About Dr. Li Jun
Dr. Li Jun is Chief of Hematology at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — one of China's foremost academic centres for haematological malignancies, CAR-T cell therapy, and haematopoietic stem cell transplantation. He is a nationally recognised leader in aggressive B-cell lymphomas, acute leukaemia, and myeloma, with particular expertise in CAR-T cell immunotherapy, autologous and allogeneic stem cell transplantation, and the management of refractory and relapsed haematological malignancies. Ruijin Hospital's haematology department was a principal clinical validation centre for relma-cel (relmacabtagene autoleucel) — China's first domestically developed CD19-targeted CAR-T cell product — and Dr. Li's team has accumulated one of the largest single-centre CAR-T treatment experiences in China. His practice is defined by the philosophy that for high-risk, treatment-refractory haematological malignancies, the combination of precision immunotherapy and consolidative transplantation offers the best prospect of durable cure — and that toxicity management expertise is as important as treatment selection in determining outcomes. Dr. Li has published extensively in Blood, Journal of Clinical Oncology, and Leukemia, and serves on the expert committees of the Chinese Society of Hematology and the Chinese CAR-T Cell Therapy Consensus Group.
Case Overview
Ms. Sophie Laurent, a 28-year-old French financial analyst, newly married with a strong fertility preservation priority, presented with a 10 x 8 cm anterior mediastinal mass and right pleural effusion. External biopsy confirmed diffuse large B-cell lymphoma; two cycles of R-CHOP failed — the mass enlarged and bone marrow biopsy revealed 15% lymphoma infiltration. Immunohistochemistry: CD20(+), CD30(+), BCL-2(+), C-MYC(-), Ki-67 80%. FISH: BCL-2, BCL-6, C-MYC all negative — excluding double/triple-hit lymphoma. Gene expression profiling confirmed PMBCL with TP53 mutation — a high-risk molecular feature associated with chemotherapy resistance. Stage IV-B; IPI 3 (high-risk); NCCN-IPI 4 (very high-risk). Dr. Li Jun designed the Ruijin sequential strategy: GDP bridging chemotherapy to reduce tumour burden, autologous T-cell apheresis, FC lymphodepletion, relma-cel CAR-T infusion (2 x 10⁶/kg), and consolidation ASCT after confirmed complete remission. At Day +28: PET-CT Deauville 1, bone marrow MRD-negative — complete remission confirmed. ASCT engrafted successfully. At 24-month follow-up: sustained complete remission, menstrual cycles resumed, patient actively planning pregnancy.
Patient Background
- Name / Nationality: Ms. Sophie Laurent (pseudonym) — French; financial analyst
- Age / Sex: 28-year-old female; newly married; no children; strong fertility preservation priority
- Chief Complaint: Cough, chest tightness, and fever for 1 month; anterior mediastinal mass on CT
- Disease Course: External biopsy: DLBCL; 2 cycles R-CHOP — primary refractory (mass enlarged); bone marrow: 15% lymphoma infiltration
- Performance Status: ECOG 2; superior vena cava compression syndrome (SVCS); platelet count below 50 x 10⁹/L
- Molecular Profile: CD20(+), CD30(+), BCL-2(+), C-MYC(-), Ki-67 80%; FISH negative; GEP: PMBCL; TP53 mutation confirmed by NGS
- Staging: Stage IV-B (bone marrow involvement); IPI 3; NCCN-IPI 4 (very high-risk)
Clinical Decision Making
Three compounding challenges defined the treatment strategy: primary R-CHOP refractoriness in a TP53-mutant PMBCL — where conventional salvage chemotherapy achieves complete remission in fewer than 25% of patients; massive tumour burden with SVCS and thrombocytopenia — creating procedural risk for T-cell apheresis; and the patient's age and fertility preservation priority — requiring avoidance of highly gonadotoxic conditioning agents.
