When "Vernal Equinox" Meets "Platelet Day" | Professor Fang Jianpei Talks about Children's ITP Management

Today's spring equinox, the earth is full of flowers, it is a good time to embrace nature and go outing.

But there is such a special group of children-children with immune thrombocytopenia (ITP) often need to be cautious everywhere, and cannot fully enjoy this great spring.

It coincides with the annual "China Platelet Day" on March 20.
Yimaitong specially invited Professor Fang Jianpei to talk about the single-center experience of the treatment of children ITP with itrobopar, which was published by the team recently.
1, to talk about the management of children with ITP.
Hope It can help children with ITP to embrace the beautiful "spring" with peace of mind.

Professor Fang Jianpei, doctoral tutor, professor, and chief physician of Sun Yat-sen University, Director of Pediatrics, Sun Yat-sen Memorial Hospital of Sun Yat-Sen University, Director of Pediatric Hematology, National Children's Medical Center, Hematology and Oncology Specialist Alliance, Member of the Chinese Medical Association's Medical Appraisal Expert Bank Member, Chinese Medical Association Pediatrics Branch , Chairman of the Primary Pediatric Development Committee, Former Chairman of the Pediatric Branch of the Guangdong Medical Association, and Leader of the Hematology Specialty Group of the Branch, Member of the Standing Committee of the Pediatric Clinic and Health Care Branch of the Chinese Eugenics Science Association.
The diagnosis and treatment status of children with ITP.
Primary ITP is an acquired self The annual incidence of immune and hemorrhagic diseases in children is about 4 to 5 per 100,000, which is higher than that in adult patients2.

There is no large-scale population-based epidemiological data survey in China, but domestic epidemiological data in South Korea and Japan in recent years show that the incidence of childhood ITP is 14.
3 per 100,000 person-years and 8.
4 per 100,000 person-years, respectively.
,4.

Although childhood ITP is a benign self-limiting disease, 80% of cases can return to normal platelet counts within 12 months after diagnosis, but there are still about 20% of children whose disease course lasts for more than 1 year.
This part of children needs to be vigilant.
Bleeding, very restricted activities, significantly affecting the quality of life2.

Since ITP is mostly self-limiting, treatment depends more on the symptoms of bleeding than on the number of platelets.

When PLT ≥ 20×109/L and there is no active bleeding, it can be observed and followed up first, and no treatment will be given.

Conventional treatment options for children with ITP usually refer to the results of adult drug research.
Consider using first-line drugs including hormones and immunoglobulins.
Second-line drugs are mainly platelet-promoting and immunosuppressive drugs, such as azathioprine and cyclosporine A.
, Cyclophosphamide and rituximab, etc.

However, no matter which kind of treatment drug is used in children with ITP, the research data is very limited.

Especially for patients with chronic ITP in children, they need to pay more attention to safety while paying attention to the efficacy in the treatment process.

The adverse reactions of hormones and immunosuppressive agents are undoubtedly more severe for children.

In recent years, the application of thrombopoiesis-promoting drugs such as Eltrombopag has provided a new and safe treatment option for patients with ITP2.

Real-world data on the treatment of Chinese children with ITP by itrobopar are freshly released.
Two previous international multi-center, double-blind, placebo-controlled trials of itrobopar in children with ITP lasting more than 6 months have shown (PETIT/PETIT2) , Eltroipopag can increase the platelet count of children with ITP over 2 years old, reduce bleeding symptoms, and is well tolerated5,6.

However, the above studies did not include Chinese children with ITP, and there is still insufficient evidence for the efficacy and safety of Itrobopar in the treatment of Chinese children with ITP, especially for Chinese research data under the age of 12 years.

Recently, Professor Fang Jianpei’s team from Sun Yat-sen Memorial Hospital of Sun Yat-sen University published retrospective data on the treatment of Chinese children with ITP in a single center of Itrobopar1.

Rapidly ascending, reducing bleeding This retrospective, single-center study included 30 children with ITP with a median age of 7 years who were treated with Eltroipopag.

The results of the study showed that 83.
3% achieved platelet count >50×109/L at least once without salvage treatment.

The median onset time is 14 days (7-35 days).

4 weeks after the start of treatment, the median platelet count was 55×109/L (15~146×109/L), 30% of patients achieved partial remission (PR), and 17% of patients achieved complete remission (CR); end of treatment for 12 weeks At that time, the median platelet count was 78×109/L (20-310×109/L), 36.
7% of patients achieved PR, and 36.
7% of patients achieved CR.

