V.; Гиндина, Т. Л.; Alyanskiy, Alexander L.; Barkhatov, I. M.; Смирнов, Б. И.; Zubarovskaya, Ludmila; Afanasyev, Boris

doi:10.18620/ctt-1866-8836-2018-7-2-20-27

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…In the present study, long-term OS (57%) and PFS (56%) were relatively high for this unfavorable group which predominantly comprised of high-risk patients. Relatively low level of CIR (23%) demonstrates fundamental opportunity of ECP to control SR cGVHD, without interfering in graft-versus-tumor effect [ 22 , 23 , 24 ]. The present study seems to be the first to demonstrate FFS in pediatric population treated with ECP.…”

Section: Discussionmentioning

confidence: 99%

Extracorporeal Photopheresis in Children with Chronic Graft-Versus-Host Disease

et al. 2021

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Chronic graft versus host disease (cGVHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It significantly decreases survival and quality of life. The present study demonstrates retrospective data on extracorporeal photopheresis (ECP) in children with cGVHD. A total of 42 children with steroid-refractory cGVHD were enrolled in the study. The majority of patients had acute leukemia (n = 32, 76%). All patients received ECP as second (n = 18, 43%) or third (n = 24, 57%) line of therapy. Initial ECP schedule consisted of bimonthly regimen for two consecutive days with possibility of further tapering according to response. Any concurrent treatment administered before ECP could be continued if considered necessary. Complete response to ECP was registered in seven (17%) patients and partial response in 24 (57%). Overall response according to organ involvement was as follows: skin (n = 24, 75%), mucous membranes (n = 16, 73%), liver (n = 8, 80%), gut (n = 4, 80%), lungs (n = 2, 22%) and joints (n = 2, 67%). Five-year overall, progression-free and failure-free survival was 57%, 56% and 30%, respectively. Non-relapse mortality at 5 years was 14%. We didn’t observe any clinically significant complications in children that could be attributed to the procedure. ECP remains important and safe treatment option in children with cGVHD.

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Section: Discussionmentioning

confidence: 99%

Extracorporeal Photopheresis in Children with Chronic Graft-Versus-Host Disease

et al. 2021

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“…Allo-HSCT of the non-manipulated primed bone marrow from a haploidentical donor proved to be an eff ective approach to achieve clinical remission in children and adolescents with malignant disorders of hematopoiesis [30]. However, the role of this type of transplantation in the treatment of adult patients is still not completely determined.…”

Section: Discussionmentioning

confidence: 99%

Haploidentical stem cell transplantation in adults for the treatment of hematologic diseases: results of a single center (CIC725)

Beinarovich¹,

Babenko²,

Moiseev³

et al. 2019

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Allogeneic HSCT (allo-HSCT) is potentially curative option for a wide variety of malignant and nonmalignant disorders of hematopoiesis. For patients who lack an HLA-matched sibling, HLA-haploidentical related donors (haplo-HSCT) can be considered as alternative sources of donor graft s. Th e benefi ts of haplo-HSCT include immediate donor availability for patients who are in urgent need of the transplant. Besides, an availability of a related donor makes post-transplant donor-derived cellular therapy more easily accessible. In addition, the greater HLA mismatch associated with haploidentical HSCT (haplo-HSCT) may potentiate graft-versus-tumor (GVT) eff ects. Th e aim of our study was to summarize our single-center experience of haplo-HSCT performed with non-manipulated graft s in adult patients with different malignant diseases. Th e study included a total of 119 patients with diff erent hematological disorders subjected to haplo-HSCT. At the time of analysis, median follow-up was 371 days (1-2219). Most frequent diagnosis in transplanted patients was acute leukemia. 67 (56%) patients received haplo-HSCT as salvage therapy. Overall survival with an observation term of 2 years was 40.3% for the general group. In particular, the two-year OS in patients transplanted in remissions of ALL and AML was 57% and 46% respectively as compared to 22% and 15% for the patients transplanted in adverse disease status). Two-year event-free survival (EFS) and GVHD-free/relapse-free survival (GRFS) group proved to be 35.7% and 21% respectively. Th e cumulative incidence of acute GVHD grade II-IV and severe aGVHD grade III-IV was 19% and 10% respectively. Th e cumulative incidence of chronic GVHD (cGVHD) was 16%. Th e cumulative incidence of relapse was 21%. Th e overall transplant-associated mortality was 43% in the studied group. In conclusion, our results show that unmanipulated haplo-HSCT is reasonable treatment option for adult patients with diff erent malignant disorders of hematopoiesis. However, such problems as higher rate graft failure, increased nonrelapse mortality (NRM) and post-transplant relapses remain extremely relevant.

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“…Чаще всего работы обобщают прогноз детей с Р-Р ЛЛ вне зависимости от терапии, так что не представляется возможным оценить эффективность именно алло-ТГСК [8,9]. Если допустить возможным простой перенос опыта применения алло-ТГСК при ОЛЛ на ЛЛ, то тогда ожидаемая долгосрочная выживаемость после алло-ТГСК будет варьировать от 40 до 70% в зависимости от различных прогностических факторов и используемой методики выполнения трансплантации [11,12]. Но существуют объективные сомнения в возможности такого механического подхода, в то же время ограниченность данных не позволяет составить определенное мнение о роли алло-ТГСК в педиатрической практике.…”

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Allogeneic hematopoietic stem cell transplantation in children with lymphoblastic lymphoma

Kozlov

Казанцев

Юхта

et al. 2021

Voprosy gematologii/onkologii i immunopatologii v pediatrii

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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.

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Ten-year experience of allogeneic haploidentical hematopoietic stem cell transplantation with non-manipulated grafts in children and adolescents with high-risk acute leukemia

Cited by 5 publications

References 14 publications

Extracorporeal Photopheresis in Children with Chronic Graft-Versus-Host Disease

Extracorporeal Photopheresis in Children with Chronic Graft-Versus-Host Disease

Haploidentical stem cell transplantation in adults for the treatment of hematologic diseases: results of a single center (CIC725)

Allogeneic hematopoietic stem cell transplantation in children with lymphoblastic lymphoma

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