Dr. Li Jun's treatment strategy: This patient has a TP53-mutant PMBCL that did not respond to R-CHOP. Standard salvage chemotherapy will not cure her. The TP53 mutation means the tumour has lost its primary chemotherapy-induced apoptosis pathway. CAR-T cells do not rely on that pathway — they kill through direct cytotoxic contact, independent of TP53 status. But CAR-T alone carries significant relapse risk in this molecular profile. ASCT after MRD-negative complete remission resets the immune environment and provides high-dose consolidation that extends the durability of the CAR-T response. CAR-T first. ASCT to consolidate. That is the Ruijin strategy for very high-risk lymphoma.
Treatment Sequence
Phase 1 — Bridging Chemotherapy and T-Cell Apheresis
GDP bridging (1 cycle): Gemcitabine, cisplatin, dexamethasone — tumour burden reduced 30%; platelets recovered to 80 x 10⁹/L. CD3+ T-cells collected (3.0 x 10⁹) under thrombocytopenic conditions with platelet transfusion support. Relma-cel manufacturing initiated — approximately 14 days production time.
Dr. Li's clinical note: The apheresis in a thrombocytopenic patient is a calculated risk. We cannot wait for spontaneous platelet recovery — the tumour will progress. We transfuse to a safe threshold, perform the apheresis efficiently, and proceed. T-cell quality in young patients is generally excellent even after prior chemotherapy. This patient's T-cells manufactured into a high-quality product.
Phase 2 — Lymphodepletion and CAR-T Infusion
FC lymphodepletion: Fludarabine 25 mg/m²/day x 3 days + cyclophosphamide 250 mg/m²/day x 3 days — depleting endogenous lymphocytes to create immunological space for CAR-T expansion. Cyclophosphamide selected over busulfan to minimise ovarian toxicity in this 28-year-old patient.
CAR-T infusion: Relma-cel at 2 x 10⁶ CAR-T cells/kg — single infusion on Day 0.
Phase 3 — CAR-T Toxicity Management (Day +1 to +14)
CRS Grade 2 (Day +3): Fever 39.5°C, hypotension (BP 85/55 mmHg), SpO₂ 92%. Management: tocilizumab 8 mg/kg IV + methylprednisolone + fluid resuscitation. Fever resolved 12 hours; haemodynamic stability 24 hours; oxygen discontinued 36 hours. No escalation to Grade 3–4.
Dr. Li's management note: We do not wait for Grade 3 CRS to use tocilizumab. Grade 2 with hypotension and oxygen requirement in a patient with a 10 cm mediastinal mass can deteriorate rapidly. Early tocilizumab at Grade 2 prevents escalation. The timing of tocilizumab is the most consequential decision in CAR-T management. Grade 2 with organ involvement is the threshold. We act at that threshold.
ICANS Grade 1 (Day +7): Confusion, expressive aphasia, hand tremor. Management: head-of-bed elevation 30 degrees; levetiracetam for seizure prophylaxis; neurological monitoring every 4 hours; electrolyte optimisation. Complete neurological recovery within 72 hours; no residual deficits.
Haematological toxicity: Prolonged pancytopenia managed with G-CSF, TPO-RA, and transfusion support. No infectious complications during the CAR-T phase.
Phase 4 — Response Assessment and ASCT Consolidation
Day +28 assessment: PET-CT: Deauville 1 — complete metabolic remission; no residual FDG uptake. Bone marrow MRD-negative by flow cytometry and NGS. Complete remission confirmed.
ASCT: CD34+ cells 4.5 x 10⁶/kg; BEAM conditioning (carmustine, etoposide, cytarabine, melphalan). Neutrophil engraftment Day +12; platelet engraftment Day +15. Discharged Day +35 post-ASCT.
