A TREOSULFAN-BASED TOXICITY-REDUCED CONDITIONING REGIMEN IS SAFE AND FEASIBLE FOR CHILDREN WITH NON-MALIGNANT DISEASES BUT INCREASES REJECTION RATES IN STEM CELL TRANSPLANTATION OF HEMOGLOBINOPATHIES
(Abstract release date: 05/19/16)
EHA Library. Malaval C. 06/09/16; 133092; E1543
Dr. Carmen Malaval
Contributions
Contributions
Abstract
Abstract: E1543
Type: Eposter Presentation
Background
Hematopoietic stem cell transplantation (HSCT) as a treatment of non-malignant diseases has improved over the last decades. Less toxic chemotherapy during conditioning aims at reducing transplant related mortality with the risk of an increased rejection rate. Non-malignant disorders are chemo-naïve and carry an increased risk of transplant rejection compared to malignant diseases.
Aims
Aim of the present study was to evaluate safety and feasibility of a treosulfan-based toxicity-reduced conditioning regimen in pediatric patients undergoing HSCT.
Methods
This retrospective study analyzed the safety and feasibility of a treosulfan-based conditioning between 2009 and 2013 in 31 pediatric HSCT recipients (17 males, 14 females) with a median age of 7.8 years (range 0.1 – 18.2 years), undergoing allogeneic HSCT for non-malignant diseases, thalassemia (n=11), leukodystrophies (n=6), severe combined immunodeficiency (n=4), sickle cell disease (n=3), familial hemophagocytic lymphohystiocytosis (n=3) and others (n=4). The chemotherapy during the conditioning regimen consisted of fludarabine 150 mg/m2 in 5 single doses (5 x 30 mg/m2) between day -7 and day -3. Treosulfan was given in a dosage of 42 g/m2 in 3 single doses (3 x 14 g/m2) between day -6 and day -4 . On day -2, thiotepa was applied in a dosage of 10 mg/kg bodyweight per day, twice a day (2 x 5 mg/kg BW). Between day -6 and day -3, patients received treatment with 4.5 mg /kg BW anti-thymocyte globulin (ATG) in 4 dosages (1 x 0.5 mg/kg BW as test dosage; 1 x 1.0 mg/kg BW; 2 x 1.5 mg/kg BW). Patients received transplants from a matched sibling donor (MSD, n=15), a matched unrelated donor (MUD, n=12), a mismatched unrelated donor (MMUD, n=1), a matched family donor (MFD, n=2), or a mismatched family donor (MMFD, n=1). The median observation period was 2.0 years (range 34 days - 5.6 years) and included the time of measurement directly before the start of conditioning until December 2014.
Results
Primary engraftment occurred in 97 % of the patients, with a median time of 15 days after transplantation to reach >1000 leukocytes per µl peripheral blood and a median time of 21 days to reach platelet counts, which did not require transfusions anymore. After re-transplantation, final engraftment occurred in 67 % of the patients. Graft-versus-Host Disease (GvHD) grade II and III-IV occurred in 6 % and 9 % of the patients, and chronic GvHD occurred in 0 % of the patients. Rate of other grade IV side effects was low, except for grade IV stomatitis that occurred in 42 % of the cases. Transplant related mortality (TRM) was observed in 7 % of the patients after one year. HSCT recipients with hemoglobinopathies were accompanied by a rejection rate of 31 % compared to 0% rejection rate among all other patients. Mixed chimerism occurred in 71 % of the cases. Mixed chimerism >50 % occurred in 42 % of the cases and mixed chimerism >80 % occurred in 23 % of the cases.
Conclusion
In conclusion, a treosulfan-based conditioning regimen resulted in excellent engraftment rates with low toxicity in children with non-malignant diseases. However, in children with hemoglobinopathies, the rejection rate was not acceptable occurring in around one third of the cases. Future prospective controlled studies will have to clarify the long-term outcome.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Pediatric, Rejection, Treosulfan
Type: Eposter Presentation
Background
Hematopoietic stem cell transplantation (HSCT) as a treatment of non-malignant diseases has improved over the last decades. Less toxic chemotherapy during conditioning aims at reducing transplant related mortality with the risk of an increased rejection rate. Non-malignant disorders are chemo-naïve and carry an increased risk of transplant rejection compared to malignant diseases.
Aims
Aim of the present study was to evaluate safety and feasibility of a treosulfan-based toxicity-reduced conditioning regimen in pediatric patients undergoing HSCT.
