The Consensus on the Monitoring, Treatment, and Prevention of Leukemia Relapse After Allogeneic Hematopoietic Stem Cell Transplantation in China (2018, English Version)
Full Title: The consensus on the monitoring, treatment, and prevention of leukemia relapse after allogeneic hematopoietic stem cell transplantation in China
Authors: Yu Wang, Hu Chen, Jing Chen, et al. (HSCT Working Group, Chinese Society of Hematology, Chinese Medical Association)
Journal: Cancer Letters, 2018 Dec 1; 438: 63–75
DOI: 10.1016/j.canlet.2018.08.030
PMID: 30217562
Core Background
Allogeneic hematopoietic stem cell transplantation (allo‑HSCT) is a curative therapy for leukemia, but relapse remains the leading cause of post‑transplant death. This consensus summarizes Chinese practices in MRD monitoring, risk‑stratified intervention, and modified donor lymphocyte infusion (DLI), with distinct features from Western guidelines.
1. Definition of Relapse
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Hematologic relapse: Reappearance of leukemia cells in peripheral blood, ≥5% blasts in bone marrow, or extramedullary infiltration in patients who achieved CR.
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Cytogenetic relapse: Re‑emergence of original cytogenetic abnormalities or mixed donor chimerism (without hematologic relapse).
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Molecular relapse: Detectable MRD by multiparameter flow cytometry (MFC) and/or PCR.
2. Monitoring of Relapse (MRD‑Centric)
2.1 MRD Detection Methods
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MFC: Leukemia‑associated aberrant immunophenotypes (LAIPs) in >90% of acute leukemia cases.
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Quantitative PCR: For fusion genes (e.g., BCR‑ABL1) or gene rearrangements.
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WT1 expression: Combined with MFC for MRD assessment in Chinese practice.
2.2 Monitoring Schedule (Recommended)
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Bone marrow morphology, MRD, and chimerism at: +1, +2, +3, +4, +6, +9, +12, +18, +24, +36, +48, +60 months post‑HSCT.
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MRD‑positive patients: Recheck within 2 weeks.
3. Prevention of Relapse (Prophylaxis)
For patients with refractory/relapsed disease pre‑transplant:
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Donor selection: Prefer haploidentical donors (HIDs) for stronger graft‑versus‑leukemia (GVL) effect, especially in pre‑transplant MRD‑positive AML.
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Conditioning: Intensify with high‑antitumor, low‑toxicity agents.
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Immunomodulation:
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Early tapering of immunosuppression (IS): Within 100 days for haplo‑HSCT, 60 days for matched sibling/umbilical cord HSCT.
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Prophylactic DLI: For Ph‑negative leukemia without active GVHD; repeated DLI guided by MRD and GVHD.
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Cytokines (IFN‑α, IL‑2) and NK cell infusions.
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Targeted prophylaxis: TKI for Ph+ ALL after hematologic recovery, even with BCR‑ABL1 negativity.
4. Preemptive Intervention (MRD‑Positive, Non‑Hematologic Relapse)
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Withdraw IS if feasible.
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Modified DLI: G‑CSF‑mobilized donor cells + short‑term immunosuppression (STI) to reduce GVHD while preserving GVL.
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Targeted agents (e.g., FLT3 inhibitors, hypomethylating agents).
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Clinical trials as first‑line option.
5. Treatment of Hematologic Relapse
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Donor cell therapy: Modified DLI remains the backbone.
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Salvage chemotherapy + targeted agents (e.g., venetoclax, sorafenib).
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CAR‑T cells for relapsed/refractory cases.
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Second allo‑HSCT for eligible patients.
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Supportive care and clinical trial enrollment.
6. Key Chinese Innovations
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MRD monitoring algorithm: Combined MFC + WT1 with standardized cutoffs for Chinese patients.
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Modified DLI: G‑CSF‑primed cells + STI to separate GVL from GVHD; severe GVHD ~9.3% vs. ~50% with conventional DLI.
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Risk‑adapted strategy: Prophylaxis → preemptive intervention → salvage treatment based on MRD and disease risk.