Original Paper Acta Haematol 2015;134:138–145 DOI: 10.1159/000370097
Received: June 12, 2014 Accepted after revision: November 25, 2014 Published online: April 24, 2015
Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes Xingxin Li Jun Shi Min Wang Neng Nie Yingqi Shao Meili Ge Jinbo Huang Zhendong Huang Jing Zhang Yizhou Zheng Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, PR China
For editorial comment see p. 135
Key Words Cyclosporine · Levamisole · Myelodysplastic syndromes
alleviated cytopenias and improved survival and freedom from evolution, suggesting that it could be reserved as an alternative choice for lower-risk MDS. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0001–5792/15/1343–0138$39.50/0 E-Mail [email protected] www.karger.com/aha
Introduction
Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by dysplasia, ineffective hematopoiesis and cytopenias, with a high risk of progression to acute myeloid leukemia [1]. Approximately half of these patients die of leukemic transformation and the remainder die from severe cytopenias, including bleeding, infection and secondary hemochromatosis. The International Prognostic Scoring System (IPSS), which was very recently revised (IPSS-R), is based on the severity of cytopenias, blast count and karyotype, has being widely used to predict survival and distinguish among various subgroups with significantly different risks of acute myeloid leukemia transformation [2, 3]. The treatment approaches for lower-risk MDS generally focus on the treatment of cytopenias and the improvement in quality of life [4]. Current options include Jun Shi, MD, PhD or Yizhou Zheng, MD, PhD Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College 288 Nanjing Road, Tianjin 300020 (PR China) E-Mail shijun1973 @ hotmail.com or zheng_yizhou @ hotmail.com
Downloaded by: Fudan University Library 61.129.42.15 - 5/15/2015 6:09:21 PM
Abstract Clinical and experimental evidence suggests an immunemediated pathophysiology in subjects with lower-risk myelodysplastic syndromes (MDS) in whom immunosuppressive therapy may be effective. The novel immunosuppressive strategy of cyclosporine A (CsA) alternately combined with levamisole (LMS; CsA + LMS regimen) can dramatically improve the response rate and survival in aplastic anemia from those of our previous study. Herein, we retrospectively analyzed the data of 89 lower-risk MDS patients who received the CsA + LMS regimen. A total of 63 patients (70.8%) achieved either complete remission or hematological improvement at 4 months. Overall, 51, 41 and 19 patients had erythroid, platelet and neutrophil responses, respectively. Following the CsA + LMS regimen, 6 patients progressed to more advanced MDS at a median interval of 5 months (range, 3–42 months). The estimated 24-month progression-free survival was 82.2% (95% CI, 72.84–91.56) for all patients. Within the median follow-up of 18.5 months (range, 7.0– 61.0), 6 patients died. In conclusion, the CsA + LMS regimen
Patients and Methods Patients We reviewed the records of all newly diagnosed patients with IPSS low- or intermediate-1-risk MDS [2] referred to our institute between August 2008 and January 2013 who were treated with the CsA + LMS regimen. Patients with secondary MDS, significant comorbidities, IPSS intermediate-2- or high-risk MDS (except 4 de novo patients with IPSS intermediate-2-risk MDS who were
CsA + LMS Regimen for Lower-Risk MDS
included as no other treatment was available), refractory anemia with excess blasts (RAEB)-I and -II were excluded, as were children younger than 12 years of age. All 89 patients were restratified according to the IPSS-R [3], and all analyses of response and survival were based on the latter. The protocol described in this study was approved by the institutional ethics committee for Medical Care and Safety. All patients or their legal guardians signed written informed consent before undertaking the CsA + LMS regimen. Therapies The CsA + LMS regimen was designed to alternately administer each agent every other day. The initial dose of CsA was 3 mg/ kg per day, with subsequent adjustment mainly according to serum urea, creatinine and bilirubin levels. Oral LMS was alternately administered at the same time with a dose of 150 mg per day in adults or 2.5 mg/kg per day in children (7 g/dl (or >9 g/dl for patients with underlying cardiopulmonary disease). Platelet concentrates were transfused prophylactically in the setting of PLT