Methods
This retrospective study analyzed the safety and feasibility of a treosulfan-based conditioning between 2009 and 2013 in 31 pediatric HSCT recipients (17 males, 14 females) with a median age of 7.8 years (range 0.1 – 18.2 years), undergoing allogeneic HSCT for non-malignant diseases, thalassemia (n=11), leukodystrophies (n=6), severe combined immunodeficiency (n=4), sickle cell disease (n=3), familial hemophagocytic lymphohystiocytosis (n=3) and others (n=4). The chemotherapy during the conditioning regimen consisted of fludarabine 150 mg/m2 in 5 single doses (5 x 30 mg/m2) between day -7 and day -3. Treosulfan was given in a dosage of 42 g/m2 in 3 single doses (3 x 14 g/m2) between day -6 and day -4 . On day -2, thiotepa was applied in a dosage of 10 mg/kg bodyweight per day, twice a day (2 x 5 mg/kg BW). Between day -6 and day -3, patients received treatment with 4.5 mg /kg BW anti-thymocyte globulin (ATG) in 4 dosages (1 x 0.5 mg/kg BW as test dosage; 1 x 1.0 mg/kg BW; 2 x 1.5 mg/kg BW). Patients received transplants from a matched sibling donor (MSD, n=15), a matched unrelated donor (MUD, n=12), a mismatched unrelated donor (MMUD, n=1), a matched family donor (MFD, n=2), or a mismatched family donor (MMFD, n=1). The median observation period was 2.0 years (range 34 days - 5.6 years) and included the time of measurement directly before the start of conditioning until December 2014.
Results
Primary engraftment occurred in 97 % of the patients, with a median time of 15 days after transplantation to reach >1000 leukocytes per µl peripheral blood and a median time of 21 days to reach platelet counts, which did not require transfusions anymore. After re-transplantation, final engraftment occurred in 67 % of the patients. Graft-versus-Host Disease (GvHD) grade II and III-IV occurred in 6 % and 9 % of the patients, and chronic GvHD occurred in 0 % of the patients. Rate of other grade IV side effects was low, except for grade IV stomatitis that occurred in 42 % of the cases. Transplant related mortality (TRM) was observed in 7 % of the patients after one year. HSCT recipients with hemoglobinopathies were accompanied by a rejection rate of 31 % compared to 0% rejection rate among all other patients. Mixed chimerism occurred in 71 % of the cases. Mixed chimerism >50 % occurred in 42 % of the cases and mixed chimerism >80 % occurred in 23 % of the cases.
Conclusion
In conclusion, a treosulfan-based conditioning regimen resulted in excellent engraftment rates with low toxicity in children with non-malignant diseases. However, in children with hemoglobinopathies, the rejection rate was not acceptable occurring in around one third of the cases. Future prospective controlled studies will have to clarify the long-term outcome.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Pediatric, Rejection, Treosulfan
Abstract: E1543
Type: Eposter Presentation
Background
Hematopoietic stem cell transplantation (HSCT) as a treatment of non-malignant diseases has improved over the last decades. Less toxic chemotherapy during conditioning aims at reducing transplant related mortality with the risk of an increased rejection rate. Non-malignant disorders are chemo-naïve and carry an increased risk of transplant rejection compared to malignant diseases.
Aims
Aim of the present study was to evaluate safety and feasibility of a treosulfan-based toxicity-reduced conditioning regimen in pediatric patients undergoing HSCT.
Methods
This retrospective study analyzed the safety and feasibility of a treosulfan-based conditioning between 2009 and 2013 in 31 pediatric HSCT recipients (17 males, 14 females) with a median age of 7.8 years (range 0.1 – 18.2 years), undergoing allogeneic HSCT for non-malignant diseases, thalassemia (n=11), leukodystrophies (n=6), severe combined immunodeficiency (n=4), sickle cell disease (n=3), familial hemophagocytic lymphohystiocytosis (n=3) and others (n=4). The chemotherapy during the conditioning regimen consisted of fludarabine 150 mg/m2 in 5 single doses (5 x 30 mg/m2) between day -7 and day -3. Treosulfan was given in a dosage of 42 g/m2 in 3 single doses (3 x 14 g/m2) between day -6 and day -4 . On day -2, thiotepa was applied in a dosage of 10 mg/kg bodyweight per day, twice a day (2 x 5 mg/kg BW). Between day -6 and day -3, patients received treatment with 4.5 mg /kg BW anti-thymocyte globulin (ATG) in 4 dosages (1 x 0.5 mg/kg BW as test dosage; 1 x 1.0 mg/kg BW; 2 x 1.5 mg/kg BW). Patients received transplants from a matched sibling donor (MSD, n=15), a matched unrelated donor (MUD, n=12), a mismatched unrelated donor (MMUD, n=1), a matched family donor (MFD, n=2), or a mismatched family donor (MMFD, n=1). The median observation period was 2.0 years (range 34 days - 5.6 years) and included the time of measurement directly before the start of conditioning until December 2014.
