When the name of a disease bears the words "refractory" and "severe", it is not difficult to imagine its danger.
In June last year, Yang Yang (pseudonym), a 5-year-old boy, was diagnosed with childhood refractory severe EBV-associated hemophagocytic syndrome, an overinflammatory response syndrome caused by immune abnormalities with a mortality rate of up to 70 percent.
After the conventional treatment was ineffective, the team of the Children's Medical Center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University "over-the-label" used a PD-1 antagonist (an immunotherapy drug), which freed Yangyang from danger and left a glimmer of life. Today, Yangyang has completed hematopoietic stem cell transplantation and is receiving treatment for anti-graft-versus-host disease. Yangyang's single father, Mr. Yan, alone bears the cost of treatment, gets up early and greedily delivers takeaways and casual work, hoping to repay the 250,000 yuan borrowed from the whole village as soon as possible.
"We all almost 'surrendered'"
"At that time, we all almost 'surrendered', and if we hadn't used this medicine boldly, the child's life might have been frozen." Professor Zhou Dunhua, director of the Children's Medical Center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, recalls the scene at that time.
Why is the disease so deadly? Zhou Dunhua introduced that EBV is a class of herpes virus, after some people with congenital genetic defects or abnormal immune systems are infected, lymphocytes and macrophages that were originally used to "defend against foreign enemies" are abnormally activated and proliferated, secreting a large number of inflammatory cytokines, forming a "cytokine storm", attacking the body's own tissues and organs, causing extremely serious damage.
To treat pediatric intractable severe Epstein-Barr virus-related hemophagocytic syndrome, it is first necessary to use drugs to "cure the symptoms", control the cytokine storm, keep the child's signs stable, and provide conditions suitable for hematopoietic stem cell transplantation to "cure the root cause". At present, hematopoietic stem cell transplantation is the only radical cure.
Since June last year, the medical team has undergone chemotherapy for Yangyang according to the hemophagocytic syndrome-1994 regimen, and the treatment has been ineffective for 4 weeks, and Yangyang still has repeated fever. From August to September last year, the team used two rescue therapies on Yangyang, which still did not work, Yangyang was repeatedly admitted to the intensive care unit, the highest body temperature exceeded 41 degrees Celsius, the three lines in the peripheral blood picture were extremely low, and the dependence on red blood transfusion and platelet therapy, especially the number of white blood cells, was "about equal to zero" in the past six months for 5 months.
On September 28, 2021, Yangyang reached an extremely critical state, with persistent high fever, shortness of breath, and mental atrophy. Zhou Dunhua admitted that most of the cases encountered in the past that were so serious have not been saved.
Through repeated literature consultations and many consultations, Zhou Dunhua and attending physician Zhang Ya stopped with the consent of Yangyang's family and treated Yangyang according to the experience of adults applying PD-1 antagonists.
Under the premise of giving positive rescue measures for the occurrence of aggravation, PD-1 antagonists are the last chance for Yangyang to survive. However, taking this treatment method may lead to a more unbalanced immune response in the child's body and "can't survive".
Fortunately, PD-1 antagonist therapy is effective for yangyang. Two or three days after receiving treatment, the peak of Yangyang's body temperature dropped, the interval between fevers became longer, white blood cells, hemoglobin, and platelets began to recover, and the EPV DNA in the plasma turned negative.
Seeing that Yangyang had once improved, considering that his family's economic conditions were not abundant, Zhou Dunhua wanted him to continue conservative treatment and wait for his own recovery. Unfortunately, Yangyang's condition is stable, but there will still be low-grade fever, mild elevation of cytokines, and hematopoietic stem cell transplantation is imperative due to the child's condition.
The new treatment has saved 4 children within 3 months
On December 21 last year, Yang Yang received a cord blood transplant from a non-blood donor, but since the fourth day after the operation, he began to have persistent high fever, frequent choking cough, increased heart rate, and convulsive attacks, and his condition was critical again. The blood and transplant specialist team immediately formed a discussion group to adjust the medication plan for Yangyang and carry out plasma exchange and other treatments to help him tide over the difficulties. At present, Yangyang vital signs are stable and is expected to be discharged from the hospital in the near future.
Fang Jianpei, academic leader and professor of the Children's Medical Center of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, believes that there are many comorbidities of Yangyang transplantation, which are related to multiple chemotherapy before transplantation, repeated infections, and serious organ damage. "If conventional treatment is ineffective, whether the use of PD-1 antagonists as early as possible can reduce the damage to the child's body by repeated chemotherapy and win more time and opportunities for subsequent hematopoietic stem cell transplantation, which is worth further study."
Fang Jianpei introduced, the use of PD-1 antagonists for the treatment of EBV-related severe refractory hemophagocytic syndrome, the mainland research is at the forefront of the world, Sichuan University West China Hospital last year reported for the first time 7 cases of adults using PD-1 antagonists for the treatment of EBV-related severe refractory hemophagocytic syndrome, of which the youngest case is 15 years old. "There are definitely risks in the use of drugs for children, there are no related cases as a basis before, we also lack experience, and it is difficult to communicate with parents." Fortunately, Yangyang's parents have great trust in doctors. ”
"The success of yangyang treatment has accumulated experience and confidence for the team." Fang Jianpei introduced that since Yangyang, there are 3 other 2-4-year-old children in the center who have received PD-1 antagonists, the effect is very good, and they have been discharged from the hospital.
Zhou Dunhua revealed that the center is currently organizing a clinical study of PD-1 antagonists for the treatment of children with EPV-related severe refractory hemophagocytic syndrome, hoping to determine the effectiveness, safety and best use of the method through clinical research, and explore whether some children do not need hematopoietic stem cell transplantation after treatment with PD-1 antagonists.
The single father wanted to pay the whole village by working part-time
Although discharge is in sight, Yangyang's family faces another serious challenge – money.
Even when the illness was the most severe and the family was most desperate, Mr. Yan, as a single father, did not want to give up treatment. His family is in the countryside of Zhaoqing, he asked more than 20 households in the village, borrowed 250,000 yuan, and Yangyang's uncle also took out all his savings to help. The family of a child who had been treated at Sun Yat-sen Memorial Hospital of Sun Yat-sen University also donated 30,000 yuan after learning the news.
Up to now, Yangyang's treatment has spent more than 500,000 yuan before and after, and the follow-up optimism is expected to receive 6-9 months of anti-rejection treatment, spending 5,000-8,000 yuan per month, plus the cost of a family living in Guangzhou, a total of tens of thousands of yuan.
Nowadays, Yangyang is mainly taken care of by his grandmother, and Mr. Yan breaks himself into two halves, on the one hand, he works as a takeaway rider, and in his free time, he also goes to the mall to help people carry fruits and vegetables and do odd jobs. Talking about the future, the 32-year-old looked up and said: "I hope that my children will grow up healthy in the future and will not get sick again." It doesn't matter if I work hard, but the borrowed money must be repaid. ”
[Reporter] Zhong Zhe
[Correspondent] Lin Weiyin Zhang Yang
【Author】 Zhong Zhe
Guangdong health headlines