598 Journal of Experimental Hematology 2012 20 3 598-602 Article ID 1009-2137 2012 03-0598 - 05 100 1 2 2 2 2 2 2 2 2 2 2 2 2* 1 100853 2 307 100071 ML AHSCT 1992 9 2010 8 307 AHSCT 100 ML AHSCT 3 5 10 OS PFS 2011 2 33. 5 > 1. 0 10 9 /L 6. 0 ± 0. 4 d 8. 2 ± 0. 4 d > 20. 0 10 9 /L 7. 1 ± 0. 8 d 11. 4 ± 2. 5 d P < 0. 05 OS 3 67. 3% 68. 9% 5 62. 8% 60. 6% 10 57. 6% 56. 2% PFS 3 63. 6% 63. 2% 5 59. 4% 58. 3% 10 50. 8% 55. 3% P > 0. 05 P > 0. 05 R733. 1 R457. 7 A Clinical Obse rvation of 100 Patie nts with Malignant Lymphoma Treating with Different Preconditioning Regimens Followed by Autologous He matopoie tic Ste m Ce ll Transplantation SHAO Lan-Lan 1 2 XIAO Xiu-Bin 2 ZHONG Kai-Li 2 LU Yun 2 CHEN Xi-Lin 2 DA Yong 2 LIU Jing 2 ZHAO Shi-Hua 2 MA Yi 2 YANG Qiu-Shi 2 SU Hang 2 ZHANG Wei-Jing 2* 1 Postgraduate Medical School of Chinese People Liberation ArmyBeijing 100853China 2 Department of LymphomaAffiliated Hospital 307Academy of Military Medical SciencesBeijing 100071 China * Corresponding Author ZHANG Wei-JingSenior Physician. Tel 010 66947166. E-mail zhangwj3072@ 163. com Abstract This study was designed to compare the curative effectprognosis and safety of different preconditioning regimens for patients who received autologous hematopoietic stem cell transplantation AHSCT for malignant lymphoma ML. The clinical data of 100 ML patients Sep 1992 to Aug 2010 in 307 Hospital were retrospectively analyzedand were divided into two groups by different preconditioning regimens the high-dose chemotherapy preconditioning group and high-dose chemotherapy /radiotherapy preconditioning group. The overall survival OS rateprogress free survival PFS rate and adverse effect were analyzed. The results showed that until Feb 2011 the median follow-up was 33. 5 months. All patients were engrafted and their hematopoiesis was reconstituted. The median time of WBC recovery up to > 1. 0 1. 0 9 /L in high-dose chemotherapy preconditioning group and high-dose chemotherapy / radiotherapy preconditioning group were 6. 0 ± 0. 4 d and 8. 2 ± 0. 4 platelet up to > 20. 0 1. 0 9 /L in two groups were 7. 1 ± 0. 8 d and 11. 4 ± 2. 5 d P < 0. 05. The 3-year OS rate of the two groups were 67. 3% and 68. 9%. 5-year OS rates of two groups were 62. 8% and 60. 6% 10-year OS rates of two groups were 57. 6% and 56. 2% respectively 3-year PFS of two group were 63. 6% and 63. 2% 5-year of two group were 59. 4% and 58. 3% 10-year of two group were 50. 8% and 55. 3% respectively P > 0. 05. Meanwhile the incidence of fever infectionbleedingsecondary cancer between two groups was not significant different P > 0. 05. It is concluded that the hematopoietic reconstitution of high-dose chemotherapy /radiotherapy preconditioning group is later than that of high-dose chemotherapy preconditioning group. However there is no significant difference in curative effect and prognosis between the two groups. Key words malignant lymphoma preconditioning regimen autologous hematopoietic stem cell transplantation J Exp Hematol 2012 20 3 598-602 *. 010 66947166. E-mail zhangwj3072@ 163. com 2012-04 - 12 2012-05 - 11
