41, may (a pseudonym) almost to despair. The sudden high fever repeatedly, put her into a nightmare. The doctor diagnosis is acute lymphoblastic leukemia, Philadelphia chromosome positive, T315I mutation. After nearly four months to three cycles of chemotherapy, after spending more than $500000, everything is back to the origin. Cancer cells in her body remained. Amy's husband for her launched an online fundraising goal for 1 million yuan. Their last hope to bet on in the CAR was still in the stage of clinical trials - T therapy, the hope can win the chance of hematopoietic stem cell transplantation. "Hope can be like the American girl Emily miracle."
Two "FeiYang" cases of hope
CAR - T, full name is the Chimeric Antigen Receptor T - Cell Immunotherapy, namely the Chimeric Antigen Receptor T Cell immune therapy. This innovative therapy in recent years in the world, was used to study the treatment of leukemia and other malignant tumors: by collecting the patient's own immune T cells, in vitro genetic engineering renovation, express related chimeric antigen receptor (CAR), and then back to the patient's body, to precision kill cancer cells.
"In 2011, the New England journal of medicine published articles with the CAR - T in the treatment of 3 cases of leukemia." The second people's hospital of guangdong province haematology department director Mr Cheung tsing led the team from late 2015 clinical research about CAR - T. Recently, a study of their results, published in the journal Medicine, this also is in guangdong region in international academic journals published the first CAR - T academic papers. Paper, according to a successful CAR - T cell therapy to treat the two cases of recurrence of Philadelphia chromosome positive acute gonorrhea.
Philadelphia chromosome is due to a normal chromosome arm of chromosome translocation formation, for the first time by the researchers in the Philadelphia area leukemia the crowd found the name. FeiYang rush drench leukemia accounts for about 20% of adult acute drench leukemia patients, such as poor response to treatment, and patients with easy relapse, under the existing chemotherapy means long-term survival rate is only less than 20%, in clinic was identified as "high risk".
In recent years, on the basis of the tyrosine kinase inhibitor (TKI) targeted therapy and chemotherapy has greatly improved the FeiYang rush drench leukemia treatment complete response rates for the first time, but for relapse after hematopoietic stem cell transplantation patients and relapse patients to TKI resistance, the current lack of effective clinical treatment, the patient mortality is higher.
Mr Cheung tsing introduction, the paper published in the journal Medicine, in both cases belong to this type. For 39 years old female, 1 patients resistant to first and second generation of TKI inhibitors, conventional chemotherapy not see results, ultimately through the CAR - T treatment and related means of chemotherapy, the patients successfully received relapse again after complete remission, and was followed by a hematopoietic stem cell transplantation. 29 year old male, 2 patients undergoing in half of the relapse after hematopoietic stem cell transplantation, still worse after taking the second generation of TKI inhibitors. After a CAR - T after treatment, the patients received complete remission, and reach the tiny residual disease negative (MRD), showed a good prognosis.
Difficult adult leukemia
Mr Cheung tsing, director of the introduction, there are three indexes to describe the disease clinical curative effect, the response rate, namely let the patient free from disease states, 2 it is the recurrence rate, the third is the long-term survival rate. For adult rush drench leukemia, if don't do hematopoietic stem cell transplant, while 60% 70% recurrence; 5 years of survival rate under 20%. And more cruel, even do the transplant, the recurrence rate is around 40%, means that almost half of all patients facing the risk of recurrence.
Like other cancers, leukemia because the hair cause of disease is difficult to clear so far. "Statistics show that 6 and 12 years old is leukemia incidence peak, another peaks at the age of 50-60 years old. But in the practical work, we have a lot in their 20 s and 30 s disease patients, but the lack of relevant epidemiological data." Such as science institute for a long time mentioned "66% of cancer is due to bad luck, cell DNA replication occurs in the process of splitting random errors", Mr Cheung tsing believes that the occurrence of leukemia can also explains. And adult leukemia relapse easily, which may be associated with treatment is difficult to remove leukemia cells, are also associated with individual immune function recovering.
And the sense of the CAR - T treatment is that it provides a chemotherapy for leukemia patients, radiation therapy and transplantation treatment way. At least can make more than half of symptomatic free from disease status in patients with refractory leukemia, for subsequent treatment in order to win the opportunity. Even if the future still has a relapse, so the CAR - can T use the second and third? This is also where science to verify.
There are many good news about the CAR - T. The first CAR - T treatment of leukemia girl EMILY Whitehead, has survived for 5 years and be the voice of the CAR - T therapy.
At the university of Pennsylvania and the children's hospital of Philadelphia did a CAR - T for the treatment of leukemia study, remission rate reached 90%.
First hospital affiliated to zhejiang university school of medicine, bone marrow transplant, director of the center for the Yellow River in 2016, a professor at the European society for blood and bone marrow transplantation (EBMT), reported 10 patients with use of the CAR - T therapy, remission rate is above 90%, survival rate of 90% a year, that figure is far more than the treatment the curative effect of using conventional scheme.
It is the good news, let may have a strong desire to survive. She has found fit like a glove hematopoietic stem cell donor. Ease as long as the illness, she would have the chance to do the transplant, even has the potential to cure.
