Hematopoietic stem cell transplantation in children and adolescents with nonremission acute lymphoblastic leukemia

Okamoto, Yasuhiro; Nakazawa, Yozo; Inoue, Masami; Watanabe, Kenichiro; Goto, Hiroaki; Yoshida, Nao; Noguchi, Maiko; Kikuta, Atsushi; Kato, Koji; Hashii, Yoshiko; Atsuta, Yoshiko; Kato, Motohiro

doi:10.1002/pbc.28732

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…This is in clear contrast to BCP‐ALL patients receiving HSCT, for whom OS is almost always approximately 10% higher than LFS 7,32 . Notably, HSCT for patients with non‐CR disease at the time of HSCT showed a dismal outcome comparable to the recent report, although it has been regarded as one of the clinical options for patients with ALL in Japan 33 . These results indicate that HSCT for non‐CR disease should be avoided, and that preparing optimal HSCT settings during CR1 is crucial for these patients.…”

Section: Discussionmentioning

confidence: 63%

“…GVHD, graft-versus-host disease; NRM, non-relapse mortality outcome comparable to the recent report, although it has been regarded as one of the clinical options for patients with ALL in Japan. 33 These results indicate that HSCT for non-CR disease should be avoided, and that preparing optimal HSCT settings during CR1 is crucial for these patients.…”

Section: Discussionmentioning

confidence: 92%

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Prognostic factors of children and adolescents with T‐cell acute lymphoblastic leukemia after allogeneic transplantation

Ishida

Kato

Kawahara

et al. 2022

Hematological Oncology

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Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, and some high‐risk patients with ALL require hematopoietic stem cell transplantation (HSCT). Mainly due to small patient numbers, studies focusing specifically on children and adolescents with T‐cell ALL (T‐ALL) are limited. Using a nationwide registry, we retrospectively analyzed data from patients under 20 years old who underwent their first HSCT for T‐ALL between 2000 and 2018. As a result, total 484 patients were included, and their median follow‐up period was 6.9 years after HSCT for survivors. While patients receiving HSCT at first complete remission (CR) showed relatively good 5‐year leukemia free survival (5yLFS, 73.5%), once relapse occurred, their prognosis was much worse (44.4%) even if they attained second remission again (p < 0.001). Among patients receiving HSCT at CR1, grade II–IV acute graft versus host disease was associated with worse overall and LFS than grade 0–I (5yLFS 69.5% vs. 82.1%, p = 0.026) mainly due to high non‐relapse mortality. Among those patients, patients receiving related bone marrow transplantation, unrelated bone marrow transplantation, or unrelated cord blood transplantation showed similar survival (5yLFS, 73.2%, 76.3%, and 77.0%, respectively). For patients undergoing cord blood transplantation at CR1, total‐body irradiation‐based myeloablative conditioning was associated with better 5yLFS than other conditioning regimens (85.4% vs. 62.2%, p = 0.044), as it reduced the risk of relapse. These results indicate that relapsed patients have much less chance of cure, and that identifying patients who require HSCT for cure and offering them HSCT with optimal settings during CR1 are crucial for children and adolescents with T‐ALL.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 92%

Prognostic factors of children and adolescents with T‐cell acute lymphoblastic leukemia after allogeneic transplantation

Ishida

Kato

Kawahara

et al. 2022

Hematological Oncology

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“…Moreover, the mortality rate at 100 days after transplantation was in ALL. Okamoto et al (23) reported a 3-year OS of 22% in children and adolescents with nonremission ALL. We believe that combined CAR-T cell therapy and HSCT has a synergistic effect.…”

Section: Discussionmentioning

confidence: 99%

Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy

Chen

Shen

et al. 2021

Front. Immunol.

