In-hospital management of patients with thrombocytopenia due to hematological diseases (6) - Thrombocytopenia due to lymphoma chemotherapy

Author: Liu Jiajun, Department of Hematology, The Third Affiliated Hospital of Sun Yat-Sen
University
Lymphomas are malignant tumors of lymph nodes and/or extranodal lymphoid tissues, and are usually divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL)
.

The incidence of lymphoma in China is about 6.
68/100,000, and it is the eighth most common malignant tumor
.

The commonly used clinical treatment strategy for lymphoma is to use a sufficient amount and full course of intense combined immunochemotherapy and chemotherapy to achieve tumor remission in a short period of time
.

Tumor CIT refers to the inhibitory effect of antitumor chemotherapeutic drugs on bone marrow, especially on megakaryocytes, resulting in platelet count in peripheral blood <100×109/L
.

There are two main reasons for the evaluation of lymphoma CIT and the process of lymphoma CIT.
One is the inhibition of megakaryocyte production by chemotherapy drugs and the insufficiency of platelet production caused by the damage effect.
For example, fludarabine monotherapy for lymphoma resulted in idiopathic thrombocytopenic purpura (ITP) in 4.
5% of patients
.

CIT is significantly associated with high-dose chemotherapy and repeated chemotherapy, and usually occurs 6-14 days after the chemotherapy cycle
.

The evaluation and procedures of lymphoma CIT are similar to those of leukemia CIT (see In-hospital management of patients with thrombocytopenia due to hematological diseases (5)—thrombocytopenia due to chemotherapy in acute leukemia), but it should be noted that different chemotherapy regimens may cause The incidence of lymphoma CIT is different, such as ICE, AI (doxorubicin, ifosfamide), MAID (doxorubicin, ifosfamide, dacarbazine).
Early, and carboplatin, melphalan, nitrosourea, these drugs caused platelet nadir relatively late
.

In addition to traditional chemotherapy drugs and chemotherapy regimens, some new targeted drugs (botemumab, lenalidomide, and chidamide, etc.
) can also cause thrombocytopenia in combination with chemotherapy
.

Even with the same chemotherapy regimen, with the increase of chemotherapy courses, the thrombocytopenia caused by the same patient will become more and more serious, which is mainly due to the continuous bone marrow suppression caused by the accumulation of chemotherapy drug doses
.

The clinical manifestations of lymphoma CIT are related to the number of platelets.
When the platelets are less than 10×109/L, there is a very high risk of spontaneous bleeding; when the platelets are less than 50×109/L, it can cause skin or mucosal bleeding, and surgical operations are often complicated by bleeding.
, cannot withstand surgical treatment and invasive procedures; when platelets are less than 100 × 109/L, and patients are given chemotherapy or radiotherapy, there will be concerns about aggravated thrombocytopenia and increased risk of bleeding
.

Treatment of lymphoma CIT In order to take into account the treatment of lymphoma, platelet growth factor and platelet transfusion are the first choice for lymphoma CIT treatment.
The second-line regimen considers chemotherapy dose reduction and/or chemotherapy delay
.

The treatment plan and medication precautions are similar to those of leukemia CIT (see In-hospital management of patients with thrombocytopenia due to hematological diseases (5) - Thrombocytopenia due to chemotherapy in acute leukemia).
Supplementation with rhIL-11 is used in the treatment of solid tumor CIT.
Patients with thrombocytopenia who do not meet the indications for platelet transfusion and patients with solid tumors should be treated with rhIL-11 when the platelet count is 25-75×109/L
.

The recommended dose is 25~50ug/kg, subcutaneous injection, once/d, for at least 7~10d, until the inhibitory effect of chemotherapy is completely disappeared and the platelets are ≥100×109/L or the platelets are higher than before treatment by more than 50×109/L time to discontinue the drug
.

Special Case Management Secondary prophylaxis should be initiated in patients at high risk of bleeding prior to initiation of the next cycle of chemotherapy
.

Those who meet one of the following conditions can use secondary prevention: (1) The lowest platelet value in the previous chemotherapy cycle is less than 50×109/L, (2) The lowest platelet value in the previous chemotherapy cycle is ≥50×109/L but <75× 109/L, meeting at least one of the following high bleeding risk factors, including a history of bleeding; receiving platinum, gemcitabine, and cytarabine anthracycline chemotherapy; targeted drugs that may lead to thrombocytopenia and thrombocytopenia Reduced combination of chemotherapy drugs; thrombocytopenia due to bone marrow infiltration of tumor cells; ECOG performance status score ≥ 2; previous or ongoing radiotherapy
.

Secondary prevention use method: (1) Start using rhTPO and/or rhIL-11 within 1-2 days after chemotherapy; (2) If the time of occurrence of the lowest platelet value is known, it can be used 10-14 days before the appearance of the lowest platelet value.
Subcutaneous injection of rhTPO, 300U/kg each time, once a day or every other day for 7-10 days
.

Precautions for using thrombopoietic drugs to prevent and treat lymphoma CIT: (1) Indications for platelet growth factor withdrawal: platelets ≥ 100 × 109/L, or until platelets increase by 50 × 109/L compared with before treatment; Patients with functional insufficiency are treated with a low cardiotoxic chemotherapy regimen; for patients with a history of fluid retention, congestive heart failure, atrial arrhythmia or coronary artery disease, especially elderly patients, thrombocytopenia during chemotherapy is not recommended.
Drugs with cardiac damage; (3) For lymphoma patients with high thrombosis risk, refer to the Chinese expert guidelines for the prevention and treatment of tumor-related venous thromboembolism, and prophylactic anticoagulation therapy can be given; (4) The timing of rhTPO administration depends on Depending on the duration of chemotherapy and the timing of platelet nadir, rhTPO may be sufficient after chemotherapy for short-course chemotherapy and/or delayed platelet nadir, but may be sufficient for long-course chemotherapy and/or earlier platelet nadir.
rhTPO needs to be given early before chemotherapy
.

Reference consensus: Chinese expert consensus on prevention and treatment of thrombocytopenia caused by lymphoma chemotherapy (2020 version) RECOMMEND recommended reading 1.
In-hospital management of patients with thrombocytopenia caused by hematological diseases (1) - immune thrombocytopenia 2.
Hematological diseases In-hospital management of patients with thrombocytopenia caused by blood system diseases (2) - aplastic anemia 3.
In-hospital management of patients with thrombocytopenia caused by blood system diseases (3) - hematopoietic stem cell transplantation 4.
Thrombocytopenia caused by blood system diseases In-hospital management of patients with acute leukemia (IV) - myelodysplastic syndrome