100 599 Table 1. Clinical data of 100 patients with malignant lymphoma Preconditioning regimen 307 High-dose High-dose Clinical date P-value 100 chemotherapy chemo / radiotherapy n % n % Sex 0. 824 1992 9-2010 8 307 100 Yes 26 37. 7 7 22. 6 No 43 62. 3 24 77. 4 No 26 37. 7 14 45. 2 100 34. 5 6-67 Pathology type 0. 084 76 24 Ann Arbor Ⅰ - HL 17 24. 6 3 9. 7 Ⅱ37 B NHL 52 75. 4 28 90. 3 Treatment before AHSCT 0. 452 53 20 10 Initial treatment 8 1 Retreatment 39 56. 5 30 43. 5 20 64. 5 11 35. 5 1 80 Status after AHSCT 0. 918 5 B 1 B CR1 35 50. 7 16 51. 6 28 Burkit 2 B CR2 3 T 2 CR3 T 8 9 PR NK /T 7 SD T 7 T 8 6 8. 7 3 4. 3 23 33. 3 2 2. 9 2 6. 5 1 3. 2 11 35. 5 1 3. 2 1 1BEAM 300 mg /m 2 100 7 d + 50-100 mg / m 12 h 1 6-3 d + 100-200 mg / m 2 12 h 1 6-3 d + 140 mg /m TBI TLI CT MRI PET- 2 d 2CBV 1. 6 g / m 2 d CT 4-2 d + 450-550 mg /m 2 8 d + 150-200 mg / m 2 12 h 1 7-5 d TBI TLI CA + Male 52 75. 4 24 77. 4 Female 17 24. 6 7 22. 6 Staging 0. 269 28 40. 6 9 29. 0 41 59. 4 22 71. 0 B-symptom 0. 137 Large tumor 0. 330 Yes 43 62. 3 17 54. 8 TBI 7-10 Gy 1 2-3 7 8 d TLI 6-8 Gy2-4 7 300 μg /d > 5. 0 10 9 /L 8 d + - 196 2-4 g /m 2 4-3 d + 100-125 mg /m 2 7-4 d
600 J Exp Hematol 2012 20 3 OS 98 150. 3 6-257 PFS PSF 135. 7 3-219 3 5 10 OS 67. 6 ± 5. 2 % 62. 4 ± 5. 9 % 5. 5 % 58. 7 ± 5. 8 % 54. 3 ± 7. 5 % OS PFS 3 V3. 0 0 - Ⅳ 2011 2 33. 5 6-257 2 2% SPSS13. 0 Kaplan-Meier Logrank χ 2 α = 0. 05 57. 6 ± 6. 3 % 3 5 10 PFS 63. 3 ± 100 > 1. 0 10 9 /L 6. 7 ± 0. 3 d > 0. 5 10 9 /L 6. 1 ± 0. 3 > 20. 0 10 9 /L 8. 4 ± 0. 9 P < 0. 052 Table 2. Time of hematopoietic reconstitution in different preconditioning regimen groups Preconditioning regimen High-dose chemotherapy High-dose chemo / radiotherapy WBC > 1. 0 10 9 /L Neutrophil Platelet > 0. 5 10 9 /L > 20. 0 10 9 /L 6. 0 ± 0. 4 5. 2 ± 0. 3 7. 1 ± 0. 8 8. 2 ± 0. 4 8. 1 ± 0. 5 11. 4 ± 2. 5 P-value 0. 022 0. 01 0. 037 Figure. Kaplan-Merier curves of lymphoma patients after transplantation. P = 0. 126 OS P = 0. 129 PFS. 100 75% Ⅰ 11% Ⅱ52% Ⅲ12% 18% Ⅰ 3% Ⅱ12% Ⅲ3% 70% 58% 28% 9
100 601 Table 3. OS and PFS rate between different preconditioning regimen groups Preconditioning regimen n OS rate % 3-year 5-year 10-year PFS rate % 3-year 5-year 10-year High-dose chemotherapy 67 67. 3 ± 6. 8 62. 8 ± 7. 7 57. 6 ± 8. 7 63. 6 ± 7. 2 59. 4 ± 6. 6 50. 8 ± 12. 8 High-dose chemo /radiotherapy 31 68. 9 ± 8. 7 60. 6 ± 9. 4 56. 2 ± 9. 7 63. 2 ± 8. 8 58. 3 ± 9. 4 55. 3 ± 5. 3 P-value 0. 126 0. 129 Table 4. Side effects in different preconditioning regimen groups Preconditioning regimen Fever n % Infection n % Bacterial Fungous Viral Bleeding n % High-dose chemotherapy 41 59. 4 9 13. 0 37 53. 6 4 5. 8 6 8. 7 10 14. 5 2 2. 9 High-dose chemo /radiotherapy 20 64. 5 5 16. 1 21 67. 7 1 3. 2 1 3. 2 5 16. 1 1 3. 2 P-value 0. 382 0. 540 0. 813 Preconditioning regimen Gastrointestinal n % Catarrh n % Death related to preconditioning regimen n % Secondary tumor n % High-dose chemotherapy 49 71. 0 12 17. 4 18 26. 1 0 0 2 1. 4 High-dose chemo /radiotherapy 23 74. 