PNH Famous Doctors Lecture Phase 3 Professor Zhang Fengkui: Treatment and follow-up of PNH

For a long time, China has been lack of effective drugs for the treatment of PNH.
Once patients have hemolysis, in order to control acute severe hemolysis, they can only use very conservative and traditional drugs such as glucocorticoids.
Long-term use of hormones will lead to hormone dependence and hormone-related.
Adverse reactions, the quality of life of the patient will also be severely reduced, and the psychological pressure will also be great
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The emergence of complement inhibitors is one of the biggest advances in the field of PNH in recent years.
Will its application change the current status of PNH treatment? This issue of "PNH Famous Doctors Lecture" Yimaitong invites Professor Zhang Fengkui from the Hematology Hospital of the Chinese Academy of Medical Sciences to share on the treatment and follow-up of PNH! Professor Zhang Fengkui, Director and Chief Physician, Anemia Center, Hematology Hospital, Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences), PhD supervisor, PhD supervisor, National New Drug Clinical Trial Institute, Member of the Red Blood Cell Disease Group, Chinese Society of Hematology, Chinese Society of Integrative Medicine Blood The vice chairman of the academic branch, the deputy editor-in-chief of the Chinese Journal of Hematology, the editorial board of the Journal of Leukemia and Lymphoma, the editorial board of the International Journal of Blood Transfusion and Hematology
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There is a deep understanding of the pathogenesis of PNH in China, but there has been a lack of effective treatments for a long time and cannot effectively inhibit hemolysis.
Therefore, the domestic treatment strategy is mainly to minimize the induction of acute hemolytic attacks
.

For patients with acute hemolytic attacks, protect important organs to avoid serious complications; for patients with long-term persistent intravascular hemolysis, due to lack of hematopoietic materials, the quality and quantity of red blood cells produced are problematic, and hematopoietic materials need to be supplemented appropriately
.

In addition, PNH patients can also try treatments that can reduce the destruction of red blood cells, such as sodium bicarbonate, vitamin E, etc.
, but these treatments have no evidence-based medical evidence and are only clinical empirical treatments
.

For patients with acute hemolytic attacks, you can try to use glucocorticoids for a short time to reduce acute hemolytic attacks, but glucocorticoids cannot be used in large doses for a long time.
After the acute hemolysis has passed, you need to stop the drug as soon as possible, and use glucocorticoids for a long time to cause infection.
The risk will increase, and infection will induce acute hemolytic attacks.
Therefore, long-term use of hormones is more harmful than effective, and long-term use is not recommended
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Anticoagulant therapy can be used for PNH patients with embolic complications, but this therapy is not supported by evidence-based medicine.
Individualized efficacy and risk assessments should be made for PNH patients
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Hematopoietic stem cell transplantation is the only cure for PNH, but hematopoietic stem cell transplantation can only be applied to patients with severe hemolysis, serious complications, or doctors who judge the disease to have a greater impact on survival
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These patients must meet the conditions of being young and having suitable donors to reduce the risk of transplantation as much as possible in order to implement the strategy of hematopoietic stem cell transplantation
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The emergence of complement inhibitors is one of the biggest advances in the field of PNH in recent years
.