Post-transplant Follow-up
- Early: WHO Grade II mucositis — resolved Day +20; CMV viraemia — ganciclovir, PCR-negative Day +28; ECOG 1 at discharge
- 3 months: Sustained CR (Deauville 1); CAR-T cells detectable; B-cell aplasia; monthly IVIG initiated
- 12 months: Sustained CR; menstrual cycles resumed Month 4; AMH reduced but recoverable; returned to full-time work; ECOG 0
- 24 months: Disease-free survival sustained; no late relapse; actively planning pregnancy with reproductive endocrinology support
Expert Commentary — Dr. Li Jun
1. Sequential CAR-T Plus ASCT: Why Two Treatments Are Better Than One
For TP53-mutant primary refractory PMBCL, neither CAR-T alone nor ASCT alone provides adequate long-term disease control. CAR-T achieves complete remission in approximately 40–50% of refractory large B-cell lymphoma patients — but without consolidation, 12-month PFS is below 40% in very high-risk patients. ASCT after MRD-negative CR adds high-dose tumour cell kill below the MRD detection threshold and creates a favourable immune environment for long-term CAR-T persistence. The sequence is critical: CAR-T must achieve MRD-negative CR before ASCT. ASCT consolidating a partial remission does not improve outcomes. ASCT consolidating an MRD-negative CR does. This patient achieved exactly that — and at 24 months she remains in complete remission.
2. CRS and ICANS: The Ruijin Standard Operating Protocol
CAR-T cannot be administered safely without a dedicated toxicity management infrastructure. Our protocol defines three principles: early recognition with standardised grading (ASTCT for CRS; ICANS Assessment Tool for neurotoxicity) every 8 hours for the first 14 days; graded intervention with tocilizumab at Grade 2 CRS with organ involvement — not waiting for Grade 3–4; and multidisciplinary support with ICU, neurology, and infectious disease on immediate standby. Early intervention at Grade 2 prevents escalation and preserves CAR-T anti-tumour efficacy. Late intervention at Grade 3–4 saves lives but at the cost of ICU admissions and prolonged recovery. We intervene early. Every time.
3. Fertility Preservation: Cure Without Sacrificing the Future
A 28-year-old patient with a curable malignancy has the right to expect both cure and the possibility of future pregnancy. Cyclophosphamide over busulfan for lymphodepletion; BEAM over TBI-containing regimens for ASCT conditioning — total body irradiation carries the highest risk of permanent ovarian failure. The result: menstrual cycles resumed at four months; AMH within the range where natural conception is possible. She is planning pregnancy. That outcome is not accidental. It is the result of deliberate treatment design.
4. The Future: Dual-Target and Universal CAR-T
The primary mechanism of CAR-T failure is antigen escape — the tumour downregulates CD19, rendering the CAR-T cells blind. Our research programme addresses this through dual-target CD19/CD22 CAR-T — making simultaneous antigen escape from both targets much less likely — and allogeneic universal CAR-T from healthy donor T-cells, providing an immediately available product for patients whose own T-cells are too exhausted after prior chemotherapy. Both are active clinical programmes at Ruijin Hospital.
How CMCS Shanghai Coordinated This Case
CMCS supported Ms. Laurent from initial inquiry through 24-month surveillance and fertility planning, including: pre-arrival review of pathology, FISH, PET-CT, bone marrow biopsy, and R-CHOP records; specialist referral to Dr. Li Jun; re-staging workup coordination (MRD assessment, GEP, TP53 NGS, repeat PET-CT); bilingual interpretation throughout all consultations; T-cell apheresis logistics with platelet transfusion coordination; CAR-T admission scheduling with ICU standby arrangement; daily toxicity monitoring communication to the French haematologist; Day +28 and 3/12/24-month PET-CT and MRD surveillance scheduling with results translation; AMH monitoring at 3, 6, and 12 months post-ASCT; reproductive endocrinology referral for pregnancy planning; and long-term surveillance protocol establishment with direct communication between Dr. Li's team and the French haematologist.
For international patients with refractory lymphoma or high-risk haematological malignancies requiring CAR-T immunotherapy and stem cell transplantation, the expertise of Dr. Li Jun's team at Ruijin Hospital represents haematological oncology care genuinely at the international frontier. CMCS connects patients with that expertise: ensuring every treatment option is evaluated, every toxicity risk explained in their language, and every step from T-cell apheresis to long-term remission surveillance coordinated across borders with precision and care.
This case report is de-identified and published for educational purposes. All clinical details have been anonymized in accordance with patient privacy standards. CMCS Shanghai is a medical concierge service and does not provide direct medical care.
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