Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia
This is a small phase I study examining the safety and efficacy of a cladribine (CLAD)-containing conditioning regimen prior to autologous hematopoietic stem cell transplantion (auto-HSCT) for patients with acute myeloid leukemia (AML). All patients, aged 15–54 years (median 32 years), had favorable...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1014306/full |
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| author | Yuan-Yuan Shi Zeng-Yan Liu Gui-Xin Zhang Yi He Ming-Zhe Han Si-Zhou Feng Rong-Li Zhang Er-Lie Jiang |
| author_facet | Yuan-Yuan Shi Zeng-Yan Liu Gui-Xin Zhang Yi He Ming-Zhe Han Si-Zhou Feng Rong-Li Zhang Er-Lie Jiang |
| author_sort | Yuan-Yuan Shi |
| collection | DOAJ |
| description | This is a small phase I study examining the safety and efficacy of a cladribine (CLAD)-containing conditioning regimen prior to autologous hematopoietic stem cell transplantion (auto-HSCT) for patients with acute myeloid leukemia (AML). All patients, aged 15–54 years (median 32 years), had favorable/intermediate risk AML (n = 20) or acute promyelocytic leukemia (APL; n = 2) and no evidence of minimal residual disease (MRD) prior to transplantation. Fourteen of the 22 patients received the conditioning regimen as follows: busulfan (Bu) + cyclophosphamide (Cy) + CLAD + cytarabine (Ara-c) or idarubicin. The conditioning regimen of 8 patients was without Cy nor idarubicin to reducing adverse cardiac reaction: the regimen of Bu + CLAD+ Ara-c for 6 patients; and the regimen of Bu + melphalan + CLAD + Ara-c for the other 2 patients. All 22 AML patients received peripheral blood stem cell transplantation. The number of infused mononuclear cells and CD34+ cells was 10.00 (2.88–20.97) × 108/kg and 1.89 (1.52–10.44) × 106/kg, respectively. Hematopoietic reconstitution was achieved in all patients, with a median time of 13 (10–34) days for neutrophils and 28 (14–113) days for platelets. Two patients suffered from pulmonary infection, 4 patients suffered from septicemia during the neutropenic stage, and the others suffered from infection or gastrointestinal reaction without exceeding grade 3 after conditioning, which were all alleviated by anti-infection and other supportive treatment. None of the patients died of transplantation-related complications. At a median follow-up of 29.5 (ranging from 4.0 to 60.0) months, three patients relapsed after auto-HSCT at a median time of 6 (ranging from 0.5 to 10.0) months. One patient died due to relapse at 18 months after auto-HSCT. The remaining 21 patients were all alive, including 19 patients with negative MRD. The other 2 patients achieved negative MRD after allogeneic HSCT or chemotherapy. The estimated 2-year survival, relapse, and Leukemia-free survival rates were 94.1 ± 5.7%, 14.7 ± 7.9% and 85.3 ± 7.9%, respectively. A CLAD-combination conditioning regimen is efficient and safe for auto-HSCT, indicating an effective approach for AML treatment. |
| first_indexed | 2024-04-10T17:43:36Z |
| format | Article |
| id | doaj.art-cd98361e4b2243ce99da35a9a0117d98 |
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| language | English |
| last_indexed | 2024-04-10T17:43:36Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-cd98361e4b2243ce99da35a9a0117d982023-02-03T06:12:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-02-011410.3389/fphar.2023.10143061014306Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemiaYuan-Yuan Shi0Zeng-Yan Liu1Gui-Xin Zhang2Yi He3Ming-Zhe Han4Si-Zhou Feng5Rong-Li Zhang6Er-Lie Jiang7State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaDepartment of Hematology, Binzhou Medical University Hospital, Binzhou, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaState Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, ChinaThis is a small phase I study examining the safety and efficacy of a cladribine (CLAD)-containing conditioning regimen prior to autologous hematopoietic stem cell transplantion (auto-HSCT) for patients with acute myeloid leukemia (AML). All patients, aged 15–54 years (median 32 years), had favorable/intermediate risk AML (n = 20) or acute promyelocytic leukemia (APL; n = 2) and no evidence of minimal residual disease (MRD) prior to transplantation. Fourteen of the 22 patients received the conditioning regimen as follows: busulfan (Bu) + cyclophosphamide (Cy) + CLAD + cytarabine (Ara-c) or idarubicin. The conditioning regimen of 8 patients was without Cy nor idarubicin to reducing adverse cardiac reaction: the regimen of Bu + CLAD+ Ara-c for 6 patients; and the regimen of Bu + melphalan + CLAD + Ara-c for the other 2 patients. All 22 AML patients received peripheral blood stem cell transplantation. The number of infused mononuclear cells and CD34+ cells was 10.00 (2.88–20.97) × 108/kg and 1.89 (1.52–10.44) × 106/kg, respectively. Hematopoietic reconstitution was achieved in all patients, with a median time of 13 (10–34) days for neutrophils and 28 (14–113) days for platelets. Two patients suffered from pulmonary infection, 4 patients suffered from septicemia during the neutropenic stage, and the others suffered from infection or gastrointestinal reaction without exceeding grade 3 after conditioning, which were all alleviated by anti-infection and other supportive treatment. None of the patients died of transplantation-related complications. At a median follow-up of 29.5 (ranging from 4.0 to 60.0) months, three patients relapsed after auto-HSCT at a median time of 6 (ranging from 0.5 to 10.0) months. One patient died due to relapse at 18 months after auto-HSCT. The remaining 21 patients were all alive, including 19 patients with negative MRD. The other 2 patients achieved negative MRD after allogeneic HSCT or chemotherapy. The estimated 2-year survival, relapse, and Leukemia-free survival rates were 94.1 ± 5.7%, 14.7 ± 7.9% and 85.3 ± 7.9%, respectively. A CLAD-combination conditioning regimen is efficient and safe for auto-HSCT, indicating an effective approach for AML treatment.https://www.frontiersin.org/articles/10.3389/fphar.2023.1014306/fullCladribineAcute Myeloid LeukemiaAutologous hematopoietic stem cell transplantationConditioning regimenefficacy and safety |
| spellingShingle | Yuan-Yuan Shi Zeng-Yan Liu Gui-Xin Zhang Yi He Ming-Zhe Han Si-Zhou Feng Rong-Li Zhang Er-Lie Jiang Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia Frontiers in Pharmacology Cladribine Acute Myeloid Leukemia Autologous hematopoietic stem cell transplantation Conditioning regimen efficacy and safety |
| title | Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia |
| title_full | Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia |
| title_fullStr | Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia |
| title_full_unstemmed | Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia |
| title_short | Safety and efficacy of a modified busulfan/cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia |
| title_sort | safety and efficacy of a modified busulfan cyclophosphamide conditioning regimen incorporating cladribine for autologous hematopoietic stem cell transplantation in acute myeloid leukemia |
| topic | Cladribine Acute Myeloid Leukemia Autologous hematopoietic stem cell transplantation Conditioning regimen efficacy and safety |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1014306/full |
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