PNH is caused by a mutation of the PIG-A gene located on the X chromosome in one or more hematopoietic stem cells, and PIGA is required for the synthesis of glycosyl phosphatidylinositol (GPI) that anchors certain proteins on the cell surface
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Therefore, abnormal hematopoietic stem cells and their progeny lack all the normally expressed GPI ankyrin
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It is precisely because of the lack of GPI-linked complement regulatory proteins (CD55 and CD59) that the clinical features of PNH are complement-mediated intravascular hemolytic anemia and hemoglobinuria
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Therefore, inhibition of the complement system may interrupt the mechanism of complement destruction of red blood cells, thereby achieving the purpose of treating PNH
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As early as 2007, the complement C5 inhibitor eculizumab has been marketed abroad for the treatment of PNH
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Eculizumab has a very good effect.
Many patients who use eculizumab have a cliff-like decline in lactate dehydrogenase levels, blood cell counts reach normal levels, and more patients have close to normal hemoglobin, and blood transfusion dependence is reduced
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The emergence of eculizumab was a revolutionary event in PNH treatment and was a great success.
After that, the long-acting complement C5 antibody ravulizumab was also marketed abroad
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Compared with eculizumab and ravulizumab, the target of crovalimab is different.
It can overcome the existing shortcomings of eculizumab and ravulizumab.
It is a very potential PNH therapeutic drug.
The second phase of crovalimab abroad Clinical trials have been completed, and domestic clinical trials are steadily carried out.
Hematology Hospital of the Chinese Academy of Medical Sciences has also participated in the clinical trial.
The preliminary results show that many patients who are ineffective in the treatment of eculizumab can still get very good results from the use of crovalimab.
Good efficacy
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Moreover, compared with eculizumab, the frequency of administration of crovalimab is significantly reduced.
Patients do not need to come to the hospital every two weeks, but can be changed to once a month.
At the same time, the administration of crovalimab is subcutaneous injection, which is very convenient After the drug is on the market, patients can even self-help treatment at home, which significantly reduces the frequency of medical treatment and treatment costs for patients
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It is hoped that this clinical trial can obtain good results as soon as possible and benefit PNH patients earlier
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For subclinical PNH, it is mainly used to treat the primary disease of bone marrow hematopoietic failure.
If PNH is associated with bone marrow hematopoietic failure, it is necessary to determine whether the main cause of blood cell reduction is PNH hemolysis or bone marrow hematopoietic failure, and then treat the main cause
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Standard follow-up of PNH patients Follow-up of patients is affected by many factors
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At present, the main reason for the relatively poor compliance of PNH patients is the lack of effective treatments
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Nevertheless, clinicians should require PNH patients to go to the hospital every three to six months for corresponding examinations to monitor their hemolysis, bone marrow hematopoietic failure, and thrombotic complications, and provide patients with active supportive treatment as much as possible Improve patients' anemia
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If there is an effective treatment method, the hardship caused by PNH can be resolved, and the patient will definitely follow the doctor's advice and go to the hospital for corresponding examinations on a regular basis
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It is believed that as the complement C5 antibody gradually enters China, after effective treatments are available, patients' compliance will become better and better
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Regarding PNHPNH, an acquired hematopoietic stem cell gene mutation caused by a defective red blood cell membrane disease, the 10-year survival rate of domestic patients is about 70%
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The clinical manifestations are mainly intravascular hemolytic anemia, which may be accompanied by symptoms such as thrombosis, renal insufficiency, and pulmonary hypertension
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Typical patients have characteristic intermittent nocturnal hemoglobinuria
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There are more male patients than females in China, and the peak age of onset is 20-40 years old
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The patient suffers from pain and suffering for a long time, and the quality of life is low
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Many patients are in the golden age of their lives.
As the backbone of their families, they have lost their labor force due to illness, causing a great social burden
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References: 1.
Journal of Mudanjiang Medical College, 1997, Volume 18, Issue 3 P-7 Report on the Availability of Drugs for Rare Diseases in China (2019) 2.
Ge, et al.
Ann Hematol (2012) 91:1121–1128 Fu, et al.
J Clin Lab Anal.
2020;34:e230083.
Parker, et al.
Hematology Am Soc Hematol Educ Program.
2016 Dec 2;2016(1):208-216.
4.
Guidelines for the diagnosis and treatment of rare diseases in China (2019 edition) 5.
Griffin M, Munir T.
Ther Adv Haematol.
2017;8:119-126.
6.
Hill A et al.
Nat Rev Dis Primers.
2017;3:17028.
RECOMMEND recommended reading 1.
PNH Lecture Hall of Famous Doctors Issue 1 | Professor Fu Rong: The pathogenesis and treatment mechanism of PNH 2.
PNH Famous Doctors Lecture 2 | Professor Zhang Fengkui: The current status of PNH and the main points of diagnosis stamp "Read the original", we will make progress together