Results
Primary engraftment occurred in 97 % of the patients, with a median time of 15 days after transplantation to reach >1000 leukocytes per µl peripheral blood and a median time of 21 days to reach platelet counts, which did not require transfusions anymore. After re-transplantation, final engraftment occurred in 67 % of the patients. Graft-versus-Host Disease (GvHD) grade II and III-IV occurred in 6 % and 9 % of the patients, and chronic GvHD occurred in 0 % of the patients. Rate of other grade IV side effects was low, except for grade IV stomatitis that occurred in 42 % of the cases. Transplant related mortality (TRM) was observed in 7 % of the patients after one year. HSCT recipients with hemoglobinopathies were accompanied by a rejection rate of 31 % compared to 0% rejection rate among all other patients. Mixed chimerism occurred in 71 % of the cases. Mixed chimerism >50 % occurred in 42 % of the cases and mixed chimerism >80 % occurred in 23 % of the cases.
Conclusion
In conclusion, a treosulfan-based conditioning regimen resulted in excellent engraftment rates with low toxicity in children with non-malignant diseases. However, in children with hemoglobinopathies, the rejection rate was not acceptable occurring in around one third of the cases. Future prospective controlled studies will have to clarify the long-term outcome.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Pediatric, Rejection, Treosulfan
Type: Eposter Presentation
Background
Hematopoietic stem cell transplantation (HSCT) as a treatment of non-malignant diseases has improved over the last decades. Less toxic chemotherapy during conditioning aims at reducing transplant related mortality with the risk of an increased rejection rate. Non-malignant disorders are chemo-naïve and carry an increased risk of transplant rejection compared to malignant diseases.
Aims
Aim of the present study was to evaluate safety and feasibility of a treosulfan-based toxicity-reduced conditioning regimen in pediatric patients undergoing HSCT.
Methods
This retrospective study analyzed the safety and feasibility of a treosulfan-based conditioning between 2009 and 2013 in 31 pediatric HSCT recipients (17 males, 14 females) with a median age of 7.8 years (range 0.1 – 18.2 years), undergoing allogeneic HSCT for non-malignant diseases, thalassemia (n=11), leukodystrophies (n=6), severe combined immunodeficiency (n=4), sickle cell disease (n=3), familial hemophagocytic lymphohystiocytosis (n=3) and others (n=4). The chemotherapy during the conditioning regimen consisted of fludarabine 150 mg/m2 in 5 single doses (5 x 30 mg/m2) between day -7 and day -3. Treosulfan was given in a dosage of 42 g/m2 in 3 single doses (3 x 14 g/m2) between day -6 and day -4 . On day -2, thiotepa was applied in a dosage of 10 mg/kg bodyweight per day, twice a day (2 x 5 mg/kg BW). Between day -6 and day -3, patients received treatment with 4.5 mg /kg BW anti-thymocyte globulin (ATG) in 4 dosages (1 x 0.5 mg/kg BW as test dosage; 1 x 1.0 mg/kg BW; 2 x 1.5 mg/kg BW). Patients received transplants from a matched sibling donor (MSD, n=15), a matched unrelated donor (MUD, n=12), a mismatched unrelated donor (MMUD, n=1), a matched family donor (MFD, n=2), or a mismatched family donor (MMFD, n=1). The median observation period was 2.0 years (range 34 days - 5.6 years) and included the time of measurement directly before the start of conditioning until December 2014.
Results
Primary engraftment occurred in 97 % of the patients, with a median time of 15 days after transplantation to reach >1000 leukocytes per µl peripheral blood and a median time of 21 days to reach platelet counts, which did not require transfusions anymore. After re-transplantation, final engraftment occurred in 67 % of the patients. Graft-versus-Host Disease (GvHD) grade II and III-IV occurred in 6 % and 9 % of the patients, and chronic GvHD occurred in 0 % of the patients. Rate of other grade IV side effects was low, except for grade IV stomatitis that occurred in 42 % of the cases. Transplant related mortality (TRM) was observed in 7 % of the patients after one year. HSCT recipients with hemoglobinopathies were accompanied by a rejection rate of 31 % compared to 0% rejection rate among all other patients. Mixed chimerism occurred in 71 % of the cases. Mixed chimerism >50 % occurred in 42 % of the cases and mixed chimerism >80 % occurred in 23 % of the cases.
Conclusion
In conclusion, a treosulfan-based conditioning regimen resulted in excellent engraftment rates with low toxicity in children with non-malignant diseases. However, in children with hemoglobinopathies, the rejection rate was not acceptable occurring in around one third of the cases. Future prospective controlled studies will have to clarify the long-term outcome.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Pediatric, Rejection, Treosulfan
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