Hematopoietic stem cell transplantation (HSCT) has become a cornerstone therapy for many malignant hematologic diseases, enabling long-term survival and, in some cases, cure. However, extensive clinical experience has shown that successful transplantation does not signify the end of treatment. Complications occurring before and after transplantation—often involving multiple organ systems—remain a major determinant of patient prognosis and quality of life.

At this critical stage, reliance on a single medical framework is frequently insufficient. Beyond precise disease control, clinicians face the challenge of stabilizing systemic function, improving physiological resilience, and guiding patients safely through a high-risk period of treatment. An integrative approach combining Western medicine and traditional Chinese medicine (TCM) offers unique clinical advantages in addressing these challenges.

Director Liu Huixia of GoBroad Healthcare Group has long specialized in integrative management of HSCT and transplant-related complications. She emphasizes that Western medicine and TCM are not competing paradigms, but rather complementary systems that can be strategically integrated to enhance clinical outcomes.

From Transplant Completion to Sustained Recovery: Complications as a Decisive Factor

For many patients with hematologic malignancies, completion of HSCT represents only one milestone in a prolonged therapeutic journey. Post-transplant complications—including fluid imbalance, infection, organ dysfunction, and prolonged systemic weakness—often play a decisive role in determining long-term survival.

Director Liu notes that after intensive chemotherapy, radiotherapy, and immunosuppressive conditioning, patients typically experience profound physiological stress. Even when the underlying malignancy is controlled, global dysregulation of metabolic, immune, and organ functions may persist, limiting recovery and increasing mortality risk. In such cases, conventional supportive care alone may reach a therapeutic ceiling.

TCM contributes an alternative perspective by focusing on restoring systemic regulation, supporting intrinsic recovery capacity, and improving overall physiological coordination, rather than targeting isolated symptoms.

Managing Severe Edema: Restoring Physiological Fluid Regulation

In one case involving a patient with refractory intestinal T-cell lymphoma, pre-transplant evaluation revealed severe generalized edema, pleural effusion, renal impairment, and hypoalbuminemia. Despite adequate fluid management and high-dose diuretics, fluid overload continued to worsen, significantly compromising transplant readiness.

Director Liu assessed that the condition was not simply due to excess fluid accumulation, but rather a failure of the body’s regulatory mechanisms responsible for fluid distribution and metabolism, compounded by reduced functional reserve. Treatment therefore focused on restoring circulatory regulation, improving renal fluid handling, and stabilizing vascular permeability.

Following integrative intervention, the patient’s urine output increased substantially, body weight decreased, and pleural effusion gradually resolved without invasive procedures. The patient subsequently completed conditioning and underwent successful stem cell transplantation. This strategy was later applied to multiple similar cases with reproducible benefits.
This experience underscores that, in transplant-related complications, addressing underlying regulatory dysfunction may be more effective than symptomatic fluid removal alone.

Collaborative Management of Severe Infection: Optimizing Systemic Resilience

Another patient with primary refractory acute leukemia presented with severe mixed infections involving multidrug-resistant bacteria, fungi, and viruses, along with strong donor-specific antibodies. Although HSCT represented the only curative option, infection control posed a major obstacle.

From a Western medicine standpoint, the multidisciplinary team continuously adjusted antimicrobial regimens based on microbiological findings, employing intensive combination therapy to gradually stabilize the infection and secure a narrow transplantation window. However, after entering the transplant unit, the patient continued to suffer from persistent cough, dyspnea, excessive sputum production, and marked intolerance to supine positioning, significantly impairing treatment tolerance.

Director Liu approached this condition by focusing on improving pulmonary function, enhancing airway clearance, and supporting respiratory resilience, while avoiding excessive suppression of the patient’s already compromised physiological state. With integrative treatment, respiratory symptoms improved rapidly. No severe pulmonary infection occurred during transplantation, imaging showed progressive resolution of inflammation, and post-transplant evaluation confirmed deep complete remission of the underlying disease.

This case illustrates the importance of strategic integration at critical clinical junctures: Western medicine controls infectious agents, while TCM-based approaches enhance systemic stability and recovery capacity.

Conceptual Framework: A Systems-Based Integrative Model

Director Liu’s clinical practice is grounded in a structured theoretical framework developed from long-term observation of transplant patients. This model conceptualizes transplant-related complications as the result of intense therapeutic stress leading to systemic disorganization and functional exhaustion.

