Traditional Chinese Medicine Is Used to the Maintenance Therapy of Diffuse Large B Cell Lymphoma

Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common malignancy hematologic disease in China. At present, the NCCN recommended first-line therapy to DLBCL is: rituximab combined with cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP) or etoposide, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-EPOCH). For the medium-risk and high-risk adult patients, autologous hematopoietic stem cell transplantation (auto-HSCT) is recommended as consolidation therapy. However, no maintenance therapy is recommended. A number of clinical trials of rituximab or lenadomide for maintenance therapy in DLBCL have been carried out, but the exact effect has not yet been confirmed. Traditional Chinese medicine (TCM) is a unique treatment in China. For economic or other reasons, many Chinese patients with DLBCL choose TCM as maintenance therapy after induction chemotherapy or auto-HSCT. Here we will introduce the application of TCM in maintenance therapy of DLBCL.

Methods: We conducted a retrospective analysis of 87 (34 males and 53 females; age ranged from 16 to 86 years old) consecutive patients diagnosed with de novo DLBCL treated at Zhongda Hospital Affiliated to Southeast University between January 2013 and March 2019. All patients were diagnosed by pathology and graded by international prognostic index (IPI) score. All patients enrolled in our cohort were received at least 4 cycles of R-CHOP or R-EPOCH regimen. Then we compared the outcome of maintenance therapy with TCM or rituximab in DLBCL patients who were received standard induction chemotherapy.

Results: Survival analysis showed that the overall survival (OS) in maintenance group (including TCM and rituximab) was significantly different from that in non-maintenance group (P=0.036). Among them, the patients received maintenance treatment with rituximab or TCM did not relapse and were still in survival state, but there was no significant difference in OS between the two groups (P>0.05). Because of the short follow-up period of this group, only 5 patients chose TCM and 7 patients chose rituximab for maintenance. Therefore, we will focus on two successful cases of TCM maintenance therapy.

Case 1. A 57-year-old woman was diagnosed with DLBCL (stage Ⅳ, group B) in December 2012. After 3 cycles of R-EPOCH regimen chemotherapy, she was assessed as complete remission (CR) by PET/CT. Then auto-HSCT was followed in in May 2013. However, the patient suffered with fatigue and loss of appetite in July 2013. Also, decreased hematopoietic cells were found. Although G-CSF, cyclosporin and androgen were used to stimulate hematopoiesis, the hematopoietic function was still not fully restored. Thinking about the toxic and side effects of chemotherapy, we treated the patient with TCM as maintenance therapy and physical conditioning. After 3 months, the hematopoietic function returned to normal gradually. The symptoms of fatigue and loss of appetite were significantly improved. Then she continued the treatment of TCM for 2 years. The patient reviewd every year and was still in CR state.

Case 2. A 46-year-old man was diagnosed with DLBCL (stageⅢ, group B) in June 2015. After 4 cycles of R-CHOP regimen chemotherapy, he was assessed as CR by PET/CT. Then auto-HSCT was followed in November 2015. Because of 2 months' bone marrow depression and skin rashes, the patient chose TCM as maintenance therapy from February 2016 to the present. Up to now, he was still alive and without disease progress.

Conclusion:

Even after first-line chemotherapy, about 30% high-risk DLBCL patients will be relapse. At present, no maintenance therapy is recommended yet, but more and more clinical trials on cancer-targeting drugs such as rituximab have been carried out these years. TCM is a therapeutic method with Chinese characteristics, which is reported to be used as adjuvant drugs for cancer chemotherapy. Maintenance therapy of TCM is a new option that is expected to be a more economical and effective alternative to rituximab. Due to the small sample size and short follow-up time, there is a certain bias. In the future, we will expand the sample size and extend the follow-up time to obtain more accurate clinical data to verify the effectiveness of TCM maintenance therapy.