A 7-Year-Old Boy with Rare Mixed Phenotype Leukemia Finds a New Beginning

Summary: Seven-year-old Xiaole developed persistent fever, thrombocytopenia, and other symptoms and was initially diagnosed with T-lymphoblastic lymphoma/leukemia with myeloid expression. Despite multiple rounds of standard chemotherapy, his disease continued to progress. After he was transferred to Beijing GoBroad Boren Hospital, Prof. Yonghong Zhang’s team brought together multidisciplinary expertise, genetic testing, and precision diagnostics to identify the underlying disease as mixed phenotype acute leukemia/lymphoma (T/B/myeloid) driven by an NRAS somatic mosaic mutation. The team then developed an individualized treatment strategy combining targeted therapy with allogeneic hematopoietic stem cell transplantation. In March 2025, Xiaole successfully underwent a related haploidentical transplant. He remains in complete remission and is steadily recovering. His story shows how an accurate diagnosis and tailored treatment can open a path forward for a child with a rare and complex blood cancer, while also highlighting the value of multidisciplinary care.

In May 2024, seven-year-old Xiaole (pseudonym) was diagnosed at another hospital with stage IV T-lymphoblastic lymphoma/leukemia with myeloid expression (CNS1). Yet after multiple rounds of standard chemotherapy, his disease still did not go into remission, and treatment seemed to have reached an impasse. In November 2024, after his local doctor invited Prof. Yonghong Zhang for a consultation, Xiaole was transferred to the Department of Pediatric Hematology & Oncology at Beijing GoBroad Boren Hospital to understand why the disease was proving so difficult to treat. The team first carried out a comprehensive review of his case, then quickly convened a multidisciplinary consultation and incorporated genetic testing and other precision diagnostic tools. This ultimately revealed the key driver of his disease: mixed phenotype acute leukemia (MPAL) driven by an NRAS somatic mosaic mutation. The team designed an individualized plan using pathway-directed targeted therapy together with chemotherapy to bring the disease under control and create the right conditions for transplantation. In March 2025, Xiaole successfully underwent a related haploidentical hematopoietic stem cell transplant. With close supportive care from the medical team, he made it through critical post-transplant challenges including infection and graft-versus-host disease (GVHD).

Today, more than 10 months after transplantation, Xiaole remains in complete remission (CR). His strength is returning, his familiar smile is back, and childhood is once again filling his days with color.

Xiaole after treatment and discharge

From Common Symptoms to a Rare Diagnosis

The story began in early 2024, when Xiaole developed a cough and fever. At first, his family thought it was simply a common cold and took him to a local hospital for symptomatic treatment. A month or two later, however, small red spots appeared on his skin, raising new concerns. His family took him from their home in Anhui to a hematology department at a hospital in Zhejiang. The initial test results were worrying: his platelet count was low, and his liver, spleen, and lymph nodes were enlarged. After a series of detailed examinations, the family received a diagnosis they had never expected: T-lymphoblastic lymphoma with myeloid expression (stage IV, CNS1), with NRAS and DDX3X mutations also identified.

“I was completely stunned. It felt like a dream. I had never even heard of lymphoma before...” Xiaole’s mother still remembers the shock and helplessness she felt when she first heard the diagnosis.

Determined to save their son, Xiaole’s family went through several courses of chemotherapy at the local hospital. But instead of improving as hoped, the disease repeatedly pushed back, leaving the family feeling that they were running out of options. At a time when they were anxious, confused, and close to despair, a message in a patient support group gave them a new lead: Prof. Yonghong Zhang’s team at Beijing GoBroad Boren Hospital was known for extensive experience in pediatric lymphoma, particularly relapsed and refractory disease. After Xiaole’s local doctor invited Prof. Zhang for a consultation, the family made the trip to Beijing in November 2024, determined to pursue every possible option.