Accordingly, treatment extends beyond managing discrete complications and instead prioritizes:

• Restoration of core physiological functions

• Re-establishment of coordination among organ systems

• Modulation of excessive treatment-related stress

• Attention to psychological and emotional well-being

Therapeutic strategies emphasize multidimensional regulation and individualized adjustment, allowing interventions to align closely with each patient’s dynamic clinical condition.

Conclusion: Integrative Medicine as an Outcome-Oriented Strategy

Director Liu emphasizes that integrative Chinese–Western medicine is not a theoretical juxtaposition, but an outcome-driven clinical strategy. In the high-risk, high-intensity context of hematopoietic stem cell transplantation, meaningful progress depends on transcending disciplinary boundaries and focusing on the patient as a complex, adaptive system.

As clinical experience expands and evidence continues to accumulate, integrative approaches are expected to evolve into more standardized and widely applicable models within hematologic transplantation—ultimately offering more patients not only the possibility of survival, but also a better quality of life.

A Difficult Start to Life

Just five days after birth in May 2020, Keke showed severe signs of anemia. After multiple hospital visits, she was diagnosed with congenital pure red cell aplasia (PRCA), a rare blood disorder requiring long-term care.

For the next four years, her life revolved around regular blood transfusions and steroid treatment.

Despite her parents’ best efforts, Keke remained unusually small and thin, and the frequent trips to the hospital became part of her childhood.

The increasing steroid doses gradually changed her appearance, affecting not only her body, but also her confidence.

 

Searching for Hope: A Mother’s Determination

Keke’s mother recalls the early struggle:

“When she was diagnosed, she was only three months old. She had even been admitted to the ICU because of severe anemia. We had no long-term plans then—just one hope: for Keke to grow up safely.”

They tried multiple treatments. Some worked briefly, but none brought lasting improvement.

 

Three Stages of Treatment

Before age one, Keke relied entirely on regular transfusions.

Each session brought short relief, but her underlying condition did not improve, and her transfusion dependence grew.

At around age one, doctors recommended steroid therapy. After eight months—just when the family’s hope was fading—her hemoglobin began to rise. It felt like a miracle.

But the medication regimen was challenging: monthly blood tests, nighttime dosing to maintain drug levels, and difficulty adding new supportive medications.

Despite their best efforts, after three years of therapy, Keke still required transfusions, and the steroids caused a pronounced “moon face.”

Her parents realized: Continuing this way was no longer sustainable. Transplantation became our only path forward.

 

A Life-Changing Decision: Hematopoietic Stem Cell Transplantation

In the summer of 2025, Keke’s family turned to the GoBroad Chunfu Hematology & Oncology Institute（GoBroad Healthcare Group）.

With the support of its expert medical team, Keke underwent hematopoietic stem cell transplantation (HSCT)—a treatment that offered her the possibility of curing PRCA.

She received stem cells from her older sister on August 26, and successfully left the transplant isolation unit on September 22.

Those 30 days in the sterile unit became a period of physical and emotional transformation for the entire family.

 

Overcoming the Most Difficult Moments

During the first days in isolation, Keke experienced fever and diarrhea due to chemotherapy, making her irritable and uncomfortable.

Her mother remembers:

“The hardest part wasn’t the care itself—it was watching my child suffer and not being able to take the pain away.”

The medical team guided and supported her, helping her stay calm and learn how to care for Keke during treatment.

Day by day, Keke’s condition improved, giving her mother renewed confidence.

 

A Gradual Transformation After Transplant

More than a month after leaving the unit:

• Her “steroid face” disappeared
• Her cheeks became rosy
• She grew lively and cheerful again
• She stopped asking, “Why am I different from others?”

 

Her mother reflects:

“Only then did I realize how deeply anemia affected her—both physically and emotionally. I’m grateful that she was born at a time when medicine could give her a future. As long as we never give up, there is always hope.”

Q1: In recent years, new treatment approaches for refractory AML—including targeted therapy, immunotherapy, and cell therapy—have emerged. How would you evaluate the current status of treatment for these patients in China?

Prof. Wang: The most significant breakthrough in AML treatment over the past years lies in our deeper understanding of the disease's pathogenesis. We first needed to clarify why some patients fail to respond well to therapy, which led researchers to systematically investigate the mutational landscape associated with treatment resistance. Based on these molecular insights, the development of mutation-specific targeted agents became possible.

