A Twenty Years Epidemiology Study of 2^nd Hematological Malignancies Post to the Initial Tumor Treatment: Report from Southern China Single Cancer Group

Objective: To investigate the clinical features of 2^nd hematological malignancies post to the initial cancer treatment.

METHODS: A retrospective study was performed to analyze the available clinical data of 116 patients diagnosed with 2^nd hematologic malignancies after treatment of various malignant tumors from June 1998 to June 2018 at Sun Yat-sen University cancer center.

RESULTS: The characteristics of the 116 patients diagnosed with 2^nd hematological cancer post to initial cancer treatment were indicated as following: 62 males and 54 females. The primary tumor category was grouped as (according to ICD-10 International Disease Code): i) 23 cases of head and neck malignant tumors (14 cases of nasopharyngeal carcinoma (C11), 3 cases of laryngeal carcinoma (C32), 3 cases of thyroid carcinoma (C73), 3 cases of other head and neck tumors (C00-10, 12-13), ii) 7 cases of chest malignant tumors (2 cases of esophageal cancer(C15), 4 cases of lung cancer and bronchial carcinoma (C33-34), 1 case of chest wall tumor(C49), iii) 31 cases of GI malignant tumor (7 cases of gastric cancer(C16), 7 cases of hepato-biliary cancer(C22-24), 17 cases of intestinal cancer(C18-21), iv) 17 cases of breast cancer (C50), v) 12 cases of gynecological malignancies (4 cases of ovarian cancer, 7 cases of cervical cancer, 1 case of endometrial cancer), vi) 7 cases of malignant genitourinary tumor (C61-68), vii) 15 cases of hematological malignancies (12 cases of lymphoma(C81-85), 3 cases of chronic lymphocytic leukemia(C91.101) ), viii) others: 2 cases of sarcoma (C80 03), 1 case of melanoma (C43), 1 case of glioma. The subtype of 2^nd hematological malignancies were indicated as following: 33 patients with acute myeloid leukemia, 9 patients with myelodysplastic syndrome, 8 patients with acute lymphoblastic leukemia, 4 patients with chronic lymphocytic leukemia, 3 patients with chronic myeloid leukemia, and 2 patients with multiple myeloma. The rest 57 cases were non-Hodgkin's lymphoma.

The median duration time for the 116 patients from starting treatment of the first tumor to the happening of the secondary hematologic tumor was 51 (range: 7-297) months, with an overall survival time 32 (range: 1-114) months. For the 50 cases diagnosed with 2^nd acute leukemia and myelodysplastic syndrome, the interval period time was 33 (range: 7-167) months. The overall survival time for the 50 cases is 12 (range: 1-61) months. The 1-year and 3-year overall survival rate was 44.5% and 11.7%, respectively.

Interestingly, of the patients' initial treatment options among the 50 cases, eight patients did not receive radiotherapy and chemotherapy beside surgery removal of the 1^st tumor. The mean survival was 36.7 ± 12.1 months in the non-radiotherapy or non-chemotherapy group (N=8) while 12.1 ± 1.9 months in the radiotherapy and/or chemotherapy group (N=42; P = 0.032). At diagnosis of the 2^nd hematological cancer of the 50 patients, i) 77% of patients had the decreased platelet count and 60% had grade III-IV platelet thrombocytopenia; ii) 82.5% of patients had elevated or decreased white blood cells count: while 40% patients had increased white blood cells >20*10^9/L, 22.5% cases had grade III-IV leukopenia; There are 72.5% patients has anemia with Hgb<9g/dL.

The median duration time from the initial 1^st tumor treatment to the occurrence of the 2^nd non-Hodgkin's lymphoma (N=57) was 74 (range: 7-297) months, with a median survival time of 65 (range: 1-114) months. The 1-year, 3- year and 5-year overall survival rate were 85.6%, 70.5%, 56.3%, respectively. For the diagnosis of 2^nd non-Hodgkin's lymphoma, 3.5% (2/57) of the patients were found by annual physicals, 61.4% (35/57) patients presented with superficial lymphadenopathy and 35.1% (20/57) cases complains of non-specific systemic symptoms: fever, night sweating, and decreased body weight.

Conclusion: In general, the outcome of secondary hematological tumors is poor. However, patients who did not receive chemo- or radiotherapy during the initial tumor treatment had a longer survival than those who did. The risk factors, potentially type of chemo-agent and cumulative dosage of drugs, which may contribute to the occurrence of 2^nd hematological malignancies, should be fully explored before formulating the initial tumor treatment plan.