Chronic Kidney Disease after Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
2007; Elsevier BV; Volume: 13; Issue: 12 Linguagem: Inglês
10.1016/j.bbmt.2007.09.005
ISSN1523-6536
AutoresHenk B. Kal, M. Loes van Kempen-Harteveld,
Tópico(s)Acute Myeloid Leukemia Research
ResumoTo the Editor:We read the article by Kersting et al [1Kersting S. Hené R.J. Koomans H.A. Verdonek C.F. Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2007; 13: 1169-1175Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] on chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) with great interest. The authors reported that 23% of the patients receiving a myeloablative conditioning regimen and total body irradiation (TBI) developed chronic kidney disease. The conditioning regimen consisted of cyclophosphamide (6 mg/kg/day for 2 days), followed by TBI (2 × 6 Gy in 2 days), with the kidneys shielded to 2 × 5 Gy. The dose rate was 9 Gy/h. Chronic renal disease after HSCT has been associated with TBI [2Leblond V. Sutton L. Jacquiaud C. et al.Evaluation of renal function in 60 long-term survivors of bone marrow transplantation.J Am Soc Nephrol. 1995; 6: 1661-1665PubMed Google Scholar, 3Miralbell R. Bieri S. Mermillod B. et al.Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.J Clin Oncol. 1996; 14: 579-585PubMed Google Scholar, 4Lawton C.A. Cohen E.P. Murray K.J. et al.Long-term results of selective renal shielding in patients undergoing total body irradiation in preparation for bone marrow transplantation.Bone Marrow Transplant. 1997; 20: 1069-1074Crossref PubMed Scopus (93) Google Scholar]. The dose of 2 × 5 Gy to the kidneys may have been beyond the tolerance dose for kidney failure.Here we comment on the TBI dose and propose a TBI regimen that possibly could result in a lower frequency of renal disease, but still provide a high antileukemic effect.Recently, we reviewed the literature, compared the results of treatments with various TBI regimens, and determined a dose–effect relationship for renal dysfunction after TBI [5Kal H.B. van Kempen-Harteveld M.L. Renal dysfunction after total body irradiation: dose-effect relationship.Int J Radiat Oncol Biol Phys. 2006; 65: 1228-1232Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar]. For intercomparison, as used in radiotherapy, the various TBI regimens were normalized (using the linear-quadratic model), and the biological effective doses (BEDs) were calculated [6Barendsen G.W. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses.Int J Radiat Oncol Biol Phys. 1982; 8: 1981-1997Abstract Full Text PDF PubMed Scopus (889) Google Scholar]. In this way, for each TBI regimen, the total dose, number of fractions, and dose rate could be included in a single BED value. We found a threshold BED of about 16 Gy for late kidney failure [5Kal H.B. van Kempen-Harteveld M.L. Renal dysfunction after total body irradiation: dose-effect relationship.Int J Radiat Oncol Biol Phys. 2006; 65: 1228-1232Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar].To prevent renal disease, the kidneys of the patients described by Kersting et al. [1Kersting S. Hené R.J. Koomans H.A. Verdonek C.F. Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2007; 13: 1169-1175Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] should have been shielded from 2 × 5 Gy (BED = 28.1 Gy) to 2 × 3.6 Gy (BED = 16.6 Gy). However, shielding will result in a lower BED not only of the shielded organ, but also of the leukemic cells present in the tissues in the shadow of the shielding block. The BED of the leukemic cells in the region shielded to 2 × 3.6 Gy was only 9.1 Gy, whereas in the unshielded tissues it was 17.4 Gy.With hyperfractionated TBI regimens, a relatively high BED for leukemic cells can be obtained, whereas shielding is relatively limited. For example, with a scheme of 6 fractions of 2.3 Gy given over 3 days at a dose rate of 9 Gy/h, the BED for leukemic cells is 16.6 Gy, and the BED of the kidney tissue is 26.0 Gy (with differences in BED values from tissue-specific parameters [5Kal H.B. van Kempen-Harteveld M.L. Renal dysfunction after total body irradiation: dose-effect relationship.Int J Radiat Oncol Biol Phys. 2006; 65: 1228-1232Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 6Barendsen G.W. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses.Int J Radiat Oncol Biol Phys. 1982; 8: 1981-1997Abstract Full Text PDF PubMed Scopus (889) Google Scholar]). With shielding of the kidneys to 6 × 1.7 Gy, the resulting BED is16.9 Gy; thus, the kidney dose reduction is only 26%. The BED for leukemic cells behind the shielding block remains 11.8 Gy. Thus, hyperfractionated TBI with proper shielding might be useful in preventing chronic renal dysfunction. To the Editor: We read the article by Kersting et al [1Kersting S. Hené R.J. Koomans H.A. Verdonek C.F. Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2007; 13: 1169-1175Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] on chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) with great interest. The authors reported that 23% of the patients receiving a myeloablative conditioning regimen and total body irradiation (TBI) developed chronic kidney disease. The conditioning regimen consisted of cyclophosphamide (6 mg/kg/day for 2 days), followed by TBI (2 × 6 Gy in 2 days), with the kidneys shielded to 2 × 5 Gy. The dose rate was 9 Gy/h. Chronic renal disease after HSCT has been associated with TBI [2Leblond V. Sutton L. Jacquiaud C. et al.Evaluation of renal function in 60 long-term survivors of bone marrow transplantation.J Am Soc Nephrol. 1995; 6: 1661-1665PubMed Google Scholar, 3Miralbell R. Bieri S. Mermillod B. et al.Renal toxicity after allogeneic bone marrow transplantation: the combined effects of total-body irradiation and graft-versus-host disease.J Clin Oncol. 1996; 14: 579-585PubMed Google Scholar, 4Lawton C.A. Cohen E.P. Murray K.J. et al.Long-term results of selective renal shielding in patients undergoing total body irradiation in preparation for bone marrow transplantation.Bone Marrow Transplant. 1997; 20: 1069-1074Crossref PubMed Scopus (93) Google Scholar]. The dose of 2 × 5 Gy to the kidneys may have been beyond the tolerance dose for kidney failure. Here we comment on the TBI dose and propose a TBI regimen that possibly could result in a lower frequency of renal disease, but still provide a high antileukemic effect. Recently, we reviewed the literature, compared the results of treatments with various TBI regimens, and determined a dose–effect relationship for renal dysfunction after TBI [5Kal H.B. van Kempen-Harteveld M.L. Renal dysfunction after total body irradiation: dose-effect relationship.Int J Radiat Oncol Biol Phys. 2006; 65: 1228-1232Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar]. For intercomparison, as used in radiotherapy, the various TBI regimens were normalized (using the linear-quadratic model), and the biological effective doses (BEDs) were calculated [6Barendsen G.W. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses.Int J Radiat Oncol Biol Phys. 1982; 8: 1981-1997Abstract Full Text PDF PubMed Scopus (889) Google Scholar]. In this way, for each TBI regimen, the total dose, number of fractions, and dose rate could be included in a single BED value. We found a threshold BED of about 16 Gy for late kidney failure [5Kal H.B. van Kempen-Harteveld M.L. Renal dysfunction after total body irradiation: dose-effect relationship.Int J Radiat Oncol Biol Phys. 2006; 65: 1228-1232Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar]. To prevent renal disease, the kidneys of the patients described by Kersting et al. [1Kersting S. Hené R.J. Koomans H.A. Verdonek C.F. Chronic kidney disease after myeloablative allogeneic hematopoietic stem cell transplantation.Biol Blood Marrow Transplant. 2007; 13: 1169-1175Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar] should have been shielded from 2 × 5 Gy (BED = 28.1 Gy) to 2 × 3.6 Gy (BED = 16.6 Gy). However, shielding will result in a lower BED not only of the shielded organ, but also of the leukemic cells present in the tissues in the shadow of the shielding block. The BED of the leukemic cells in the region shielded to 2 × 3.6 Gy was only 9.1 Gy, whereas in the unshielded tissues it was 17.4 Gy. With hyperfractionated TBI regimens, a relatively high BED for leukemic cells can be obtained, whereas shielding is relatively limited. For example, with a scheme of 6 fractions of 2.3 Gy given over 3 days at a dose rate of 9 Gy/h, the BED for leukemic cells is 16.6 Gy, and the BED of the kidney tissue is 26.0 Gy (with differences in BED values from tissue-specific parameters [5Kal H.B. van Kempen-Harteveld M.L. Renal dysfunction after total body irradiation: dose-effect relationship.Int J Radiat Oncol Biol Phys. 2006; 65: 1228-1232Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar, 6Barendsen G.W. Dose fractionation, dose rate and iso-effect relationships for normal tissue responses.Int J Radiat Oncol Biol Phys. 1982; 8: 1981-1997Abstract Full Text PDF PubMed Scopus (889) Google Scholar]). With shielding of the kidneys to 6 × 1.7 Gy, the resulting BED is16.9 Gy; thus, the kidney dose reduction is only 26%. The BED for leukemic cells behind the shielding block remains 11.8 Gy. Thus, hyperfractionated TBI with proper shielding might be useful in preventing chronic renal dysfunction. Chronic Kidney Disease after Myeloablative Allogeneic Hematopoietic Stem Cell TransplantationBiology of Blood and Marrow TransplantationVol. 13Issue 10PreviewBecause survival of recipients of allogeneic hematopoietic stem cell transplantation (HSCT) has improved, long-term complications become more important. We studied the incidence and risk factors of chronic kidney disease in these patients and evaluated associated posttransplant complications and mortality. We performed a retrospective cohort study of 266 adults who received myeloablative allogeneic HSCT and who survived for >6 months in an 11-year period at a Dutch university medical center. Primary outcome was the incidence of chronic kidney disease defined as a glomerular filtration rate (GFR) of <60 mL/min/1.73 m2. Full-Text PDF Open Archive
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