Currently, the range of targeted drugs available in clinical practice is expanding. A milestone example is imatinib, the first targeted therapy for hematologic malignancies worldwide, which revolutionized chronic myeloid leukemia (CML) by precisely targeting the BCR-ABL fusion gene—turning CML into a manageable chronic condition, and even achieving clinical cures.

For AML, the introduction of targeted therapies has improved outcomes for some refractory patients. For those unresponsive to conventional chemotherapy, combining targeted drugs can induce remission. However, these agents have notable limitations—monotherapy rarely prevents relapse. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), the traditional curative approach, also faces significant challenges: patients who undergo transplant without achieving remission have a much higher relapse rate, and even those transplanted successfully remain at risk of relapse.

Targeted therapies have transformed transplant strategies in two key ways:

• Pre-transplant: For chemotherapy-resistant patients, targeted drugs can induce remission, creating an opportunity for transplantation.
• Post-transplant: Maintenance therapy with targeted agents significantly reduces relapse risk. Clinical data show that integrating targeted drugs improves transplant success rates primarily by effectively controlling relapse.

In contrast to lymphoid leukemias, progress in cellular therapies for AML has been relatively slow. Despite numerous clinical trials, challenges such as difficult target selection and high tumor heterogeneity have hindered breakthroughs. Consequently, the combination of targeted therapy and allo-HSCT remains the primary curative strategy for AML today.

 

Q2: Allogeneic HSCT is still regarded as the most important “potentially curative” approach for refractory AML. In which patients should transplant be considered as early as possible?

Prof. Wang: AML treatment strategies are now very clear—precision risk stratification is key. Previously, we leaned toward transplanting all patients. Today, we recognize that some patients can achieve long-term survival with chemotherapy alone, minimizing treatment burden. Therefore, our main task is to identify these patients through precise risk assessment.

The widely adopted European Leukemia Net (ELN) classification divides patients into favorable, intermediate, and adverse risk groups:

• Favorable risk: Transplant is not recommended; chemotherapy alone can achieve cure rates of 50–60%.
• Adverse risk: Due to poor genetic profiles, nearly all patients relapse after chemotherapy, so allo-HSCT is necessary regardless of remission status; otherwise, prognosis is extremely poor.
• Intermediate risk: This group remains the most controversial. According to ELN guidelines and Chinese clinical practice, allo-HSCT is still advised for these patients, as current chemotherapy and targeted approaches remain suboptimal.

Our ultimate goal is to achieve maximal survival benefit with minimal treatment burden. While transplant remains a high-risk and technically demanding “last resort,” for intermediate-risk patients, its feasibility should still be discussed at diagnosis.

 

Q3: Post-transplant relapse remains the leading cause of treatment failure in refractory AML. How do you optimize risk stratification and monitoring in clinical practice?

Relapse after allo-HSCT continues to be the primary cause of transplant failure. Advances in supportive care have significantly reduced mortality from GVHD and infections, bringing relapse into sharper focus. To address this challenge, we emphasize three key areas:

1. Pre-transplant optimization: Ideally, patients should achieve MRD (measurable residual disease) negativity before transplant. However, in practice, there are two special groups: patients who cannot achieve hematologic remission and high-risk patients requiring urgent transplantation. At our center, 78% of transplant cases are in non-remission states, posing higher relapse risks.
2. Conditioning regimen design: The key lies in balancing intensity—overly aggressive regimens increase transplant-related mortality, while insufficient intensity raises relapse risk.
3. Post-transplant strategies:
• Comprehensive MRD monitoring: We use multiparametric approaches, including flow cytometry, chimerism analysis, and genetic testing, to detect relapse before hematologic recurrence (where salvage therapy success is only 20–30%).
• Targeted maintenance therapy: Evidence shows that graft-versus-leukemia (GVL) effect alone is insufficient to prevent relapse. Early intervention with targeted agents significantly lowers relapse rates.
• Immunomodulation: Our center adopts an interferon-based strategy—early tapering of immunosuppressants combined with long-acting interferon—to enhance GVL in a safer and more controllable way than donor lymphocyte infusion, which carries risks of severe GVHD or marrow suppression.

It is worth noting that our team was among the first in China to apply chimerism monitoring in clinical practice, a technique now widely adopted. By integrating these strategies, we have improved relapse control and overall survival outcomes for transplant patients.

