Guide Interpretation·Professors Shen Zhixiang, Qiu Lugui, Zhang Qingyuan, and Xu Wei at the Roundtable: Pay attention to the "CSCO Guidelines for Raising Whiteness v2021" to reduce the risk of hematological tumor agranulocytosis and fever

Editor's note In 2021, under the coordination of the Guidelines Working Committee of the Chinese Society of Clinical Oncology, under the guidance of Academicians Jin Ming, Academicians Martin, Academician Xu Binghe, and Professor Shen Zhixiang, and the writings of Professor Qin Shukui and Professor Ma Jun, in the 2017 "Tumor Radiation and Chemotherapy Related On the basis of "Guidelines for the Standardized Management of Neutropenia", combined with China's national conditions and the latest evidence-based medical evidence updates, the "Chinese Society of Clinical Oncology (CSCO) Standardized Management Guidelines for Tumor Chemoradiation and Chemotherapy-Associated Neutropenia (2021)" ( Abbreviated as "CSCO Promotion Guide v2021", the same below), it is an important supplement to the CSCO guide series
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"Physician Daily" keeps up with the forefront and practices the norms, and specially invites Professor Shen Zhixiang (Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine), Professor Qiu Lugui (Hematology Hospital, Institute of Hematology, Chinese Academy of Medical Sciences), and Professor Zhang Qingyuan (Harbin) from the guideline expert group.
The Cancer Hospital Affiliated to Medical University) and Professor Xu Wei (The First Affiliated Hospital of Nanjing Medical University) interpreted the relevant content of the new guideline for hematological tumors
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01Professor Shen Zhixiang: G-CSF has a lower risk of inducing second tumors.
Whether hematopoietic growth factors (such as G-CSF) will induce second tumors is a clinical concern.
Professor Shen Zhixiang said that there are many reports of chemotherapy drugs causing second tumors.
However, there is currently no clear evidence that hematopoietic growth factors can lead to the occurrence of second tumors
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A randomized, prospective follow-up study in 2020 included 192 patients with severe aplastic anemia who received standard immunosuppressive regimen ± G-CSF treatment.
The median follow-up time was 11.
7 years.
A total of 9 patients developed MDS or AML, 10 Clonal cytogenetic abnormalities occurred in 7 patients, solid tumors occurred in 7 patients, and there were no significant differences in the incidence of second tumors and chromosomal abnormalities in patients who received or did not receive G-CSF
.

The cumulative incidence of MDS, AML, or solitary cytogenetic abnormality was 8.
5±3% in the G-CSF group and 8.
2±3% in the non-G-CSF group at 15 years of follow-up, P = 0.
90
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1 This study confirmed that G-CSF caused no difference in the risk of second tumors compared with the blank group
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Conversely, the lack of G-CSF for the second tumor would lead to extremely low neutrophil counts and a near-term increase in mortality
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Prof.
Zhixiang Shen emphasized that clinicians should rationally apply G-CSF under the guidance of the "CSCO Whitening Guidelines v2021" to reduce the risk of FN and avoid the death of patients due to serious infection during treatment, and should not be overly concerned about the second tumor
.

02Professor Qiu Lugui: Bendamustine is included in the risk category of FN, and G-CSF prevention improves the final curative effect.
The rate gradually increases, and the bendamustine ± rituximab (B ± R) regimen is an important targeted drug combination chemotherapy regimen
.

A study showed that the incidence of FN in NHL patients treated with the B±R regimen was as high as 16.
8%2, and the NCCN guidelines have listed the B±R regimen for NHL as a medium risk for FN.
The mustine regimen was included in the FN medium-risk category (Table 1)
.

At the same time, malignant hemolymphatic disease is a definite risk factor for FN in CSCO, and NHL patients treated with bendamustine regimen meet the "high risk factors of FN medium-risk chemotherapy regimen combined with increased risk of FN" and require G-CSF primary prevention
.

Targeted drugs combined with chemotherapy have significantly improved the prognosis of hematological tumors.
More attention should be paid to whether the risk of infection is increased when multiple drugs are combined for treatment
.

The occurrence of infection during treatment may lead to delay in treatment, thereby affecting the curative effect of patients.
No matter which plan is chosen, the curative effect can only be guaranteed if the treatment is carried out according to the course of treatment.

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Professor Qiu Lugui suggested that patients treated with targeted drugs combined with chemotherapy should use long-acting G-CSF prophylaxis 24 hours after the application of cytotoxic drugs to reduce the risk of FN or treatment delay, reduce hospitalization time, and improve the final efficacy
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In addition, NHL-related studies have shown that interruption of G-CSF prophylaxis in high-risk FN patients significantly increases the incidence of FN3, so the "CSCO Whitening Guidelines v2021" pointed out that high-risk patients should use G-CSF prophylaxis every cycle and avoid interruption
.

 03 Prof.
Zhang Qingyuan: During the use of G-CSF, it is necessary to carefully identify the leukemia reaction when the leukocyte count is more than 50X109/L.
It is especially necessary to identify the primary disease and the leukocytosis caused by G-CSF
.