Precision Diagnosis: Finding the Driver and a Path Forward

Faced with this unusually complex case, Prof. Yonghong Zhang’s team immediately began a comprehensive review. The new evaluation revealed a more complicated picture: in addition to hepatosplenomegaly, Xiaole’s bone marrow contained three populations of tumor cells with abnormal T-cell, B-cell, and myeloid phenotypes, consistent with a mixed-lineage leukemia. NGS screening for susceptibility genes related to hematologic and immune disorders also showed an NRAS variant allele frequency of 93.36%, yet the variant was not inherited from either parent. Through a joint molecular and clinical review, the team determined that the NRAS change was a somatic mosaic mutation arising early in embryonic development. Because it was neither an inherited germline variant nor a tumor-specific mutation, it helped explain the highly unusual clinical presentation.

That precise diagnosis became the turning point. Early in treatment, the team tried several combinations of chemotherapy and targeted agents, but the disease continued to progress. In February 2025, as the tumor burden remained difficult to control, Prof. Zhang’s team rapidly convened another multidisciplinary consultation. After repeated review and discussion, they reached the integrated diagnosis of mixed phenotype acute leukemia/lymphoma. The NRAS somatic mosaic mutation was driving a malignant hematopoietic stem-cell clone capable of differentiating along multiple lineages, helping explain why several lines of chemotherapy had failed to achieve a meaningful response.

The experts agreed that allogeneic hematopoietic stem cell transplantation offered the only realistic path toward rebuilding Xiaole’s blood-forming and immune systems and pursuing a potential cure. Before transplantation, however, the disease first had to be controlled. Prof. Zhang’s team therefore developed a bridging regimen combining two targeted agents. Encouragingly, after only four days of targeted therapy, Xiaole’s enlarged spleen had already shrunk noticeably. That early response gave both the family and the medical team renewed confidence that transplantation might now be within reach.

Through the Darkest Days: A Vigil in the Transplant Unit

On February 19, 2025, Xiaole entered the transplant unit and began conditioning. His hematopoietic stem cells were infused over two days, March 5 and 6. For his family, these “seeds of life” carried their deepest hopes, as well as the medical team’s careful preparation for what came next.

The conditioning regimen took a heavy toll on Xiaole. The wait for blood-cell recovery was filled with uncertainty, and the fear of infection weighed constantly on the family. His mother later described that period as “the darkest time of our lives,” when every day seemed to bring a new worry.

But Xiaole was not facing it alone. The medical team stayed close throughout the transplant journey. With careful monitoring and supportive care, his neutrophils engrafted on day 16 and his platelets on day 25. He then faced one challenge after another, including infection and intestinal GVHD. Each time, the team responded promptly and precisely, helping him safely through the complications.

The signs of a new beginning became clearer with each follow-up. At one month after transplantation, imaging showed no obvious tumor lesions, bone marrow testing showed complete donor chimerism, and the NRAS mutation was no longer detected in either bone marrow or peripheral blood. At the two-month assessment, Xiaole had achieved complete remission, confirming that the disease was under effective control.

Xiaole returned to the general ward after leaving the transplant unit

A New Beginning: Gratitude for the Return of Everyday Happiness

Today, more than 10 months after his transplant, Xiaole remains in complete remission and continues to regain his strength. The child who once spent his days consumed by illness is now laughing and playing with friends again, just like other children his age. “The best decision I made was bringing him to Boren,” his mother said. Her voice still trembled as she looked back on the journey - with memories of how difficult it had been, but also with gratitude for where her son is today.

In a thank-you letter to the hospital, Xiaole’s mother wrote: “Looking back on this journey, I know clearly that the expertise of the Boren medical team paved the way for his recovery... What you protected was not only his health, but the ordinary days and future that every family treasures most.” She also shared how much Xiaole enjoyed the hospital’s regular arts-and-crafts classes and holiday activities. These seemingly simple moments helped preserve the fun, interaction, and sense of childhood he deserved, bringing warmth and color to an otherwise difficult treatment journey.

“To families facing something similar, I want to say this: no matter how complicated or rare the disease is, keep looking for answers and don’t give up on finding a way forward for your child. Trust an experienced medical team.” These are the words Xiaole’s mother most hopes other families in difficult situations can hear.

Thank-you letter from Xiaole’s mother