 

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapeutic approach for hematologic malignancies such as leukemia and has been widely adopted both domestically and internationally. Among the various modalities, T-cell-depleted transplantation (TCD-HSCT) is a specialized form of allo-HSCT in which donor T lymphocytes are removed from the graft to reduce the incidence of graft-versus-host disease (GVHD), thereby improving transplant success rates and patient survival. Despite significant progress in TCD-HSCT, many patients still have questions regarding its indications, pre-transplant preparation, procedural risks, post-transplant care, and prognosis.

In this article, Professor Chunfu Li, Director of the Nanfang Chunfu Institute of Hematology, provides a detailed overview of TCRαβ+ T cell-depleted hematopoietic stem cell transplantation (TDH), explaining its mechanisms, evolution, advantages, and applications in hematologic and immune disorders.

I. Mechanism and Development of TDH Transplantation

Currently, clinical transplantation protocols are broadly divided into two categories:

1. T-cell-replete transplantation (TCR-HCT)
2. Ex vivo T-cell-depleted transplantation (TCD-HCT)

• T-cell-replete HCT involves grafts that retain a high number of T cells and includes matched sibling donor (MSD) transplants, matched unrelated donor (MUD) transplants, and haploidentical transplants (Haplo-HCT). Haplo-HCT includes the ATG-based (Beijing protocol) and PTCy-based (U.S. protocol) approaches. Both methods aim to suppress T cells in vivo through anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy) to reduce GVHD.
• Ex vivo TCD-HCT removes T cells from the graft prior to infusion and has undergone four developmental stages:

Stage 1: In the 1990s, physicians attempted CD34+ stem cell selection, infusing only CD34+ cells. Outcomes were suboptimal.

Stage 2: Negative selection techniques emerged, depleting CD3+ (T) cells. Although outcomes improved, efficacy remained limited.

Stage 3: CD45RA depletion targeted naïve T cells, but results were still unsatisfactory.

Stage 4: The current TDH approach enables selective depletion of αβ T cells while retaining γδ T cells and natural killer (NK) cells, which are critical for antitumor and anti-infective immunity.

In fact, TDH technology represents a step forward toward precision transplantation.

II. Rationale for αβ T Cell Depletion

While T cells (CD3+ cells) are generally considered the primary mediators of GVHD, they are composed of αβ and γδ subsets. αβ T cells are the main drivers of GVHD, whereas γδ T cells and NK cells contribute to tumor surveillance and infection control. Thus, selectively removing αβ T cells mitigates GVHD risk while preserving beneficial immune functions.

Immunomagnetic bead sorting is commonly used to deplete αβ T cells. Magnetic beads specifically bind to αβ T cells, forming bead-cell complexes, which are then removed by magnetic columns, leaving behind a graft enriched in CD34+ stem cells, γδ T cells, and NK cells. The αβ T cell content is reduced to less than 1×10⁵/kg.

These enriched grafts help reconstruct hematopoiesis (via CD34+ cells) and provide immune protection (via NK and γδ T cells).

Since around 2008, TDH technology has evolved. Initially, CD3+ T cell depletion yielded limited efficacy (6–8×10⁵), requiring immunosuppressive therapy. By 2014, depletion efficiency improved to 1–5×10⁵ for TCRαβ+ cells, but immunosuppressants were still necessary. Post-2015, the technique matured, reducing residual αβ T cells to <5×10⁴, eliminating the need for immunosuppressive therapy and minimizing GVHD risk while maintaining robust hematopoietic recovery and antitumor effect.

III. Advantages of TDH Technology

Let us examine how TDH transplantation reduces risks and improves outcomes in allo-HSCT.

Major risks of allo-HSCT include:

• Graft failure (implantation failure, incidence <5%)
• GVHD (usually >20%)
• Relapse (approximately 20%, varies by disease and transplant conditions)
• Infection (nearly universal, with ~10% mortality)

IV. How does TDH technology reduce these post-transplantation risks and thereby increase the success rate of transplantation?

1. Enhancing Graft Success Rate

In diseases like thalassemia, which have higher graft failure rates, TDH transplantation has reduced failure rates to below 2% in our center. In other diseases, the failure rate is even lower.

2. Reducing GVHD and Infection

TDH enables infusion of a large number of CD34+ stem cells, expediting hematopoietic recovery. Faster recovery of neutrophils and platelets shortens inpatient time, reduces hemorrhagic complications, and lowers infection risks. International studies show TDH is associated with the lowest incidence of both acute and chronic GVHD.

