Editor’s Note: Therapy-related myeloid neoplasms (t-MN) are a distinct type of myeloid tumor that occur after cytotoxic or radiation therapy. In the 2022 WHO classification of hematopoietic and lymphoid tissue tumors, these were termed secondary myeloid neoplasms, including those related to cytotoxic treatment and genetic susceptibility. Compared to newly diagnosed AML, therapy-related AML (t-AML) has a poorer prognosis, including poor chemotherapy response, low rates of remission, and overall lower survival rates. From April 14-17, 2024, the 50th European Society for Blood and Marrow Transplantation (EBMT 2024) held its annual meeting in Glasgow, UK. Dr. Yan Shu from the team of Professor Deyan Liu at Hebei Yanda Lu Daopei Hospital presented a clinical study (abstract number 391) that demonstrated allogeneic hematopoietic stem cell transplantation significantly improved survival rates in patients with t-MN.
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Research Method
A retrospective analysis was conducted on the clinical data of patients with therapy-related myeloid neoplasms (t-MN) who underwent allogeneic hematopoietic stem cell transplantation at Hebei Yanda Lu Daopei Hospital from January 2019 to January 2023.
Research Results
The clinical characteristics of the patients are detailed in Tables 1 and 2. The study included 21 patients: 5 with myelodysplastic syndromes, 14 with acute myeloid leukemia (AML), and 2 with mixed phenotype acute leukemia. Among the AML cases, 7 were classified as M5, 2 evolved from MDS, and 1 from chronic myelomonocytic leukemia (CMML). There were 7 male and 14 female patients, with a median age of 36 years (range 4-55 years), and 16 patients were older than 14 years.
The distribution of primary tumor types was as follows: 8 cases of breast cancer, 2 cases of thyroid cancer, 2 cases of liver cancer, and 1 case each of kidney cancer, lung cancer, osteosarcoma, yolk sac tumor of the vagina, intracranial germ cell tumor, primitive neuroectodermal tumor, embryonal rhabdomyosarcoma, fibromatosis, and bladder cancer. The median interval between the primary cancer and the subsequent secondary myeloid neoplasm was 24 months (range 5-96 months).
Pre-transplant disease status included 3 patients in partial remission (PR), 9 in no response (NR), and 9 in complete remission (CR). Types of transplants performed were 5 from sibling matched donors and 16 from haploidentical donors.
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All patients successfully achieved hematopoietic engraftment after transplantation. The median time to white blood cell engraftment was day +13 (range 10-20 days), and the median time to platelet engraftment was day +14 (range 7-40 days). Post-transplant, 6 patients developed acute graft-versus-host disease (GVHD), with 4 cases being grade III-IV. There were 7 instances of leukemia relapse, and one patient achieved remission again after treatment for MRD relapse. As of the last follow-up on October 22, 2023, out of the 21 patients, 13 were alive and 8 had died. The overall survival rates at 1, 2, and 3 years post-transplant were 70.59%, 58.26%, and 58.26%, respectively, as shown in Figure 1.
The overall survival rates at 1, 2, and 3 years post-transplant for patients in the CR+PR group compared to the NR group were 82.50% vs. 66.67%, 73.33% vs. 55.56%, and 73.33% vs. 41.67%, respectively. Statistical analysis showed no significant differences between the two groups, with a P-value >0.05%, as depicted in Figure 2.
Analysis of the causes of death for the 8 deceased patients revealed the following: 5 patients died from leukemia relapse, 1 patient died from acute severe GVHD following NK cell infusion due to positive genetics, 1 patient died from viral encephalitis, and 1 patient died from infectious shock with pulmonary hemorrhage following a second transplant due to MDS relapse. Post-transplant maintenance therapy was administered to 4 patients, including 3 cases using azacitidine and 1 case using decitabine, all of whom are surviving without disease.
Research Conclusion
Therapy-related myeloid neoplasms (t-MN) typically have a poor prognosis and belong to a high-risk group. Conventional chemotherapy is often ineffective, and there is no standardized chemotherapy regimen. The pathogenesis of t-MN differs from that of primary MN and is closely related to genetic mutations in the primary disease and the impact of therapeutic agents. Early reports from the EBMT in 2009 on 461 cases of t-MN undergoing allogeneic transplantation showed a 3-year relapse-free survival rate of 33% and an overall survival rate of 35%. Multifactorial analysis revealed that adverse prognostic factors primarily included older age, abnormal cytogenetics, and disease non-remission. A study published by CIBMTR in 2010 analyzing 868 cases of HSCT data from 1990 to 2004, including t-AML (N=545) and t-MDS (N=323), showed a 5-year OS of 22% and a 5-year DFS of 21%. In 2015, the Italian Cooperative Study on Secondary Leukemias demonstrated that allogeneic hematopoietic stem cell transplantation significantly improved overall survival time, with a median survival time of 58.8 months, compared to only 12.1 months for patients not undergoing transplantation. Only 17% of t-MN patients received allogeneic hematopoietic stem cell transplantation. In 2016, Professor Finke analyzed 79 transplanted t-MN patients, showing a 5-year overall survival rate of 38% and a 10-year OS rate of 24%.
Allogeneic hematopoietic stem cell transplantation can improve t-MN outcomes. Our retrospective data from the hospital revealed a 3-year survival rate post-transplantation of 73.33%. Moreover, patients in remission before transplantation had a higher survival rate compared to those not in remission. Therefore, achieving complete remission before transplantation is the most crucial factor in improving transplant survival rates.
Dr. Deyan Liu
Director of Hematopoietic Stem Cell Transplantation Department, Lu Daopei Hospital
Member of the Stem Cell Engineering Technology Branch of the Chinese Biomedical Engineering Society
Member of the Hematologic Translational Medicine Professional Committee of the Chinese Anti-Cancer Association
Member of the Langfang Anti-Cancer Association and the First Drug Clinical Trial Safety Evaluation Professional Committee
With over 17 years of experience in hematology and hematopoietic stem cell transplantation, Dr. Liu has completed over 800 hematopoietic stem cell transplantation surgeries, with the youngest patient being 1 year old and the median age being 15 years old. He specializes in the application of allogeneic hematopoietic stem cell transplantation to various malignant hematological diseases, such as acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, and refractory and relapsed lymphoma. Dr. Liu has accumulated rich experience in treating non-malignant hematological diseases, including aplastic anemia, congenital pure red cell aplasia, paroxysmal nocturnal hemoglobinuria, and congenital immunodeficiency diseases. He has also conducted early work on allogeneic hematopoietic stem cell transplantation for various rare diseases, including familial erythroid syndromes, Langerhans cell histiocytosis, X-linked chronic granulomatous disease, and congenital keratosis combined with recurrent disorders. His key research direction is the enhancement of pre-transplant conditioning regimens for refractory and relapsed leukemia and lymphoma and the prevention and treatment of severe graft-versus-host disease (GVHD) after transplantation.
Dr. Shu Yan
Attending Physician, Hematopoietic Stem Cell Transplantation Department
Dr. Yan graduated from Xiamen University Medical College with a bachelor’s degree and received her master’s degree from the Department of Hematology at China Medical University. Since graduating in 2012, she has been working in the transplantation department of Daopei Medical Team and has participated in the completion of more than 350 allogeneic hematopoietic stem cell transplantations. Dr. Yan is proficient in common hematological diseases such as leukemia, MDS, AA, and ITP, and has extensive experience in the treatment of various hematopoietic stem cell transplantation programs and transplant-related complications. She completed a short-term international academic visit at the City Of Hope cancer center’s Blood Transplantation Center in the United States in 2022.