2 7 22. 6 15 48. 4 2 6. 5 2 6. 5 P-value 0. 176 0. 028 0. 402 6 4 P = 0. 001 5 OS 52% 32% P = 4 3 2 0. 038 Lee 3 154 NK /T 5% 7% 5 OS 91% Ⅰ 87. 3% 67. 8% P = 24% Ⅱ48% Ⅲ12% Ⅳ7% 0. 027 33% 2% OS PFS 4 30 d 4% 2 5 1 100 150. 3 PFS 1 135. 7 3 5 10 OS 67. 6% 62. 4% 1-5 57. 6% 3 5 10 PFS 63. 3% 58. 7% 4 54. 3% Haioun Montoto 6 693 1 916 5 10 8 OS 64% 49% P = 0. 15 PFS 44% 31% 27% 04 PFS 55% 39% P = 0. 02 Philip TBI 2 109 P < 0. 05 Emmanouilides 7 156 5 PFS 46% 12% TBI 4 OS
602 J Exp Hematol 2012 20 3 66% 59% P = 0. 48 TBI P < 0. 01 Wei 8 73 TBI BEAM 5 OS 53. 9% 63. 8% P = 0. 492 5 50. 0% 50. 7% P = 0. 808 9 56 TBI BEAM 5 57. 1 % 61. 4 % P > 0. 05 TBI BEAM 3 5 10 OS PFS P > 0. 05 Transplant2006 37 4 7 Emmanouilides CWolf CScott Set al. Localized radiation increases morbidity and mortality after TBI-containing autologous stem cell transplantation in patients with lymphoma. Bone Marrow Trans- OS PFS 1365 Krishnan 10 92 Z-BEAM study. Leukemia2007 21 11 2324-2331 TBI 4 OS 81% 52. 7% P = 0. 01 4 PFS 59. 6% 42% P = 0. 10 TBI Evens 11 plantation2003 32 9 863-867 48 32 16 stem cell transplantation for non-hodgkin' s lymphoma. 5 OS Oncology Biol2010 78 2 513-520 9 PFS 48% 44% 5 56 OS PFS 61% 63% 11 948-951 5 OS PFS 27% 6% P < 0. 01 for Poor-Risk Diffuse Large Cell Lymphoma. Transplant2010 18 3 441-450 OS PFS 1 Haioun CLepage EGisselbrecht C et al. Survival benefit of highdose therapy in poor-risk aggressive non-hodgkin's lymphoma Final analysis of the prospective LNH 87-2 protocol- A groupe d'etude des lymphomes de l'adulte study. J Clin Oncol2000 18 3025-3030 2 Philip TGuglielmi CHagenbeek Aet al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapsed of chemotherapy-sensitive non-hodgkin's lymphoma. J N Engl Med 1995 33 23 3 1540-1545 3 Lee JPark MJKim Ket al. Autologous Hematopoietic Stem Cell Transplantation in Extranodal Natural Killer /T Cell Lymphoma A MultinationalMulticenterMatched Controlled Study. Biol Blood Marrow Transplant2008 14 12 1356-1364 4 Suzuki RSuzumiya JNakamura Set al. Hematopoietic stem cell transplantation for natural killer-cell lineage neoplasms. Bone Marrow 425-431 5 Josting ASieniawski MGlossmann JP et al. High-dose sequential chemotherapy followed by autologous stem cell transplantation in relapsed and refractory aggressive non-hodgkin's lymphoma results of a multicenter phase Ⅱstudy. Ann Oncol2005 16 8 1359-6 Montoto SRohatiner AZSSureda Aet al. Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma an EBMT registry 8 Liu HWSeftel MDRubinger Met al. Total body irradiation compared with beam long-term outcomes of peripheral blood autologous Radiation.. 2003 83 10 Krishnan ANademanee AThomas SHet al. Matched-Cohort Analysis of Autologous Hematopoietic Cell Transplantation with Radioimmunotherapy versus Total Body Irradiation-Based Conditioning Biol Blood Marrow 11 Evens AMAltman JKMittal BBet al. Phase I /II trial of total lymphoid irradiation and high-dose chemotherapy with autologous stem-cell transplantation for relapsed and refractory Hodgkin' s lymphoma. Annals Oncology 2007 18 4 679-688