The initial response rate (week 12) was 73.
3%3.

Accurate dosage, convenient and safe The treatment dosage selection of the center of etrobopar, refer to the "Guidelines for the diagnosis and treatment of primary immune thrombocytopenia in children (2019 edition)": the starting dose of etrobopar for children 6 years and older is daily The starting dose of 50 mg, 1 to 6 years old or children weighing less than 27 kg is 1.
5 mg/kg·d.

Once the treatment with Eltropopag is started, it can be increased by 12.
5 mg every 2 weeks to achieve a platelet count> 50×109/L and not exceed the target range of 150×109/L.
The maximum dose is 75 mg per day.

If the platelet>150×109/L, the target platelet range can be reached by reducing 12.
5mg every 2 weeks.
If the platelet count exceeds 400×109/L, the treatment will be interrupted.
When the patient’s platelet count drops below 150×109/L, Increase the dose based on 12.
5 mg to resume treatment3.

In terms of safety: the overall tolerability is very good.
Only 1 patient (3.
3%) experienced vomiting during treatment, and no headaches and other serious adverse events were found.

One case (3.
3%) had a transient elevation of transaminases (more than twice the normal value), but there were no clinical symptoms and direct bilirubin elevation.

After temporarily reducing the dose of Eltropopag, transaminase returned to normal.

No patients withdrew from the study due to adverse events.

No malignant tumors or thrombosis were found during the study period.

Megakaryocyte count ≥100/slice and Treg% ≥4.
5%, better effect Univariate analysis showed that among 20 patients with megakaryocyte count ≥100/slide, 61.
8% patients had sustained remission, and 10 had megakaryocyte counts < Only 40% of patients with 100/slide had a lasting remission (P=0.
047).

Among the 18 patients with Treg%≥4.
5%, 75.
8% had a lasting response, while only 31.
2% of the 12 patients with Treg%<4.
5% had a lasting response (P=0.
037).

Multivariate analysis also showed that the megakaryocyte count ≥100/piece (RR=4.
281, 95%CI 1.
184-15.
473, P=0.
027) and Treg%≥4.
5% (RR=4.
355, 95%CI 1.
217-15.
589, P=0.
024 ) Is an independent prognostic factor that affects the continued remission of children3.

A message from experts: Severe bleeding in children with ITP can occur at any location and at any time during the course of ITP.
Bleeding is an important clinical manifestation of children with ITP.
Even 6 months after diagnosis, the bleeding rate is still as high as 34%7.

Severe children may also have occult bleeding in the gastrointestinal or urinary tract, and the incidence is significantly higher than that of significant bleeding8.

The spring is just right, but the children who should have been arrogant have suffered from ITP and are afraid of bleeding out of outdoor sports.
The quality of life of parents and children is very low.

It is reported in the literature that 19% of children with ITP never participate in any sports, and only 56% of children participate in contact sports9.

The bleeding risk of patients with ITP is related to the platelet count10.
Eltroipopag is a small molecule non-peptide TPO-RA that non-competitively binds to MPL and promotes platelet production.

Previous foreign studies have shown that Eltropapax can significantly increase platelet counts and reduce the risk of bleeding in patients with ITP11.

However, the efficacy of Eltrombopag in Chinese children with ITP is still unclear.

The conclusions of this retrospective study of our center are consistent with foreign studies, further confirming the lifting effect of itrobopar, and bringing good news to Chinese children with ITP, so that children with ITP can also have fun in the spring! References: 1.
Chen M, Fang JP, Zhou CX, Li XY, Lin SF, Xu LH.
Efficacy and safety of eltrombopag in the treatment of Chinese children with chronic immune thrombocytopenia.
Hematology.
2021 Dec;26(1):31 -36.
doi: 10.
1080/16078454.
2020.
1856511.
PMID: 33357172.
2.
Guidelines for the diagnosis and treatment of primary immune thrombocytopenia in children (2019 edition) 3.
Lee JY, Lee JH, Lee H, et al.
Epidemiology and management of primary immune thrombocytopenia: A nationwide population-based study in Korea[J].
Thrombosis Research, 2017, 155:86.
4.
Higashigawa M, Maeyama T, Yoshino A, et al.
Incidence of childhood primary immune thrombocytopenic purpura[J].
Pediatrics International Official Journal of the Japan Pediatric Society, 2015, 57(5):1041-1043.
5.
Bussel JB, de Miguel PG, Despotovic JM, et al. Poke "read the original text" and we will make progress together