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Early response could be obtained in most patients with relapsed or refractory B cell lymphoblastic leukemia (R/R B-ALL) treated with chimeric antigen receptor T-cell (CAR-T) therapy, but relapse occurs in some patients. There is no consensus on treatment strategy post CAR-T cell therapy. In this retrospective study of humanized CD19-targeted CAR-T cell (hCART19s) therapy for R/R B-ALL, we analyzed the patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) or received a second hCART19s infusion, and summarized their efficacy and safety. We retrospectively studied 28 R/R B-ALL patients treated with hCART19s in the Affiliated Hospital of Xuzhou Medical University from 2016 to 2020. After the first hCART19s infusion, 10 patients received allo-HSCT (CART+HSCT group), 7 patients received a second hCART19s infusion (CART2 group), and 11 patients did not receive HSCT or a second hCART19s infusion (CART1 group). The safety, efficacy, and long-term survival were analyzed. Of the 28 patients who received hCART19s treatment, 1 patient could not be evaluated for efficacy, and 25 (92.6%) achieved complete remission (CR) with 20 (74.7%) achieving minimal residual disease (MRD) negativity. Seven (25%) patients experienced grade 3-4 CRS, and one died from grade 5 CRS. No patient experienced ≥3 grade ICANS. The incidence of second CR is higher in the CART+HSCT group compared to the CART2 group (100% vs. 42.9%, p=0.015). The median follow-up time was 1,240 days (range: 709–1,770). Significantly longer overall survival (OS) and leukemia-free survival (LFS) were achieved in the CART+HSCT group (median OS and LFS: not reached, p=0.006 and 0.001, respectively) compared to the CART2 group (median OS: 482; median LFS: 189) and the CART1 group (median OS: 236; median LFS: 35). In the CART+HSCT group, the incidence of acute graft-versus-host disease (aGVHD) was 30% (3/10), and transplantation-related mortality was 30% (3/10). No chronic GVHD occurred. Multivariate analysis results showed that blasts ≥ 20% in the bone marrow and MRD ≥ 65.6% are independent factors for inferior OS and LFS, respectively, while receiving allo-HSCT is an independent factor associated with both longer OS and LFS. In conclusion, early allo-HSCT after CAR-T therapy can achieve long-term efficacy, and the adverse events are controllable.

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“…receives super doses of chemotherapy and radiation to kill the malignant cells in their body. The collected autologous cells are then transfused back to rebuild hematopoietic and immune functions to cure patient (17,18). However, Cooley (19) found that there were very few malignant cells in the bone marrow or peripheral blood during the continuous remission period of leukemia, they could be regarded as "normal" cells, but they were also malignant cells.…”

Section: Discussionmentioning

confidence: 99%

Systematic review and meta-analysis: transplanted hematopoietic stem cells and killer cells on leukemia

Zhang¹,

Song²,

Ni³

et al. 2021

Ann Palliat Med

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Background: meta-analysis was performed to study the therapeutic effect of hematopoietic stem cell transplantation combined with killer cells (important immune cells of the body) on leukemia, hoping to enhance the postoperative therapeutic efficiency.Methods: literatures were searched with "Hematopoietic stem cell transplantation", "killer cell", "leukemia", "Cytokine induction", etc. as search terms using Boolean logic search. Review Manager was utilized for meta-analysis after literature screening.Results: eleven literatures were included, most of which were of low-risk bias (medium-high quality).Through meta-analysis, statistical heterogeneity was found in non-recurring mortality (NRM) between control group and experimental group (Chi 2 =15.69, I 2 =62%, P=0.02). The leukemia-free survival rate between two groups was not heterogeneous (Chi 2 =13.16, I 2 =32%, P=0.16), without considerable difference between groups (Z=1.52, P=0.13). The incidence of graft-versus-host disease (GvHD) between the two groups was statistically heterogeneous (Chi 2 =21.38, I 2 =67%, P=0.003). The incidence of graft-versus-host disease in experimental group was greatly inferior to controls (Z=3.87, P=0.0001).Discussion: hematopoietic stem cell transplantation combined with killer cells can effectively reduce the incidence of GvHD after stem cell transplantation in patients. The prognosis of transplantation was good, and it had no obvious effect on the overall survival rate and recurrence rate.

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Hematopoietic stem cell transplantation in children and adolescents with nonremission acute lymphoblastic leukemia

Cited by 7 publications

References 29 publications

Prognostic factors of children and adolescents with T‐cell acute lymphoblastic leukemia after allogeneic transplantation

Prognostic factors of children and adolescents with T‐cell acute lymphoblastic leukemia after allogeneic transplantation

Humanized Anti-CD19 CAR-T Cell Therapy and Sequential Allogeneic Hematopoietic Stem Cell Transplantation Achieved Long-Term Survival in Refractory and Relapsed B Lymphocytic Leukemia: A Retrospective Study of CAR-T Cell Therapy

Systematic review and meta-analysis: transplanted hematopoietic stem cells and killer cells on leukemia

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