When G-CSF is used in the course of tumor treatment, when white blood cells increase rapidly, infection should be excluded first.
Bacterial infection is easy to be complicated by tumor chemotherapy.
In case of sepsis, the white blood cell count can reach more than 100×109/L
.

Secondly, it is necessary to rule out that the patient is in the recovery period of agranulocytosis.
In the process of G-CSF treatment, immature granulocytes may appear in the peripheral blood, and occasionally the white blood cell count exceeds 50 × 109/L and lasts for 1-3 weeks
.

Finally, it is necessary to rule out poor control or recurrence of hematological diseases by other testing methods such as flow cytometry and genetics
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Professor Zhang Qingyuan pointed out that the increase of leukocytes during G-CSF treatment generally does not require special treatment
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Leukemia-like reaction is a rare adverse reaction of G-CSF newly added in "CSCO Whitening Guidelines v2021".
The patient's peripheral blood leukocytes can reach more than 50×109/L, and the white blood cell count can return to normal after G-CSF is discontinued
.

The use of G-CSF will not directly lead to the white blood cell count exceeding 100x109/L, and leukocyte apheresis can be considered to avoid leukocyte stasis when intractable hyperleukemia occurs
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In clinical practice, careful identification and precise treatment are required
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04Professor Xu Wei: The incidence of FN in hematological tumors is high, and the management level needs to be further improved.
FN is relatively common in hematological tumors.
The incidence of FN in patients with hematopoietic malignancies after chemotherapy for ≥ 1 course exceeds 80%.
The cumulative incidence was as high as 81.
9% (Figure 1) 4
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Almost 100% of patients with agranulocytosis in hematological tumors develop infection and fever if they have central venous catheterization, gastrointestinal mucositis, exposure to broad-spectrum antibiotics within the past 90 days, or duration of agranulocytosis >7 days
.

Figure 1 Analysis of the cumulative incidence of neutropenia with fever in patients with hematological diseases.
There are still many deficiencies in the management of neutropenia in hematological tumors
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Professor Xu Wei pointed out that, in many cases, doctors have insufficient understanding of the relationship between myelosuppression and chemotherapy, and insufficient prediction of myelosuppression after chemotherapy
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In China, the reduction of chemotherapy dose is still used to deal with post-chemotherapy myelosuppression, and insufficient attention is paid to the decrease in efficacy caused by chemotherapy dose reduction.
It is necessary to recognize that neutropenia is still the main reason for chemotherapy dose reduction or chemotherapy delay, and G -CSF to ensure the smooth progress of chemotherapy
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The "CSCO Guidelines for Ascension of Whiteness v2021" recommends that hematologic tumor agranulocytosis and fever are managed according to FN risk stratification, but the practical application may still be affected by external conditions such as drug availability, patient economic conditions, and insurance coverage
.

In the past, the dose and timing of G-CSF were highly arbitrary in clinical practice, and there were cases where different doses were given in response to reference body weight, commercial dosage forms, or increased white blood cells
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It is believed that with the update and implementation of the "CSCO Promotion Guidelines v2021", the use of G-CSF will be more standardized
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05Professor Shen Zhixiang concluded that G-CSF has a low risk of inducing second tumors, and clinicians should rationally apply G-CSF under the guidance of "CSCO Whitening Guidelines v2021" to reduce the risk of FN and prevent patients from dying due to serious infections during treatment
.

The "CSCO Whitening Guidelines v2021" included the bendamustine regimen of NHL in the FN medium-risk category, emphasizing the importance of using G-CSF every cycle to prevent and avoid interruptions in high-risk patients
.

Although leukemia-like reactions may occasionally occur during G-CSF treatment, they need to be carefully differentiated from infection and disease recurrence, and generally do not require special treatment
.

The update of the "CSCO Whitening Guidelines v2021" is more detailed and accurate than the previous version, and proposes a more in-depth and clinically suitable FN risk stratification and management plan, which effectively promotes the development of FN management in the blood field
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Expert Profile Prof.
Zhixiang Shen Former professor, professor of internal medicine, chief physician, doctoral supervisor, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine Journal (English version)" and other magazine editorial board Professor Shen has published more than 100 papers and monographs in domestic and foreign magazines, and edited "Malignant Hematology", "Lymphoma", "Concise Clinical Hematology", "Hematology".
He has published eight monographs including "Progress in Disease Research", and participated in the preparation of more than 10 monographs
.

He has successively won the second prize of the National Natural Science Award, the third prize of the Science and Technology Progress Award, the second prize of the Chinese Medical Science and Technology Award, the second prize of the Shanghai Medical Achievement Award, and the third prize of the Medical Achievement Award.
In 1999, he won the number of citations for a single international paper.
National third place individual
.

The first prize of China Medical Science and Technology Award in 2004, the first prize of Shanghai Medical Award in 2004, and the second prize of National Natural Science Award in 2004
.

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