Received: June 12, 2014 Accepted after revision: November 25, 2014 Published online: April 24, 2015
Cyclosporine Combined with Levamisole for Lower-Risk Myelodysplastic Syndromes Xingxin Li Jun Shi Min Wang Neng Nie Yingqi Shao Meili Ge Jinbo Huang Zhendong Huang Jing Zhang Yizhou Zheng Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, PR China
For editorial comment see p. 135
Key Words Cyclosporine · Levamisole · Myelodysplastic syndromes
alleviated cytopenias and improved survival and freedom from evolution, suggesting that it could be reserved as an alternative choice for lower-risk MDS. © 2015 S. Karger AG, Basel
© 2015 S. Karger AG, Basel 0001–5792/15/1343–0138$39.50/0 E-Mail [email protected] www.karger.com/aha
Introduction
Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by dysplasia, ineffective hematopoiesis and cytopenias, with a high risk of progression to acute myeloid leukemia [1]. Approximately half of these patients die of leukemic transformation and the remainder die from severe cytopenias, including bleeding, infection and secondary hemochromatosis. The International Prognostic Scoring System (IPSS), which was very recently revised (IPSS-R), is based on the severity of cytopenias, blast count and karyotype, has being widely used to predict survival and distinguish among various subgroups with significantly different risks of acute myeloid leukemia transformation [2, 3]. The treatment approaches for lower-risk MDS generally focus on the treatment of cytopenias and the improvement in quality of life [4]. Current options include Jun Shi, MD, PhD or Yizhou Zheng, MD, PhD Severe Aplastic Anemia Studying Program, State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences and Peking Union Medical College 288 Nanjing Road, Tianjin 300020 (PR China) E-Mail shijun1973 @ hotmail.com or zheng_yizhou @ hotmail.com
Downloaded by: Fudan University Library 61.129.42.15 - 5/15/2015 6:09:21 PM
Abstract Clinical and experimental evidence suggests an immunemediated pathophysiology in subjects with lower-risk myelodysplastic syndromes (MDS) in whom immunosuppressive therapy may be effective. The novel immunosuppressive strategy of cyclosporine A (CsA) alternately combined with levamisole (LMS; CsA + LMS regimen) can dramatically improve the response rate and survival in aplastic anemia from those of our previous study. Herein, we retrospectively analyzed the data of 89 lower-risk MDS patients who received the CsA + LMS regimen. A total of 63 patients (70.8%) achieved either complete remission or hematological improvement at 4 months. Overall, 51, 41 and 19 patients had erythroid, platelet and neutrophil responses, respectively. Following the CsA + LMS regimen, 6 patients progressed to more advanced MDS at a median interval of 5 months (range, 3–42 months). The estimated 24-month progression-free survival was 82.2% (95% CI, 72.84–91.56) for all patients. Within the median follow-up of 18.5 months (range, 7.0– 61.0), 6 patients died. In conclusion, the CsA + LMS regimen
Patients and Methods Patients We reviewed the records of all newly diagnosed patients with IPSS low- or intermediate-1-risk MDS [2] referred to our institute between August 2008 and January 2013 who were treated with the CsA + LMS regimen. Patients with secondary MDS, significant comorbidities, IPSS intermediate-2- or high-risk MDS (except 4 de novo patients with IPSS intermediate-2-risk MDS who were
CsA + LMS Regimen for Lower-Risk MDS
included as no other treatment was available), refractory anemia with excess blasts (RAEB)-I and -II were excluded, as were children younger than 12 years of age. All 89 patients were restratified according to the IPSS-R [3], and all analyses of response and survival were based on the latter. The protocol described in this study was approved by the institutional ethics committee for Medical Care and Safety. All patients or their legal guardians signed written informed consent before undertaking the CsA + LMS regimen. Therapies The CsA + LMS regimen was designed to alternately administer each agent every other day. The initial dose of CsA was 3 mg/ kg per day, with subsequent adjustment mainly according to serum urea, creatinine and bilirubin levels. Oral LMS was alternately administered at the same time with a dose of 150 mg per day in adults or 2.5 mg/kg per day in children (7 g/dl (or >9 g/dl for patients with underlying cardiopulmonary disease). Platelet concentrates were transfused prophylactically in the setting of PLT
![[Myelodysplastic syndromes].](/assets/img/hold.png)