CAR - T treatment management complications is the key
By the medical profession, however, had high hopes of CAR - T therapy, may still exist in the process of treatment of complications, the doctor's role is particularly important at this time.
Mr Cheung tsing, told reporters on the 2 patients with refractory leukemia were mentioned in the article, in the use of the CAR - T have taken place in the serious complications after therapy. "In clinical trials, also is to use the CAR - T die of the infection cases after treatment, the treatment exist considerable risk."
This risk comes from "cytokine storm", also known as cytokine release syndrome. Usually human T cells to kill other cells, such as bacteria, virus, will release a lot of proteins called cytokines, function more immune cells are activated to combat pathogens. This is the inflammatory response in clinic. Due to the CAR - T quick kill cancer cells, and release a large number of cytokines, can cause immune response, patients with clinical manifestations is super high fever is not retreated, if control is not good, may accident, doctor need to pay close attention to in the process of treatment, timely response.
Mr Cheung tsing introduction, the first female patients in a CAR - T after infusion, had been a cytokine storm, accompanied by such problems as the performance of the central nervous system abnormalities, 2 patients had persistent fever and hypotension.
Acute graft versus host disease (aGVHD) is a multisystem damage after bone marrow transplantation, systemic disease is primarily due to immune genetic differences between for receptor, immune active cells in the bone marrow transplantation, such as T cells proliferation in the body to a certain degree of some tissues and organs of receptor attack on the "friendly fire". Past medical literature thought, allogeneic CD19 CAR - T therapy can effectively treat B cell malignant tumor recurrence after transplantation, and will not result in a new graft versus host disease. Province second onset in the CAR - T treatment of 2 cases of recurrence after transplantation patients, observe the new graft versus host disease happening, and anti-rejection measures should be taken in a timely manner, to make things get effective control, the patient eventually got complete remission. This is also known in the industry for the first time report the CAR - T in the process of the treatment of patients with recurrence after transplantation rush drench leukemia produce new graft versus host disease.
Clinical application has yet to "rules of the game"
The heat of the CAR - T also attract a lot of capital. Incomplete statistics show that at least seven domestic listed companies invested in the CAR - T. Novartis, Juno and Kite in the United States became hot in this area. Reports suggest that the United States novartis and Kite company has respectively presented to the American FDA in early 2017, CAR - T treat urgent drench the commercialization of leukemia and lymphoma treatment application, the industry is widely expected to the FDA will approve the first CAR in years - T commercial therapy.
The second people's hospital of guangdong province onset used CAR - T technology for Stan game company in Shanghai. Si Dan relevant controller introduces, according to the company so far has been to Beijing, Shanghai, guangzhou, tianjin, zhejiang, hubei, and other 10 nationwide 3 armour hospital to complete the 41 cases of acute lymphocytic leukemia clinical trials, including 34 patients achieved complete remission, 33 to tiny residual negative disease (MRD), complete remission rate and small residual negative rate were 82.9% and 80.4% respectively.
In the treatment of refractory leukemia, CAR - T therapy is the major strides forward. "Although the long-term curative effect has yet to be the accumulation of cases, but at least the CAR - T therapy can create conditions for hematopoietic stem cell transplantation, otherwise, there is no chance to do transplant patients." Mr Cheung tsing said.
On January 12 this year, the national development and reform commission formally issued a "much starker choices-and graver consequences-in" biological industry development plan, put forward to the development of chimeric antigen receptor (CAR - T) T cell immune therapy such as biological treatment products, accelerate the immune cell therapy in acute B cell leukemia to demonstrate the application and promotion in the field of malignant tumor. "I was in the country's relevant planning separately produced a disease is rare, it also reflects the CAR side - T therapy might be expected."
It is reported, at present in guangzhou, in addition to the second people's hospital of guangdong province, zhongshan university, zhujiang hospital, southern medical university affiliated tumor hospital is to carry out the relevant clinical trials.
"Wei west after the incident, the domestic research process of cellular immune therapy almost to a standstill state", the CPPCC national committee, director of the xuanwu hospital neurosurgery LingFeng has called on the two sessions this year start review in this field to register as soon as possible.
Domestic CAR - T therapy clinical application could soon be approved? Stan race officials pointed out that commercial therapy, you first need to further define the nature of cell therapy departments and issuing and perfecting relevant regulatory policies. At present there are two sets of cell therapy in the context of the global main review mechanism: represented by American FDA European EMA tendency, based on the principles of drug evaluation model and represented by the Japanese ministry of according to the medical technology assessment model. The industry have a view that Japan's management mode is more advantageous to stem cell and cellular therapy technology innovation, application and the benefit of patients. In China due to historical reasons, cell therapy technology according to the ministry of health published in 2009 "medical technology clinical practice management method" in the third class medical technology, then did not release new division classification and regulatory authority in the field of cell therapy of guidance documents. Last December 16, the state food and drug supervision and administration bureau (CFDA) drug approval center released "cellular products research and evaluation of technical guidelines" (draft), provides a basis for further standardize cell therapy industry, however, when the guiding principle to officially promulgated timing, cell products specification is still no definite timetable. "What is the most suitable for China's national conditions and the future can promote innovation, and achieve innovation and healthy China's management mode, still need to management department and the pioneers in the field of active exploration."
And for may have a strong will to live, the hope is that Emily can reproduce and moving story. |