3. Lowering Relapse Rates

Relapse remains the most challenging issue post-HSCT. Once relapse occurs, survival drops below 20%. Thus, prevention is key. Why the rate of relapse is high? In haploidentical transplants using ATG or PTCy, T cell and NK cell recovery is hindered, impairing graft-versus-leukemia effects. Furthermore, T-cell-replete transplants require immunosuppressive therapy (IST), which suppresses T/NK cell function and contributes to relapse.

Contrary to early beliefs that TCD increases relapse risk (due to immature CD34+ selection methods), modern TCRαβ+ depletion allows infusion of large numbers of NK and γδ T cells with strong antitumor activity.

Studies have shown that a graft NK cell count >6.33×10⁶/kg reduces relapse risk by 90%. In our 83 TDH transplant recipients with leukemia, the median NK cell count reached 110.5×10⁶/kg, well above this threshold, with high γδ T cell counts as well.

In cord blood transplantation, NK cells are the first to recover. Their robust reconstitution reduces relapse. Similarly, early post-transplant recovery of γδ T cells within 30 days correlates with improved survival and lower relapse. Critically, TDH eliminates the need for IST, and does not require preconditioning with ATG/PTCy, allowing for rapid T cell recovery and enhanced antileukemic effect.

The trend in HSCT is moving toward minimizing or eliminating ATG. Previously, limited understanding of immunotherapy led to reliance on ATG. Now, as immunotherapy advances, ATG is increasingly seen as unnecessary. TDH serves as a platform for integrating immunotherapy, helping further reduce relapse and improve long-term survival.

On September 13, after more than 100 days of careful treatment by doctors of GoBroad Transplantation Center, Mr. Sun (a pseudonym), a patient with acute myeloid leukemia, was successfully discharged from the hospital. At the age of 73, Mr. Sun set a new record for the oldest allogeneic hematopoietic stem cell transplant patient in the transplant team, as well as in the hospital.

At the beginning of this year, Mr. Sun always felt foot pain, body weakness, appetite is also much worse. In the following month, Mr. Sun's symptoms worsened, with foot pain that made it difficult to walk, inability to eat, abdominal distension and irritability. Unable to tolerate the discomfort, Mr. Sun decided to go to the hospital for further evaluation. Routine blood and bone marrow tests revealed that Mr. Sun most likely had leukemia.

On May 3, Sun arrived at Beijing GoBroad Boren Hospital accompanied by his family. Although it was a holiday, Mr. Sun went through the admission process smoothly under the coordination of Wu Tong, Director of the Transplant Center.

Leukemia MICM typing is very important, which helps to determine the type of leukemia, formulate the appropriate treatment plan, and monitor the effect of treatment. After further extensive testing, Sun was finally diagnosed with acute myeloid leukemia with bZIP, CEBPA, CSF3R and NRAS mutations. After 3 rounds of chemotherapy, Sun's condition went into complete remission.

However, the disease was more cunning than expected, and during the subsequent consolidation phase, Mr. Sun was found to have 0.02% suspicious primitive myeloid cells in MRD during a routine examination. This meant that he had to undergo hematopoietic stem cell transplantation.

Mr. Sun's age was a major hurdle for the transplant. In general, transplantation for elderly patients is more difficult and risky than for normal patients. To ensure the best treatment outcome, the medical team conducted a thorough pre-transplant evaluation and assessment of Sun and carefully designed a reduced-intensity pre-treatment program that best suited his needs.

On July 22-23, Mr. Sun was successfully infused with his son's hematopoietic stem cells. 11 days after the transplantation, platelets were viable, and 14 days after the transplantation, neutrophils were viable, and hematopoietic reconstruction was successful. By September, Mr. Sun's condition was stable and he was discharged from the hospital.

Mr. Sun is especially grateful to the hospital and the medical team for their professional treatment and careful care. He said, "It's the right time to come to the hospital!" He is also very grateful to his family for their companionship and support. Since his illness, his family has been with him all the time, from financial support, spiritual encouragement, physical care to the details of his life, they have taken care of Sun without reservation and in every detail, which also inspired his courage and strength to overcome the illness. Sun's wife was a head nurse at the hospital before she retired, with rich medical and nursing experience, and he was able to be discharged from the hospital without her meticulous care. Although he cannot return to his hometown for the time being, Mr. Sun still feels very happy to have crossed the "line between life and death," and he said that what he wants most at the moment is to have a family reunion.