"King of Blood Cancers" Hard to Treat and Prone to Relapse? Zhejiang Second Hospital's Self-Developed Upgraded CAR-NK Cell Therapy Strikes Back!

"My waist suddenly hurt so much I couldn't straighten up. When I went to the hospital, I unexpectedly found a 20-centimeter 'big lump' in my abdomen!" Five years ago, 68-year-old Aunt Yu never imagined that this painless mass would set her on a five-year anti-cancer journey.

She was diagnosed with diffuse large B-cell lymphoma (DLBCL), known as the "king of blood cancers." This disease progresses rapidly with a high recurrence rate, and many patients struggle to overcome the hurdle of "refractory and relapsed" disease.

Five-Year Anti-Cancer Journey: Treatments Again and Again, But Relapses Persist

Aunt Yu's twists and turns in fighting cancer began more than five years ago. She sought medical treatment for waist pain at a hospital in Shanghai and accidentally discovered a approximately 20cm mass in the retroperitoneum. A retroperitoneal puncture confirmed diffuse large B-cell lymphoma, which had already involved the bone marrow.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of malignant lymphoma in adults. Due to its strong invasiveness and rapid progression, it is often called the "king of cancers" in the field of hematological tumors.

Doctors in Shanghai adopted the international standard "R-CHOP regimen" (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone). After 8 courses of chemotherapy, all indicators showed that the disease had achieved complete remission (CR)—meaning the tumor was temporarily controlled, and Aunt Yu thought she had won.

But the good times didn't last. In May 2020, a mass suddenly swelled in Aunt Yu's neck. The test result was like a bolt from the blue: pathological examination indicated lymphoma recurrence. Since then, her treatment journey has fallen into a cycle of "relapse - treatment - progression":

· First, she received 4 courses of BR regimen (bendamustine combined with rituximab) chemotherapy, but the disease progressed instead of being controlled;

· She participated in a BTK inhibitor clinical trial for 2 months, but the efficacy was unsatisfactory;

· She switched to the R2 regimen (rituximab combined with lenalidomide) plus 27 sessions of radiotherapy, which still failed to stop the disease progression;

· In July of the same year, she participated in a related CAR-T clinical trial at another hospital, but the treatment effect did not meet expectations;

· In February 2022, she received 1 course of venetoclax combined with selinexor treatment, and the mass shrank compared with before, with the disease temporarily controlled;

· Aunt Yu heard that Zhejiang Second Hospital had made remarkable achievements in cell therapy. She consulted Professor Qian Wenbin's outpatient clinic in the Department of Hematology and participated in the CAR-NK cell clinical trial at Zhejiang Second Hospital. In August of the same year, she completed three CAR-NK cell infusions, which stabilized her condition for 3 years;

· In August 2025, bad news came again: B-ultrasound indicated that the cervical lymph nodes had enlarged again, and Aunt Yu's disease progressed once more.

On August 29, experts from the Department of Ultrasound Medicine at Zhejiang Second Hospital performed a core needle biopsy of Aunt Yu's left lymph node. The pathological result confirmed that the long-gone diffuse large B-cell lymphoma had indeed returned! Moreover, the latest and most advanced PET-CT examination at Zhejiang Second Hospital found that the lymphoma had extensively involved the whole body, and death was approaching step by step...

Upgraded CAR-NK Cell Therapy: Tumors Almost Completely Disappeared

The upgraded innovative CAR-NK cell therapy developed by Professor Qian Wenbin's team from the Department of Hematology launched an attack!

Faced with Aunt Yu's complex situation where she had almost used all lymphoma drugs, the team led by Liu Hui, deputy director of the Department of Hematology, quickly formulated an individualized treatment plan:

CAR-NK Cell Infusion

After clearing obstacles with a lymphodepletion regimen, the crucial step arrived. On September 19, 23, and 25, Aunt Yu received three doses of CAR-NK cell infusions (the upgraded CAR-NK cells independently produced by The Second Affiliated Hospital of

Zhejiang University School of Medicine were slowly infused back into her body to engage in a fierce battle with cancer cells).

 Process of producing CAR-NK cells and treating patients at the Biotherapy Center of Zhejiang Second Hospital

During the treatment, Aunt Yu experienced fluctuations in body temperature, reaching a maximum of 39°C. Doctors judged it to be "cytokine release syndrome" (simply put, a reaction produced by immune cells when "killing tumors"). Fortunately, it was only mild. After taking antipyretic drugs and receiving fluid replacement, her condition stabilized quickly without severe side effects.

One month later, Aunt Yu underwent a re-examination with PET-CT, and the result relieved everyone: the tumors that had previously spread to the neck, mediastinum, and bones either had reduced metabolism or disappeared! Doctors said this meant the treatment was "significantly effective," and Aunt Yu's condition was finally relieved.

(Image: PET-CT examinations of Aunt Yu before and after the upgraded CAR-NK cell treatment, showing that multiple lymphomas in the neck and groin completely disappeared)

Doctors' Insights: For Refractory and Relapsed Lymphoma, Don't Give Up Hope

Aunt Yu's diagnosis and treatment process provides multiple inspirations for the treatment of patients with refractory and relapsed diffuse large B-cell lymphoma:

1. Understanding the "enemy" thoroughly is crucial: Through multiple needle biopsies, immunohistochemistry, PET-CT and other examinations, clarifying the tumor type, spread range, and disease progression can provide an accurate basis for subsequent plan adjustments;

2. Treatment plans should be flexibly adjusted according to the condition: From the initial R-CHOP regimen, to BR and R2 regimens after recurrence, then CAR-T, targeted drugs (venetoclax, selinexor), and finally the upgraded CAR-NK cell therapy, each plan adjustment is based on changes in the condition, reflecting the treatment principle of "individualization and dynamic adjustment";

3. Novel cell therapy shows potential: As an emerging cellular immunotherapy method, CAR-NK cell therapy can still be effective in patients who have failed CAR-T treatment. With mild CRS (cytokine release syndrome) reaction and good safety, it provides a new treatment option for refractory and relapsed patients and is expected to become an important treatment direction for such patients in the future;

4. Adverse reaction management is a guarantee: Timely and effective handling of adverse reactions such as myelosuppression after chemotherapy and CRS (cytokine release syndrome) related to cell therapy is the key for patients to successfully complete treatment. Prevention should be done before treatment, close monitoring during treatment, and timely intervention after treatment.

The treatment of diffuse large B-cell lymphoma is constantly evolving, with new drugs and treatment technologies emerging continuously. Aunt Yu's five-year anti-cancer journey has proven that even in the face of multiple relapses and refractory dilemmas, it is still possible to achieve disease remission through accurate diagnosis, formulation of individualized treatment plans, and strict adverse reaction management, which also brings anti-cancer confidence to more patients.

Today, more and more "refractory and relapsed" patients like Aunt Yu have found new hope at Zhejiang Second Hospital. If you or someone around you is facing related troubles, don't be afraid. Seek medical treatment in a timely manner—maybe the next miracle will happen.