Editorial Note: Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) and Chimeric Antigen Receptor T-cell (CAR-T) therapy have become crucial in the treatment of leukemia. However, the effectiveness and safety of these treatments continue to be hot topics of research. Recent breakthrough studies have provided valuable insights, particularly in the treatment of children with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), prevention and monitoring of graft-versus-host disease (GVHD), and management of complications following CAR-T therapy. The 50th European Society for Blood and Marrow Transplantation (EBMT) annual meeting, held from April 14 to 17, 2024, in Glasgow, UK, focused on the latest advancements in stem cell transplantation and cellular therapy, pushing forward better clinical outcomes for hematologic patients. At this conference, Professor Shaoyan Hu and her team from the Children's Hospital of Soochow University reported on six studies. Oncology Frontier - Hematology Frontier specially invited Professor Shaoyan Hu and her team members to share their research findings on the efficacy and safety of allo-HSCT and CAR-T cell therapy in pediatric leukemia patients in a roundtable discussion format and to provide insightful commentary on these six studies.


Comparative Prognosis of CAR-T Cell Therapy or Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: Multicenter Study CCCG-ALL-2015

Reported by  Bohan Li

Background Relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) is a major cause of morbidity and mortality in children. Patients with R/R B-ALL typically undergo consolidation with allogeneic hematopoietic stem cell transplantation (allo-HSCT) following chimeric antigen receptor (CAR) T-cell therapy or chemotherapy to maintain long-term remission. However, the efficacy and safety of allo-HSCT post-CAR-T therapy remain controversial. This study aims to investigate the prognosis in pediatric B-ALL patients undergoing allo-HSCT after CAR-T therapy compared to those following chemotherapy.

Methods In this multicenter clinical study, we analyzed the outcomes of 269 pediatric R/R B-ALL patients who underwent allo-HSCT after CAR-T treatment (CAR-T-allo-HSCT group, n=142) or chemotherapy (chemo-allo-HSCT group, n=127). The study included patients diagnosed with ALL between January 2015 and December 2022 at 20 hospitals. Prior to receiving allo-HSCT, all patients were treated according to the Chinese Children Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and were registered with the China Clinical Trials Registry (ChiCTR-IPR-14005706).

Results Compared to the chemo-allo-HSCT group, the CAR-T-allo-HSCT group had a higher rate of achieving a second complete remission (CR) (78.6% vs. 58.0%; P<0.001) and more patients achieving MRD negativity (86.9% vs. 66.2%; P<0.001). The incidence of moderate/severe chronic graft-versus-host disease (mod/sev cGVHD) was higher in the CAR-T-allo-HSCT group (19.09% [95% CI: 12.15-26.03%] vs. 7.33% [95%CI: 25.2-26.0%]; P=0.016). In the CR1 subgroup, the overall survival (OS) was lower in the CAR-T-allo-HSCT group (41.30% [95%CI: 21.60-78.90%] vs. 84.80% [95%CI: 74.20-96.90%]; P=0.006), and rates of grade II-IV acute GVHD, mod/sev cGVHD, and GVHD-free, relapse-free survival (GRFS) were also lower (32.10% [95%CI: 14.60-70.50%] vs. 66.90% [95%CI: 53.60-83.60%]; P=0.02). Non-relapse mortality (NRM) was higher compared to the chemo group (40.74% [95% CI: 11.82-69.22%] vs. 10.29% [95%CI: 0.50-20.09%]; P=0.03). Furthermore, in the CAR-T-allo-HSCT group, patients who had a longer interval (>61 days) between CAR-T treatment and allo-HSCT had higher GRFS (64.3% [95%CI: 52.74-75.86%] vs. 38.3% [95%CI: 25.95-50.65%]; P=0.001) and lower rates of grade II-IV aGVHD (19.44% [95% CI: 10.28-28.65%] vs. 41.27% [95%CI: 29.00-53.54%]; P=0.003) and grade III-IV aGVHD (6.94% [95%CI: 1.04-12.84%] vs. 26.98% [95%CI: 15.80-37.99%]; P=0.001).

Conclusions CAR-T therapy can eliminate MRD prior to allo-HSCT, with OS and RFS similar to the chemotherapy group. However, the incidence of mod/sev cGVHD is higher in the CAR-T-allo-HSCT group. In the CR1 subgroup, the prognosis is poorer compared to the chemo-allo-HSCT group. Patients with an interval of over 61 days between CAR-T treatment and allo-HSCT showed higher GRFS and lower rates of grade II-IV and III-IV aGVHD.

Expert Commentary

Professor Shaoyan Hu: Our research focuses on leukemia, transplantation, and CAR-T, which reflects the specialty of our department. At present, the scale of Hematology department has 250 beds, finishing 220-230  cases of hematopoietic stem cell transplants per year and 60-70 cases with CAR-T treatments annually. Meanwhile, an increasing number of patients are treated with blinatumomab which targets CD19 positive B cells of acute lymphoblastic leukemia(ALL), and we have published three papers related to blinatumomab, which is part of cell immunotherapy. Thus, our team has achieved excellent results in the treatment of leukemia, cell immunotherapy, and bone marrow transplantation.

Besides, we are joined (CCCG-ALL-2015) multicenter cIinical trial of ALL and produced a series of publications, we also launched multicenters of AML clnical trial comparing the low-dose chemotherapy regimen with standard dose chemotherapy, and the results has been reported by Dr. Gao Li at the American Society of Hematology (ASH) annual meeting in December 2023. Whether in diagnosing and treating leukemia, bone marrow transplantation for leukemia treatment, preventing relapse, or early intervention, we have achieved very good outcomes.

A020: Impact of Low-Dose Hypomethylating Agents on Preventing Relapse in High-Risk Pediatric AML Patients Post-HSCT

Reported by Qingwei Wang

Background Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for high-risk (HR) acute myeloid leukemia (AML) in children. However, 20% to 50% of patients may relapse, which is a major cause of mortality post-HSCT. Maintenance therapy post-HSCT might improve relapse-free survival (RFS) for HR AML. Using low-dose hypomethylating agents (HMAs) post-HSCT has shown positive effects in adult AML, but data for children are limited.

Methods A retrospective study was conducted at the Affiliated Children’s Hospital of Soochow University. From August 2019 to April 2023, 173 pediatric AML patients were treated with HSCT for HR (n=103), refractory or relapsed (RR, n=40), or combined HR+RR (n=30) conditions (excluding second transplants). The cohort included 100 boys and 73 girls, with a median age of 6 years and 9 months (range: 3 months to 16 years). All patients were in complete remission before starting HMA treatment post-HSCT. Fifty-three patients received HMA maintenance therapy (decitabine administered subcutaneously at 10-15 mg/m^2 daily for 3-5 days every 28 days, for at least 4 cycles; or azacitidine at 32 mg/m^2 daily for 3-5 days every 28 days, for at least 4 cycles). The median time to intervention was day 123 post-HSCT. The control group (n=120) did not receive HMA intervention. All patients were followed up until October 2023.

Results As of the last follow-up, the median number of cycles was 4. A total of 31 children completed at least 4 cycles, and 17 discontinued maintenance due to various reasons (liver dysfunction [n=4], renal dysfunction [n=1], pulmonary infection [n=1], MOG antigen-related optic neuritis [n=1], graft-versus-host disease [GVHD][n=2], relapse [n=5], unspecified reasons [n=3]). No severe adverse events occurred during maintenance. The overall survival (OS) and RFS for the HMA group were 94.3% vs. 77.5% and 90.6% vs. 66.7% respectively, compared to the control group. HMAs as maintenance therapy significantly improved OS and RFS ([95%CI: 38.84-43.78; P=0.006] and [95%CI: 31.45-37.23; P=0.001]). HMAs benefited patients with CBF-AML and KIT mutations (P=0.044) and those with KMT2A rearrangements (P=0.037), but did not improve outcomes for patients with FUS::ERG (P=0.655) or CBFA2T3::GLIS2 (P=0.181). In terms of GVHD, there were no significant differences in either acute or chronic GVHD between the HMA group and the control group.

Conclusion HMAs can prevent relapse post-HSCT in pediatric HR AML patients, are safe and well-tolerated, and do not increase the risk of GVHD. The varied clinical effects of different HR fusion genes help identify patients who may benefit most from HMA maintenance therapy.

Expert Commentary

Professor Shaoyan Hu: Our poster session includes a study on preventing relapse in leukemia patients post-hematopoietic stem cell transplantation. Over 50 leukemia patients were given hypomethylating agents post-transplant, which significantly prevented relapse. We also discovered that molecular-level recurrence interventions with hypomethylating agents were much more effective than complete hematological relapse. Hence, in my patients bone marrow aspirations were done monthly post-transplant in the first year in case to intervene as early at the molecular stage as possible, which is crucial for improving prognosis. Our study’s data emphasize the importance of early detection and intervention at the molecular level for better treatment outcomes.


Expert Profiles

Professor Shaoyan Hu

  • Position: Chief Physician, Second-Level Professor, Doctoral Supervisor, and Director of the Department of Hematology at the Affiliated Children’s Hospital of Soochow University
  • Awards and Honors:
    • Jiangsu Province “333” Second Level Leading Talent
    • Mid-aged Expert with Special Contributions in Jiangsu Province
    • Key Talent in the “Six Talents Peak” of Jiangsu Province
    • Leading Talent in “Science and Education Leading Health” and “Innovative Team” in Jiangsu Province
    • One of Jiangsu’s “Hundred Stars of Medical Ethics”
    • Gusu Health Leading Talent in Suzhou City
    • Awarded “The Most Beautiful Pediatrician” by the Pediatric Branch of the Chinese Medical Doctor Association
  • Leadership Roles:
    • Member of the National Health Commission’s Expert Committee on Pediatric Blood Diseases
    • Vice Chair of the Clinical Diagnosis and Treatment Working Group of the National Health and Family Planning Commission’s Expert Committee on Child Leukemia
    • Vice Chair of the Pediatric Hematology Group of the Chinese Medical Association
    • Former Chair of the Pediatric Hematology Group of Jiangsu Medical Association
  • Research and Achievements:
    • Principal investigator for multiple national natural science funds and key provincial projects
    • Recipient of several provincial and ministerial science and technology progress awards and new technology introduction awards
    • Author of multiple SCI papers

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Last updated on 2024.06.17